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This study, conducted at two university-based infectious disease clinics, included 216 patients with chronic hepatitis C. The primary objective was to assess the positive and negative predictive values, sensitivity, and specificity of achieving a sustained virological response (SVR) at 4 weeks compared to 12 weeks post-therapy. The results demonstrated a maximum sensitivity of 100% for achieving SVR at 12 weeks after reaching SVR at 4 weeks for all analyzed genotypes, except for genotype 1b treated with EBR/GZR therapy, where the specificity was 75%. Additionally, younger age and less advanced liver fibrosis were identified as independent predictors of achieving a sustained virological response at both 4 and 12 weeks. The significant normalization of various biochemical parameters was observed after treatment, indicating an overall improvement in liver function. This study suggests that shortening the monitoring period to 4 weeks might be effective for younger patients without significant fibrosis, potentially reducing loss to follow-up, which is a critical issue in HCV treatment. These findings align with the "test and treat" approach. Further research is needed to confirm these findings and incorporate them into official guidelines, which could simplify and enhance the effectiveness of HCV treatment protocols, aiding global efforts to eliminate HCV as a public health issue by 2030. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) impairs glucose homoestasis, thus influences its clinical picture and prognosis. This study aimed at evaluating Diabetes mellitus (DM) on Egyptian patients with chronic hepatitis C (CHC), and its impact on their virologic response when treated with directly acting antiviral (DAA) medications. Adult patients with CHC were divided into 2 groups; Diabetic patients, and Non diabetic patients serving as control group. All patients were subjected to thorough clinical evaluation, basic biochemical laboratory tests including fasting blood glucose/glycosylated haemoglobin (HbA1C), and virologic assay. They were treated with various combined DAAs, and were monitored during, at and after end of treatment. Diabetic patients constituted 9.85 % of CHC, and had generally worse laboratory tests (significantly higher transaminases, platelet count, Fib4 and hepatic steatosis) than non diabetic patients, and a less sustained virologic response (SVR) (significantly in Sofosbuvir (SOF) + pegylated interferon (PegIFN) + ribavirin (RBV), SOF + RBV, SOF + daclatasvir (DAC)). Although DM did not play a significant influence on SVR, yet Fib4 and SOF + RBV + PEG-IFN were significant factors affecting SVR among diabetics, while female gender and viraemia were significant factors affecting SVR among non diabetics. Hepatic fibrosis and SOF/RBV significantly influenced SVR in both groups. Diabetic patients with CHC have worse liver biochemical profile, yet DM per se did not influence the virologic response to DAAs, however, some factors played roles in affecting SVR among them. [ABSTRACT FROM AUTHOR]

This study, conducted at two university-based infectious disease clinics, included 216 patients with chronic hepatitis C. The primary objective was to assess the positive and negative predictive values, sensitivity, and specificity of achieving a sustained virological response (SVR) at 4 weeks compared to 12 weeks post-therapy. The results demonstrated a maximum sensitivity of 100% for achieving SVR at 12 weeks after reaching SVR at 4 weeks for all analyzed genotypes, except for genotype 1b treated with EBR/GZR therapy, where the specificity was 75%. Additionally, younger age and less advanced liver fibrosis were identified as independent predictors of achieving a sustained virological response at both 4 and 12 weeks. The significant normalization of various biochemical parameters was observed after treatment, indicating an overall improvement in liver function. This study suggests that shortening the monitoring period to 4 weeks might be effective for younger patients without significant fibrosis, potentially reducing loss to follow-up, which is a critical issue in HCV treatment. These findings align with the “test and treat” approach. Further research is needed to confirm these findings and incorporate them into official guidelines, which could simplify and enhance the effectiveness of HCV treatment protocols, aiding global efforts to eliminate HCV as a public health issue by 2030.

Background : We aimed to investigate the correlation between hepcidin mRNA expression and the pathophysiology of the liver or the long-term prognosis in patients with chronic hepatitis C (CHC) or liver cirrhosis (LC). Methods : A total of 82 patients with CHC or LC who underwent liver biopsy were included in this study. Hepcidin mRNA expression was detected in the frozen liver tissues obtained from patients with CHC or LC who underwent liver biopsy. Hepcidin mRNA expression in frozen liver tissues was assessed using real-time quantitative polymerase chain reaction. We previously reported that the extent of proliferation of atypical hepatocytes (POAH) within the six-cell lesion of irregular regeneration (IR) of hepatocytes is a signifi cant histological fi nding associated with the development of hepatocellular carcinoma (HCC) from CHC or LC. Therefore, we investigated the association between hepcidin mRNA expression and disease severity, pathological fi ndings such as the extent of POAH, and the incidence of HCC development from CHC and LC. Furthermore, we compared hepcidin mRNA expression with serum cytokine and chemokine levels using a Bio-plex suspension array system (Bio-Rad Laboratories, CA, USA). Results: Hepcidin mRNA expression was associated with serum ferritin concentration ( p =0.009) and unsaturated ironbinding capacity (P=0.0003) in the serological parameters, but no association was found with histological parameters. The cumulative incidence of HCC development was signifi cantly higher in the low hepcidin mRNA expression group than in the high hepcidin mRNA expression group ( p =0.003). Additionally, patients with lower hepcidin mRNA levels tended to exhibit more extensive POAH ( p =0.0089). Hepcidin mRNA expression was also signifi cantly associated with apoptosis-related and anti-infl ammatory cytokines/chemokines. Conclusions: Low hepcidin mRNA expression may be a risk factor for carcinogenesis in patients with CHC or LC. [ABSTRACT FROM AUTHOR]

Hepatitis C virus infection causes chronic diseases such as cirrhosis and hepatocellular carcinoma. Metabolomics research has been shown to be linked to pathophysiologic pathways in liver illnesses. The aim of this study was to investigate the serum metabolic profile of patients with chronic hepatitis C (CHC) infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Nuclear magnetic resonance (NMR) was used to evaluate the sera of 83 patients with CHC virus and 52 healthy control volunteers (NMR). Then, multivariate statistical analysis was used to find distinguishing metabolites between the two groups. Sixteen out of 40 metabolites including include 3‐HB, betaine, carnitine, creatinine, fucose, glutamine, glycerol, isopropanol, lysine, mannose, methanol, methionine, ornithine, proline, serine, and valine—were shown to be significantly different between the CHC and normal control (NC) groups (variable importance in projection >1 and p < 0.05). All the metabolic perturbations in this disease are associated with pathways of Glycine, serine, and threonine metabolism, glycerolipid metabolism, arginine and proline metabolism, aminoacyl‐tRNA biosynthesis, cysteine and methionine metabolism, alanine, aspartate, and glutamate metabolism. Multivariate statistical analysis constructed using these expressed metabolites showed CHC patients can be discriminated from NCs with high sensitivity (90%) and specificity (99%). The metabolomics approach may expand the diagnostic armamentarium for patients with CHC while contributing to a comprehensive understanding of disease mechanisms. [ABSTRACT FROM AUTHOR]

Abstract Background Patients infected with Hepatitis C virus (HCV) are recommended to receive treatment with direct-acting antiviral agents (DAAs), which have been certified to obtain a high sustained virological response (SVR). However, little is known about the benefits of successful anti-viral treatment to elderly patients with hepatic fibrosis. In this study, we aimed to assess degree of fibrosis in elderly patients with chronic hepatitis C (CHC) treated with DAAs, and to evaluate the correlations between identified factors associated with these changes. Methods This study retrospectively enrolled elderly patients with CHC who received DAAs in Tianjin Second People’s Hospital from April 2018 to April 2021. The degree of liver fibrosis was assessed using serum biomarkers and transient elastography (TE) expressed as the liver stiffness (LSM), while the hepatic steatosis was evaluated by controlled attenuated parameter (CAP). Changes in factors related to hepatic fibrosis were examined following treatment with DAAs, and associated prognostic factors were further evaluated. Results We included 347 CHC patients in our analysis, where 127 of these were elderly patients. For the elderly group, the median LSM was 11.6 (7.9–19.9) kPa, and this value was significantly reduced to 9.7 (6.2–16.6) kPa following DAA treatment. Similarly, GPR, FIB-4 and APRI indices were significantly reduced from 0.445 (0.275–1.022), 3.072 (2.047–5.129) and 0.833 (0.430–1.540) to 0.231 (0.155–0.412), 2.100 (1.540–3.034) and 0.336 (0.235–0.528), respectively. While in younger patients, the median LSM reduced from 8.8 (6.1–16.8) kPa to 7.2 (5.3–12.4) kPa, and the trends of GPR, FIB-4 and APRI were also consistent. The CAP in younger patients increased with statistical significance, but we did not observe any significant change in CAP for the elderly group. Based on multivariate analysis, age, LSM, and CAP before baseline were identified as determinants for LSM improvement in the elderly. Conclusion In this study, we found that elderly CHC patients treated with DAA had significantly lower LSM, GPR, FIB-4, and APRI values. DAA treatment did not significantly change CAP. Furthermore, we observed correlations between three noninvasive serological evaluation markers and LSM. Finally, age, LSM, and CAP were identified as independent predictors of fibrosis regression in elderly patients with CHC.

