Real‐world impact following initiation of interferon‐free hepatitis C regimens on liver‐related outcomes and all‐cause mortality among patients with compensated cirrhosis

Few studies have investigated clinical outcomes among patients with cirrhosis who were treated with interferon (IFN)‐free direct‐acting antiviral (DAA). We aimed to quantify treatment impact on first decompensated cirrhosis hospital admission, first hepatocellular carcinoma (HCC) admission, liver‐related mortality and all‐cause mortality among a national cohort of cirrhotic patients. Through record linkage between Scotland's HCV Clinical Database and inpatient/day‐case hospitalization and deaths records, a study population comprising chronic HCV‐infected patients with compensated cirrhosis and initiated on IFN‐free DAA between 1 March 2013 and 31 March 2018 was analysed. Cox regression evaluated the association of each clinical outcome with time‐dependent treatment status (on treatment, responder, nonresponder or noncompliant), adjusting for patient factors including Child‐Pugh class. Among the study population (n = 1073) involving 1809 years of follow‐up, 75 (7.0%) died (39 from liver‐related causes), 47 progressed to decompensated cirrhosis, and 28 developed HCC. Compared with nonresponders, treatment response (96% among those attending their 12 weeks post‐treatment SVR test) was associated with a reduced relative risk of decompensated cirrhosis (hazard ratio [HR] = 0.14; 95% CI: 0.05‐0.39), HCC (HR = 0.17; 95% CI: 0.04‐0.79), liver‐related death (HR = 0.13; 95% CI: 0.05‐0.34) and all‐cause mortality (HR = 0.30; 95% CI: 0.12‐0.76). Compared with responders, noncompliant patients had an increased risk of liver‐related (HR = 6.73; 95% CI: 2.99‐15.1) and all‐cause (HR = 5.45; 95% CI: 3.07‐9.68) mortality. For HCV patients with cirrhosis, a treatment response was associated with a lower risk of severe liver complications and improved survival. Our findings suggest additional effort is warranted to address the higher mortality among the minority of cirrhotic patients who do not comply with DAA treatment or associated RNA testing.     

Temporal trend and risk determinants of hepatocellular carcinoma in chronic hepatitis B patients on entecavir or tenofovir

This study aimed to elucidate the temporal change and determinants for the risk of HCC in patients with chronic hepatitis B continuously receiving NUC. Through analysis of the national healthcare database in Taiwan, we screened a total of 65 426 infected patients receiving entecavir or tenofovir for at least 3 months and excluded those with lamivudine, adefovir or telbivudine exposure, malignancy, end‐stage renal failure or a diagnosis of HCC within 3 months of starting treatment. Eligible patients (N = 27 820) were followed until HCC occurrence, completion of the allowed 3‐year regimen or 31 December 2013. During a median follow‐up of 25.1 (12.1‐35.6) months, 802 patients developed HCC, with 1‐, 2‐ and 3‐year cumulative incidence of 1.82% (95% CI, 1.66‐1.99%), 3.05% (95% CI, 2.82‐3.28%) and 4.06% (95% CI, 3.77‐4.36%), respectively. HCC annual incidence decreased with an adjusted IRR of 0.73 (95% CI, 0.66‐0.80) per yearly interval and was associated with cirrhosis (IRR, 10.07; 95% CI, 6.00‐16.90 in age <40 years; 4.69; 95% CI, 3.94‐5.59 in age ≧40 years), age (IRR, 3.38; 95% CI, 2.10‐5.47 for 40‐50 years; 6.92; 95% CI, 4.27‐11.21 for 50‐60 years; 12.50; 95% CI, 7.71‐20.25 for ≧60 years; <40 years as reference), male sex (IRR, 1.71; 95% CI, 1.44‐2.04), HCV coinfection (IRR, 1.27; 95% CI, 1.02‐1.58) and diabetes (IRR, 1.24; 95% CI, 1.05‐1.45). In conclusion, the risk of HCC in patients with chronic hepatitis B receiving entecavir or tenofovir declines over time and is determined by cirrhosis, age, male sex, HCV coinfection and diabetes.     

Outcome of hepatitis B and C virus‐associated hepatocellular carcinoma occurring after renal transplantation

Kidney transplant recipients (KTR) are subjected to immunosuppressive therapy that can enhance hepatitis B and C virus replication, leading to cirrhosis and hepatocellular carcinoma (HCC). The aim of this study was to assess the prevalence and outcome of HCC in KTR. Case‐control study. Patients with chronic HBV and/or HCV infection who underwent kidney transplantation between 1976 and 2011 and subsequently developed HCC were compared to a control group of patients with chronic HBV and/or HCV infection, matched for gender and age at HCC diagnosis, who did not receive kidney transplantation. Among 2944 KTR, 330 had hepatitis B and/or C. Fourteen developed HCC, a period prevalence of 4.2%. Age at HCC diagnosis was 52.6 ± 6.5 years (53.5 ± 5.7 in controls, P=.76). Time between transplantation and HCC diagnosis was 16.7 ± 2.7 years. Six HCCs were related to HBV, six to HCV and two to co‐infection with HBV and HCV. Immunosuppressive therapy was comparable in HBV, HCV and HBV+HCV patients. At diagnosis, 71% of patients met Milan criteria (65% in the control group, P=.4). Alpha‐fetoprotein levels, tumour characteristics and treatment modalities were comparable between both groups. Patient survival 2 years after HCC diagnosis was 28% in KTR, compared to 68% in controls (P=.024). Survival after HCC diagnosis is significantly worse in KTR compared to nontransplanted patients with HBV and/or HCV. Prevention is crucial and should be based on viral eradication/suppression before or after transplantation.     

