Search

Hepatitis C viral (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis, including cerebrovascular atherosclerosis. The aim of this study was to assess cerebrovascular reactivity in patients with chronic hepatitis C. Seventeen patients with chronic hepatitis C infection, as well as 11 healthy blood donors in the control group, were assessed for cerebrovascular reactivity according to the well-established breath-holding test that uses the transcranial color Doppler for measurement of blood flow velocity. Results obtained during the breath-holding revealed significantly lower average peak systolic (AvPS start, P = 0.018), end-diastolic (AvED start, P = 0.031) and mean velocity values at the very beginning of the breath-holding procedure (AvmeanV start, P = 0.02), as well as a lower mean peak systolic velocity at the end of the breath-holding test (AvPS max, P = 0.02) in the hepatitis C group. Vascular reactivity values, calculated as the breath-holding index, were also significantly lower (P = 0.045) in the hepatitis C group. In conclusion, the results of this study suggest an association between chronic HCV infection and altered cerebrovascular reactivity which may ultimately have an unfavorable effect on cerebrovascular hemodynamics and lead to increased risk of cerebrovascular diseases. [ABSTRACT FROM AUTHOR]

Context: In Pennsylvania, reporting of viral hepatitis B (HBV) and viral hepatitis C (HCV) infections to CDC has been mandated since 2002. Underreporting of HBV and HCV infections has long been identified as a problem. Few reports have described the accuracy of state surveillance case registries for recording clinically-confirmed cases of HBV and HCV infections, or the characteristics of populations associated with lower rates of reporting. Objective: The primary objective of the current study is to estimate the proportion of HBV and HCV infections that went unreported to the Pennsylvania Department of Health (PDoH), among patients in the Geisinger Health System of Pennsylvania. As a secondary objective, we study the association between underreporting of HBV and HCV infections to PDoH, and the select patient characteristics of interest: sex, age group, race/ethnicity, rural status, and year of initial diagnosis. Design: Per medical record review, the study population was limited to Geisinger Health System patients, residing in Pennsylvania, who were diagnosed with a chronic HBV and/or HCV infection, between 2001 and 2015. Geisinger Health System patient medical records were matched to surveillance records of confirmed cases reported to the Pennsylvania Department of Health (PDoH). To quantify the extent that underreporting occurred among the Geisinger Health System study participants, we calculated the proportion of study participants that were not reported to PDoH as confirmed cases of HBV or HCV infections. An analysis of adjusted prevalence ratio estimates was conducted to study the association between underreporting of HBV and HCV infections to PDoH, and the select patient characteristics of interest. Results: Geisinger Health System patients living with HBV were reported to PDoH 88.4% (152 of 172) of the time; patients living with HCV were reported to PDoH 94.6% (2,257 of 2,386) of the time; and patients who were co-infected with both viruses were reported to PDoH 72.0% (18 of 25) of the time. Patients living with HCV had an increased likelihood of being reported if they were: less than or equal to age 30 vs ages 65+ {PR = 1.2, [95%CI, (1.1, 1.3)]}, and if they received their initial diagnosis of HCV during the 2010–2015 time period vs the 1990–1999 time period {PR = 1.08, [95%CI, (1.05, 1.12)]}. Conclusion: The findings in this study are promising, and suggests that PDoH has largely been successful with tracking and monitoring viral hepatitis B and C infections, among persons that were tested for HBV and/or HCV. Additional efforts should be placed on decreasing underreporting rates of HCV infections among seniors (ages 65 and over), and persons who are co-infected with HBV and HCV. [ABSTRACT FROM AUTHOR]

Background and aims: Hepatitis C virus (HCV) infection is associated with insulin resistance, which may lead to type 2 diabetes and its complications. Although HCV infects mainly hepatocytes, it may impair insulin sensitivity at the level of uninfected extrahepatic tissues (muscles and adipose tissue). The aim of this study was to assess whether an interferon-free, antiviral therapy may improve HCV-associated hepatic vs. peripheral insulin sensitivity. Methods: In a single-arm exploratory trial, 17 non-diabetic, lean chronic hepatitis C patients without significant fibrosis were enrolled, and 12 completed the study. Patients were treated with a combination of sofosbuvir/ledipasvir and ribavirin for 12 weeks, and were submitted to a 2-step euglycemic hyperinsulinemic clamp with tracers, together with indirect calorimetry measurement, to measure insulin sensitivity before and after 6 weeks of antivirals. A panel of 27 metabolically active cytokines was analyzed at baseline and after therapy-induced viral suppression. Results: Clamp analysis performed in 12 patients who achieved complete viral suppression after 6 weeks of therapy showed a significant improvement of the peripheral insulin sensitivity (13.1% [4.6–36.7], p = 0.003), whereas no difference was observed neither in the endogenous glucose production, in lipolysis suppression nor in substrate oxidation. A distinct subset of hepatokines, potentially involved in liver-to-periphery crosstalk, was modified by the antiviral therapy. Conclusion: Pharmacological inhibition of HCV improves peripheral (but not hepatic) insulin sensitivity in non-diabetic, lean individuals with chronic hepatitis C without significant fibrosis. [ABSTRACT FROM AUTHOR]

Chronic hepatic disease can present a diagnostic challenge with different etiologies being associated with similar clinical and laboratory findings. The histopathological assessment of a liver biopsy specimen is usually required in order to make a definitive diagnosis and the availability of non-invasive prognostic biomarkers is limited. The emerging science of metabolomics is used to detect changes in endogenous low molecular weight metabolites in biological samples and offers the possibility of identifying noninvasive markers of disease. The objective of this study was to investigate differences in the urine metabolome between healthy dogs, dogs with chronic hepatitis, dogs with hepatocellular carcinoma, and dogs with a congenital portosystemic shunt. Stored urine samples from 10 healthy dogs, 10 dogs with chronic hepatitis, 6 dogs with hepatocellular carcinoma, and 5 dogs with a congenital portosystemic shunt were analyzed. The urine metabolome was analyzed by gas chromatography–quadrupole time of flight mass spectrometry and 220 known metabolites were identified. Principal component analysis and heat dendrogram plots of the metabolomics data showed clustering between groups. Random forest analysis showed differences in the abundance of various metabolites including putrescine, gluconic acid, sorbitol, and valine. Based on univariate statistics, 37 metabolites were significantly different between groups. In, conclusion, the urine metabolome varies between healthy dogs, dogs with chronic hepatitis, dogs with hepatocellular carcinoma, and dogs with a congenital portosystemic shunt. Further targeted assessment of these metabolites is needed to assess their diagnostic utility. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the relationship between spleen stiffness value, splenic volume and the liver fibrosis stages. Materials and methods: This retrospective study was approved by the institutional review board of our institute. We enrolled 109 patients that had undergone abdominal MR imaging and histopathological examination. The preoperative MR imaging, MR elastography and laboratory data were reviewed. Liver stiffness and spleen stiffness were determined with MR elastography, and splenic volume was calculated. Liver fibrosis stage was determined using surgical pathology. Results: The correlation coefficient between the liver stiffness and the fibrosis stage was r = 0.72 and r = 0.62 when the passive driver was on right chest wall and the left chest wall, respectively. The correlation coefficient between the spleen stiffness and the fibrosis stage was r = 0.63 and r = 0.18 when the passive driver was on the left chest wall and the right chest wall, respectively. The correlation coefficient between the splenic volume and the fibrosis stage was r = 0.31. The diagnostic performance of spleen stiffness was similar to liver stiffness in prediction of advanced liver fibrosis. The combination of spleen stiffness and liver stiffness provided greater sensitivity in prediction of advanced fibrosis than spleen or liver stiffness alone, but no significant difference was found. Conclusion: According to our study, the spleen stiffness value was useful in staging liver fibrosis. The combination of spleen stiffness and liver stiffness could provide higher diagnostic sensitivity than liver stiffness alone in prediction of advanced fibrosis. [ABSTRACT FROM AUTHOR]

Objective: Anemia of chronic disease (ACD) refers to hypoproliferative anemia in the context of acute or chronic activation of the immune system. There is a paucity of prospective data addressing the risk factors for ACD development. An association between common chronic diseases and ACD was examined cross-sectionally and longitudinally. Method: A cohort of 265,459 healthy participants without ACD at baseline were prospectively followed annually or biennially. Results: During average follow-up period of 62 months, 4,906 participants developed ACD (incidence rate 3.58 per 1000 person-years). Multivariable-adjusted hazard ratio (HR) [95% confidence interval (CI)] for incident ACD comparing estimated glomerular filtration rate 30–60 and < 30 vs. ≥ 60 ml/min/1.73 m2 were 3.93 [3.18–4.85] and 39.11 [18.50–82.69]; HRs [95% CI] for ACD comparing prediabetes and diabetes vs. normal were 1.19 [1.12–1.27] and 2.46 [2.14–2.84], respectively. HRs [95% CI] for incident ACD comparing body-mass-index (BMI) of < 18.5, 23–24.9 and ≥ 25 vs. 18.5–22.9 kg/m2 were 0.89 [0.78–1.00], 0.89 [0.80–0.99] and 0.78 [0.66–0.91], respectively. HRs [95% CI] for incident ACD comparing prehypertension and hypertension vs. normal were 0.79 [0.73–0.86] and 1.10 [0.99–1.23], respectively. Metabolic syndrome, hypertension, chronic liver disease, and chronic obstructive pulmonary disease were not associated with incident ACD. Conclusions: The severity of chronic kidney disease and diabetic status were independently associated with an increased incidence of ACD, whereas prehypertension and an increasing BMI were significantly associated with decreased risk of ACD. [ABSTRACT FROM AUTHOR]

