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Patients with hepatitis B-related cirrhosis complicated with thrombocytopenia have a higher risk of bleeding, which may lead to higher mortality. We aimed to explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) in the treatment of hepatitis B-related cirrhosis complicated with severe thrombocytopenia. Patients with hepatitis B-related compensated liver cirrhosis complicated with severe thrombocytopenia were divided into four groups according to the treatment method for thrombocytopenia. Platelet counts, the appearance of bleeding symptoms and adverse events were evaluated during the observation period. Also during the observational period, the platelet counts in the prednisone group, rhTPO group and prednisone plus rhTPO group were higher than those in the no treatment group. Patients without splenomegaly reacted better to rhTPO. Fewer bleeding events of grade 2 or worse were observed in the three treatment groups compared to the no treatment group. The platelet counts at baseline and treatment with rhTPO and/or prednisone were factors associated with bleeding events of grade 2 or worse in multivariate analysis. There could be a potential advantage for the use of rhTPO plus prednisone based on higher platelet counts and fewer bleeding events. Treatment with rhTPO was more effective in patients without splenomegaly., (© 2022 John Wiley & Sons Ltd.)

Primary liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death. Advances in sequencing technology are opening genomics to widespread application for diagnosis and research. The poor prognosis of advanced HCC warrants a personalized approach. The objective was to assess the value of genotyping for risk stratification and prognostication of HCC. We performed a systematic review of manuscripts published on MEDLINE from 1 January 2009 to 1 January 2022, addressing the value of genotyping for HCC risk stratification and prognostication. Publication information for each has been collected using a standardized data extraction form. Twenty‐five articles were analysed. This study showed that various genomics approaches (i.e., NGS, SNP, CASP or polymorphisms in circadian genes' association) provided predictive and prognostic information, such as disease control rate, median progression‐free survival, and shorter median overall survival. Genotyping, which advances in understanding the molecular origin, could be a solution to predict prognosis or treatment response in patients with HCC. [ABSTRACT FROM AUTHOR]

Previous evidence suggests that sialic acid‐binding Ig‐like lectin 7 (Siglec‐7) protein is significantly increased in patients with chronic hepatitis C virus (HCV) infection and directly correlates with clinical parameters of liver inflammation and fibrosis. The aim of this study was to determine the diagnostic value of Siglec‐7 as a non‐invasive tool to assess liver fibrosis in patients with chronic hepatitis C in a cross‐sectional study. Serum levels of Siglec‐7 were retrospectively tested in 1007 consecutive patients with chronic HCV infection recruited at three different European sites and data examined by the 'imperfect gold‐standard' statistical analysis. Liver stiffness obtained by transient elastography (TE) was considered the standard reference. Liver fibrosis was staged according to published cut‐offs of liver stiffness measurement by TE. Accuracy of detection of liver fibrosis stage was not increased by Siglec‐7 alone. However, we developed a new index (SiGAP) including Siglec‐7, γ‐glutamyl transferase, age and platelet count which showed increased sensitivity and specificity in predicting fibrosis compared with APRI or FIB4 indices. The AUROC of SiGAP for the diagnosis of significant (≥F2) and advanced liver fibrosis (≥F3) showed significantly higher values than those of APRI and FIB‐4. Siglec‐7 may be useful as a complementary tool to assess liver fibrosis stage in patients with chronic hepatitis C when included in a specifically designed algorithm, which showed high level of accuracy in the detection of F2 and F3 fibrosis stage. [ABSTRACT FROM AUTHOR]

