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Background: Identification of risk factors for hepatitis C virus (HCV) transmission will help in targeted screening of people who are at risk for HCV. Method: Indian studies, published between January 1989 and June 2020, were systematically reviewed to identify the relevant studies. We searched electronic databases including PubMed/Medline, Embase, Scopus, and Google scholar to identify the original data published in English language. The full-text studies, published in any form, which reported data on risk factors for HCV transmission among low-risk population were selected. The studies which exclusively included high-risk groups were excluded. Results: Data were extracted from 31,176 participants included in 25 studies (median [range] 40 [7-20,113). The participants were HCV infected patients who visited the hospital (n = 10), community population (n = 6), pregnant women (n = 5), blood donors (n = 2), people with diabetes mellitus (n = 1), army recruits (n = 1), or slum dwellers (n = 1). These studies provided data on blood transfusion, use of unsafe injections, minor or major surgery, unsafe dental procedures, tattooing, body piercing, obstetrical procedures, unsafe shaving, intravenous drug use, and unsafe sexual practices as risk factors for HCV transmission. Conclusion: Unsafe injections, body piercing, unsafe dental procedure, unsafe shaving, and tattooing were identified as major risk factors for reported by HCV population participants.More data are needed to identify the risk factors for HCV in Indian population. Risk-factor-targeted screening may increase the yield and reduce the cost of HCV screening in India.

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Background & Aims: Significant scale-up of treatment among people who inject drugs (PWID) is crucial to achieve WHO HCV elimination targets. We explored the impact of on-site HCV diagnosis and treatment on PWID in an externalised hepatology clinic at the biggest harm reduction centre (HRC) in Barcelona attending to a marginalised PWID population with ongoing high-risk practices. Methods: On-site HCV point-of-care testing was performed for diagnosis and treatment delivery. HCV-RNA was assessed at SVR12 (sustained virologic response at 12 weeks) and every 6 months. The programme included behavioural questionnaires at baseline and after treatment. Results: Between 2018 and 2020, 919 individuals were prospectively enrolled. Of these, only 46% accepted HCV screening. HCV-RNA+ prevalence was 55.7% (n = 234). Of the 168 (72%) individuals starting treatment, 48% were foreigners, 32% homeless, 73% unemployed, and 62% had a history of incarceration. At enrolment, 70% injected drugs daily and 30% reported sharing needles or paraphernalia. Intention-to-treat SVR12 was 60%; only 4% were virological failures, the remaining were either early reinfections (20%) or losses to follow-up (16%). The overall reinfection rate during follow-up was 31/100 persons/year. HIV coinfection and daily injection were associated with a higher risk of reinfection. Nonetheless, beyond viral clearance, antiviral therapy was associated with a significant reduction in injection frequency, risk practices, and homelessness. Conclusions: HCV treatment can be successfully delivered to active PWID with high-risk practices and has a significant benefit beyond HCV elimination. However, approaching this difficult spectrum of the PWID population implies significant barriers such as low rate of screening acceptance and high dropout and reinfection rates. Lay summary: People who inject drugs attending harm reduction centres represent the most difficult population to treat for hepatitis C. We show that hepatitis C treatment has a significant benefit beyond viral cure, including improving quality of life, and decreasing injection frequency and risk practices. However, intrinsic barriers and the high reinfection rates hamper the achievement of viral microelimination in this setting.

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Background: Concerns about HBV reactivation (HBVr) have been raised with the introduction of DAA for HCV treatment. The aim of the study was to assess the risk of HBVr in chronic HCV patients during or after DAA. Methods: A cohort of 166 chronic HCV patients who were treated with SOF-based DAA regimens and initially positive for HBcAb total were evaluated; 10 HBsAg-positive, 156 had past HBV exposure (HBsAg-negative/HBcAb-positive). Laboratory investigations, including liver functions tests, HBV-DNA, LSM by Transient elastography, and ARFI together with serum markers of fibrosis; APRI and FIB-4 were done at baseline and after 12 weeks of DAAs therapy. HBV-DNA levels and liver functions were monitored for assessment of HBVr. Results: Virological HBVr was diagnosed by ≥ 1 log10 IU/ml HBV-DNA levels in 2/166 patients (1.2%) among the whole HCV cohort, who were initially positive for HBsAg; 20%. Clinical HBVr (>3 folds liver enzyme elevation) was detected in one patient with virological HBVr. Conversely, none of past HBV-infected patients experienced HBVr. All patients achieved SVR12 and had a significant decline in serum transaminases, bilirubin, APRI, and LSM measurements after HCV eradication. Conclusion: HBVr might be considered after successful eradication of HCV following DAAs therapy, especially among patients who are positive for HBsAg, while past HBV infection does not seem to be a predisposing condition to HBVr.