Background: Newer direct-acting antiviral therapies are increasingly becoming the therapy of choice in patients with hepatitis C virus (HCV) infection. Here, we report the safety and effectiveness of sofosbuvir/velpatasvir (SOF/VEL) and ledipasvir/sofosbuvir (LDV/SOF) in real-world cohorts in Germany. Methods: Patients initiated on SOF/VEL 12 weeks or LDV/SOF 8, 12 or 24 weeks regimens in a single German centre were included in this study. Data on treatment outcomes and adverse events (AE) were analysed in patients with available sustained virologic response 12 weeks after cessation of treatment (SVR12) information overall and by subgroups. Results: This study included 115 patients who received SOF/VEL from July-2016 to July-2017, and 249 patients who received LDV/SOF from November-2014 to September-2015. Overall, SVR12 was achieved in 99% of patients on SOF/VEL ± ribavirin 12 weeks independent of HCV genotype, treatment history, or cirrhosis status, and in 96% of patients treated with LDV/SOF 8 weeks or LDV/SOF ± ribavirin 12 or 24 weeks. In genotype 1 treatment-naïve, non-cirrhotic patients, ≥99% achieved SVR12 across SOF/VEL and LDV/SOF regimens. Likewise, 100% of genotype 3-cirrhotic patients on SOF/VEL ± ribavirin regimens achieved SVR12. Grade 3/4 AE were reported in 13 (5.2%) patients on LDV/SOF and in 1 (<1%) patient on SOF/VEL. Conclusion: Overall, SOF/VEL and LDV/SOF achieved high SVR rates in a broad patient population. We showed the effectiveness of SOF/VEL as a pan-genotypic regimen, and regardless of treatment history or cirrhosis status. Use of such therapies improves outcomes and contributes towards the global efforts to eradicate HCV. [ABSTRACT FROM AUTHOR]

Background and aim: Transient elastography and fibrosis-4 index (FIB-4) have been proposed to access hepatic fibrosis and steatosis for patients with chronic liver disease. This study was to determine the changes of liver stiffness (LS), controlled attenuation parameter (CAP) value and FIB-4 and their associated factors for chronic hepatitis C (CHC) patients who underwent direct-acting antivirals (DAAs). Patients and methods: Consecutive patients with CHC in advanced fibrosis or compensated cirrhosis undergoing paritaprevir/ritonavir/ombitasvir plus dasabuvir therapy and with LS and CAP before and 12 weeks after treatment were enrolled. The demographics, clinical characteristics and treatment outcomes were reviewed. The changes of LS, FIB-4, CAP and their associated factors were analyzed. Results: A total of 213 patients (mean age: 63.7 years) with complete recommended treatment were enrolled. All patients achieved sustained virological response at 12 weeks (SVR12) of follow-up. The mean values of LS, CAP and FIB-4 index before treatment were 18.5kPa, 283dB/m and 5.05 respectively. While there was no significant change in CAP, LS and FIB-4 decreased significantly at the time of SVR12 (p<0.001). Compared with follow-up period, LS and FIB-4 decreased rapidly during DDAs. Multivariate analysis showed that higher baseline LS and FIB-4 were associated with greater reductions at the time of SVR12. Conclusion: For CHC patients in advanced fibrosis or compensated cirrhosis, DAAs improved LS and FIB-4 index at SVR12. Higher baseline LS and FIB-4 contributed to greater reductions. However, there was no significant change in CAP value. [ABSTRACT FROM AUTHOR]

Background and aims: The present study aimed to report our real-life experience of the TPO receptor agonist lusutrombopag for cirrhotic patients with low platelet counts. Methods: We studied platelet counts in 1,760 cirrhotic patients undergoing invasive procedures at our hospital between January 2014 and December 2017. In addition, we studied 25 patients who were administered lusutrombopag before invasive procedures between June 2017 and January 2018. Effectiveness of lusutrombopag to raise platelet counts and to avoid transfusion and treatment-related adverse events were analyzed. Results: In 1,760 cirrhotic patients without lusutrombopag prior to invasive procedures, proportion of patients whose platelet counts <50,000/μL and needed platelet transfusions were 66% (n = 27/41) for radiofrequency ablation, 43% (n = 21/49) for transarterial chemoembolization, and 55% (n = 21/38) for endoscopic injection sclerotherapy / endoscopic variceal ligation, respectively. In 25 cirrhotic patients treated by lusutrombopag prior to the invasive procedures, platelet counts significantly increased compared with baseline (82,000 ± 26,000 vs. 41,000 ± 11,000/μL) (p < 0.01). Out of 25 patients, only 4 patients (16%) needed platelet transfusion before the invasive procedures. The proportion of patients with low platelet count and who needed platelet transfusions was significantly low in patients treated with lusutrombopag compared to those not treated with lusutrombopag (16% (4/25) vs. 54% (69/128), p = 0.001). Platelet counts after lusutrombopag treatment and prior to invasive procedures were lower in patients with a baseline platelet count ≤30,000/μL (n = 8) compared with those with a baseline platelet count >30,000/μL (n = 17) (50,000 ± 20,000 vs 86,000 ± 26,000/μL, p = 0.002). Patients with a baseline platelet count ≤30,000/μL with spleen index (calculated by multiplying the transverse diameter by the vertical diameter measured by ultrasonography) ≥40 cm2 (n = 3) had a lower response rate to lusutrombopag compared to those with spleen index <40 cm2 (n = 5) (0% vs. 100%, p = 0.02). Hemorrhagic complication was not observed. Recurrence of portal thrombosis was observed and thrombolysis therapy was required in one patient who had prior history of thrombosis. Conclusions: Lusutrombopag is an effective and safe drug for thrombocytopenia in cirrhotic patients, and can reduce the frequency of platelet transfusions. [ABSTRACT FROM AUTHOR]

Semaphorins are a diverse family of immunoregulators recently recognized to play a major role in various phases of immune responses. Their role in chronic viral hepatitis C (CHC) and contribution to the progression of liver disease is unknown. The aim of this study was to analyse the association of secreted semaphorins with the severity of liver disease in patients with CHC. Serum concentrations of semaphorins were measured in 114 treatment-naive CHC patients and 36 healthy controls. Serum concentrations of SEMA3A, SEMA3C, SEMA5A, SEMA6B and SEMA6D were significantly increased in patients with CHC compared to controls. While serum concentrations of SEMA3C and SEMA6D significantly increased with fibrosis stage in both HCV-g1 and HCV-g3 infections, the concentration of SEMA5A inversely correlated with fibrosis stage in both HCV genotypes. ROC analysis showed that serum concentrations of SEMA3C (>4.0ng/mL, AUC 0.88) and SEMA6D (>4.5, AUC 0.82) had higher AUC than widely used APRI (AUC 0.71) and FIB-4 (AUC 0.74) scores. Serum concentrations of SEMA3C and SEMA6D significantly decreased after DAA and PEG IFN-α/ribavirin therapy, while the serum concentration of SEMA5A significantly increased after DAAs therapy. Immunohistochemistry confirmed the expression of SEMA3C and SEMA5A in hepatocytes, endothelial cells and lymphocytes of cirrhotic livers from CHC patients but not in controls. In conclusion, we provide the first evidence that SEMA3C, SEMA5A and SEMA6D can be considered as markers of liver injury in CHC. [ABSTRACT FROM AUTHOR]

Chronic hepatitis is the most common hepatic disease in dogs. Copper accumulation is an important cause of chronic hepatitis in dogs; however, the etiology in most dogs cannot be determined. Clinical signs of chronic hepatitis are often non-specific; therefore, this disease is frequently diagnosed in an advanced stage that makes successful intervention less likely. Early diagnosis of chronic hepatitis in dogs would thus be beneficial. The identification of proteins that are differentially expressed in dogs with chronic hepatitis could contribute to the development of novel diagnostic markers for this disease and provide insight into its pathogenesis. The objective of this study was to identify novel proteins that are differentially expressed in the liver of dogs with chronic hepatitis. Hepatic tissue was collected from 8 healthy dogs during ovariohysterectomy and from 8 dogs with histologically confirmed chronic hepatitis. The proteome of the liver samples was extracted by mechanical disruption and detergent-based cell lysis and differentially labeled prior to analysis by 2-dimensional fluorescence difference gel electrophoresis. Spots with an absolute fold change value > 2.0 were selected for further analysis. Protein identification was achieved by nanoflow liquid chromatography tandem mass spectrometry. Differential expression of select proteins was validated by Western blot. Five protein spots were differentially expressed between patients with chronic hepatitis and healthy control dogs. From these 5 protein spots 11 proteins were identified. Differential expression of cytokeratin 18 and annexin 5 were confirmed by Western blot analysis. Differential protein expression was shown between dogs with chronic hepatitis and healthy control dogs. Upregulation of cytokeratin 18 in chronic hepatitis may suggest increased hepatocellular apoptosis and necrosis, whereas upregulation of annexin 5A suggests increased hepatocellular apoptosis. Further studies are needed to determine whether either protein has diagnostic utility. [ABSTRACT FROM AUTHOR]

Background: Elimination of hepatitis C virus (HCV) infection requires high diagnostic rates and universal access to treatment. Around 40% of infected individuals are unaware of their infection, which indicates that effective screening strategies are needed. We analyzed the efficiency (incremental cost-utility ratio, ICUR) of 3 HCV screening strategies: a) general population of adults, b) high-risk groups, and c) population with the highest anti-HCV prevalence plus high-risk groups. Methods: An analytical decision model, projecting progression of the disease over a lifetime, was used to establish the candidate population for HCV screening. HCV data were obtained from the literature: anti-HCV prevalence (0.56%-1.54%), viremic patients (31.5%), and percentage of undiagnosed persons among those with viremia (35%). It was assumed that most patients would be treated and have HCV therapy response (98% SVR); transition probabilities, utilities, and disease management annual costs were obtained from the literature. Efficiency over the life of patients under the National Health System perspective was measured as quality-adjusted life years (QALY) and total cost (screening, diagnosis, pharmacological and disease management). A discount rate of 3% was applied to costs and outcomes. Results: Screening of the adult population would identify a larger number of additional chronic hepatitis C cases (N = 52,694) than screening the highest anti-HCV prevalence population plus high-risk groups (N = 42,027) or screening high-risk groups (N = 26,128). ICUR for the general population vs. high-risk groups was €8914/QALY gained per patient (€18,157 incremental cost and 2.037 QALY). ICUR for the general population vs. population with highest anti-HCV prevalence plus high-risk groups was €7,448/QALY gained per patient (€7,733 incremental cost and 1.038 QALY). These ICUR values are below the accepted efficiency threshold (€22,000-€30,000). Conclusion: HCV screening and treatment of the general adult population is cost-effective compared to screening of high-risk groups or the population with the highest anti-HCV prevalence plus high-risk groups. [ABSTRACT FROM AUTHOR]