Accurate HCV prevalence estimates are necessary for guiding elimination policies. Our aim was to determine the HCV prevalence and assess the cost‐effectiveness of a screen‐and‐treat strategy in the Spanish population. A population‐based, cross‐sectional study (PREVHEP‐ETHON Cohort, Epidemiological sTudy of Hepatic infectiONs; NCT02749864) was performed from July 2015‐April 2017. Participants from three Spanish regions were selected using two‐stage conglomerate sampling, and stratified by age, with randomized subject selection. Anthropometric and demographic data were collected, and blood samples were taken to detect anti‐HCV antibodies/quantify HCV RNA. The cost‐effectiveness of the screening strategies and treatment were analysed using a Markov model. Among 12 246 participants aged 20‐74 (58.4% females), the overall anti‐HCV prevalence was 1.2% (95% CI 1.0‐1.4), whereas the detectable HCV‐RNA prevalence was 0.3% (0.2‐0.4). Infection rates were highest in subjects aged 50‐74 years [anti‐HCV 1.6% (1.3‐1.9), HCV RNA 0.4% (0.3‐0.6]. Among the 147 anti‐HCV + subjects, 38 (25.9%) had active infections while 109 (74.1%) had been cleared of infection; 44 (40.4%) had cleared after antiviral treatment, whereas 65 (59.6%) had cleared spontaneously. Overall, 59.8% of the anti‐HCV + participants were aware of their serological status. Considering a cost of treatment of €7000/patient, implementing screening programmes is cost‐effective across all age cohorts, particularly in patients aged 50‐54 (negative incremental cost‐effectiveness ratio which indicates a cost‐saving strategy). The current HCV burden is lower than previously estimated, with approximately 25% of anti‐HCV + individuals having an active infection. A strategy of screening and treatment at current treatment prices in Spain is cost‐effective across all age cohorts. [ABSTRACT FROM AUTHOR]

Adjuvant pegylated interferon plus ribavirin treatment (Peg IFN/ RBV) reduces recurrence and prolongs survival in early stage hepatocellular carcinoma ( HCC) patients with chronic hepatitis C ( CHC) infection receiving resection or ablation. However, the impact of antiviral therapy in intermediate and advanced stage of CHC- HCC patients is uncertain. This study aimed to investigate the impact Peg IFN/ RBV treatment on recurrence-free interval and survival in patients with HCC receiving transarterial chemoembolization ( TACE). From 2010 to 2013, 274 CHC patients from a 1073 patient-based cohort composed of freshly diagnosed HCC and receiving TACE treatment the Chang Gung Memorial Hospital, Linkou Medical Center were recruited. Propensity score matching ( PSM) (age, gender, AST to Platelet Ratio Index ( APRI), tumour size, tumour number and Child-Turcotte-Pugh score) with the ratio 1:2 for patients with and without Peg IFN/ RBV treatment was performed. Statistics were performed with SPSS V.20 ( IBM, USA). After matching, 153 patients were analysed and 27 patients (17.6%) achieved sustained virologic response ( SVR). The 2-year cumulative overall survival rate and recurrence-free survival rate among patients with SVR, non- SVR, and untreated were 85.2% vs 58.3% vs 69.6% ( P=.001) and 73.3% vs 53.8% vs 58.5% ( P=.013). By Cox regression analysis, non- SVR, untreated, increase CTP score and nonresponder to TACE were independent factors related to mortality. The SVR achieved by Peg IFN/ RBV treatment markedly improves survival and reduces tumour recurrence in CHC- HCC patients receiving TACE treatment after complete response. [ABSTRACT FROM AUTHOR]

It is still controversial, whether and to what amount cirrhosis and portal hypertension are reversible in patients with hepatitis C virus ( HCV)-associated cirrhosis and sustained virologic response ( SVR) after interferon-free antiviral therapy. In this study, we prospectively evaluated dynamics of liver and spleen stiffness in HCV-infected patients with advanced liver disease and SVR after interferon-free treatment. A total of 54 patients with HCV-associated cirrhosis and SVR were included. Liver and spleen stiffness was measured at therapy baseline ( BL), end of treatment ( EOT) and 24 weeks after EOT ( FU24) by transient liver elastography (L- TE) as well as by acoustic radiation force impulse of the liver (L- ARFI) and spleen (S- ARFI), as well as biochemical, virologic and clinical data. Improvement of liver and spleen stiffness was found in 44 of 50 (88%), 31 of 54 (57%) and 25 of 54 (46%) of patients assessed by L- TE, L- ARFI and S- ARFI between baseline and FU24. Liver stiffness assessed by L- TE improved between BL [median (range), 32.5 (9.1-75) kPa] and EOT [median (range), 21.3 (6.7-73.5) kPa; ( P<.0001)], and between BL and FU24 [median (range), 21.2 (5.4-70) kPa; ( P<.0001)]. Liver stiffness assessed by L- ARFI improved between BL [median (range), 2.7 (1.2-4.1) m/s] and FU24 [median (range), 2.4 (1.2-3.9) m/s; P=.002), while spleen stiffness remained unchanged. Our data suggest that improvement of liver stiffness may be rather due to reduced necroinflammation and may be due to a less extent to regression of cirrhosis, as dynamics of liver stiffness improvement was more pronounced between BL and EOT than BL and FU24. [ABSTRACT FROM AUTHOR]