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Background & objectives: There are reports of worsening renal functions with sofosbuvir, but there are no comparative data of different direct-acting antivirals (DAAs) on serum creatinine. In this retrospective cohort analysis, we examined the treatment effect of two commonly used regimens, sofosbuvir/ledipasvir (SOF/LDV) and glecaprevir/pibrentasvir (GLE/PIB), on serum creatinine. Methods: We included all patients treated with SOF/LDV (n = 825) and GLE/PIB (n = 116) between December 1, 2014, and December 31, 2018. An increase of serum creatinine ≥0.3 mg/dL was considered clinically significant. The change of creatinine values from pretreatment to posttreatment between two treatment groups was tested in unadjusted and adjusted generalized linear model, and risk factors associated with creatinine change were assessed. In addition, GLE/PIB-treated patients were matched 1:2 to SOF/LDV-treated patients using propensity scores, and then serum creatinine changes were compared. Results: The mean baseline creatinine was higher in the GLE/PIB group vs. SOF/LDV group (1.39 ± 1.86 vs. 0.91 ± 0.24, P = 0.007). When compared to baseline, serum creatinine at posttreatment week 4 was significantly higher in SOF/LDV group (0.97 ± 0.4 vs.0.91 ± 0.24, P < 0.001), but there was no significant change in the GLE/PIB group (1.41 ± 1.73 vs. 1.39 ± 1.86, P = 0.52). Overall, there was no significant change in serum creatinine between posttreatment week 4 and week 24 (P = 0.6). Clinically significant increase in serum creatinine was seen in 6% (46/825) of SOF/LDV and 7% (8/116) of GLE/PIB (P = 0.6). The unadjusted and adjusted models indicated that the changes in creatinine from baseline to posttreatment week 4 and week 24 were not associated with the type of DAA combination. Conclusion: Treatment of chronic hepatitis C infection with both SOF/LDV and GLE/PIB regimens may result in an increase of creatinine, and 6-7% will have an increase in serum creatinine of ≥0.3 mg/dL. The increase in creatinine, however, is unrelated to the type of DAA combination.

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Introduction: This study analyzes the changing levels of circulating inflammatory cytokines Interferon gamma (IFN-γ) and interleukin (IL)-10 (as the main cytokines of T-helper-1 and T-helper-2 immune responses) in patients with chronic hepatitis C virus (HCV) infection undergoing therapy with direct-acting antivirals (DAAs) and to correlate them with laboratory markers. Methods: This Pilot study included 50 HCV monoinfected patients who received DAAs for 12 or 24 weeks. They were followed up monthly during therapy and 3 months after the end of the treatment. Liver disease was determined by transient elastography, in addition to FIB-4 indices. Analysis of IFN-gamma and IL-10 was carried out using an enzyme-linked immunosorbent assay. Results: All patients carried HCV genotype 4. The Sustained virological response was 100% and 92% in cirrhotics and noncirrhotics, respectively. There was no significant difference between groups in baseline IL-10 or IFN-gamma. In noncirrhotics, IL-10 showed a significant reduction at Week 4 after treatment start. In cirrhotics, IL-10 showed a significant reduction at Week 4 after treatment starts and a significant reduction at Week 12 after the end of the treatment. At Week 12 after the end of the treatment, serum IL-10 levels were significantly lower in cirrhotics. IFN-γ showed nonsignificant changes in noncirrhotics. A significant increase of IFN-γ occurred in cirrhotics from Week 4 after treatment starts to 12 weeks after the end of the treatment. IFN-γ was significantly higher in cirrhotics at Week 12 after the end of the treatment. IFN-γ and IL-10 showed different correlations with laboratory markers. Conclusion: Viral eradication induced by DAAs caused a significant change in IL-10 and IFN-gamma.