Background: Patients infected with Hepatitis C virus (HCV) are recommended to receive treatment with direct-acting antiviral agents (DAAs), which have been certified to obtain a high sustained virological response (SVR). However, little is known about the benefits of successful anti-viral treatment to elderly patients with hepatic fibrosis. In this study, we aimed to assess degree of fibrosis in elderly patients with chronic hepatitis C (CHC) treated with DAAs, and to evaluate the correlations between identified factors associated with these changes. Methods: This study retrospectively enrolled elderly patients with CHC who received DAAs in Tianjin Second People's Hospital from April 2018 to April 2021. The degree of liver fibrosis was assessed using serum biomarkers and transient elastography (TE) expressed as the liver stiffness (LSM), while the hepatic steatosis was evaluated by controlled attenuated parameter (CAP). Changes in factors related to hepatic fibrosis were examined following treatment with DAAs, and associated prognostic factors were further evaluated. Results: We included 347 CHC patients in our analysis, where 127 of these were elderly patients. For the elderly group, the median LSM was 11.6 (7.9–19.9) kPa, and this value was significantly reduced to 9.7 (6.2–16.6) kPa following DAA treatment. Similarly, GPR, FIB-4 and APRI indices were significantly reduced from 0.445 (0.275–1.022), 3.072 (2.047–5.129) and 0.833 (0.430–1.540) to 0.231 (0.155–0.412), 2.100 (1.540–3.034) and 0.336 (0.235–0.528), respectively. While in younger patients, the median LSM reduced from 8.8 (6.1–16.8) kPa to 7.2 (5.3–12.4) kPa, and the trends of GPR, FIB-4 and APRI were also consistent. The CAP in younger patients increased with statistical significance, but we did not observe any significant change in CAP for the elderly group. Based on multivariate analysis, age, LSM, and CAP before baseline were identified as determinants for LSM improvement in the elderly. Conclusion: In this study, we found that elderly CHC patients treated with DAA had significantly lower LSM, GPR, FIB-4, and APRI values. DAA treatment did not significantly change CAP. Furthermore, we observed correlations between three noninvasive serological evaluation markers and LSM. Finally, age, LSM, and CAP were identified as independent predictors of fibrosis regression in elderly patients with CHC. [ABSTRACT FROM AUTHOR]

Objectives. To analyze the natural course of liver cirrhosis caused by the hepatitis C virus (HCV) and to evaluate the effectiveness of the related therapy with direct-acting antivirals (DAAs). Material and methods. The natural course of HCV-related cirrhosis was analyzed in 132 dispensary patients, and the effectiveness of antiviral interferon-free therapy was evaluated in 85 of them. Results. The incidence of liver cirrhosis in HCV-infected patients (9.4%) significantly exceeded that in hepatitis B virus-infected patients (2.6%). Among the dispensary patients with HCV-related cirrhosis, 46.2% were correspondingly diagnosed on registration or during the first year of dispensary observation, and 31% developed cirrhosis during the first five years of follow-up observation. The average and median terms for cirrhosis development made up 4.6 and 3.0 years, respectively. The administration of DAAs to patients with HCV-related cirrhosis resulted in a sustained virologic response in 95.3% of all cases. The absence of the effect was mainly observed in patients with liver HCV-related cirrhosis of genotype 3a (11.1%), the proportion of which in Vitebsk region reaches 29.2% in patients with chronic hepatitis C and 37.12% in patients with HCV-related cirrhosis. The rapid tests employed for the detection of antibodies to the HCV during screening were found to be more suitable for the widespread use and cost-effective. Conclusions. The treatment of patients with HCV-related cirrhosis of all genotypes with DAAs elicited no sustained virologic response in 4.7% of all cases and in 11.1% of cases with genotype 3a. The rapid progression of liver fibrosis in patients under dispensary observation highlights the need to improve diagnostics and thus enable the efficient early detection of chronic hepatitis C and timely antiviral therapy prescription.

An 8-week regimen of glecaprevir/pibrentasvir is recommended for treatment-naïve patients with chronic hepatitis C (CHC). In alignment with the Taiwanese government's objective to eliminate hepatitis C by 2025, this study aimed to provide real-world evidence on the use of this regimen in treatment-naïve patients with chronic kidney disease (CKD) by using data from the Taiwan Association for the Study of the Liver HCV Registry (TACR). CKD was defined by an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m 2 or higher with proteinuria persisting for over 3 months. Patients were categorized as having early CKD (eGFR ≥45 mL/min/1.73 m 2 ) or pre-end-stage renal disease (pre-ESRD) (eGFR <45 mL/min/1.73 m 2 ). Among 1072 patients who received at least one dose of the regimen, 1054 had available data for assessing sustained virologic response at 12 weeks posttreatment (SVR12). The overall SVR12 rate was 99.6%, with rates of 99.7% for pre-ESRD patients and 99.6% for early CKD patients. Subgroup analysis showed 100% efficacy for genotype 3 and dyslipidemia, 99.5% for diabetes, 99.4% for cardiovascular disease, 96.9% for a history of cerebral vascular accident, and 95.5% for patients with a history of drug injection or HIV co-infection. Adverse events were reported in 16.8% of patients, with 0.8% experiencing serious events, and only two cases were treatment-related. Renal function significantly improved, with overall eGFR increasing from 39.2 to 41.9 mL/min/1.73 m 2 . Early CKD patients showed an eGFR rise from 53.5 to 57.1, while pre-ESRD patients improved from 27.1 to 29.2 at SVR12. The study concluded that the 8-week regimen is highly effective, well-tolerated, and associated with significant renal function improvement in treatment-naïve CHC patients with both early CKD and pre-ESRD., (© 2025 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Interferon (IFN) is a multifaceted immunomodulator that is effective against many diseases, including chronic hepatitis B and chronic hepatitis C infection. IFN defends against viral infection, but may also cause various side effects, such as ulcerative colitis (UC). Herein, we present a case of UC triggered by pegylated interferon alpha-2b (PEG-IFN-α-2b) therapy in a patient with concurrent chronic hepatitis B (CHB) infection. The diagnosis was based on typical clinical symptoms, colonoscopy findings, colonic mucosal biopsy, and histopathology. Accordingly, treatment with mesalazine was initiated without stopping PEG-IFN-α-2b. Fortunately, UC relieved gradually without compromising the effects of treatment. Simultaneously, we conducted a literature review of previously published case reports on the side effect of UC in patients with underlying chronic hepatitis. Various reactions have been reported, including induction, exacerbation, and no change. This is the first report of UC triggered by PEG-IFN-α-2b in a CHB patient. We recommend that physicians pay attention to the rare side effect of UC during administration of PEG-IFN-α-2b. Mesalazine can relieve UC with sustained use of PEG-IFN-α-2b.