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level. [ABSTRACT FROM AUTHOR]

. Anaemia is a common side effect of ribavirin (RBV) which is used for the treatment of hepatitis C. Inosine triphosphatase gene polymorphism (C to A) protects against RBV-induced anaemia. The aim of our study was to genotype patients for inosine triphosphatase gene polymorphism rs1127354 SNP (CC or CA) and associate treatment-induced anaemia with gene expression profile and genotypes. We used 67 hepatitis C patients with available gene expression, clinical, laboratory data and whole-blood samples. Whole blood was used to determine inosine triphosphatase gene polymorphism rs1127354 genotypes (CC or CA). The cohort with inosine triphosphatase gene polymorphism CA genotype revealed a distinct pattern of protection against anaemia and a lower drop in haemoglobin. A variation in the propensity of CC carriers to develop anaemia prompted us to look for additional predictors of anaemia during pegylated interferon (PEG-IFN) and RBV. Pretreatment blood samples of patients receiving a full course of PEG-IFN and RBV were used to assess expression of 153 genes previously implicated in host response to viral infections. The gene expression data were analysed according to presence of anaemia and inosine triphosphatase gene polymorphism genotypes. Thirty-six genes were associated with treatment-related anaemia, six of which are involved in the response to hypoxia pathway (HIF1A, AIF1, RHOC, PTEN, LCK and PDGFB). There was a substantial overlap between sustained virological response (SVR)-predicting and anaemia-related genes; however, of the nine JAK-STAT pathway-related genes associated with SVR, none were implicated in anaemia. These observations exclude the direct involvement of antiviral response in the development of anaemia associated with PEG-IFN and RBV treatment, whereas another, distinct component within the SVR-associated gene expression response may predict anaemia. We have identified baseline gene expression signatures associated with RBV-induced anaemia and identified its functional pathways. In particular, we identified the hypoxia response pathway and the apoptosis/survival-related gene network, as differentially expressed in chronic hepatitis C patients with anaemia. [ABSTRACT FROM AUTHOR]

Summary. Combined pegylated interferon (PegIFN) and ribavirin represents the standard therapy for patients with chronic hepatitis C (CHC), which allows for sustained viral response (SVR) in up to 90% of patients depending on certain viral and host factors. Clinical studies have demonstrated the importance of adherence to therapy, that is, the ability of patients to tolerate and sustain a fully dosed therapy regimen. Adherence is markedly impaired by treatment-related adverse effects. In particular, haemolytic anaemia often requires dose reduction or termination of ribavirin treatment, which compromises treatment efficacy. Recent evidence points to a beneficial role of recombinant erythropoietin (EPO) in alleviating ribavirin-induced anaemia thereby improving quality of life, enabling higher ribavirin dosage and consequently improving SVR. However, no general consensus exists regarding the use of EPO for specific indications: its optimal dosing, treatment benefits and potential risks or cost efficiency. The Swiss Association for the Study of the Liver (SASL) has therefore organized an expert meeting to critically review and discuss the current evidence and to phrase recommendations for clinical practice. A consensus was reached recommending the use of EPO for patients infected with viral genotype 1 developing significant anaemia below 100 g/L haemoglobin and a haematocrit of <30% during standard therapy to improve quality of life and sustain optimal ribavirin dose. However, the evidence supporting its use in patients with pre-existing anaemia, non-1 viral genotypes, a former relapse or nonresponse, liver transplant recipients and cardiovascular or pulmonary disease is considered insufficient. [ABSTRACT FROM AUTHOR]

Thrombocytopenia (TCP) is a haematological condition known to occur in chronically infected hepatitis C (HCV) patients and may interfere with diagnostic procedures, such as liver biopsy, because of risk of bleeding. It may also exclude patients from effective antiviral treatment. We conducted a systematic literature review of articles and conference abstracts, to assess the prevalence of TCP among those with HCV and to describe demographics, liver disease stage and treatment characteristics of these patients. Studies of individuals with confirmed chronic HCV infection were included in the review if the study had a clear definition of thrombocytopenia and a sample size of at least 50 subjects. The final selection included 27 studies (21 articles and six abstracts). The definitions of thrombocytopenia varied between studies and were based either on platelet counts, with threshold levels ranging between ≤100 × 10 and ≤180 × 10/L, or on criteria set in haematological guidelines. The prevalence of TCP ranged from 0.16% to 45.4% and more than half of the studies reported a TCP prevalence of 24% or more. Because of the different TCP definitions, heterogeneity in study design and insufficient data on study characteristics such as age, gender, HCV treatment rates and disease severity an overall summary estimate of TCP prevalence among patients with HCV was not feasible. However, the relatively large prevalence in the majority of the studies suggests that there may be a substantial number of HCV patients at risk of bleeding complications and reduced likelihood of successful HCV antiviral treatment [ABSTRACT FROM AUTHOR]