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INTRODUCTION AND OBJECTIVES: Sustained virologic response (SVR) is achieved in most cases of C-type liver disease after direct-acting antiviral (DAA) therapy. Although liver fibrosis improves, the degree of improvement is different. This study aimed to analyze the factors involved in improving liver fibrosis using the fibrosis 4 (FIB-4) index. MATERIAL AND METHODS: Patients were monitored for >3 years after SVR. At the start of therapy (SOT), liver fibrosis was categorized as either mild (<1.45 n = 28), moderate (1.45-3.25 n = 139), or advanced (>3.25 n = 236) based on the FIB-4 index. The FIB-4 index in the advanced group decreased significantly compared to that of the other two, so we selected the advanced group as the analysis target. SOT and end of therapy (EOT) factors that contributed to the FIB-4 index ≤3.25 at 3 years after therapy were examined using a multivariate analysis. RESULTS: Among the SOT factors, age (<72 years old), absence of liver cirrhosis (LC), alanine transferase (ALT) (≥50 U/L), platelet (PLT) (≥10.2 × 104/mm3), and total bilirubin (T.Bil) (<0.8 mg/dl) were the significant factors contributing to the improvement of the FIB-4 index. Among the EOT factors, age (<72 years), PLT (≥12.0 × 104/mm3), and hemoglobin (Hb) (≥12.1 g/dl) were the significant factors contributing to the improvement of FIB-4 index. CONCLUSIONS: Factors involved in the improvement of liver fibrosis after SVR were young age, absence of LC, low T.Bil., high ALT, high PLT, and high Hb levels. The levels of T.Bil, PLT, and Hb were considered to be related to portal hypertension. Aging strongly impaired the improvement in liver fibrosis.

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Envejecimiento , Antivirales/uso terapéutico , Hepacivirus , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/etiología , Respuesta Virológica Sostenida , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven

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BACKGROUND: Direct-acting antivirals (DAAs) treatment, although highly efficacious for the treatment of hepatitis C virus (HCV) infection, may not completely reconstitute the HCV-mediated dysregulated immune system, especially in patients co-infected with human immunodeficiency virus (HIV) and HCV. OBJECTIVES: We aimed to evaluate the impact of HCV eradication following DAA therapy on the immune system and liver disease improvement through comparative monitoring of 10 HCV mono-infected and 10 HCV/HIV co-infected patients under combined antiretroviral therapy (cART). Early and late longitudinal phenotypic changes in peripheral blood mononuclear cell (PBMC) subsets, T-cell activation, differentiation and exhaustion, as well as inflammatory biomarkers, indoleamine 2-3 dioxygenase (IDO) activity, and liver stiffness, APRI and FIB-4 scores were assessed. MATERIALS AND METHODS: Samples were obtained at baseline (T0), week 1 (T1), week 2 (T2), week 12 (T3, end of treatment, EOT), and month 9 (T4, end of follow-up, 36 weeks post EOT). RESULTS: All patients achieved a sustained virological response (SVR 12) after DAA treatment. Overall, changes of the T-cell immune phenotypes were greater in HCV/HIV co-infected than in HCV mono-infected, due to an increase in CD4+ and CD8+ T-cell percentages and of CD8+ T-cell activation and memory markers, in particular at the end of follow-up. On the other end, HCV mono-infected showed changes in the activation profile and in the memory CD4+ T-cell compartment. In HCV/HIV co-infected, a decrease in the IDO activity by DAA treatment was observed; conversely, in HCV mono-infected, it resulted unmodified. Regarding inflammatory mediators, viral suppression was associated with a reduction in IP-10 levels, while interferon regulatory factor (IRF)-7, interferon (IFN)-ß, and interferon (IFN)-γ levels were downregulated during therapy and increased post therapy. A decrease in liver stiffness, APRI, and FIB-4 scores was also observed. CONCLUSIONS: Our study suggests that, although patients achieved HCV eradication, the immune activation state in both HCV mono-infected and HCV/HIV co-infected patients remains elevated for a long time after the end of DAA therapy, despite an improvement of liver-specific outcomes, meanwhile highlighting the distinct immunophenotypic and inflammatory biomarker profile between the groups of patients.