Backgrounds and Aims: Chronic hepatitis C (CHC) infection can leads to chronic liver disease, fibrosis, then cirrhosis, and, finally, hepatocellular carcinoma (HCC); moreover, it is the most common indication for liver transplantation. Liver biopsy is still the gold standard method for the staging of liver fibrosis as it is an invasive procedure with complications. There are some noninvasive methods such as fibroscan that are now the investigation of choice; FIB-4 and aminotransferase to platelet ratio index (APRI) are other noninvasive tools to assess liver fibrosis by using aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet count, and age. This study aims to evaluate the efficacy and performance of FIB-4 and APRI against fibroscan in patients infected with the hepatitis C virus. Method: It is a cross-sectional study that was conducted in a tertiary health care center in Uttar Pradesh, India, from January 2017 to January 2020. Fibroscan was done for all patients. A blood sample was used to determine AST, ALT, and platelet count. FIB-4 and APRI were calculated from laboratory data. Result: 187 of the 487 patients in the study have F0-F1 fibrosis, 69 have F2, 53 have F3 fibrosis, and 178 have cirrhosis. Based on receiver operating characteristic (ROC) analysis, single optimum cut-offs for diagnosing significant fibrosis and cirrhosis were 1.2 for APRI and 2.25 for FIB-4. Conclusions: Compared with Fibroscan, APRI and FIB-4 showed good performance in detecting the patients without liver fibrosis as well as satisfactory performance in detecting significant fibrosis. These scores should be used in combination with other noninvasive scores for an accurate assessment of liver fibrosis.

Background & Aims: We recently analysed and reported the features of the micro biome under hepatitis C virus (HCV) infection, but the effect of HCV infection on bile acid (BA) metabolism in the gut‐liver axis remains poorly understood. The aim of this study was to clarify the characteristics of the gut‐liver axis in HCV‐infected patients. Methods: The faecal BAs composition and gut microbiota from 100 chronic hepatitis C (CHC) patients were compared with those from 23 healthy individuals. For transcriptional analysis of the liver, 22 mild CHC (fibrosis stages [F] 0‐2) and 42 advanced CHC (F3‐4) cases were compared with 12 healthy individuals. The findings were confirmed using chimeric mice with human hepatocytes infected with HCV HCR6. Results: Chronic hepatitis C patients, even at earlier disease stages, showed BA profiles distinct from healthy individuals, in which faecal deoxycholic acid (DCA) was significantly reduced and lithocholic acid or ursodeoxycholic acid became dominant. The decrease in faecal DCA was correlated with reduction in commensal Clostridiales and increase in oral Lactobacillales. Impaired biosynthesis of cholic acid (CA) was observed as a reduction in the transcription level of cytochrome P450 8B1 (CYP8B1), a key enzyme in CA biosynthesis. The reductions in faecal DCA and liver CYP8B1 were also observed in HCV‐infected chimeric mice. Conclusions: Chronic hepatitis C alters the intestinal BA profile, in association with the imbalance of BA biosynthesis, which differs from the pattern in NAFLD. These imbalances appear to drive disease progression through the gut‐microbiome‐liver axis. [ABSTRACT FROM AUTHOR]

Backgrounds and Aims: Chronic hepatitis C (CHC) infection can leads to chronic liver disease, fibrosis, then cirrhosis, and, finally, hepatocellular carcinoma (HCC); moreover, it is the most common indication for liver transplantation. Liver biopsy is still the gold standard method for the staging of liver fibrosis as it is an invasive procedure with complications. There are some noninvasive methods such as fibroscan that are now the investigation of choice; FIB-4 and aminotransferase to platelet ratio index (APRI) are other noninvasive tools to assess liver fibrosis by using aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet count, and age. This study aims to evaluate the efficacy and performance of FIB-4 and APRI against fibroscan in patients infected with the hepatitis C virus. Method: It is a cross-sectional study that was conducted in a tertiary health care center in Uttar Pradesh, India, from January 2017 to January 2020. Fibroscan was done for all patients. A blood sample was used to determine AST, ALT, and platelet count. FIB-4 and APRI were calculated from laboratory data. Result: 187 of the 487 patients in the study have F0-F1 fibrosis, 69 have F2, 53 have F3 fibrosis, and 178 have cirrhosis. Based on receiver operating characteristic (ROC) analysis, single optimum cut-offs for diagnosing significant fibrosis and cirrhosis were 1.2 for APRI and 2.25 for FIB-4. Conclusions: Compared with Fibroscan, APRI and FIB-4 showed good performance in detecting the patients without liver fibrosis as well as satisfactory performance in detecting significant fibrosis. These scores should be used in combination with other noninvasive scores for an accurate assessment of liver fibrosis. [ABSTRACT FROM AUTHOR]

During the clinical trial development of directly acting antivirals (DAAs), evidence regarding the treatment efficacy in chronic hepatitis C patients with hepatocellular carcinoma (HCC) was scarce because these patients have always been excluded. Apart from the clinical trials, more HCC patients are currently being treated in daily practice, given that these treatments are highly effective and involve well-tolerated regimens. Large scale, real-world studies have demonstrated potentially suboptimal antiviral treatment efficacy in HCC patients who received DAAs. It is postulated that the impairment of the bioavailability of DAAs may account for the inferior treatment response. However, the results could not be generalized across all studies. The differing results were attributed to diverse patient characteristics, suboptimal regimens or imprecise definitions of active cancer statuses at the time of treatment initiation. Additional large-scale studies that utilize the treatment of choice in clearly defined HCC patients with different disease severities are warranted to clarify the issue.

Introduction Chronic hepatitis C (CHC) remains a significant public health concern due to both hepatic and extrahepatic manifestations associated with substantial morbidity and mortality. The emergence of SARS-CoV-2 has raised concerns about the outcomes of COVID-19 in CHC patients. Method We conducted a retrospective analysis of patients with CHC and SARS-CoV-2 infection admitted to a tertiary care hospital between 2020 and 2023. We performed a global analysis of the entire batch of patients and, later, we evaluated the patients according to the severity of the SARS-CoV-2 infection Results The cohort included 89 patients (63 females, 26 males) with a median age of 65 years. Most patients were hospitalized in 2021. Common clinical manifestations included fever, cough, digestive symptoms, and headache. The most frequent comorbidities were renal disease, thyroid disorders, and cancer. Univariate logistic regression analysis identified older age, hospitalization in 2021, and respiratory failure as risk factors for severe COVID-19. Elevated lactate dehydrogenase levels were also associated with an increased risk of severe COVID-19. Regarding CHC, detectable hepatitis C virus viremia was associated with more severe liver disease (p<0.01). Conclusion Patients with CHC and SARS-CoV-2 infection have a substantial risk of severe outcomes. Early identification and management of these patients are crucial to improve their prognosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutuional Review Board of ”Dr. Victor Babeș” Hospital issued approval 19909. The current study protocol recived the ethical approval of the Institutuional Review Board of ”Dr. Victor Babeș” Hospital with the approval number 19909 from 28th of December 2020. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Lazar et al.)

Background Liver cirrhosis (LC) caused by chronic hepatitis C (CHC) infection is a major global public health concern. This study will look at the risk factors for progressive fibrosis and cirrhosis in patients with persistent hepatitis C virus (HCV) infection. Methods In this cohort study, a total of 300 patients were included. We collected comprehensive diagnostic records for the entire study group of 200 people with chronic hepatitis C infection. For the comparison, 100 healthy people were recruited and assessed. FibroScan (Echosens, Paris, France) scores were used to categorize liver fibrosis stages: F0-F1 (no or mild fibrosis, <7 kPa), F2 (moderate fibrosis, 7-8.99 kPa), F3 (significant fibrosis, 9-12.49 kPa), and F4 (cirrhosis, ≥12.5 kPa). Their demographic, biochemical, and serological data were evaluated and compared. Results Most patients were males (47% females and 53% males). In the CHC group, the mean age of diagnosis was 37.68±11.57 years, whereas in the chronic hepatitis C-related liver cirrhosis (CHC-LC) group, the mean age was 48.89±12.30 years (p=0.01). Compared to normal individuals, CHC patients had higher body mass index (BMI) (22.37±1.89 versus 21.72±1.95, p=0.01), alanine aminotransferase (ALT) (36.70±7.13 versus 82.78±82.53, p=0.01), and aspartate aminotransferase (AST) (34.96±6.04 versus 80.82±91.77, p=0.01). However, compared to the patients with CHC, the patients with LC have lower platelet (PLT) count (1.51±0.78 versus 1.7±0.41, p=0.01) and higher liver enzymes (AST: 117.7±186.9 versus 80.8±91.7, p=0.01; ALT: 86.71±80.24 versus 82.78±82.53, p=0.01). On regression analysis, higher BMI, older age, low hemoglobin (Hb), and higher bilirubin, ALT, AST, and prothrombin time (PT) were associated with LC. Conclusion It is imperative to shift toward prevention and early intervention as the new approach to managing patients with HCV-related cirrhosis. Cirrhosis should be suspected in older patients with CHC who are obese and have low platelet counts with higher liver enzymes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Institutional Ethics Committee of King George's Medical University issued approval 537/Ethics/R/Cell17. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Deep et al.)