Background and aim: The role of non-invasive methods to evaluate fibrosis severity of chronic hepatitis C (CHC) subjects in community needs to be explored. This study investigated FIB-4 and transient elastography (TE) in staging liver fibrosis of CHC subjects in community. Methods: A total of 905 subjects who were positive for anti-HCV antibody from five districts of Tainan City of Taiwan were invited to participate in surveillance activities for CHC. FIB-4 and TE were measured for each participant. Results: A total of 502 subjects with detectable HCV RNA and valid TE were enrolled. The distribution of FIB-4 and TE values differed markedly. Both methods exhibited a strongest correlation in subjects with at age 50~60 years (r = 0.655, p <0.001). FIB-4 score increased proportionally with age (p <0.001), but TE did not (p = 0.142). The intraclass correlation efficient of both methods was 0.255 (p <0.001). Subjects with TE defined advanced fibrosis exhibited younger age, higher BMI, higher platelet count, lower FIB-4 score, higher incidence of fatty liver and splenomegaly, and higher controlled attenuation parameter value than those defined by FIB-4. By multivariate logistic regression analysis, higher ALT levels, higher incidence of fatty liver, and presence of splenomegaly were the independent factors associated with advanced fibrosis defined by TE rather than defined by FIB-4. Conclusions: FIB-4 and TE defined different distribution of fibrosis stages in same HCV population. FIB-4 was deeply influenced by age whereas TE was not. TE had the advantages over than FIB-4 in strong association with splenomegaly and in detecting the role of non-alcoholic fatty liver disease in advanced fibrosis. [ABSTRACT FROM AUTHOR]

Background: Chronic infection with hepatitis B or C virus (HBV/HCV) can progress to cirrhosis, liver cancer, and even death. In a low endemic country as the Netherlands, migrants are a key risk group and could benefit from early diagnosis and antiviral treatment. We assessed the cost-effectiveness of screening foreign-born migrants for chronic HBV and/or HCV using a societal perspective. Methods: The cost-effectiveness was evaluated using a Markov model. Estimates on prevalence, screening programme costs, participation and treatment uptake, transition probabilities, healthcare costs, productivity losses and utilities were derived from the literature. The cost per Quality Adjusted Life Year (QALY) gained was estimated and sensitivity analyses were performed. Results: For most migrant groups with an expected high number of chronically infected cases in the Netherlands combined screening is cost-effective, with incremental cost-effectiveness ratios (ICERs) ranging from €4,962/QALY gained for migrants originating from the Former Soviet Union and Vietnam to €9,375/QALY gained for Polish migrants. HBV and HCV screening proved to be cost-effective for migrants from countries with chronic HBV or HCV prevalence of ≥0.41% and ≥0.22%, with ICERs below the Dutch cost-effectiveness reference value of €20,000/QALY gained. Sensitivity analysis showed that treatment costs influenced the ICER for both infections. Conclusions: For most migrant populations in a low-endemic country offering combined HBV and HCV screening is cost-effective. Implementation of targeted HBV and HCV screening programmes to increase early diagnosis and treatment is important to reduce the burden of chronic hepatitis B and C among migrants. [ABSTRACT FROM AUTHOR]

Background: Direct-acting antivirals (DAA) have demonstrated high efficacy to achieve sustained virological response (SVR) in chronic hepatitis C patients. We aim to assess the change in health-related quality of life (HRQoL) among patients successfully treated, and to identify predictors of this variation. Methods: In a prospective observational study, patients with chronic hepatitis C who started DAA therapy between May 2016 and April 2017 completed the EQ-5D-5L questionnaire at baseline and 12 weeks after the end of therapy before knowing the virological result. Analysis included all patients with SVR. Results: Median baseline EQ-5D-5L scores of the 206 enrolled patients were 0.857 utility and 70.0 visual analogue scale (VAS). Following SVR, a reduction occurred in the proportion of patients with mobility problems (35% vs 24%, p = 0.012), pain/discomfort (60% vs 42%, p<0.001) and anxiety/depression (57% vs 44%, p = 0.012), with an increase in utility (+0.053, p<0.001) and VAS (+10, p<0.001). Score improvements were also observed in cirrhotic (+0.048 utility, p = 0.027; +15 VAS, p<0.001) and HIV co-infected patients (+0.039 utility, p = 0.036; +5 VAS, p = 0.002). In multivariate analyses, middle age (45–64 years) and baseline anxiety/depression were associated to greater improvement in utility after SVR, and moderate-advanced liver fibrosis and cirrhosis to greater increase in VAS score. Low baseline values were associated to greater improvements in utility value and VAS score. Conclusions: The cure of chronic hepatitis C infection with DAA has a short term positive impact on HRQoL with improvement in mobility, pain/discomfort, anxiety/depression, utility value and VAS score. Patients with poor baseline HRQoL were the most beneficed. [ABSTRACT FROM AUTHOR]

Aim: Health-related quality of life is impaired in patients with autoimmune hepatitis, but the association between health-related quality of life and patients’ backgrounds remains unknown. We assessed health-related quality of life in patients with autoimmune hepatitis and identified factors associated with its impairment. Methods: We assessed health-related quality of life in patients with autoimmune hepatitis, patients with chronic hepatitis C, and healthy subjects using the Japanese version of the Chronic Liver Disease Questionnaire and the 36-Item Short Form Survey. We compared health-related quality of life in patients with autoimmune hepatitis with that of patients with chronic hepatitis C and healthy subjects. Results: A total of 265 patients with autoimmune hepatitis, 88 patients with chronic hepatitis C, and 97 healthy subjects were enrolled; most patients were women. The median ages of patients were 65, 66, and 57 years, respectively. Of these patients with autoimmune hepatitis, 10.6% and 57.0% had cirrhosis and comorbid diseases, respectively. The overall Chronic Liver Disease Questionnaire scores (5.5 vs. 6.2, P < 0.001) and physical (48.1 vs. 54.2, P < 0.001) and mental (51.8 vs. 55.0, P = 0.004) component summaries of 36-Item Short Form Survey were significantly lower in patients with autoimmune hepatitis than in healthy subjects, and similar to scores in patients with chronic hepatitis C. Having cirrhosis, comorbid diseases, and treatment for autoimmune hepatitis were associated with impaired health-related quality of life among patients with autoimmune hepatitis. In particular, prednisolone use was associated with lower scores on the worry domain of the Chronic Liver Disease Questionnaire. Conclusions: Patients with autoimmune hepatitis showed impairment in health-related quality of life, which was associated with not only disease progression, but also comorbid diseases and treatment. Ways to improve health-related quality of life should be considered in patients with AIH when disease outcome is not favorable and when using prednisolone. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) transmission through infected blood and blood products has already been described. However, little is known about the bone marrow (BM) as source of HEV infection. Our study aimed to investigate the presence of HEV antigen (Ag) and histological changes in BM of cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with HEV. Four cynomolgus monkeys with acute, and two with chronic hepatitis E ─ after immunosuppressive therapy with tacrolimus ─ were compared with one colony-bred animal naturally infected. Both, natural and experimental infections were characterized by anti-HEV IgG seroconversion detected by ELISA, and viral RNA isolation confirmed by RT-qPCR and qualitative nested RT-PCR. BM biopsies were collected from all animals, submitted to histology and indirect immunofluorescence techniques and observed, respectively, by light and confocal microscopy. The HEV Ag-fluorescent-labeled cells were detected from BM biopsies obtained from three monkeys with acute and one with chronic hepatitis E, and also from the naturally infected monkey. In the experimentally infected animals with acute hepatitis, HEV Ag detection occurred at 160 days post-infection, even after viral clearance in serum, feces, and liver. Double-stranded RNA, a replicative marker, was detected in BM cells from both acute and chronically infected animals. Major histological findings included vacuolization in mononuclear and endosteal cells, an absence of organized inflammatory infiltrates, and also some fields suggesting displasic focal BM disease. These findings support the hypothesis of BM cells as secondary target sites of HEV persistence. Further experimental studies should be carried out to confirm the assumption of HEV transmission through BM transplantation. [ABSTRACT FROM AUTHOR]

Objective(s): To describe the clinical, virological and immune characteristics of internationally adopted children on arrival in France and after 6-months follow-up. Design: Multicenter retrospective study. Methods: 30 centers from 24 cities were asked to include, after informed consent, HIV+ children living in France and internationally adopted between 1st Jan 2005 and 1st Jan 2015. Sociodemographic, medical and biological variables collected during the first medical evaluation in France and 6 months later were analyzed. Results: 41 HIV+ adoptees were included (female: 56%; median age: 3.91 years) in 14 centers. Adoptees tend to represent an increasing part of newly diagnosed HIV positive children over the years. The majority came from East-Asia. At arrival, one child was diagnosed with lymphobronchial tuberculosis and three with latent chronic hepatitis B, cleared HBV infection and chronic active hepatitis C, respectively. The mean CD4% was 32.8 ± 9% (range: 13–49%). The 34 children (83%) have been initiated on treatment from their countries of origin. Of these, 25 (74%) had an undetectable viral load (VL) on arrival. Resistance to ART was detected in five. At 6 months, 36 adoptees received ART, and the VL was undetectable in 29 children (71%), with one acquired resistance to NRTI & NNRTI. Conclusions: An increasing number of HIV-infected children have been internationally adopted in France since 2005. Most of the children have been initiated on treatment from their countries of origin, had good immunity, with few opportunistic infections, and infrequently detectable VL. Low level of mutation conferring resistance was detected. [ABSTRACT FROM AUTHOR]

Background: Risk factors for hepatocellular carcinoma (HCC) have not been well characterized among African immigrants with chronic hepatitis B virus (HBV) infection. We conducted a case-control study to identify demographic and clinical factors associated with HCC among a diverse cohort of patients with chronic HBV infection seen in a large academic health setting. Methods: We identified a total of 278 patients with HCC and chronic HBV seen at two medical centers in a 14-year span from January 2002 to December 2015. These cases were age- and sex-matched in a 1:3 ratio with 823 non-cancer control subjects with chronic HBV. Conditional logistic regression was used to estimate the odds of HCC by race, with black race stratified by African-born status, after adjusting for diabetes, HIV or HCV coinfection, alcohol misuse and cirrhosis. Results: Of the 278 HCC cases, 67% were 60 years of age or older, 78% were male, 87% had cirrhosis and 72% were Asian. HIV infection was present in 6% of cases. Only 7% (19 of 278) of HCC cases were black, of whom 14 were African immigrants. The median age at HCC diagnosis was 44 years in Africans. Notably, nearly all (93%) of the African-born patients with HCC were diagnosed at an age younger than 60 years compared with 52% of Asian cases (P<0.001). The main factors independently associated with greater odds of HCC overall were Asian race (adjusted odds ratio [aOR] 3.3, 95% confidence interval [CI] 1.9–5.5) and cirrhosis (aOR 19.7, 95% CI 12.2–31.8). Conclusion: African immigrants accounted for a small proportion of HBV-associated HCC cases overall compared with Asians but appeared to have greater likelihood of early-onset HCC. Optimal strategies for HCC prevention in these key subroups with chronic HBV warrant further study. [ABSTRACT FROM AUTHOR]