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BACKGROUND & AIMS: The Liver Cancer Risk test algorithm (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein-A1 and haptoglobin), known hepatocellular carcinoma (HCC) risk factors (sex, age, and gamma-glutamyl transferase), a marker of fibrosis (alpha2-macroglobulin) and alpha-fetoprotein (AFP), a specific marker of HCC. The aim was to externally validate the LCR1-LCR2 in patients with chronic HCV (CHC) treated or not with antivirals. METHODS: Pre-included patients were from the Hepather cohort, a multicentre prospective study in adult patients with CHC in France. LCR1-LCR2 was assessed retrospectively in patients with the test components and AFP, available at baseline. The co-primary study outcome was the negative predictive value (NPV) of LCR1-LCR2 for the occurrence of HCC at 5 years and for survival without HCC according to the predetermined LCR1-LCR2 cut-offs. The cut-offs were adjusted for risk covariables and for the response to HCV treatment, and were quantified using time-dependent proportional hazards models. RESULTS: In total, 4,903 patients, 1,026 (21.9%) with baseline cirrhosis, were included in the study. Patients were followed for a median of 5.7 (IQR 4.2-11.3) years. A total of 3,788/4,903 (77.3%) patients had a sustained virological response. There were 137 cases of HCC at 5 years and 214 at the end of follow-up. HCC occurred at 5 years in 24/3,755 patients with low-risk LCR1-LCR2 compared with 113/1,148 patients with high-risk LCR1-LCR2. The NPV was 99.4% (95% CI 99.1-99.6). Similar findings (hazard ratio, 10.8; 95% CI, 8.1-14.3; p <0.001) were obtained after adjustment for exposure to antivirals, age, sex, geographical origin, HCV genotype 3, alcohol consumption, and type 2 diabetes mellitus. CONCLUSIONS: The results showed that LCR1-LCR2 can be used to successfully identify patients with HCV at very low risk of HCC at 5 years. LAY SUMMARY: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide and the fastest growing cause of cancer death in many countries. We constructed and internally validated a new multianalyte blood test to assess this Liver Cancer Risk (LCR1-LCR2). This study confirmed the performance of LCR1-LCR2 in patients with chronic HCV in the national French cohort Hepather, and its ability to identify patients at a very low risk of HCC at 5 years. CLINICAL TRIALS REGISTRATION: The study is registered at ClinicalTrials.gov (NCT01953458).

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BACKGROUND & AIMS: Health-related quality of life (HRQoL) determined by patient-reported outcomes (PROs) is impaired in chronic hepatitis B (CHB) and C patients, but there are no data regarding patients with chronic hepatitis D (CHD). The aim of this study was to assess PRO scores in untreated patients with CHD and compare them with those obtained for patients with CHB. METHODS: Patients with CHD completed 3 PRO instruments (Chronic Liver Disease Questionnaire [CLDQ], Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F], and Work Productivity and Activity Impairment [WPAI]), and the results were compared with those of patients mono-infected with CHB. RESULTS: In total, 125 patients were included: 43 with CHD and 82 with CHB. Overall, baseline PROs showed differences between both groups. Several assessments, such as the worry score from CLDQ (p = 0.0118), functional well-being from FACIT-F (p = 0.0281), and activity impairment from WPAI (p = 0.0029) showed a significant trend to worse scores in patients with CHD than with CHB. In addition, the linear regression model supports the finding that having CHD as opposed to having CHB was a predictor of a higher worry score (CLDQ) and a higher activity impairment (WPAI). CONCLUSIONS: In this first assessment in CHD, PROs recorded in patients with CHD showed a significant impairment in some domains of HRQoL questionnaires in comparison with those with CHB. Studies in larger cohorts with lengthier follow-up are needed to fully assess patient-reported quality of life over the course of CHD. LAY SUMMARY: Chronic hepatitis D (CHD) is a viral disease that causes rapid evolution to liver cirrhosis, amongst other severe complications, when compared to patients with chronic hepatitis B (CHB). Health-related quality of life in chronic hepatitis C and CHB has been reported widely, but no studies have been performed on patient-reported outcomes in patients with CHD. Results showed that CHD patients reported worse outcomes in psychological domains such as worry and emotional well-being, as well as in physical domains such as abdominal symptoms, physical well-being, and activity impairment in comparison with patients with CHB.

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The use of direct-acting antiviral agents (DAAs) in patients with chronic HCV genotype (GT) 1 infection results in sustained virologic response (SVR) rates of 95%-97%, but 3%-5% of patients experience virologic failure. We observed 41 patients infected with HCV subtype 1b who failed previous treatment with DAAs, including 37 subjects (90.2%) with liver cirrhosis. In total, 30 (73.2%) subjects previously received NS5A inhibitors of the first generation (ledipasvir, daclatasvir, or ombitasvir) and 11 subjects (26.8%) received NS5A inhibitors of the second generation (velpatasvir). All patients received retreatment with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D) with sofosbuvir (SOF) and ribavirin (RBV). We compared SVR12 rates depending on fibrosis stage, presence of just single or double NS5A mutation (L31M/V/I and/or Y93H), and the generation of previously used NS5A inhibitors. Observed SVR12 rates were as follows: 97.6% (40/41 patients) overall; 100% in patients without cirrhosis (n = 4) versus 97.3% in those with cirrhosis (n = 37); 100% with single L31M/V/I or Y93H mutation (n = 22) versus 94.4% with double mutations (n = 18); 100% in patients who failed previous treatment with first-generation (n = 30) versus 90.9% in those who failed previous treatment with second-generation NS5A inhibitors (n = 11). Retreatment with 3D + SOF + RBV was highly effective and safe in patients with chronic HCV GT1b infection, including those with liver cirrhosis, who failed previous treatment with DAA containing NS5A inhibitors. Fibrosis stage and single or simultaneous presence of NS5A RASs L31M/V/I and Y93H at the baseline, as well as the generation of previously used NS5A inhibitors, did not impact SVR12 rates.