Background: Eradication of hepatitis C virus (HCV) promotes an improvement in liver disease and the deactivation of the immune system. Here, we aimed to evaluate the changes in liver disease scores and plasma biomarkers following HCV clearance with direct-acting antivirals (DAAs) in HIV-infected patients with advanced HCV-related cirrhosis.Methods: We performed an observational study of 50 patients with advanced cirrhosis who received DAAs therapy. Variables were assessed at baseline and 48 weeks after HCV treatment completion. Epidemiological and clinical data were collected through an online form. Liver stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and Child-Pugh-Turcotte (CTP) were evaluated by physicians. Plasma biomarkers were measured by multiplex immunoassay.Results: We found significant decreases in severity scores of liver disease [LSM (q-value < 0.001), HVPG (q-value = 0.011), and CTP (q-value = 0.045)] and plasma biomarkers [LBP (q-value < 0.001), IP-10 (q-value < 0.001), IL-8 (q-value < 0.001), IL-18 (q-value < 0.001), IL-1RA (q-value = 0.013), OPG (q-value < 0.001), sVCAM-1 (q-value < 0.001), sICAM-1 (q-value < 0.001), PAI-1 (q-value = 0.001), and VEGF-A (q-value = 0.006)]. We also found a significant direct association between the change in LSM values and the change in values of LBP (q-value < 0.001), IP-10 (q-value < 0.001), MCP-1 (q-value = 0.008), IL-8 (q-value < 0.001), IL-18 (q-value < 0.001), OPG (q-value = 0.004), sVCAM-1 (q-value < 0.001), sICAM-1 (q-value < 0.001), and PAI-1 (q-value = 0.002). For CTP values, we found significant positive associations with IP-10 (q-value = 0.010), IL-6 (q-value = 0.010), IL-1RA (q-value = 0.033), and sICAM-1 (q-value = 0.010).Conclusion: The HCV eradication with all-oral DAAs in HIV/HCV-coinfected patients with advanced cirrhosis promoted an improvement in the severity of advanced cirrhosis and plasma biomarkers (inflammation, coagulopathy, and angiogenesis). The decrease in plasma biomarkers was mainly related to the reduction in LSM values.

Hepatitis C virus (HCV) is one of the most epidemic viral infections in the world. Three-quarters of individuals infected with HCV become chronic. As a consequence of persistent inflammation, a considerable percentage of chronic patients progress to liver fibrosis, cirrhosis, and finally hepatocellular carcinoma. Cytokines, which are particularly produced from T-helper cells, play a crucial role in immune protection against HCV and the progression of the disease as well. In this study, the role of interleukins IL-33, IL-17, and IL-25 in HCV patients and progression of disease from chronicity to hepatocellular carcinoma will be characterized in order to use them as biomarkers of disease progression. The serum levels of the tested interleukins were measured in patients suffering from chronic hepatitis C (CHC), hepatocellular carcinoma (HCC), and healthy controls (C), and their levels were correlated to the degree of liver fibrosis, liver fibrosis markers and viral load. In contrast to the IL-25 serum level, which increased in patients suffering from HCC only, the serum levels of both IL-33 and IL-17 increased significantly in those patients suffering from CHC and HCC. In addition, IL-33 serum level was found to increase by liver fibrosis progression and viral load, in contrast to both IL-17 and IL-25. Current results indicate a significant role of IL-33 in liver inflammation and fibrosis progress in CHC, whereas IL-17 and IL-25 may be used as biomarkers for the development of hepatocellular carcinoma.

Background: Pegylated interferon (PEG-IFN) plus ribavirin combination was the main treatment for chronic hepatitis C (CHC) patients in Pakistan till 2016. An important side effect of this combination was thyroid dysfunction (TD). Objectives: To evaluate thyroid function abnormalities in Chronic Hepatitis C patients treated with PEG-IFN and ribavirin. Study Design: Descriptive study. Setting: Outpatient Department of Gastroenterology and Hepatology, Nishtar Hospital Multan. Period: January to September 2016. Methods: Using non-probability consecutive sampling. There were 337 CHC patients enrolled in the study who fulfilled the inclusion criteria. Patients were given PEG-IFN plus ribavirin combination therapy and at 12 weeks their serum Thyroid Stimulating Hormone (TSH) levels were measured to identify any TD. Data was entered and analyzed by computer program SPSS-17. Results: Of these 337 cases, 211 (62.6%) were male patients while 126 (37.4%) were female patients. Mean age of our cases was noted to be 30.92 ± 5.84 years. Mean disease duration was 16.19 ± 6.42 months. In our study 98 patients (29.1%) had genotype 2 while 239 (70.9%) had genotype 3. TD was seen in 28 (8.3%) patients, 70% of whom were females. Equal number of cases of Hypothyroidism and hyperthyroidism were seen (14 each). Hypothyroidism was significantly associated with relatively older age group patients and genotype 3 (p value <0.05). A statistically significant association (p<0.05) was found between hyperthyroidism and genotype 3, female gender and younger patients. Conclusion: PEG-IFN plus ribavirin combination therapy induces TD among patients with CHC with equal incidence of hypothyroidism and hyperthyroidism. [ABSTRACT FROM AUTHOR]

Background Patients on hemodialysis (HD) are most likely to contract hepatitis C (HCV) infection, which is associated with significant morbidity and disease progression. Direct-acting antivirals (DAAs) are safe and tolerable in chronic kidney disease (CKD) with a 90-100% cure rate, and limited data exist regarding their efficacy in end-stage renal disease (ESRD), particularly for HD patients in South Asia. The study aimed to assess the outcome of a 12-week sofosbuvir (SOF) and velpatasvir (VEL) treatment regimen on ESRD patients with chronic HCV infection undergoing HD in the Pakistani Asian population. Methodology This prospective cohort study was conducted between January 2022 and January 2023 at the outpatient nephrology and gastroenterology clinic of Sheikh Zayed Medical College and Hospital, Rahim Yar Khan, Pakistan. This study included a total of 220 ESRD patients fulfilling the inclusion criteria, aged 20-55 years, who had been undergoing weekly HD sessions for at least two years, with acquired HCV infection. Data on demographic and clinical characteristics were collected through patient interviews. Laboratory and dialysis profiling was executed to assess ESRD and discover the underlying cause by ultrasound abdomen, blood pressure measurement by sphygmomanometer, random blood sugar for diabetes, and taking note of the duration and frequency of dialysis. HCV RNA PCR was done at selected intervals to evaluate the virological response to treatment. Sustained virological response (SVR), liver cirrhosis status, and number of weekly HD sessions were compared at one year of SOF/VEL regimen. Results The mean age of patients with ESRD was 41.8 with a standard deviation (SD) of 9.3 years, and HCV diagnosis was 1.3 years with SD of 0.4 years; 52.7% (n=116) were males, 47.3% (n=104) were females, 75% (n=165) were urban dwellers, and 93.6% (n=206) were married. CKD that requires dialysis was caused mainly by hypertension (78, 35%), diabetes mellitus type 2 (52, 24%), bilateral small kidney disease (40, 18%), and others (34, 16%). One hundred and six (48.2%) received dialysis thrice weekly, 83 (37.7%) twice, and 31 (14.1%) once weekly. The study monitored the rapid virological response (RVR) at four weeks of SOF/VEL regimen in 89.5% of ESRD patients, observed end-of-treatment response (ETR) at 12 weeks in 93.2%, and noted 91.4% SVR response at one year. Only four (1.8%) relapses were observed in the study, which was statistically insignificant. The status of liver cirrhosis showed a 50% improvement, decreasing from 40% to 20%. The frequency of weekly HD sessions decreased from thrice to twice-thrice a week. Conclusion The prevalence of contracting HCV is high among CKD and dialysis ESRD patients. All-oral DAA therapy has revolutionized HCV treatment with co-morbidities. Renal functions improved after the SOF/VEL regimen for chronic HCV infection in ESRD patients undergoing HD, with the number of weekly dialysis sessions reduced and SVR reaching 91.4%. Thus, a single-tablet, pan-genotypic DAA regimen of SOF/VEL for 12 weeks is safe, effective, and tolerable regardless of the underlying etiology of ESRD, complications of cirrhosis, HCV genotype, or previous treatment exposure. The successful treatment of HCV and achieving SVR lowers the risk of ESRD complications, improves extra-hepatic manifestations, and greatly enhances survival. Further studies are warranted after the availability of other DAAs to confirm findings with no limitations., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Shahid et al.)