Background: Tooth loss has been reported to be associated with the risk of liver cancer in several prior studies in economically advantaged countries. Whether this relationship is also evident in economically disadvantaged populations is not known. Methods: We analyzed data from the Nutrition Intervention Trials, two randomized placebo-controlled trials of vitamin/mineral supplementation in Linxian, China. Participants who reported having lost permanent teeth were examined to determine the number of teeth remaining. In the 30-year follow-up period, 329 liver cancers were diagnosed and 368 chronic liver disease deaths occurred. Tooth loss was categorized based on loess smoothed age-specific predicted quartiles. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the two outcomes. Results: Overall, persons in the highest quartile of age-specific tooth loss had an increased risk of liver cancer (HR = 1.27, 95%CI: 0.96, 1.67) which was not statistically significant. Results varied by sex and body mass index (BMI), however. Women in the highest quartile of age-specific tooth loss had a significantly increased risk (HR = 1.64, 95%CI: 1.04, 2.59), while men did not (HR = 1.08, 95%CI = 0.75, 1.57), and persons with a BMI > 23.0 kg/m2 (HR = 1.71, 95%CI: 1.00, 2.92) had a significantly increased risk, while persons with a BMI <23.0 kg/m2 did not (HR = 1.14, 95%CI: 0.82, 1.5). No relationships with chronic liver disease mortality were observed. Conclusions: In a rural, economically disadvantaged population, persons with the highest levels of age-specific tooth loss had an increased risk of liver cancer. The results, which were stronger among women and persons with greater BMI, suggest that periodontal disease may increase risk of liver cancer. [ABSTRACT FROM AUTHOR]

Objective: Establishing normal liver stiffness (LS) values in healthy livers is a prerequisite to differentiate normal from pathological LS values. Our aim was to define normal LS using two novel elastography methods head-to-head and to assess the number of measurements, variability and reproducibility. Materials and methods: We evaluated shear wave elastography (SWE) methods integrated in Samsung RS80A and GE S8 by obtaining LS measurements (LSM) in 100 healthy subjects (20–70 years). Transient Elastography (TE) was used as reference method. Data were analyzed according to age, sex, BMI and 5 vs. 10 measurements. All subjects underwent B-mode ultrasound examination and lab tests to exclude liver pathology. Interobserver variation was evaluated in a subset (n = 24). Results: Both methods showed excellent feasibility, measuring LS in all subjects. LSM-mean for GE S8 2D-SWE was higher compared to TE (4.5±0.8 kPa vs. 4.2±1.1, p<0.001) and Samsung RS80A (4.1±0.8 kPa, p<0.001). Both methods showed low intra- and interobserver variation. LSM-mean was significantly higher in males than females using 2D-SWE, while a similar trend for Samsung SWE did not reach significance. No method demonstrated statistical significant difference in LSM across age and BMI groups nor between LSM-mean based on 5 vs. 10 measurements. Conclusion: LSM was performed with high reproducibility in healthy adult livers. LSM-mean was significantly higher for GE S8 2D-SWE compared to Samsung RS80A and TE in healthy livers. Males had higher LSM than females. No method demonstrated statistical significant difference in LSM-mean across age- and non-obese BMI groups. Our results indicate that five LSM may be sufficient for reliable results. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to reveal the clinical and histopathological features of HBsAg-positive and HBeAg-positive chronic hepatitis B infected patients with high level of HBV DNA, from 17 hospitals and medical centres in China, with alanine aminotransferase levels within the lower region of normal range versus those with levels within the upper region of normal range and to investigate the clinical risk factors for the requirement of treatment through the examination of liver biopsy. Methods: Liver biopsy was performed on high level of HBV DNA of 455 patients with HBsAg-positive and HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase level. Liver necroinflammation and fibrosis were graded per the Knodell histological activity index and Ishak’s fibrosis score, respectively. Univariate analysis of the clinical parameters versus necroinflammation and fibrosis was carried out. Results: Of the subjects in this multicentre-based study, 5.49% and 10.11% had significant necroinflammation with Knodell histological activity index ≥ 9 and hepatic fibrosis stages with Ishak scores ≥ 3, respectively. The subjects were stratified into three age groups (30–39, 40–49 and ≥ 50 years), and our data clearly suggested that age, particularly in the age group over 50, was an independent predictor of liver necroinflammation and fibrosis. Lower HBV-DNA viral levels were found in patients with Knodell histological activity index ≥ 9 or advanced fibrosis (Ishak scores ≥ 3). Conclusion: Our results showed that histological changes in liver tissues were observed in a significant proportion of patients with persistently normal alanine aminotransferase level. According to the data evaluation results, liver biopsy is advisable for HBeAg-positive chronic hepatitis B infected patients aged older than 40 and high HBV-DNA viral load in China. [ABSTRACT FROM AUTHOR]

Background: We previously developed a logistic regression algorithm that uses AFP, age, gender, ALK and ALT levels to improve the detection of hepatocellular carcinoma (HCC). In 3,158 patients from 5 independent sites, this algorithm, referred to as the “Doylestown” algorithm, increased the AUROC of AFP 4% to 12% and had equal benefit regardless of tumor size or the etiology of liver disease. Aims: Analysis of the Doylestown algorithm using samples from individuals taken before their diagnosis of HCC. Methods: Here, the algorithm was tested using samples at multiple time points from (a) patients with established chronic liver disease, without HCC (120 patients) and (b) 116 patients with HCC diagnosis (85 patients with early stage HCC and 31 patients with recurrent HCC), taken at the time of, and up to 12 months prior to cancer diagnosis. Results: Among patients who developed HCC, comparing the Doylestown algorithm at a fixed cut-off to AFP at 20 ng/mL, the Doylestown algorithm increased the True Positive Rate (TPR) in identification of HCC from 36 to 50%, at a time point of 12 months prior to the conventional HCC detection. Similar results were obtained in those patients with recurrent HCC, where the Doylestown algorithm increased TPR in detection of HCC from 18% to 59%, at 12 months prior to detection of recurrence. Conclusions: This algorithm significantly improves the prediction of HCC by AFP alone and may have value in the early detection of HCC. [ABSTRACT FROM AUTHOR]

Background: Elimination of hepatitis C virus (HCV) among people who inject drugs (PWID) is a costly investment, so strategies should not only focus on eliminating the disease, but also on preventing disease resurgence. The aims of this study are to compute the minimum necessary antiviral therapies to achieve elimination with and without the additional expansion of harm reduction (HR) programs and to examine the sustainability of HCV elimination after 2030 if treatment is discontinued. Method: We considered two types of epidemic (with low (30%) and high (50%) proportion of PWID who engage in sharing equipment (sharers)) within three baseline chronic HCV (CHC) prevalence settings (30%, 45% and 60%), assuming a baseline HR coverage of 40%. We define sustainable elimination strategies, those that could maintain eliminations results for a decade (2031–2040), in the absence of additional treatment. Results: The model shows that the optimum elimination strategy is dependent on risk sharing behavior of the examined population. The necessary annual treatment coverage to achieve HCV elimination under 45% baseline CHC prevalence, without the simultaneous expansion of HR programs, ranges between 4.7–5.1%. Similarly, under 60% baseline CHC prevalence the needed treatment coverage varies from 9.0–10.5%. Increasing HR coverage from 40% to 75%, reduces the required treatment coverage by 6.5–9.8% and 11.0–15.0% under 45% or 60% CHC prevalence, respectively. In settings with ≤45% baseline CHC prevalence, expanding HR to 75% could prevent the disease from rebounding after elimination, irrespective of the type of the epidemic. In high chronic HCV prevalence, counseling interventions to reduce sharing are also needed to maintain the HCV incident cases in low levels. Conclusions: Harm reduction strategies have a vital role in HCV elimination strategy, as they reduce the required number of treatments to eliminate HCV and they provide sustainability after the elimination. The above underlines that HCV elimination strategies should be built upon the existing HR services, and argue for HR expansion in countries without services. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis B is a serious public health problem across sub-Saharan Africa. Sierra Leone has no national hepatitis B strategy plan or high quality estimates of prevalence. Healthcare workers are perceived as an at-risk group for hepatitis B. We assessed the prevalence of hepatitis B among healthcare workers at two hospital sites in Freetown, Sierra Leone. Methods: In October 2017, healthcare workers were offered voluntary testing for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) using rapid lateral flow assay for all samples, followed by Enzyme Immunosorbent Assay to confirm positive results. Participants completed a questionnaire about knowledge, attitudes and practices concerning hepatitis B. HBsAg positive participants were invited to a clinic for further assessment. Results: Overall, 447 participants were tested for hepatitis B. Most (90.6%, 405/447) participants were nurses, 72.3% (323/447) were female and 71.6% (320/447) were 30 years or older. The prevalence of chronic hepatitis B (HBsAg positivity) was 8.7% (39 / 447, 95% CI 6.3–11.7%). There was no significant difference in prevalence by sex, age group, site of work or type of job. None of the 66.7% (26 / 39) of participants with chronic hepatitis B who attended the clinic met the 2015 WHO criteria to start treatment for hepatitis B on the basis of cirrhosis. Most participants (96.9% 432 / 446) stated that they were worried about their risk of hepatitis B at work. Conclusions: Hepatitis B is highly prevalent among healthcare workers in Sierra Leone. It is unclear whether this reflects high community prevalence or is due to occupational risk. No participants with chronic hepatitis B needed to start treatment. In order to achieve the WHO target of elimination of viral hepatitis by 2030, introduction of birth dose vaccine for infants and catch-up vaccines for healthcare workers and healthcare students, together with a national hepatitis B screen and treat programme is advisable for Sierra Leone. [ABSTRACT FROM AUTHOR]