Interferon (IFN)-based combination therapy with ribavirin has become the gold standard for the treatment of chronic hepatitis C virus infection. Haematologic toxicities, such as neutropenia, thrombocytopenia, and anaemia, however, frequently cause poor treatment tolerance, resulting in poor therapeutic efficacy. The aim of this study was to identify host genetic polymorphisms associated with the efficacy or haematologic toxicity of IFN-based combination therapy in chronic hepatitis C patients. We performed comprehensive single nucleotide polymorphism detection in all exonic regions of the 12 genes involved in the IFN signalling pathway in 32 healthy Japanese volunteers. Of 167 identified polymorphisms, 35 were genotyped and tested for an association with the efficacy or toxicity of IFN plus ribavirin therapy in 240 chronic hepatitis C patients. Multiple logistic regression analysis revealed that low viral load, viral genotypes 2 and 3, and a lower degree of liver fibrosis, but none of the genetic polymorphisms, were significantly associated with a sustained virologic response. In contrast to efficacy, multiple linear regression analyses demonstrated that two polymorphisms ( IFNAR1 10848-A/G and STAT2 4757-G/T) were significantly associated with IFN-induced neutropenia ( P = 0.013 and P = 0.011, respectively). Thrombocytopenia was associated with the IRF7 789-G/A ( P = 0.031). In conclusion, genetic polymorphisms in IFN signalling pathway-related genes were associated with IFN-induced neutropenia and thrombocytopenia in chronic hepatitis C patients. In contrast to toxicity, the efficacy of IFN-based therapy was largely dependent on viral factors and degree of liver fibrosis. [ABSTRACT FROM AUTHOR]

The most frequent and the most troublesome adverse effect of interferon plus ribavirin-based therapy is anaemia. The aim of this analysis was to determine the incidence and risk factors of anaemia (Hb < 10 g/dL) in human immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy. We reviewed all cases of anaemia occurring among 416 patients participating in a randomized, controlled 48-week trial comparing peginterferon (peg-IFN) alpha 2b plus ribavirin with interferon alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, HCV therapy and clinical and laboratory findings. Sixty-one (15.9%) of the 383 patients who received at least one dose of anti-HCV treatment developed anaemia. In multivariate analysis the risk of anaemia was significantly associated with zidovudine (OR, 3.27 95% CI, 1.64–6.54, P = 0.0008) and peg-IFN (OR, 2.35; 95% CI, 1.16–4.57, P = 0.0179). The risk of anaemia was lower in patients with higher baseline haemoglobin levels (OR, 0.35 95% CI, 0.26–0.49, P < 0.0001) and in patients receiving protease inhibitor-based antiretroviral therapy (OR, 0.51 95% CI, 0.30–0.86, P = 0.0114). Zidovudine discontinuation could help to avoid anaemia associated with anti-HCV therapy. [ABSTRACT FROM AUTHOR]

We compared sustained virological response (SVR) in chronic hepatitis C patients with severe fibrosis treated with pegylated interferon (Peg-IFN) α-2b 1.5 μg/kg/week or 0.75 μg/kg/week in combination with ribavirin 800 mg/day for 48 weeks. This was a multicentre randomized controlled study. SVR was observed in 44.5% (45/101) of patients treated with the standard dose of Peg-IFN and 37.2% (38/102) of patients treated with the low dose (NS). In patients with genotypes 1, 4 and 5, SVR was observed in 25.0% of patients who received the standard dose and 16.9% of patients who received the low dose of Peg-IFN ( P = NS). In patients with genotypes 1, 4 and 5 and low viraemia, SVR was obtained in 27.3% of patients treated with the standard dose and 25.8% of patients treated with the low dose ( P = NS). In the high-viraemia subgroup, SVR was obtained in 24.0% and 9.1% of patients, respectively. In patients with genotypes 2 and 3, SVR was similar in both groups (73.2% vs 73.0%). Thus, (1) patients with genotypes 2 and 3 and severe fibrosis can be treated with low dose of Peg-IFN and ribavirin, (2) this study suggests that patients with genotypes 1, 4 and 5 and high viraemia could receive a standard dose of Peg-IFN associated with ribavirin for 48 weeks, (3) side effects limit the efficacy of the treatment with standard dose of Peg-IFN in patients with genotypes 1, 4 and 5 and low viraemia, (4) more studies are needed for patients with genotype 2 or 3 to define the optimal duration (24 or 48 weeks) in patients with severe fibrosis. [ABSTRACT FROM AUTHOR]