Reduced low-density lipoprotein (LDL) cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV) infection. However, abnormality in serum triglyceride (TG) has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b) infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated intofour classes: chylomicron, very low-density lipoprotein (VLDL), LDL, and high-density lipoprotein (HDL). Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles. [ABSTRACT FROM AUTHOR]

Objective: To determine frequency of thrombocytopenia in patients with Chronic Hepatitis C infection. Methods: A 6 months cross sectional study was carried out to determine frequency of thrombocytopenia in all patients admitted with chronic hepatitis c infection in all medical units at Civil Hospital Karachi, from April 2, 2012 to October 1, 2012. Patients with platelet count <150,000/microL was labeled as having thrombocytopenia and categorized according to the Child-Pugh Scoring. Patients with Child-Pugh score <7 was categorized in Grade A, 7-9 in Grade B and >9 in Grade C. Results: Out of 141 patients, 46(32.6%) were male and 65(46%) were female with 1.17:1 male to female ratio. The average age of patients was 47.25 ± 11.52 years (95%CI: 45.33 to 49.17). Similarly average duration of illness was 3.06 ± 1.78 Years (Range 8 months to 9 Years) and average platelet count was 165156.74± 176324.9. Seventy five patients (53%) had thrombocytopenia (platelet count <150000/microL). The average age of thrombocytopenic patients was 48.53±12.34 years and duration of illness was 3.7 ± 1.81 years. Regarding child Pugh class, 35(24.8%) cases had in class A, 49(34.8%) in class B and 57(40.4%) in class C. Thrombocytopenia was most common in above 60 years of age that is 10.7% (8/75) and 22.7% to 32% in all age groups. Conclusions: In our study the frequency of thrombocytopenia was found to be higher. Patients of age more than 60 years and of child-Pugh class C affected the most. [ABSTRACT FROM AUTHOR]

Background IL-10+ regulatory B (Bregs), CD4+Foxp3+ regulatory T (Tregs), and CD4+CXCR5+Foxp3+ follicular regulatory T (TFR) cells regulate the progression of infection disease. This study aimed at examining how those cells associated with the development of chronic hepatitis B (CHB) and chronic hepatitis C (CHC) in a Chinese population. Methods The numbers of circulating IL-10+ Bregs, Tregs and TFR cells in 31 CHC, 58 CHB patients and 22 healthy controls (HC) were examined by flow cytometry. The potential association of those cells with clinical measures was analyzed. Results The numbers of CD5+CD19+CD1dhighIL-10+ Bregs, Tregs and TFR cells and the levels of serum IL-10, IFN-γ and IL-2 in the CHB, and IL-10 and IFN-γ in the CHC patients were significantly higher than that in the HC (p < 0.05). Furthermore, the numbers of circulating IL-10+ Bregs and the levels of serum IL-10, but not other cytokines tested were positively correlated with the levels of serum HBV DNA and ALT in the HBeAg- CHB patients as well as HCV RNA and ALT in CHC patients. Additionally, the numbers of circulating TFR cells were positively correlated with the levels of serum HBV DNA and ALT in the CHB patients as well as HCV RNA and ALT in the CHC patients. Conclusions Increased numbers of circulating IL-10+ Bregs and TFR cells are associated with poor virus eradication and liver injury in CHB and CHC patients. Furthermore, the levels of serum IL- 10 is associated with the hepatic flares. [ABSTRACT FROM AUTHOR]

Highlights: [•] Dermatological AEs were recorded in 18.4% patients during antiviral treatment. [•] Skin AEs can involve the skin, mucous membrane, hair, and nails. [•] Eczematous skin reactions were the most commonly skin AEs. [•] We examined the risk factors associated with dermatological AEs. [•] Skin reactions were mild to moderate and do not warrant discontinued treatment. [Copyright &y& Elsevier]

Background & Aims: Fibrosis blood tests have been validated in chronic hepatitis C. Their diagnostic accuracy is less documented in hepatitis B. The aim of this study was to describe the diagnostic performance of FibroTest®, FibroMeter®, and HepaScore® for liver fibrosis in hepatitis B compared to hepatitis C. Methods: 510 patients mono-infected with hepatitis B or C and matched on fibrosis stage were included. Blood tests were performed the day of the liver biopsy. Histological lesions were staged according to METAVIR. Results: Fibrosis stages were distributed as followed: F0 n=76, F1 n=192, F2 n=132, F3 n=54, F4 n=56. Overall diagnostic performance of blood tests were similar between hepatitis B and C with AUROC ranging from 0.75 to 0.84 for significant fibrosis, 0.82 to 0.85 for extensive fibrosis and 0.84 to 0.87 for cirrhosis. Optimal cut-offs were consistently lower in hepatitis B compared to hepatitis C, especially for the diagnosis of extensive fibrosis and cirrhosis, with decreased sensitivity and negative predictive values. More hepatitis B than C patients with F ⩾3 were underestimated: FibroTest®: 47% vs. 26%, FibroMeter®: 24% vs. 6%, HepaScore®: 41% vs. 24%, p <0.01. Multivariate analysis showed that hepatitis B (0R 3.4, 95% CI 1.2–19.2, p <0.02) and low γGT (OR 7.3, 95% CI 2.0–27.0, p <0.003) were associated with fibrosis underestimation. Conclusion: Overall the diagnostic performance of blood tests is similar in hepatitis B and C. The risk of underestimating significant fibrosis and cirrhosis is however greater in hepatitis B and cannot be entirely corrected by the use of more stringent cut-offs. [ABSTRACT FROM AUTHOR]

Background & Aims: Histopathological scoring of liver fibrosis mainly measures architectural abnormalities and requires a minimum biopsy size (⩾10mm). Liver collagen quantification may allow use of small size biopsies and improve the prediction of clinical outcomes. This study evaluated the ability of the collagen proportional area (CPA) measurement to predict clinical outcomes. Methods: Clinical outcomes were determined using population based data-linkage for chronic hepatitis C (CHC) patients from 1992 to 2012. Quantitative digital image analysis of liver biopsies was used for CPA measurement. Results: 533 patients with a biopsy size ⩾5mm were included. Median follow up was 10.5years. 26 developed hepatocellular carcinoma (HCC), 39 developed liver decompensation and 33 had liver related death. 453 had Metavir F0-F2 and 80 had F3-F4. CPA ranged from 1.3% to 44.6%. CPA and Metavir stage were independently associated with liver related death. Metavir stage, CPA stage and age were independently associated with HCC. CPA stage (C1: 0%–5%, C2: 5%–10%, C3: 10%–20%, C4: >20%) stratified risk and a significant difference in outcomes was present between all CPA stages for HCC and between C2-C3 and C3-C4 for decompensation and liver related death. The 15year composite endpoint-free survival was 97% for C1, 89% for C2, 60% for C3, 7% for C4. C4 had significantly worse survival than ⩽C3 (p <0.001) in cirrhotic patients. Conclusions: CPA stage gave additional information regarding risk stratification for adverse clinical outcomes independent of Metavir stage. [Copyright &y& Elsevier]