Background: In 2016, the World Health Organization (WHO) and 69th World Health Assembly approved the first global health sector strategy (GHSS) on viral hepatitis with the goal to eliminate hepatitis C virus (HCV) infections worldwide. The aim is a 90% reduction of new infections and 65% reduction of HCV-related deaths by 2030. Aim: This study reports on the epidemiology of HCV infections in the Austrian state of Tyrol (total population 750,000) and uses a predictive model to identify how the WHO strategy for elimination of HCV can be achieved. Methods: We developed a regional disease burden model based on observed local diagnosis data from 2001 to 2016. Scenarios were developed to evaluate the impact of diagnosis and treatment on HCV-related outcomes (viremic prevalence, decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths) from 2015 through 2030. Results: In the last 15 years, 1,721 patients living in Tyrol have been diagnosed with chronic HCV infection. When ageing, mortality and treatment were factored in, there were an estimated 2,043 viremic HCV infections in 2016, of which 1,136 cases had been diagnosed. A baseline model predicts a decrease of 588 HCV cases from 2015 to 2030, which would not translate into the significant reduction of infections needed to achieve WHO global health recommendations. A total of 1,843 infected individuals need to be identified and treated to achieve the WHO goals by 2030 (1,254 averted cases as compared to baseline model). Implementation of this strategy would avoid 523 new HCV infections and decreases HCV-related mortality by 73%. Conclusion: HCV elimination and >65% reduction of associated mortality are possible for Tyrol, but requires a significant increase in new diagnoses and treatment rate. The model presented in this study could serve as an example for other regions to reliably predict regional disease burden and estimate how WHO goals can be met in the future. [ABSTRACT FROM AUTHOR]

Background: Direct-acting antivirals (DAA) have dramatically increased HCV cure rates with minimal toxicity in HIV-HCV co-infected patients. This study aimed to compare the socio-behavioral characteristics of patients initiating pegylated-interferon (PEG-IFN)-based HCV treatment with those of patients initiating DAA-based treatment. Methods: ANRS CO13 HEPAVIH is a national multicenter prospective cohort started in 2005, which enrolled 1,859 HIV-HCV co-infected patients followed up in French hospital outpatient units. Both clinical/biological and socio-behavioral data were collected during follow-up. We selected patients with socio-behavioral data available before HCV treatment initiation. Results: A total of 580 patients were included in this analysis. Of these, 347 initiated PEG-IFN-based treatment, and 233 DAA-based treatment. There were significant differences regarding patient mean age (45 years±6 for the PEG-IFN group vs. 52 years±8 for the DAA group, p<0.001), unstable housing (21.4% vs. 11.2%, p = 0.0016), drug use (44.7% vs. 29.6%, p = 0.0003), regular or daily use of cannabis (24.3% vs. 15.6%, p = 0.0002), a history of drug injection (68.9% vs 39.0%, p<0.0001) and significant liver fibrosis (62.4% vs 72.3%, p = 0.0293). In multivariable analysis, patients initiating DAA-based treatment were older than their PEG-IFN-based treatment counterparts (aOR = 1.17; 95%CI [1.13; 1.22]). Patients receiving DAA treatment were less likely to report unstable housing (0.46 [0.24; 0.88]), cannabis use (regular or daily use:0.50 [0.28; 0.91]; non-regular use: 0.41 [0.22; 0.77]), and a history of drug injection (0.19 [0.12; 0.31]). Conclusion: It is possible that a majority of patients who had socio-economic problems and/or a history of drug injection and/or a non-advanced disease stage were already treated for HCV in the PEG-IFN era. Today, patients with unstable housing conditions are prescribed DAA less frequently than other populations. As HCV treatment is prevention, improving access to DAA remains a major clinical and public health strategy, in particular for individuals with high-risk behaviors. [ABSTRACT FROM AUTHOR]

Background: Cancer causes significant morbidity and mortality among HIV patients in the US due to extended life expectancy with access to effective antiretroviral therapy. Low, detectable HIV RNA has been studied as a risk factor for adverse health outcomes, but its clinical impact on cancer risk remains unclear. The objective of this study was to determine whether HIV RNA <1,000 copies/mL six months after starting therapy was associated with 10-year first cancer risk. Methods: We followed 7,515 HIV therapy initiators from a US-based multicenter clinical cohort from 1998 to 2014. We used nonparametric multiple imputation to account for viral loads that fell below assay detection limits, and categorized viral loads six months after therapy initiation into four groups: <20, 20–199, 200–999, and >999 copies/mL. We calculated estimates of the cumulative incidence of cancer diagnosis, accounting for death as a competing event. Inverse probability of exposure and censoring weights were used to control for confounding and differential loss to follow up, respectively. Results: Crude 10-year first cancer risk in the study sample was 7.03% (95% CI: 6.08%, 7.98%), with the highest risk observed among patients with viral loads between 200 and 999 copies/mL six months after ART initiation (10.7%). After controlling for baseline confounders, 10-year first cancer risk was 6.90% (95% CI: 5.69%, 8.12%), and was similar across viral load categories. Conclusion: Overall risk of first cancer was not associated with incomplete viral suppression; however, cancer remains a significant threat to HIV patients after treatment initiation. As more HIV patients gain access to treatment in the current “treat all” era, occurrences of incomplete viral suppression will be observed more frequently in clinical practice, which supports continued study of the role of low-level HIV RNA on cancer development. [ABSTRACT FROM AUTHOR]

Background & aims: Many individuals are infected with hepatitis B virus (HBV) worldwide, and this virus is commonly controlled by treatments with interferon (IFN)-alpha and nucleoside analogues (NA). However, the complete elimination of HBV by these treatments is difficult and, thus, the development of new treatments is needed. Host immune responses are closely involved in the elimination of HBV, suggesting the usefulness of immunotherapy. In the present study, we attempted to identify novel cytotoxic T-lymphocyte (CTL) epitopes that are useful for immunotherapy against HBV. Methods: CTL epitopes were predicted using computer software. Immune responses to each peptide were evaluated by IFN-γ ELISPOT and cytotoxic assays. The relationships between the immune responses to these newly identified CTL epitopes and the clinical backgrounds of patients and administration of NA were analyzed. Peptides were administered to mice as vaccines and peptide-specific T-cell induction was measured in vivo. Results: Positive reactions to 10 synthesized peptides were detected in 3 or more patients using the IFN-γ ELISPOT assay, and concentration-dependent cytotoxicity against 2 of these peptides was observed in the cytotoxic assay. Some peptides that correlated with serum ALT, HBsAg, and HBV core-related antigen (HBcrAg) levels were identified. Immune reactions against some peptides were enhanced by the administration of NA. Regarding their effects as a vaccine, peptide-specific T-cells were induced by four peptides in vivo. Conclusions: Novel HBV epitopes that correlated with HBsAg and HBcrAg levels were identified. These newly identified epitopes may be useful in the analysis of immune responses to HBV and development of immunotherapy against HBV. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to reveal the factors associated with virologic failure in sofosbuvir and ledipasvir (SOF/LDV)-treated patients, and identify baseline NS5A or NS5B resistance-associated substitutions (RASs). Methods: Four hundred ninety-three patients with Hepatitis C Virus (HCV) genotype 1b infection were treated with SOF/LDV; 31 had a history of interferon (IFN)-free treatment with daclatasvir and asunaprevir. The effect of baseline RASs on the response to SOF/LDV therapy was analyzed. Results: Overall, a sustained virologic response at 12 weeks (SVR12) was achieved in 476 patients (96.6%). The SVR12 rates in the patients with IFN-free treatment-naïve and retreatment were 97.6% and 80.6%, respectively. HCV elimination was not achieved in 17 patients, 11 (including 5 with IFN-free retreatment) of whom had virologic failure. Eight patients had coexisting NS5A RASs of Q24, L28 and/or R30, L31, or Y93 and one patient had coexisting NS5A RASs of P32L and A92K. Interestingly, 10 and 8 patients had NS5B A218S and C316N RAS respectively. According to a multivariate analysis, coexisting NS5A RASs, NS5A P32 RAS, NS5B A218 and/or C316 RASs, and γ-glutamyltranspeptidase were associated with virologic failure. In the naïve patients, all patients without NS5B A218 and/or C316 RAS achieved an SVR12. Notably, the SVR12 rates of patients with coexisting NS5A and NS5B RASs were significantly lower (83.3%). Conclusions: Although SOF/LDV therapy resulted in a high SVR12 rate, coexisting NS5A and NS5B RASs were associated with virologic failure. These results might indicate that the coexisting baseline RASs influence the therapeutic effects of SOF/LDV. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C is the second fastest growing infectious disease in China. The standard-of-care for chronic hepatitis C in China is Pegylated interferon plus ribavirin (PR), which is associated with tolerability and efficacy issues. An interferon- and ribavirin-free, all-oral regimen comprising daclatasvir (DCV) and asunaprevir (ASV), which displays higher efficacy and tolerability, has recently been approved in China. Objectives: This study is to estimate the cost-effectiveness of DCV+ASV (24 weeks) for chronic hepatitis C genotype 1b treatment-naïve patients compared with PR regimen (48 weeks) in China. Methods: A cohort-based Markov model was developed from Chinese payer perspective to project the lifetime outcomes of treating 10,000 patients with an average age of 44.5 with two hypothetical regimens, DCV+ASV and PR. Chinese-specific health state costs and efficacy data were used. The annual discount rate was 5%. Base-case analysis and sensitivity analysis were conducted. Results: For HCV Genotype 1b treatment-naïve patients, DCV+ASV proved to be dominant over PR, with a cost saving of ¥33,480(5,096 USD) and gains in QALYs and life years of 1.29 and 0.85, respectively. The lifetime risk of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver-related death was greatly reduced with DCV+ASV. Univariate sensitivity analysis demonstrated that key influencers were the discount rate, time horizon, initial disease severity and sustained virological response rate of DCV+ASV, with all scenarios resulting in additional benefit. Probabilistic sensitivity analysis demonstrated that DCV+ASV has a high likelihood (100%) of being cost-effective. Conclusion: DCV+ASV is not only an effective and well-tolerated regimen to treat chronic HCV genotype 1b infection treatment-naïve patients, but also is more cost-effective than PR regimen. DCV+ASV can benefit both the public health and reimbursement system in China. [ABSTRACT FROM AUTHOR]