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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Retratamiento , Proteínas no Estructurales Virales/antagonistas & inhibidores , 2-Naftilamina/uso terapéutico , Anilidas/uso terapéutico , Ciclopropanos/uso terapéutico , Farmacorresistencia Viral/efectos de los fármacos , Farmacorresistencia Viral/genética , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/virología , Humanos , Lactamas Macrocíclicas/uso terapéutico , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Mutación , Prolina/análogos & derivados , Prolina/uso terapéutico , Ribavirina/uso terapéutico , Ritonavir/uso terapéutico , Sofosbuvir/uso terapéutico , Sulfonamidas/uso terapéutico , Respuesta Virológica Sostenida , Uracilo/análogos & derivados , Uracilo/uso terapéutico , Valina/uso terapéutico , Proteínas no Estructurales Virales/genética

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BACKGROUND & AIMS: The incidence of primary liver cancer (PLC) is increasing in Western Europe. To understand trends over time and the current burden in the UK, a detailed analysis of the epidemiology of PLC and its subtypes was conducted. METHODS: Data on PLCs diagnosed during 1997-2017 were obtained from population-based, nationwide registries in the UK. European age-standardised incidence (ASR) and incidence-based mortality rates (ASMR) per 100,000 person-years were calculated overall and by sex and UK-nation. Annual percentage change in rates was estimated using Joinpoint regression. One-, 2-, and 5-year age-standardised net survival was estimated. RESULTS: A total of 82,024 PLCs were diagnosed. Both hepatocellular carcinoma (HCC) incidence and mortality rates trebled (ASR 1.8-5.5 per 100,000, ASMR 1.3-4.0). The rate of increase appeared to plateau around 2014/2015. Scottish men consistently had the highest HCC incidence rates. PLC survival increased, driven by a substantial increase in the proportion that are HCC (as prognosis is better than other PLCs) and in HCC survival (change in 1-year survival 24-47%). Intrahepatic cholangiocarcinoma was the most common PLC in women and 1-year survival improved from 22.6% to 30.5%. CONCLUSIONS: PLC incidence has been increasing rapidly but, as most risk factors are modifiable, it is largely a preventable cancer. This rate of increase has slowed in recent years, possibly attributable to effective treatment for hepatitis C. As other risk factors such as obesity and diabetes remain prevalent in the UK, it is unlikely the considerable burden of this disease will abate. While improvements in survival have been made, over half of patients are not alive after 1 year, therefore further progress in prevention, early detection, and treatment innovation are needed. LAY SUMMARY: Many more people are getting liver cancer, particularly the subtype hepatocellular carcinoma, than 20 years ago. Men in Scotland are most likely to get liver cancer and to die from it. Survival after liver cancer diagnosis is getting longer but still less than half are alive after 1 year.

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BACKGROUND: Direct-acting antivirals (DAAs) are expected to improve outcomes for patients with hepatitis C virus (HCV) infection after liver transplantation (LT). We aim to evaluate trends in post-LT outcomes with availability of DAAs. METHODS: We retrospectively evaluated US adults transplanted from January 1, 2002, to March 31, 2018, using the United Network for Organ Sharing Registry, stratified by pre-DAA (January 1, 2002- to December 31, 2013) vs. post-DAA (January 1, 2014-, to March 31, 2018) eras. Adjusted multivariate Cox regression analyses and competing risk models evaluated likelihood of graft failure, death, and retransplantation (re-LT). RESULTS: Among 97,147 patients, 30.2% had HCV infection and 19.4% had hepatocellular carcinoma (HCC). Of all patients, 31.9% experienced graft failure, 27.1% died after LT, and 4.7% underwent re-LT. The post-DAA era experienced lower likelihood of graft failure (hazard ratio [HR] = 0.69, p < 0.001). Although patients with HCV infection (HR = 1.18, p < 0.001) and HCC (HR = 1.11, p < 0.001) had higher likelihood of graft failure in the pre-DAA era, no differences were seen in the post-DAA era. Although patients with HCV infection (HR = 1.20, p < 0.001) and HCC (HR = 1.17, p < 0.001) had higher likelihood of death after LT in the pre-DAA era, no differences were seen in the post-DAA era. The post-DAA era had lower likelihood of post-LT death when stratified by non-HCC (HR = 0.70, p < 0.001) and HCC cohorts (HR = 0.67, p < 0.001) or by non-HCV (HR = 0.73, p < 0.001) and HCV (HR = 0.58, p < 0.001) cohorts. CONCLUSION: Although patients with HCV infection and HCC had higher risk of post-LT graft failure and death in the pre-DAA era, the disparity disappeared in the post-DAA era independently of each other. This likely reflects impact of DAAs on improving post-LT outcomes among patients with HCV infection and improved selection of patients with HCC for LT after 2014.