Background & Aims: Hepatitis C (HCV) is a common cause of chronic liver disease worldwide. Current standard treatment for genotype-1 patients uses a triple combination of pegylated-interferon alpha (IFN), ribavirin (RBV) and a direct-acting antiviral agent (DAA) with 75–80% sustained virologic response (SVR) rates. The aim is to determine cost-effectiveness of staging-guided vs. treat all HCV genotype-1 patients with interferon-based vs. interferon-free regimens. Methods: A decision analytic Markov model simulating patients until death compared four strategies for treating HCV genotype-1: Triple therapy (IFN, RBV, DAA) with staging-guidance or treat all, and oral IFN-free regimen with staging-guidance or treat all. Strategies with staging initiated treatment at fibrosis stages F2-F4, with staging repeated every 5years until age 70. The reference case was a treatment-naïve 50-year-old. Analysis was repeated for 50% increase in cost of oral therapy. Effectiveness was measured in quality-adjusted life years (QALYs). Results: Treatment of all patients with oral IFN-free regimen was the most cost-effective strategy, with an ICER of $15,709/QALY at baseline cost of oral therapy. The ICER remained below $50,000/QALY in sensitivity analyses for baseline and +50% cost of oral therapy scenarios. The treat all strategy was also the most effective strategy; associated with the lowest risk of developing advanced liver disease. Conclusions: Treating all HCV patients with oral IFN-free regimen reduced the number of patients developing advanced liver disease and increased life expectancy. Additionally, IFN-free regimen without staging may be the most cost-effective approach for treating HCV genotype-1 patients. The efficacy and safety of these regimens must be confirmed using randomized clinical trials. [ABSTRACT FROM AUTHOR]

Background & Aims: Oncostatin M (OSM) is an inflammatory cytokine which interacts with a heterodimeric receptor formed by gp130 and either OSMRβ or LIFR. Here we have analysed OSM and its receptors in livers with chronic hepatitis C (CHC) and studied the factors that regulate this system. Methods: OSM, OSM receptors and OSM-target molecules were studied by immunohistochemistry and/or qPCR analysis in livers from CHC patients and controls. We determined the production of OSM by CD40L-stimulated antigen presenting cells (APC) and its biological effects on HuH7 cells containing HCV replicon (HuH7 Core-3′). Results: OSM was upregulated in livers with CHC and its production was mapped to CD11c+ cells. OSM levels correlated directly with inflammatory activity and CD40L expression. In vitro studies showed that OSM is released by APC upon interaction with activated CD4+ T cells in a CD40L-dependent manner. Culture of HuH7 Core-3′ cells with supernatant from CD40L-stimulated APC repressed HCV replication and induced IL-7 and IL-15Rα. These effects were dampened by antibodies blocking OSM or gp130 and by silencing OSMRβ. In CHC livers OSMRβ and LIFR were significantly downregulated and their values correlated with those of OSM-induced molecules. Experiments in HuH7 cells showed that impaired STAT3 signaling and exposure to TGFβ1, two findings in CHC, are factors involved in repressing OSMRβ and LIFR, respectively. Conclusions: OSM is a cytokine possessing vigorous antiviral and immunostimulatory properties which is released by APC upon interaction with CD40L present on activated CD4+ T cells. In livers with CHC, OSM is overexpressed but its biological activity appears to be hampered because of downregulation of its receptor subunits. [Copyright &y& Elsevier]

We are at the cusp of significant new alternatives for the treatment of chronic hepatitis C. Among more than 100 drugs in development, some are ready to be approved and in the market as soon as next year. The protease inhibitors Telaprevir and Boceprevir, will change the SOC treatment to triple therapy, (combined with peg IFN and RBV), with duration of treatment guided by rapid virological response. In this article we present the data supporting the approval of Telaprevir and Boceprevir, and information on polymerase inhibitors and IFN free proof of concept trials. Finally we discuss which patients should wait for DAA based therapies and which should be considered for peg IFN/RBV now.In the next 5 years our patients can expect higher response rates and truncated duration of therapy. They can expect drug cocktails or combos but for the next years these novel drugs will still require peg IFN and RBV. Also, a new era of resistance as a barrier to therapy will require sub typing and more viral monitoring. Overall, improved outcomes will come at the expense of more adverse events and increased costs of treatment.

Background & Aims: There is a paucity of unbiased data on the natural history of hepatitis C virus (HCV) infection in injecting drug users (IDUs). The purpose of this study was to assess the risk of developing advanced fibrosis associated with chronic hepatitis C (CHC) infection among injecting drug users (IDUs) who underwent an autopsy. Methods: A longitudinal cohort design was applied, in which the stage of liver fibrosis in anti-HCV positive IDUs with or without chronic HCV infection was assessed in liver tissue from autopsies performed up to 35years after HCV exposure. The cohort originated from 864 IDUs consecutively admitted for drug abuse treatment 1970–1984. Stored sera, mostly drawn at the time of admission for drug treatment, were available in 635 subjects. 220 out of 523 anti-HCV positive subjects had died before 2009. Liver tissue from autopsies was available from 102/220 subjects, of which 61 were HCV RNA positive. Liver sections were classified according to METAVIR scores for fibrosis. Two pathologists, both blinded for serologic results, scored sections of liver tissue. Results: Among HCV RNA positive subjects 16.4% (10/61) had septal fibrosis (F3) or cirrhosis (F4) compared to 2.4% (1/41) among anti HCV positive/HCV RNA negative subjects (p =0.026). Of 18 HCV RNA positive subjects autopsied <15years after HCV exposure none had F3 or F4. Among subjects autopsied >25years after exposure 35% (6/17) had F3–F4. Conclusions: Among IDUs chronically infected by HCV, 1/3 developed septal fibrosis or cirrhosis 25years or more after exposure. [Copyright &y& Elsevier]

Background & Aims: The cannabinoid receptor 2 (CB2) has been implicated in liver disease. The single-nucleotide polymorphism rs35761398 in cannabinoid receptor 2 gene (CNR2), which encodes the CB2, substitutes glutamine (Q) 63 with arginine (R), and reduces the function of the gene product. We investigated the effects of CNR2 rs35761398 in patients with hepatitis C virus (HCV) infection. Methods: We studied 169 consecutive patients with asymptomatic chronic hepatitis (tested positive for anti-HCV and HCV RNA) at 2 liver units in southern Italy. First, liver biopsy samples were collected from July 2009 through December 2011. All patients were naive to antiviral therapy; CNR2 genotype was determined by polymerase chain reaction analysis. Results: Patients with the CB2-63 QQ variant had higher serum levels of aminotransferase than those with the CB2-63 QR or RR variants; they also had higher histologic activity index (HAI) scores (8.6 ± 3.8) than patients without the CB2-63 RR variant (5.3 ± 3.6; P < .005) or those with the CB2-63 QR variant (5.8 ± 3.3; P < .001). Patients with the different variants of CNR2 did not differ in fibrosis stage or steatosis score. Moderate or severe chronic hepatitis (HAI score, >8) was identified more frequently (55.5%) in patients with the CB2-63 QQ variant than in those with the 63 QR (20%; P < .005) or RR variants (17.4%; P < .005). In logistic regression analysis, the CB2-63 QQ variant and fibrosis score were independent predictors of moderate or severe chronic hepatitis (HAI score, >8; P < .0001). Conclusions: The CB2-63 QQ variant of CNR2 is associated with more severe inflammation and hepatocellular necrosis in patients with HCV infection. [Copyright &y& Elsevier]

Highlights: [•] The protumorigenic role of HCV with overweight and obesity is suspected. [•] PNPLA3 I148M variant is not associated with HCV clearance process. [•] PNPLA3 I148M confers susceptibility to liver cancer in a homozygous state M/M. [•] The proportion of M alleles is more important in women with HCC than in males. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Chronic hepatitis C virus (HCV) infection represents a leading worldwide medical and social problem. The expanding knowledge of HCV lifecycle has led to the development of novel antiviral agents that: a) specifically target a viral function (direct-acting antivirals), or b) specifically inhibit viral replication. The present review describes the novel anti-HCV drugs that have been better studied at the time of this writing and the current two types of treatment, namely interferon-based and interferon-free regimens. In addition, predictive factors, virological responses, side-effects, and resistance mechanisms of the novel agents are summarized. Conclusions: The introduction of novel antiviral agents is remarkably changing the therapeutic combinations aimed at improving virological responses both for easy-to-cure and difficult-to-treat patients. Since additional, effective drugs are under advanced development, it seems reasonable to expect that further therapeutic and prognostic improvements will be achieved in the near future. [Copyright &y& Elsevier]