Sustained virological response (SVR) rates have increased remarkably since the introduction of direct-acting antiviral agents (DAAs) for chronic hepatitis C. Autotaxin (ATX) is a secreted enzyme converting lysophosphatidylcholine to lysophosphatidic acid and a newly established biomarker for liver fibrosis. Interferon-free DAA regimens for chronic hepatitis C could improve liver stiffness in SVR patients according to several non-invasive evaluation methods, but the clinical response and significance of ATX in this context have not yet been defined. We therefore investigated sequential serum ATX levels at baseline, 4 weeks after the start of treatment, and 24 weeks after treatment in 159 hepatitis C virus (HCV)-infected patients who received DAA therapy. Other non-invasive fibrosis markers (aspartate aminotransferase-to-platelet ratio and FIB-4 index) were examined as well. Baseline median ATX levels were comparable between the 144 patients who achieved a SVR and the 15 who did not (1.54 vs. 1.62 mg/L), but median ATX levels became significantly decreased during and after DAA therapy in the SVR group only (from 1.54 to 1.40 and 1.31 mg/L, respectively; P < 0.001). ATX was significantly decreased between baseline and 4 weeks of treatment in overall, male, and female SVR patients (all P < 0.001). In subjects with low necroinflammatory activity in the liver (i.e., alanine aminotransferase < 30 U/L), ATX levels were significantly reduced from baseline to 4 weeks of treatment and remained low (P < 0.001) in patients with a SVR. Thus, interferon-free DAA therapy was associated with a significant decrease in serum ATX levels in patients achieving a SVR, suggesting early regression of liver fibrosis in addition to inflammation treatment. [ABSTRACT FROM AUTHOR]

Objective: To assess the cost-effectiveness of the elbasvir/grazoprevir (EBR/GZR) regimen in patients with genotype 1 chronic hepatitis C virus (HCV) infection with severe and end-stage renal disease compared to no treatment. Design: This study uses a health economic model to estimate the cost-effectiveness of treating previously untreated and treatment experienced chronic hepatitis C patients who have severe and end stage renal disease with the elbasvir-grazoprevir regimen versus no treatment in the French context. The lifetime homogeneous markovian model comprises of forty combined health states including hepatitis C virus and chronic kidney disease. The model parameters were from a multicentre randomized controlled trial, ANRS CO22 HEPATHER French cohort and literature. 1000 Monte Carlo simulations of patient health states for each treatment strategy are used for probabilistic sensitivity analysis and 95% confidence intervals calculations. The results were expressed in cost per quality-adjusted life year (QALY) gained. Patients: The mean age of patients in the HEPATHER French cohort was 59.6 years and 56% of them were men. 22.3% of patients had a F0 fibrosis stage (no fibrosis), 24.1% a F1 stage (portal fibrosis without septa), 7.1% a F2 stage (portal fibrosis with few septa), 21.4% a F3 stage (numerous septa without fibrosis) and 25% a F4 fibrosis stage (compensated cirrhosis). Among these HCV genotype 1 patients, 30% had severe renal impairment stage 4, 33% had a severe renal insufficiency stage 5 and 37% had terminal severe renal impairment stage 5 treated by dialysis. Intervention: Fixed-dose combination of direct-acting antiviral agents elbasvir and grazoprevir compared to no-treatment. Results: EBR/GZR increased the number of life years (6.3 years) compared to no treatment (5.1 years) on a lifetime horizon. The total number of QALYs was higher for the new treatment because of better utility on health conditions (6.2 versus 3.7 QALYs). The incremental cost-utility ratio (ICUR) was of €15,212 per QALY gained for the base case analysis. Conclusions: This cost-utility model is an innovative approach that simultaneously looks at the disease evolution of chronic hepatitis C and chronic kidney disease. EBR/GZR without interferon and ribavirin, produced the greatest benefit in terms of life expectancy and quality-adjusted life years (QALY) in treatment-naïve or experienced patients with chronic hepatitis C genotype 1 and stage 4–5 chronic kidney disease including dialysis patients. Based on shape of the acceptability curve, EBR/GZR can be considered cost-effective at a willingness to pay of €20,000 /QALY for patients with renal insufficiency with severe and end-stage renal disease compared to no treatment. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis C infection is a major public health concern, with a high burden in Sub-Saharan Africa. There is growing evidence that chronic hepatitis C virus (HCV) infection causes neurological complications. This study aimed at assessing the prevalence and factors associated with neurological manifestations in chronic hepatitis C patients. Methods: Through a cross-sectional design, a semi-structured questionnaire was used to collect data from consecutive chronic HCV infected patients attending the outpatient gastroenterology unit of the Douala General Hospital (DGH). Data collection was by interview, patient record review (including HCV RNA quantification, HCV genotyping and the assessment of liver fibrosis and necroinflammatory activity), clinical examination complemented by 3 tools; Neuropathic pain diagnostic questionnaire, Brief peripheral neuropathy screen and mini mental state examination score. Data were analysed using Statistical package for social sciences version 20 for windows. Results: Of the 121 chronic hepatitis C patients (51.2% males) recruited, 54.5% (95% Confidence interval: 46.3%, 62.8%) had at least one neurological manifestation, with peripheral nervous system manifestations being more common (50.4%). Age ≥ 55 years (Adjusted Odds Ratio: 4.82, 95%CI: 1.02–18.81, p = 0.02), longer duration of illness (AOR: 1.012, 95%CI: 1.00–1.02, p = 0.01) and high viral load (AOR: 3.40, 95% CI: 1.20–9.64, p = 0.02) were significantly associated with neurological manifestations. Peripheral neuropathy was the most common neurological manifestation (49.6%), presenting mainly as sensory neuropathy (47.9%). Age ≥ 55 years (AOR: 6.25, 95%CI: 1.33–29.08, p = 0.02) and longer duration of illness (AOR: 1.01, 1.00–1.02, p = 0.01) were significantly associated with peripheral neuropathy. Conclusion: Over half of the patients with chronic hepatitis C attending the DGH have a neurological manifestation, mainly presenting as sensory peripheral neuropathy. Routine screening of chronic hepatitis C patients for peripheral neuropathy is therefore necessary, with prime focus on those with older age and longer duration of illness. [ABSTRACT FROM AUTHOR]

Background: Control of hepatitis C virus infection (HCV) is an increasingly important issue. Enhancing screening coverage is necessary to discover more HCV infected subjects in community. However, a substantial population is unaware of HCV infection that needs more attention. Aim: The aims of this study were to evaluate the status of HCV infected residents in remote villages, to compare characteristics between already known and unaware HCV infection subjects, and to analyze the disease insights. Patients and methods: Screening intervention for liver diseases was conducted in remote villages of Tainan City of southern Taiwan from August 2014 to July 2016. Items of screening examinations included questionnaire, blood sampling for liver tests and viral hepatitis markers (hepatitis B surface antigen and anti-HCV antibody), abdominal sonography survey, and liver stiffness measurement by transient elastography. Quantitation of HCV RNA was measured for residents with positive anti-HCV antibody. Results: A total of 194 (13.5%) out of 1439 participants showed positive for anti-HCV antibody. HCV viremia was detected in 119 (61.3%) residents. Previously unaware HCV infection by questionnaire record was present in 68 (35.1%) of ant-HCV positive residents. By multivariate logistic analysis, unaware HCV infected residents exhibited significantly mild liver fibrosis (OR 0.876, 95% CI 0.782~0.981, p = 0.022), more prevalent of heart diseases (OR 6.082, 95% CI 1.963~18.839, p = 0.002), and less cluster of family history of liver diseases (OR 0.291, 95% CI 0.113~0.750, p = 0.011) when comparing with already known HCV infected residents. Among the 126 already know HCV infected residents, only 59 (46.8%) received antiviral treatment or regular follow-up. No concept or no willing to receive medical care was observed in 44 (34.9%) residents. Conclusion: In HCV endemic villages of Taiwan, residents with unaware HCV infection comprised about one third of HCV infected residents and exhibited obscure characteristics to identify. Less than half of already known HCV infected residents received adequate medical care. To eliminate HCV infection, vigorous efforts on enhancing screening coverage, educating update knowledge of liver diseases, and linking to medical care are urgently needed. [ABSTRACT FROM AUTHOR]

Background: HBeAg-negative chronic hepatitis B patients require long-term nucleos(t)ide analogues(NAs) because loss of surface antigen (HBsAg) is unusual. Low quantitative HBsAg (qHBsAg) levels can identify patients with higher probability of seroclearance. The aim of our study was to evaluate qHBsAg in HBeAg-negative patients receiving NAs to predict a reduction of HBsAg levels and seroclearance. Methods: Retrospective analysis of qHBsAg in HBeAg-negative patients before and at years 1, 3, 5, 8 and over of NAs treatment. Results: From 1999 to 2015, HBsAg was quantified in 358 serum samples from 95 HBeAg-negative patients. Low qHBsAg (<120 IU/mL) was identified at baseline or during follow-up in 14% of patients and HBsAg loss in 4%. No baseline variables predicted seroclearance and only treatment duration predicted low qHBsAg. The annual decline of qHBsAg was -0.102 log IU/mL and the median time to HBsAg loss was 6.04 years. The decline was greater in patients achieving low HBsAg levels (-0.257) than in those who did not (-0.057)(p<0.001). The diagnostic accuracy (ROC curve, 95%CI) of qHBsAg delta at year 3 was 0.89 (0.81–0.97), with cut-off >0.3 log IU/mL showing a positive and negative predictive value of 42% and 100% to identify patients achieving low levels of HBsAg. Conclusions: Reduction of qHBsAg is slow in HBeAg-negative patients receiving NAs, although low levels or faster qHBsAg decline may occur in 14%. A qHBsAg reduction >0.3 log IU/mL at year 3 can identify patients with a higher probability of achieving low levels and HBsAg seroclearance. [ABSTRACT FROM AUTHOR]

Background: The joint effect of the interaction of alcohol intake, hepatitis B virus (HBV) and hepatitis C virus (HCV) on the risk of cirrhosis is still unexplored because a large sample size is required for this investigation. Objective: Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis. Design: We analysed 12,262 consecutive patients with chronic liver disease of various aetiologies referring to 95 Italian liver units in 2001 or 2014. To evaluate the interaction between alcohol abuse, HBV infection, and HCV infection, patients unexposed to either factors were used as reference category. Adjustment for BMI and age was done by multiple logistic regression analysis. Results: Females were older than males (p<0.01) and less frequently showed HBV and alcoholic aetiology (p<0.01). In both sexes, an overtime increasing age and an increasing proportion of subjects with liver cirrhosis was observed, reflecting a better survival (0.01). An additive interaction is observed in females: the O.R. generated by the simultaneous presence of HBV, HCV, and alcohol (5.09; 95% C.I. 1.06–24.56) exceeds the sum (4.14) of the O.R. generated by a single exposure (O.R. = 0.72 for HBsAg positivity, OR = 1.34 for anti-HCV positivity, and O.R. = 2.08 for alcohol intake). No interaction is observed in male sex. Conclusions: The observed gender difference suggests that the simultaneous presence of HBV/HCV coinfection and risky alcohol intake enhances the mechanism of liver damage to a greater extent in females than in males. [ABSTRACT FROM AUTHOR]