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Variations in the interferon sensitivity-determining region (ISDR) within the NS5A region were related to the development of hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV). The aim of the study was to investigate a relationship between ISDR/PKR substitutions and their association with liver fibrosis or HCC development. A total of 316 patients infected with HCV and treated with DAAs were evaluated. HCV RNA was quantified and sequenced before treatment. The liver fibrosis stage was assessed by transient elastography and equalized to METAVIR scores. Multivariate analysis showed that ≥3 substitutions in ISDR and ≥6 in PKR-bd were significantly associated with advanced fibrosis. Advanced fibrosis was observed in patients with higher substitutions in ISDR and PKR-bd. A higher correlation between advanced fibrosis and a high frequency of ≥3 substitutions in ISDR and ≥6 in PKR-bd was observed in patients infected with genotype 2c. In addition, in a higher proportion of HCC patients, advanced fibrosis (40.4% vs. 88.2%; p < 0.001) and ≥6 substitutions in PKR-bd (15.4% vs. 41.2%; p = 0.01) was observed. In conclusion, a higher number of substitutions in ISDR and PKR-bd were associated with advanced liver fibrosis, suggesting a use of like predictors for progression in the liver damage. A significantly higher number of PKR-bd substitutions was observed in HCC patients; in particular, in patients infected with HCV genotype 2c.

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Hepacivirus/fisiología , Hepatitis C Crónica/metabolismo , Hepatitis C Crónica/virología , Interacciones Huésped-Patógeno , Dominios y Motivos de Interacción de Proteínas , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Anciano , Carcinoma Hepatocelular/etiología , Biología Computacional/métodos , Femenino , Hepatitis C Crónica/complicaciones , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Unión Proteica , ARN Viral , Proteínas no Estructurales Virales/química

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BACKGROUND: Improved efforts in screening and treating chronic hepatitis C virus (HCV) infection are expected to reduce its burden among adults on the liver transplantation (LT) waitlist (WL). We aim to evaluate birth cohort-specific liver disease etiology trends in US adults listed for and receiving LT. METHODS: We evaluated 2005-2016 United Network for Organ Sharing LT registry data to evaluate birth cohort-specific trends in LT WL registrants and recipients in the US. Annual trends in etiology of liver disease at listing were compared between the 1945-1965 birth cohort and the non-1945-1965 birth cohort, were stratified by presence of hepatocellular carcinoma (HCC vs. non-HCC), and were focused on the four leading indications for LT in the US, nonalcoholic steatohepatitis (NASH), HCV infection, alcoholic liver disease (ALD), and those with combined alcoholic cirrhosis with HCV (HCV/ALD). RESULTS: From 2005 to 2016, although HCV infection was a leading indication for LT WL registration among the 1945-1965 birth cohort patients until 2015, NASH overtook HCV infection as the leading indication in 2016. When stratified by HCC status, both ALD and NASH surpassed HCV infection as the leading indication among 1945-1965 birth cohort WL registrants without HCC, whereas HCV infection remained the leading indication among patients with HCC. When evaluating trends in patients who received LT, HCV infection remained the leading indication among the 1945-1965 birth cohort patients. CONCLUSION: In 2016, NASH surpassed HCV infection as the leading indication for WL registration among the 1945-1965 birth cohort patients. Improved HCV screening, increased availability of effective HCV infection treatment, and rising prevalence of nonalcoholic fatty liver disease may explain changes in LT indication among this group.

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INTRODUCTION: Concerns were raised about a high occurrence of hepatocellular carcinoma (HCC) after successful treatment of chronic hepatitis C (CHC) by direct-acting antivirals (DAAs). AREAS COVERED: The authors summarize the clinical studies reporting the occurrence rate and risk factors of HCC after DAAs in CHC. EXPERT OPINION: The recent introduction of all-oral DAAs has substantially changed the scenario of CHC, achieving a sustained virological response (SVR) in >90% of cases. Earlier concerns raised about an increasing incidence of HCC post-DAAs were flawed by large heterogeneity of patients, the limited number of well-designed prospective studies (only nine, up to date) and the inclusion of a large number of patients with advanced liver disease, previously excluded from interferon-based studies. Current data on DAAs have shown a lower risk of HCC development; however, they were unable to identify patients at greater risk for HCC occurrence after SVR. Surveillance strategy, likely lifelong, is mandatory in these patients according to general expert opinion.