Background & Aims: Unhealthy food intake, specifically fructose, has been associated with metabolic alterations and with the severity of liver fibrosis in patients with non-alcoholic fatty liver disease. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of fructose intake with the severity of liver histology. Methods: Anthropometric and metabolic factors, including waist circumference (WC), waist-to-hip ratio (WHR), dorso-cervical lipohypertrophy and HOMA were assessed in 147 consecutive biopsy-proven G1 CHC patients. Food intake, namely industrial and fruit fructose, was investigated by a three-day structured interview and a computed database. All biopsies were scored by an experienced pathologist for staging and grading (Scheuer classification), and graded for steatosis, which was considered moderate-severe if ⩾20%. Features of non-alcoholic steatohepatitis (NASH) in CHC were also assessed (Bedossa classification). Results: Mean daily intake of total, industrial and fruit fructose was 18.0±8.7g, 6.0±4.7g, and 11.9±7.2g, respectively. Intake of industrial, not fruit fructose, was independently associated with higher WHR (p =0.02) and hypercaloric diet (p <0.001). CHC patients with severe liver fibrosis (⩾F3) reported a significantly higher intake of total (20.8±10.2 vs. 17.2±8.1g/day; p =0.04) and industrial fructose (7.8±6.0 vs. 5.5±4.2; p =0.01), not fruit fructose (12.9±8.0 vs. 11.6±7.0; p = 0.34). Multivariate logistic regression analysis showed that older age (OR 1.048, 95% CI 1.004–1.094, p =0.03), severe necroinflammatory activity (OR 3.325, 95% CI 1.347–8.209, p = 0.009), moderate-severe steatosis (OR 2.421, 95% CI 1.017–6.415, p = 0.04), and industrial fructose intake (OR 1.147, 95% CI 1.047–1.257, p = 0.003) were independently linked to severe fibrosis. No association was found between fructose intake and liver necroinflammatory activity, steatosis, and the features of NASH. Conclusions: The daily intake of industrial, not fruit fructose is a risk factor for metabolic alterations and the severity of liver fibrosis in patients with G1 CHC. [ABSTRACT FROM AUTHOR]

Background & Aims: Adherence to antiviral treatment is important to achieve sustained virological response (SVR) in chronic hepatitis C (CHC). We evaluated the efficiency of a multidisciplinary support programme (MSP), based on published HIV treatment experience, to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in CHC. Methods: 447 patients receiving antiviral treatment were distributed into 3 groups: control group (2003–2004, n=147), MSP group (2005–2006, n=131), and MSP-validation group (2007–2009, n=169). The MSP group included two hepatologists, two nurses, one pharmacist, one psychologist, one administrative assistant, and one psychiatrist. Cost-effectiveness analysis was performed using a Markov model. Results: Adherence and SVR rates were higher in the MSP (94.6% and 77.1%) and MSP-validation (91.7% and 74.6%) groups compared to controls (78.9% and 61.9%) (p <0.05 in all cases). SVR was higher in genotypes 1 or 4 followed by the MSP group vs. controls (67.7% vs. 48.9%, p =0.02) compared with genotypes 2 or 3 (87.7% vs. 81.4%, p =n.s.). The MSP was the main predictive factor of SVR in patients with genotype 1. The rate of adherence in patients with psychiatric disorders was higher in the MSP groups (n=95, 90.5%) compared to controls (n=28, 75.7%) (p =0.02). The cost per patient was € 13,319 in the MSP group and € 16,184 in the control group. The MSP group achieved more quality-adjusted life years (QALYs) (16.317 QALYs) than controls (15.814 QALYs) and was dominant in all genotypes. Conclusions: MSP improves patient compliance and increases the efficiency of antiviral treatment in CHC, being cost-effective. [Copyright &y& Elsevier]

Background & Aims: Occult hepatitis B virus infection (OBI) frequently occurs in patients with hepatitis C virus (HCV) related chronic hepatitis (CHC), but the influence of OBI on the CHC outcome is still uncertain. This observational cohort study evaluated the clinical evolution of CHC patients according to their OBI status. Methods: From 1991 to 2000, 326 hepatitis B surface antigen negative CHC patients were tested for OBI by the analysis of liver biopsy DNA extracts. A total of 128/326 cases (39.2%) tested OBI positive and 198/326 (60.8%) OBI negative. Ninety-four of 326 patients (37 OBI positive, 57 OBI negative) were followed-up for a median time of 11years (range 5–19years). During the follow-up, 79/94 patients underwent anti-HCV treatments and 26 achieved a sustained virological response that occurred independently of their OBI status. Results: Eighteen patients (13/37 OBI positive, 5/57 OBI negative, p <0.01) developed hepatocellular carcinoma (HCC). Among the 76 non-HCC individuals, 15 subjects (8/24 OBI positive, 7/52 OBI negative, p <0.05) developed advanced forms of cirrhosis. Eighteen patients died during follow-up and 2 underwent liver transplantation. OBI positive individuals had a cumulative survival rate significantly shorter than OBI negative individuals (p =0.003). Liver-related deaths were more frequently found in OBI positive than OBI negative patients (12/37 OBI positive vs. 6/57 OBI negative patients respectively, p <0.01). Finally, non-response to anti-HCV therapy was significantly associated with lower survival (p =0.02). Conclusions: Among CHC patients, occult HBV co-infected individuals are a category at high risk of progression toward cirrhosis, HCC development, and lower survival. [Copyright &y& Elsevier]

Background & Aims: Randomised controlled trials (RCTs) show that triple therapy (TT) with peginterferon alfa, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective than peginterferon-ribavirin dual therapy (DT) in the treatment of genotype 1 (G1) chronic hepatitis C (CHC) patients with previous relapse (RR), partial response (PAR), and null-response (NR). We assess the cost-effectiveness of TT compared to no therapy in the treatment of patients previously treated with G1 CHC. Methods: The available published literature provided the data source. The target population was made up of previously treated Caucasian patients with G1 CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euro at 2012 value), life years gained (LYG), quality adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER).The robustness of the results was evaluated by one-way deterministic and multivariable probabilistic sensitivity analyses. Results: In RR patients, ICER per LYG compared to no therapy was €9555 for BOC-LEAD-IN-RR and €7910 for TVR-LEAD-IN-RR, being BOC dominated by TVR. In PAR patients, ICER for LYG was €11,947 for BOC-LEAD-IN-PAR and €14,931 for TVR-PAR, being TVR cost-effective compared to BOC (ICER for QALY €22,258). In NR patients, ICER for LYG was €26,499 for TVR-LEAD-IN-NR. The models were sensitive to likelihood of sustained virological response and to BOC/TVR prices. Conclusions: 1st generation HCV PI is highly cost-effective compared to no therapy in RR and PAR G1 CHC patients. TVR dominated BOC in RR, and was cost-effective compared to BOC in PAR patients. In NR patients an assessment of the response after a lead-in period should be performed to improve safety and cost-effectiveness. [Copyright &y& Elsevier]

Abstract: Background: Liver stiffness has been suggested as a parameter of fibrosis progression/regression in hepatitis C virus (HCV) patients. Aim: To evaluate stiffness before and after peginterferon–ribavirin treatment. Methods: Stiffness was prospectively measured in 74 HCV patients, 32 genotypes 1/4 (43.25%) and 42 genotypes 2/3 (56.75%), before, at end of treatment, and after 3 years of follow-up (49 patients). On the same study day, 21 patients underwent liver biopsy. Results: In 55 patients with sustained virological response (74.32%), liver stiffness decreased significantly at end of therapy (6.8±4.9kPa) vs. baseline (9.5±6.9kPa, p =0.04). The decrease vs. baseline was maintained in 30 sustained virological response patients after 3 years follow-up (6.8±4.6kPa vs. 10.8±8.5kPa, p =0.0141). No difference was found at end of treatment vs. baseline (10.1±4.7kPa vs. 9.7±4.2kPa, p =0.825) and after 3 years of follow-up vs. baseline (10.2±3.4kPa vs. 9.7±4.2kPa, p =0.765) in null responders. Similar results were found in relapsers at end of treatment vs. baseline (13.7±7.7kPa vs. 15.2±8.2kPa, p =0.74), and after 3 years of follow-up vs. baseline (16.9±10.0kPa vs. 15.2±8.2kPa, p =0.734). Pre-treatment stiffness >12kPa was significantly associated with no SVR (p <0.025), RR=2.44 (95%C.I. 1.17–5.07). Conclusion: Liver stiffness may be useful to assess long-term antiviral treatment response. [Copyright &y& Elsevier]