Aim: This systematic review and meta-analysis was carried out to compare the diagnostic accuracy of Magnetic resonance elastography (MRE) and Fibroscan for detecting liver fibrosis in Chronic Hepatitis B (CHB) patients. Methods: The PubMed, the Cochrane Library, and the Web of science databases were searched for studies that evaluated the diagnostic value of MRE and Fibroscan for liver fibrosis in CHB patients until March 1st 2017. The quality of the included studies was assessed by the revised Quality Assessment for Studies of Diagnostic Accuracy tool (QUADAS-2). Meta-disc 4.1 was used to summary the area under receiver operating characteristics curve (AUROC), sensitivity, specificity, diagnostic odds ratios to assess the accuracy of staging liver fibrosis using MRE and Fibroscan. Results: A total of nine MRE studies with 1470 patients and fifteen Fibroscan studies with 3641 patients were included in this systematic review. The summary AUROC values using MRE and Fibroscan for detecting significant fibrosis, advanced fibrosis and cirrhosis were 0.981 vs. 0.796(p<0.001), 0.972 vs. 0.893(p<0.001), and 0.972 vs. 0.905 (p<0.001). The pooled sensitivity and specificity using MRE for the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis were 92.8% and 93.7%, 89.6% and 93.2%, 89.5% and 92.0%, respectively. The pooled sensitivity and specificity using Fibroscan for the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis were 71.6% and 81.6%, 79.0% and 84.6%, 80.0% and 86.6%, respectively. Conclusion: MRE is more accurate than Fibroscan in diagnosing liver fibrosis in CHB patients, especially in diagnosing significant fibrosis and advanced fibrosis. [ABSTRACT FROM AUTHOR]

Objective: Assessing risk of adverse outcomes among patients with chronic liver disease has been challenging due to non-linear disease progression. We previously developed accurate prediction models for fibrosis progression and clinical outcomes among patients with advanced chronic hepatitis C (CHC). The primary aim of this study was to validate fibrosis progression and clinical outcomes models among a heterogeneous patient cohort. Design: Adults with CHC with ≥3 years follow-up and without hepatic decompensation, hepatocellular carcinoma (HCC), liver transplant (LT), HBV or HIV co-infection at presentation were analyzed (N = 1007). Outcomes included: 1) fibrosis progression 2) hepatic decompensation 3) HCC and 4) LT-free survival. Predictors included longitudinal clinical and laboratory data. Machine learning methods were used to predict outcomes in 1 and 3 years. Results: The external cohort had a median age of 49.4 years (IQR 44.3–54.3); 61% were male, 80% white, and 79% had genotype 1. At presentation, 73% were treatment naïve and 31% had cirrhosis. Fibrosis progression occurred in 34% over a median of 4.9 years (IQR 3.2–7.6). Clinical outcomes occurred in 22% over a median of 4.4 years (IQR 3.2–7.6). Model performance for fibrosis progression was limited due to small sample size. The area under the receiver operating characteristic curve (AUROC) for 1 and 3-year risk of clinical outcomes was 0.78 (95% CI 0.73–0.83) and 0.76 (95% CI 0.69–0.81). Conclusion: Accurate assessments for risk of clinical outcomes can be obtained using routinely collected data across a heterogeneous cohort of patients with CHC. These methods can be applied to predict risk of progression in other chronic liver diseases. [ABSTRACT FROM AUTHOR]

There is a paucity of health policy relevant data for chronic liver disease from India, impeding formulation of an interventional strategy to address the issue. A prospective, multicentric study to delineate the etiology and clinical profile of chronic liver disease in India is reported here. A centrally coordinated and monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and analyzed. Eleven hospitals from different parts of India participated. Data were uploaded into a web based proforma and monitored by a single centre according to a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383) attending the eleven participating hospitals of India had liver disease. 65807 (24·68%) were diagnosed for the first time (new cases). Of these, 13014 (19·77%, median age 43 years, 73% males) cases of chronic liver disease were finally analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34·3% of 4413) was the commonest cause of cirrhosis while Hepatitis B (33·3%) was predominant cause of chronic liver disease in general and non-cirrhotic chronic liver disease (40·8% out of 8163). There was significant interregional differences (hepatitis C in North, hepatitis B in East and South, alcohol in North-east, Non-alcoholic Fatty Liver Disease in West) in the predominant cause of chronic liver disease. Hepatitis B (46·8% of 438 cases) was the commonest cause of hepatocellular Cancer.11·7% had diabetes. Observations of our study will help guide a contextually relevant liver care policy for India and could serve as a framework for similar endeavor in other developing countries as well. [ABSTRACT FROM AUTHOR]

The presence of significant fibrosis is an indicator for liver disease staging and prognosis. The aim of the study was to determine reproducibility of real-time shear wave elastography using a hepatic biopsy as the reference standard to identify patients with chronic liver disease. Forty patients with chronic liver disease and 12 normal subjects received shear wave elastography performed by skilled operators. Interoperator reproducibility was studied in 29 patients. Fibrosis was evaluated using the Metavir score. The median and range shear wave elastography values in chronic liver disease subjects were 6.15 kPa and 3.14–16.7 kPa and were 4.49 kPa and 2.92–7.32 kPa in normal subjects, respectively. With respect to fibrosis detected by liver biopsy, shear wave elastography did not change significantly between F0 and F1 (p = 0.334), F1 and F2 (p = 0.611), or F3 and F4 (0.327); a significant difference was observed between the F0-F2 and F3-F4 groups (p = 0.002). SWE also correlated with inflammatory activity (Rs = 0.443, p = 0.0023) and ALT levels (Rs = 0.287, p = 0.0804). Age, sex and body mass index did not affect shear wave elastography measurements. Using receiver operator characteristic curves, two threshold values for shear wave elastography were identified: 5.62 kPa for patients with fibrosis (≥F2; sensitivity 80%, specificity 69.4%, and accuracy 77%) and 7.04 kPa for patients with severe fibrosis (≥F3; sensitivity 88.9%, specificity 81%, and accuracy 89%). Overall interobserver agreement was excellent and was analysed using an interclass correlation coefficient (0.94; CI 0.87–0.97).This study shows that shear wave elastography executed by skilled operators can be performed on almost all chronic liver disease patients with high reproducibility. It is not influenced by age, sex or body mass index, identifies severely fibrotic patients and is also related to inflammatory activity. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a common complication of chronic viral hepatitis. In support of this notion, we have reported that hepatitis B surface antigen (HBsAg)-specific CD8+ T lymphocytes critically contribute to inducing chronic liver cell injury that exerts high carcinogenic potential in a hepatitis B virus (HBV) transgenic mouse model. The dynamics of the molecular signatures responsible for hepatocellular carcinogenesis are not fully understood. The current study was designed to determine the serial changes in gene expression profiles in a model of chronic immune-mediated hepatitis. Methods: Three-month-old HBV transgenic mice were immunologically reconstituted with bone marrow cells and splenocytes from syngeneic nontransgenic donors. Liver tissues were obtained every three months until 18 months at which time all mice developed multiple liver tumors. Nitrative DNA lesions and hepatocyte turnover were assessed immunohistochemically. Gene expression profiles were generated by extracting total RNA from the tissues and analyzing by microarray. Results: The nitrative DNA lesions and the regenerative proliferation of hepatocytes were increased during the progression of chronic liver disease. In a gene expression profile analysis of liver samples, the chemokine- and T cell receptor (TCR)-mediated pathways were enhanced during chronic hepatitis, and the EGF- and VEGF-mediated pathways were induced in HCC. Among these molecules, the protein levels of STAT3 were greatly enhanced in all hepatocyte nuclei and further elevated in the cytoplasm in HCC tissue samples at 18 months, and the levels of phosphorylated TP53 (p-p53-Ser 6 and -Ser 15) were increased in liver tissues. Conclusions: HBV-specific immune responses caused unique molecular signatures in the liver tissues of chronic hepatitis and triggered subsequent carcinogenic gene expression profiles in a mouse model. The results suggest a plausible molecular basis responsible for HBV-induced immune pathogenesis of HCC. [ABSTRACT FROM AUTHOR]

Background & aims: Treatment rates with interferon-based therapies for chronic hepatitis C have been low. Our aim was to perform a systematic review of available data to estimate the rates and barriers for antiviral therapy for chronic hepatitis C. Methods: We conducted a systematic review and meta-analysis searching MEDLINE, SCOPUS through March 2016 and abstracts from recent major liver meetings for primary literature with available hepatitis C treatment rates. Random-effects models were used to estimate effect sizes and meta-regression to test for potential sources of heterogeneity. Results: We included 39 studies with 476,443 chronic hepatitis C patients. The overall treatment rate was 25.5% (CI: 21.1–30.5%) and by region 34% for Europe, 28.3% for Asia/Pacific, and 18.7% for North America (p = 0.008). On multivariable meta-regression, practice setting (tertiary vs. population-based, p = 0.04), region (Europe vs. North America p = 0.004), and data source (clinical chart review vs. administrative database, p = 0.025) remained significant predictors of heterogeneity. The overall treatment eligibility rate was 52.5%, and 60% of these received therapy. Of the patients who refused treatment, 16.2% cited side effects, 13.8% cited cost as reasons for treatment refusal, and 30% lacked access to specialist care. Conclusions: Only one-quarter of chronic hepatitis C patients received antiviral therapy in the pre-direct acting antiviral era. Treatment rates should improve in the new interferon-free era but, cost, co-morbidities, and lack of specialist care will likely remain and need to be addressed. Linkage to care should even be of higher priority now that well-tolerated cure is available. [ABSTRACT FROM AUTHOR]