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Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Neoplasias Hepáticas/epidemiología , Carcinoma Hepatocelular/etiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Incidencia , Neoplasias Hepáticas/etiología , Proyectos de Investigación , Factores de Riesgo , Respuesta Virológica Sostenida , Resultado del Tratamiento

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BACKGROUND: Sofosbuvir (SOF), a direct acting antiviral, has revolutionized the treatment of chronic Hepatitis C Virus (HCV) infection. However, data is scarce about efficacy of SOF plus Ribavarin (RBV) in Indian patients with decompensated cirrhosis. We evaluated the efficacy of SOF plus RBV in decompensated cirrhosis, and compared the outcome with compensated cirrhosis and non-cirrhotics. PATIENTS AND METHODS: Consecutive decompensated cirrhotic patients of chronic HCV with detectable HCV RNA were treated with 24-week course of SOF (400 mg) plus weight based RBV. Sustained Virological Response (SVR), Child Turcotte Pugh (CTP) and Model for Endstage Liver Disease (MELD) scores were assessed at 36 weeks (i.e. 12 weeks after completion of therapy). Non-cirrhotic chronic hepatitis C patients and patients with compensated cirrhosis treated with SOF plus RBV during the same period were used as controls. During the period of this study ledipasvir and daclatasvir were not available in India. RESULTS: A total of 47 patients [median age 50 (29-82) years, 64% males] with decompensated cirrhosis were included as 'cases' in the study; while, 27 patients with compensated cirrhosis and 29 patients with chronic hepatitis were included as 'controls'. Age, gender, HCV RNA levels, and genotype distribution were similar in cases and controls. The median CTP and MELD scores of cases were 8 (7-12) and 13 (6-25), respectively. Among cases 39 (83%) could complete the therapy, while 1 (2%) was intolerant and 7 (15%) died before completion of therapy. End of Treatment Response (ETR) was achieved in 37/39 (95%) cases. Of these, another 3 died before SVR, and 7 failed to achieve SVR, thus 27/34 (79%) could achieve SVR. Thus according to intention-to-treat analysis, only 27/47 (57%) cases could achieve SVR. In comparison, 24/28 (86%) compensated cirrhotics and 27/28 (96%) of chronic hepatitis achieved SVR. There was a significant improvement in mean CTP score in cases who achieved SVR (P < 0.01) compared to those who did not achieve SVR/ETR. On multivariate analysis the only independent factor influencing successful outcome patients was a serum albumin >3.5 g/dL. CONCLUSIONS: A 24-week course of SOF plus ribavirin in decompensated HCV cirrhosis could lead to SVR in only 57% of patients. The failure of therapy in 43% patients was either due to non-response, intolerance, or death. A serum albumin of more than 3.5 is associated with success of antiviral therapy. Thus an early initiation of antiviral therapy is recommended before decompensation sets in as it precludes successful outcome.

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BACKGROUND: Hepatitis C infection is known to increase the morbidity in patients with end stage renal disease (ESRD). Interferon based treatment is poorly tolerated and has limited cure rates in these patients. In limited available data, sofosbuvir based regimens have been shown to have favorable outcomes in these patients. METHODS: We treated 7 patients with ESRD on hemodialysis, 6 with chronic hepatitis C and one with acute hepatitis C. Two of them were cirrhotic of which one was decompensated. All patients were treated with sofosbuvir 200 mg with daclatasvir 60 mg or ribavirin 200 mg once daily. Patients with evidence of cirrhosis were treated for 24 weeks, others were treated for 12 weeks. HCV RNA quantitative PCR was monitored at weeks 2, 4, 12, end of therapy and after 12 weeks of end of treatment (SVR12). RESULTS: The study cohort included five males and two females, aged (48.4 ± 14.5 years). Four patients had genotype 1 and three had genotype 3. One patient was treated with sofosbuvir and ribavirin while others were treated with sofosbuvir and daclatasvir. One patient died of unrelated cause during the therapy. One patient who received sofosbuvir and daclatasvir, could not complete the therapy beyond 20 weeks because she developed recurrent hypoglycemia, which improved after stopping the therapy, all the other patients had SVR 12. There was no change in Hb levels or erythropoietin requirement in the patients receiving sofosbuvir and daclatasvir. CONCLUSION: Our data suggest that sofosbuvir based therapy is effective in patients with ESRD and hepatitis C, including those with liver cirrhosis. Its use may be recommended especially in countries where other drugs are not available. Due to limited experience however, patients should be closely monitored for adverse effects. Hypoglycemia may be a potential adverse effect of sofosbuvir and daclatasvir therapy.