The combination of pegylated interferon and ribavirin is the most effective therapy in patients with chronic hepatitis C. We evaluated this combination in unselected patients with bridging fibrosis or cirrhosis. Eighty patients were treated with peginterferon alpha-2b plus ribavirin. Hepatitis C virus serum RNA was monitored. Tolerance and safety were evaluated by the rate of treatment's discontinuation for any reason, and occurrence of serious clinical adverse events, respectively. Sustained virologic response (SVR) rate was 36.3% overall, and was observed in every group of patients except those who had previously failed to respond to the combination of interferon and ribavirin. No serious clinical adverse event occurred. Treatment was withdrawn in 18.7% of patients. Variables associated with discontinuation of treatment were low prothrombin index [OR: 1.16 (1.05;1.27)] and low body mass index [OR: 1.47 (1.12;1.92)]. Initial blood count abnormalities were not associated with cessation of treatment. Furthermore, early virologic response at week 8 and week 12 of treatment had similar predictive value for SVR. Combination therapy with peginterferon plus ribavirin seems effective in this group of patients, except in those who had previously failed to respond to the combination of interferon and ribavirin. This therapy is safe with appropriate monitoring, but tolerance seems worse in patients with the most advanced liver disease. [ABSTRACT FROM AUTHOR]

Interferon alpha and ribavirin (REV) combination therapy is associated with decreases in haemoglobin (Hb) concentrations and anaemia. The aim of this analysis was to better characterize the magnitude and frequency of Hb changes and risk factors. This retrospective analysis evaluated treatment-related changes in Hb in 677 patients who participated in either of two interferon alpha-2b plus RBV studies for chronic hepatitis C virus (HCV) infection. Study 1 included 192 interferon alpha-naïve patients randomized to receive RBV 1000-1200 mg/day plus interferon alpha-2b 3 million 11.1 daily or three times weekly for 48 weeks. Study 2 included 485 interferon alpha-experienced patients randomized to receive RBV 1000-1200 mg daily plus interferon alpha-2b 3 million R.J daily or three times weekly for 4 weeks, followed by three times weekly dosing for 44 weeks. More than 50% of all patients experienced a decrease in Hb ≥ 30 g/L. Women were 4.4 times as likely as men to experience a Hb level of <100 g/L; however, men were at a 40% higher risk to experience a Hb decline of >30 gIL from baseline. Daily use of interferon alpha-2b did not impact the magnitude of Hb decrease. In this pooled analysis, RBV dose reduction resulted in increases in Hb concentration of approximately 10 g/L. Lower baseline creatinine clearance, higher baseline Hb levels and increased age were independently associated with increased risk of Hb decreases of >27.7%. Lower baseline weight was not associated with increased risk of Hb decrease. Substantial Hb decreases occur frequently with interferon alpha/REV combination therapy. Sex, the magnitude of the Hb decline and renal function are potentially important factors to consider in patients receiving REV. Further research is needed to determine the impact on virological response and to develop strategies to manage the medical consequences. [ABSTRACT FROM AUTHOR]

Extensive studies of GBV-C/HGV in acute and chronic hepatitis non-A-non-E have failed to provide hard evidence for a major role in this disease. Persistent GBV-C/HGV viraemia is in most cases associated with normal ALT levels, and only in a minority of patients are mild elevations of aminotransferases found. Its disease-inducing capacity is questionable and the findings accumulated so far are best explained by looking at GBV-C/HGV as a well-adapted, predominantly parenterally transmitted, persistent virus; it might be transmitted concomitantly with another, still unidentified hepatitis non-A-non-E virus. This does not exclude the possibility that GBV-C/HGV might, in some rare cases and under certain circumstances, induce a hepatitis-like illness as seen with other viruses such as EBV or CMV. GBV-C/HGV definitely plays a minor role only, if any, in post-transfusion and community-acquired hepatitis non-A-non-E. [ABSTRACT FROM AUTHOR]