Background: The VEGF gene polymorphism rs699947 related to clinical pathology, mortality, and recurrence of HCC. Few studies mentioned an association between VEGF gene polymorphisms with illness progression in chronic liver disease. We aimed to explore differences of VEGF gene polymorphism rs699947 in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma patients in Indonesian population. Methods: A cross-sectional study with consecutive sampling and without matching was performed during a 3 years period (2011–2014) at Dr. Sardjito General Hospital Yogyakarta, Indonesia. Blood DNA was sequenced from 123 subjects with chronic liver diseases [39 chronic hepatitis (CH), 39 liver cirrhosis (LC), and 45 hepatocellular carcinoma (HCC)]. 59 healthy subjects also participated. Using isolated VEGF genes for specific primers for rs699947, blood samples were examined by targeting DNA sequences with Applied Bio systems. All data were analyzed using STATA version 11.0 with significance level at P<0.05. Results: The mean of age in HCC and LC subjects were older than in CH and healthy (P value <0.05); there were more males in LC, HCC and the healthy groups but not in CH (P>0.05). HBV was the dominant etiology in HCC, LC, and CH besides HCV and non HBV-HCV (P<0.05). There were significant differences in the SNP -2578 distributions of allele C compared to allele A in all subjects (healthy vs. LC, and HCC; LC vs. CH (P<0.05), but no significant difference A>C vs. C>C, and genotypes distribution. Proportion of SNP -2578 A>C vs. C>C CH 1.8:1; HCC 1.4:1; healthy 1.7:1; but its proportion in LC was inversed (1:1.2). Genotype A was low in all subjects (5%-11%). Significant difference of allele distribution was found in healthy vs. LC, and HCC; CH vs. LC. Based on HWE analyses, distribution of allele C was dominant. There were not significant differences in deletion, insertion-deletion at -2547 until -2526, and haplotype (Ht) CCGACCCC (P>0.05). The OR analyses of allele and SNP showed that allele A can be a predictor of disease progression in LC to HCC (OR 2.26) and healthy to LC (OR 1.65); and SNP A>C also can be a predictor in healthy to HCC (OR 1.41) and CH (OR 1.14). Conclusion: The occurrence of allele A and SNP A>C VEGF gene (-2578) might predict illness progression from healthy to CH, LC or HCC and LC to HCC. [ABSTRACT FROM AUTHOR]

Background/aims: Recent studies have demonstrated the utility of the FibroScan® device in diagnosing liver steatosis, but its usefulness has not been thoroughly appraised. We investigated the usefulness of the controlled attenuation parameter (CAP) in detecting and quantifying liver steatosis. Methods: A prospective analysis was applied to 79 chronic liver disease patients who underwent a liver biopsy, a FibroScan investigation, ultrasonography, and hepatic steatosis index (HSI). The presence and degree of steatosis as measured by the FibroScan device, ultrasonography and HSI were compared with the results for the liver biopsy tissue. Results: There was substantial concordance between the liver biopsy results and the CAP as evaluated by the kappa (κ) index test for detecting liver steatosis (κCAP = 0.77, P<0.001; κultrasonography = 0.60, P<0.001; κHSI = 0.47, P<0.001). The areas under the receiver operating characteristic curve (AUROCs) of the CAP, ultrasonography, and HSI were 0.899 [95% confidence interval (CI) = 0.826–0.972)], 0.859 (95% CI = 0.779–0.939), and 0.766 (95% CI = 0.655–0.877), respectively. The optimal CAP cutoff value for differentiating between normal and hepatic steatosis was 247 dB/m, which produced sensitivity and specificity values of 91.9% and 85.7%, respectively, as well as a positive predictive value of 85.0% and a negative predictive value of 92.3%. Conclusion: The CAP produces results that are highly concordant with those of a liver biopsy in detecting steatosis. Therefore, the CAP is a noninvasive and reliable tool for evaluating liver steatosis, even in the early stages. [ABSTRACT FROM AUTHOR]

The risk of hepatocellular carcinoma (HCC) development is reduced following viral elimination by interferon therapy in chronic hepatitis C patients. However, the risk in patients treated with interferon-free direct-acting antivirals (DAAs) is unknown. We evaluated chronic hepatitis C patients who achieved viral eradication by pegylated-interferon plus ribavirin (PEG-IFN/RBV, n = 244) or daclatasvir plus asunaprevir (DCV/ASV, n = 154) therapy. None of the patients had prior history of HCC or antiviral therapy. The median observation period after the end of treatment for the PEG-IFN/RBV and DCV/ASV groups were 96 (range 10–196) and 23 (range 4–78) months, respectively. During the observation period, HCC developed in 13 (5.3%) and 7 (4.5%) patients in the PEG-IFN/RBV and DCV/ASV groups, respectively. The cumulative HCC development rate after 1-, 3- and 5-years (0.4%, 3% and 5% for the PEG-IFN/RBV group and 0.6%, 9% and 9% for the DAA group, respectively) were similar between the two groups. Propensity score matching analysis also showed no significant difference in HCC development rates between the two groups. Serum AFP levels decreased to similar levels between PEG-IFN/RBV and DCV/ASV groups following the achievement of viral eradication. The risk for HCC development following viral eradication by IFN-free DAA therapy may be similar to that in IFN-based therapy. [ABSTRACT FROM AUTHOR]

Objective: This is the first study to analyze the impact of the rs35761398 variant of the CNR2 gene leading to the substitution of GLN (Q) of codon 63 of the cannabinoid receptor 2 (CB2) with ARG (R) on the clinical presentation of chronic hepatitis in HIV/HCV coinfected patients. Methods: Enrolled in this study were 166 consecutive HIV/HCV coinfected patients, naïve for HCV treatment. A pathologist unaware of the patients’ condition graded liver fibrosis, necroinflammation (Ishak) and steatosis. All patients were screened for the CB2 rs35761398 polymorphism. Results: Of the 166 HIV/HCV coinfected patients, 72.9% were males, 42.5% were infected with HCV-genotype-3 and 60.2% had been intravenous drug users. The median age was 40.6 years and the immunological condition good (median CD4+ cells/mm3 = 507, IQR: 398.0–669.5). Thirty-five (21.1%) patients were naive for ART and 131(78.9%) were on ART. The CB2-RR variant was detected in 45.8% of patients, QR in 38.6% and QQ in 15.7%. Patients with CB2-RR showed a necroinflammation score (HAI) ≥9 more frequently than those with CB2-QQ or CB2-QR (32.9% vs. 11.5% and 14.1%, respectively, p≤0.001). In the multivariate analysis, the CB2-RR variant (p = 0.03) and liver fibrosis were both identified as independent predictors of the entity of liver necroinflammation (p = 0.0001). Conclusion: This study shows interesting interplay between the CB2-RR variant and liver necroinflammation in chronic hepatitis patients with HIV/HCV coinfection, an observation of clinical value that coincides with the interest in the use of the CB2 agonists and antagonists in clinical practice emerging from the literature. [ABSTRACT FROM AUTHOR]

Background and aim: Among various symptoms accompanied with chronic liver disease, pruritus affects the quality of life of patients, causing physical and mental stress, and worsens hepatic function. Recently, κ-opioid receptor agonist, nalfurafine hydrochloride was approved to treat central pruritus in patients with liver disease in Japan. This study aimed to assess the long-term efficacy and safety of nalfurafine hydrochloride on pruritus in chronic liver disease patients. Methods: A patient-reported outcome using questionnaire-based methods was used for 41 liver disease patients with or without pruritus symptoms. Nalfurafine hydrochloride (2.5 μg/day) was orally administered to 18 patients suffering from pruritus symptoms and whose current treatment was not effective. The same questionnaires and visual analogue scales (VAS) were repeatedly followed up for the patients for the entire follow-up period, and biochemical analyses were performed to evaluate the safety of the treatment. Results: Pruritus completely disappeared in seven of 18 cases, and VAS scores showed a decreasing trend over time from the start of nalfurafine hydrochloride administration in all patients who received the medication. Among 11 patients who were followed up for more than 12 weeks, nine patients showed continuous improvement of symptoms, and this progress was still apparent at ≥20 weeks after starting administration (p < 0.0001). The medication was discontinued in four patients because of progression of primary disease, high cost, oral dryness, and anemia. No significant toxicity was observed on the serum biochemical analyses. Conclusions: Nalfurafine hydrochloride contributed to long-term suppression of pruritus without significant safety problems. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection remains a serious public health problem worldwide. Mother-to-child transmission (MTCT) of HBV is the major mode of transmission in HBV-endemic areas, including China, where little is known about pregnant women’s knowledge of and attitudes towards HBV infection and MTCT. Methods: A cross-sectional survey, conducted in pregnant women in Guangdong Province, China, measured HBV knowledge and attitudes using a questionnaire, at one tertiary and two rural hospitals. Results: The total response rate was 94.5% (737/780). Of the 11 knowledge questions, the mean score was 6.73 ± 3.04 (mean ± SD). Most pertinent to preventing MTCT, 53.3% of the respondents did not know that HBV can be transmitted through unprotected sexual intercourse and nearly 20% did not know that HBV can be transmitted from mother to infant. The results of the four attitude questions was better with 83% and 85% being willing to be screened for HBV and let their baby receive HBV vaccine and HBIg, respectively. However, only 16.5% of respondents agreed that they would be willing to take drugs that are known not to harm the fetus to prevent MTCT of HBV. In multivariable analysis, higher education level was associated with better knowledge and attitude scores. Conclusions: Knowledge about HBV among pregnant women was poor and needs to be improved to prevent MTCT of HBV. Health education needs to be directed towards pregnant mothers, particularly less educated mothers, in high HBV endemicity settings. [ABSTRACT FROM AUTHOR]

Background: Bacteremic pneumonia is considered a potential cause of distal organ abscess formation. Therefore, we hypothesize that pneumonia is a risk factor for pyogenic liver abscess (PLA).The aim of this study is to explore the association between pneumonia and PLA. Methodology/Principal findings: A nationwide, population-based, nested, case–control study was conducted using data from the Taiwan National Health Insurance Research Database. In total, 494 patients with PLA and 1,976 propensity score matched controls were enrolled. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) in patients with exposure to pneumonia before PLA. After matched and adjusted for confounding factors including age, sex, urbanization, income, chronic liver disease, alcohol-related disease, biliary stone, chronic kidney disease, diabetes mellitus, chronic liver disease, and cancer, hospitalization for pneumonia remained an independent risk factor for PLA with an aORs of 2.104 [95% confidence interval (CI) = 1.309–3.379, p = 0.0021]. Moreover, the aORs were significantly higher among patients hospitalized for pneumonia within 30 days (aORs = 10.73, 95% CI = 3.381–34.054), 30–90 days (aORs = 4.698, 95% CI = 1.541–14.327) and 90–180 (aORs = 4.000, 95% CI = 1.158–13.817) days before PLA diagnosis. Conclusion: Pneumonia is an independent risk factor for subsequent PLA. Moreover, hospitalization for pneumonia within 180 days before PLA diagnosis was associated with an increased risk of PLA. [ABSTRACT FROM AUTHOR]