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INTRODUCTION: Results of Sofosbuvir based regimens for hepatitis C (HCV) recurrence after liver transplantation are available from well-designed clinical trials. Most of the data is from deceased donor liver transplant (DDLT) setting, and data on "real world" experience for HCV recurrence after living donor liver transplantation (LDLT) is limited. MATERIAL AND METHODS: Consecutive 78 patients who completed Sofosbuvir based HCV treatment after liver transplantation were included. Following Sofosbuvir based regimens were used; Sofosbuvir + Ribavirin (n = 58), Sofosbuvir + Ledipasvir ± Ribavirin (n = 5), Sofosbuvir + Daclatasvir ± Ribavirin (n = 15). Treatment was given for 12 weeks (triple therapy) or 24 weeks (dual therapy). RESULTS: A total of 74/78 (94.8%) patients achieved end of treatment response (ETR) while 4 did not achieve ETR. A total of 68/76 (89.4%) patients achieved sustained virological response at 12 weeks (SVR12). while 2 are waiting for 12 weeks follow up after ETR. Twelve patients had history of failed previous treatment with Peginterferon and Ribavirin after LDLT, all these patients achieved ETR and 11/12 had SVR12. There was no statistical difference in response rates between genotype 1 or 3. Eighteen patients (16 on Ribavirin) had hemoglobin < 8 g/dl; two patients complained fatigue in absence of anemia. CONCLUSION: Sofosbuvir based regimens are safe and highly effective in treatment of HCV recurrence after LDLT.

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Hepatitis C Virus (HCV)-related Mixed Cryoglobulinemia (MC) is a unique condition with complex pathogenesis that involves HCV antigen-driven B-lymphocyte clonal proliferation and mutagenesis. Clinical spectrum of MC ranges from asymptomatic state to clinically-apparent vasculitis involving multiple organs. In the era of Direct-Acting Antiviral (DAA) therapy, patients with HCV-related MC achieve high rates of viral clearance that is commonly accompanied by an improvement in clinical symptoms as well as immunological profiles. Rituximab, either alone or in combination with DAA, has also been shown to be effective. Nevertheless, there have been limited and somewhat conflicting data, particularly over the long-term, regarding the rate and degree of clinical response of MC following DAA therapy. It appears that we have come quite a long way in the last decade with this condition. As with non-MC related HCV, undoubtedly long term outcome data will be forthcoming over the next few years. As we move forward successful therapy of HCV is not likely to be a challenge in contrast to access to therapy.

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AIM: To assess the clinical profile of 80 chronic hepatitis C patients in a tertiary health care center in Northern India and also to study the efficacy and tolerability of pegylated interferon (Peg-IFN) α 2b and ribavirin therapy in a cohort of chronic hepatitis C patients. METHODS: Thirty subjects with chronic hepatitis C (CH-C) with genotypes 2 and 3 received Peg-IFN α 2b 1.5 µg/kg subcutaneously weekly plus daily ribavirin 800 mg for 24 weeks .Subjects with genotype 1 infection received therapy for 48 weeks with ribavirin 1000 mg/day and Peg-IFN α 2b dose remained the same. The primary end point was the sustained viral response (SVR). Drug dosage was modified or temporarily discontinued if anemia or bone marrow suppression developed. RESULTS: The clinical profile of chronic hepatitis C infected patients showed decompensated cirrhosis in the more elderly patients. Genotype 3 was the commonest genotype and was seen in 21 (70%) patients. The mean baseline HCV RNA was high. SVR was achieved less commonly with genotype 1 than with genotype 2/3. Patients who became negative for HCV RNA at 4-weeks (rapid virological response or RVR) and 12 weeks (early virological response or EVR) of treatment showed significantly higher sustained virological response (SVR) rates. Similarly, patients who showed normalization of ALT level at 4-weeks and 12-weeks of treatment showed significant high rate of SVR. Overall treatment was well tolerated. CONCLUSION: In our region, CHC subjects have high viral load and genotype 3 being the most common. Treatment with Peg-IFN α 2b and ribavirin is effective and well tolerated. Genotype 1 was more resistant to the treatment. Patients who achieved RVR and EVR are more likely to achieve SVR. Although the numbers of patients in this study was small, considering the paucity of data of treatment from India, the data is relevant.