Background & Aims: Vitamin D deficiency has been frequently reported in advanced liver disease. However, its influence on alcoholic liver disease (ALD) has been poorly elucidated. We investigated the association of vitamin D with clinical, biological, and histological parameters and survival in ALD patients. Furthermore, we explored the effect of vitamin D treatment on ALD patient peripheral blood mononuclear cells (PBMCs), and in a murine experimental model of ALD. Methods: Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined in 324 Caucasian ALD patients and 201 healthy controls. In vitro experiments on vitamin D pre-treated PBMCs evaluated TNFα production by ELISA in culture supernatants. Mice were submitted to an ethanol-fed diet and some of them were orally supplemented three times per week with 1,25(OH)2D. Results: Severe deficiency in 25(OH)D (<10ng/ml) was significantly associated with higher aspartate aminotransferase levels (p =1.00×10−3), increased hepatic venous pressure gradient (p =5.80×10−6), MELD (p =2.50×10−4), and Child-Pugh scores (p =8.50×10−7). Furthermore, in multivariable analysis, a low 25(OH)D concentration was associated with cirrhosis (OR=2.13, 95% CI=1.18–3.84, p =0.013) and mortality (HR=4.33, 95% CI=1.47–12.78, p =7.94×10−3) at one year. In addition, in vitro, 1,25(OH)2D pretreatment decreased TNFα production by stimulated PBMCs of ALD patients (p =3.00×10−3), while in vivo, it decreased hepatic TNFα expression in ethanol-fed mice (p =0.04). Conclusions: Low 25(OH)D levels are associated with increased liver damage and mortality in ALD. Our results suggest that vitamin D might be both a biomarker of severity and a potential therapeutic target in ALD. [ABSTRACT FROM AUTHOR]

Background & Aims: Progressive fibrosis is a major cause of morbidity and mortality in chronic liver disease. To replace liver biopsy for disease staging, multiple serum markers are under evaluation with multiparametric panels yielding the most promising results. The Enhanced Liver Fibrosis (ELF) score is an ECM marker set consisting of tissue inhibitor of metalloproteinases 1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP) and hyaluronic acid (HA) showing good correlations with fibrosis stages in chronic liver disease. Methods: The ELF score was measured in 400 healthy controls and 79 chronic hepatitis C patients using an ADVIA Centaur automated system. The ELF score was calculated using the published algorithm combining TIMP-1, PIIINP and HA values. Patients’ fibrosis stage was defined histologically. ROC analyses were performed to study marker validity. Reference values and influence factors for the ELF score were validated. Results: ELF score reference values ranged from 6.7 to 9.8 and were significantly higher for men vs. women (7.0–9.9 vs. 6.6–9.3, respectively). Afternoon values were slightly higher than morning values (6.7–9.9 vs. 6.6–9.5, respectively). Age was a notable influence factor. We identified three cut-off values: 7.7 for a high sensitivity exclusion of fibrosis, 9.8 for a high specificity identification of fibrosis (sensitivity 69%, specificity 98% for moderate fibrosis), and 11.3 to discriminate cirrhosis (sensitivity 83%, specificity 97%). ELF score validity was superior to the results of the single tests. Conclusions: The ELF score can predict moderate fibrosis and cirrhosis. However, influence factors such as gender and age need to be taken into account. [Copyright &y& Elsevier]

Background & Aims: We estimated HCV reinfection rate and its associated risk factors in inmates with chronic hepatitis C who had achieved sustained virological response (SVR) after completing combination therapy while in prison. Methods: Individuals who had achieved an SVR after treatment provided from January 2003 to December 2009 at four prisons in Catalonia, had been tested annually for HCV RNA and were in prison during 2010, were invited to complete a questionnaire regarding risk factors for reinfection. Incidence rate was calculated as 100 person-years of follow-up. Risk factors potentially associated with reinfection were evaluated by bivariate log-rank test and multivariate Cox regression analysis. Results: One hundred and nineteen subjects who had achieved an SVR agreed to participate. 98% were male, with a median age of 33.3±6.3years and 81% had a history of injection drug use (IDU). After a mean follow-up of 1.4years, HCV reinfection was identified in nine former IDUs, seven with HCV genotype switch, for an overall reinfection rate of 5.27 cases per 100 person-years. Reinfection incidence was significantly higher among active drug users (HR=12.47; 95% CI: 2.90–53.71), HIV co-infected (HR=9.95; 95% CI: 1.73–57.34), and those engaging in more than one risk behaviors after treatment (HR=7.47; 95% CI: 1.19–46.89). Conclusions: HCV reinfection among inmates after successful treatment is high especially in those with ongoing IDU. Preventative interventions at diagnosis and during and after HCV treatment should be strongly reinforced. [ABSTRACT FROM AUTHOR]

Background & Aims: To examine the antiviral activity of boceprevir, a hepatitis C virus (HCV) protease inhibitor, in HCV genotype (G) 2/3-infected patients. Methods: We assessed boceprevir and telaprevir activity against an HCV G2 and G3 isolates enzyme panel, in replicon, and in phenotypic cell-based assays. Additionally, a phase I study evaluated the antiviral activity of boceprevir monotherapy (200mg BID, 400mg BID, or 400mg TID) vs. placebo for 14days in HCV G2/3 treatment-naive patients. Results: Boceprevir and telaprevir similarly inhibited G1 and G2 NS3/4A enzymes and replication in G1 and G2 replicon and cell-based assays. However, telaprevir demonstrated lower potency than boceprevir against HCV G3a enzyme (K i =75nM vs. 17nM), in the G3a replicon assay (EC50 =953nM vs. 159nM), and against HCV G3a NS3 isolates (IC50 =3312nM vs. 803nM) in the cell-based assay. In HCV G2/3-infected patients, boceprevir (400mg TID) resulted in a maximum mean decrease in HCV RNA of −1.60log vs. −0.21log with placebo. Conclusions: In vitro, boceprevir is more active than telaprevir against the HCV G3 NS3/4A enzyme in cell-based and biochemical assays and against G3 isolates in replicon assays. In HCV G2/3-infected treatment-naive patients, decreases in HCV RNA levels with boceprevir (400mg TID) were comparable to those observed with the same dose in HCV treatment-experienced G1-infected patients. [Copyright &y& Elsevier]

Highlights: [•] Th1/Th2 cytokine profiles induced by F protein in HCV patients were studied. [•] Levels of IFN-γ, IL-2, IL-4, IL-5 in PBMC post F protein were compared. [•] Different Th1/Th2 cytokine profiles exhibited in patients with and without anti-F. [•] F protein may contribute to the Th1/Th2 response imbalance in CHC patients. [•] F protein may involve in the progress of HCC pathogenesis. [Copyright &y& Elsevier]

Direct-acting antiviral agents in combination with pegylated interferon (PEG-IFN) and ribavirin (RBV) significantly improve sustained virologic response rate and reduce duration of therapy among both treatment-naïve and treatment-experienced patients with genotype 1 chronic hepatitis C. One of the most important considerations with both boceprevir and telaprevir is the potential development of resistant variants with therapy. Patients with poor intrinsic responsiveness to interferon, and those with incomplete virological suppression on protease inhibitor therapy, appear to be at higher risk for resistance. In this article we will define antiviral resistance and review the data on both in vitro and in vivo resistance to protease inhibitors, concentrating on data on boceprevir and telaprevir. We will also explore the significance of resistant variants present at the baseline, as well as the fate of the resistant variants and the ways to minimize the development of resistance to protease inhibitors. [ABSTRACT FROM AUTHOR]