B.A.R.C.O.S. (Brazilian Argentine Hepatitis C Collaborative Observational Study): Effectiveness and clinical outcomes of HCV treatment with daclatasvir and sofosbuvir with or without ribavirin

Real‐world data evaluating the effectiveness of direct‐acting antivirals (DAAs) in hepatitis C virus (HCV) treatment have been reported from different regions. Our aim was to evaluate the effectiveness and clinical outcomes of daclatasvir (DCV) and sofosbuvir (SOF) ± ribavirin (RBV) in a prospective multicentre cohort study including patients from Argentina and Brazil who received DCV/SOF ± RBV for 12 or 24 weeks from 2015 to 2018. Multivariable logistic regression models were carried out to identify factors associated with failure to achieve sustained virologic response (SVR) as a primary end point, and to death, decompensation, hepatocellular carcinoma (HCC) or liver transplantation (LT) as a composite secondary end point. From a total of 1517 patients treated with DCV/SOF, 906 completed 12 weeks post‐treatment evaluation and were included in the analysis. Overall SVR12 rate was 96.1% (95% CI: 94.6%‐97.2%), and 95% (95% CI: 92.8%‐96.6%) in patients with cirrhosis. LT recipients and presence of cirrhosis were independently associated with failure to achieve SVR. During post‐SVR12 follow‐up, cumulative incidence of the secondary end point was 2.4% (95% CI: 1.5%‐3.6%); two patients died from nonliver‐related causes and two from HCC, five underwent LT, 12 developed HCC and 17 patients developed hepatic decompensation. Independent variables associated with these composite secondary end points were prior to HCV treatment and presence of cirrhosis. In conclusion, although the high pangenotypic effectiveness of DCV/SOF ± RBV was confirmed in our real‐life cohort, patients with compensated and decompensated cirrhosis showed higher risk of non‐SVR and complication appearance during treatment or after achieving SVR.     

Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study

This study evaluates trends in hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct‐acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995‐2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001‐2012/2013/2014, respectively) and mortality (1995‐2013/2014/2015, respectively). Age‐standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid‐2000s, HCC diagnosis numbers increased in all jurisdictions. Age‐standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001‐2006 and 2007‐2011) and NSW (0.9 years in 2001‐2006 and 2007‐2013) and improved in Scotland (0.7 years in 2001‐2006 to 1.5 years in 2007‐2014). Across the settings, HCC burden increased, individual‐level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon‐based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.     

Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic HCV infection and psychiatric disorders: An integrated analysis

Although direct‐acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection are highly efficacious and safe, treatment initiation is often limited in patients with neuropsychiatric disorders due to concerns over reduced treatment adherence and drug–drug interactions. Here, we report adherence, efficacy, safety and patient‐reported outcomes (PROs) from an integrated analysis of registrational studies using the pangenotypic DAA regimen of glecaprevir and pibrentasvir (G/P). Patients with chronic HCV genotypes 1‐6 infection with compensated liver disease (with or without cirrhosis) receiving G/P for 8, 12 or 16 weeks were included in this analysis. Patients were classified as having a psychiatric disorder based on medical history and/or co‐medications. Primary analyses assessed treatment adherence, efficacy (sustained virologic response at post‐treatment week 12; SVR12), safety and PROs. Among 2522 patients receiving G/P, 789 (31%) had a psychiatric disorder with the most common diagnoses being depression (64%; 506/789) and anxiety disorders (27%; 216/789). Treatment adherence was comparably high (>95%) in patients with and without psychiatric disorders. SVR12 rates were 97.3% (768/789; 95% CI = 96.2‐98.5) and 97.5% (1689/1733; 95% CI = 96.7‐98.2) in patients with and without psychiatric disorders, respectively. Among patients with psychiatric disorders, SVR12 rates remained >96% by individual psychiatric diagnoses and co‐medication classes. Overall, most adverse events (AEs) were mild‐to‐moderate in severity with serious AEs and AEs leading to G/P discontinuation occurring at similarly low rates in both patient populations. In conclusion, G/P treatment was highly efficacious, well‐tolerated and demonstrated high adherence rates in patients with chronic HCV infection and psychiatric disorders.     

The number needed to treat to prevent mortality and cirrhosis‐related complications among patients with cirrhosis and HCV genotype 1 infection

Cirrhotic patients with chronic hepatitis C virus (HCV) infection remain at risk for complications following sustained virological response (SVR). Therefore, we aimed to evaluate treatment efficacy with the number needed to treat (NNT) to prevent clinical endpoints. Mortality and cirrhosis‐related morbidity were assessed in an international multicentre cohort of consecutively treated patients with HCV genotype 1 infection and cirrhosis. The NNT to prevent death or clinical disease progression (any cirrhosis‐related event or death) in one patient was determined with the adjusted (event‐free) survival among patients without SVR and adjusted hazard ratio of SVR. Overall, 248 patients were followed for a median of 8.3 (IQR 6.2–11.1) years. Fifty‐nine (24%) patients attained SVR. Among patients without SVR, the adjusted 5‐year survival and event‐free survival were 94.4% and 80.0%, respectively. SVR was associated with reduced all‐cause mortality (HR 0.15, 95% CI 0.05–0.48, P = 0.002) and clinical disease progression (HR 0.16, 95% CI 0.07–0.36, P < 0.001). The NNT to prevent one death in 5 years declined from 1052 (95% CI 937–1755) at 2% SVR (interferon monotherapy) to 61 (95% CI 54–101) at 35% SVR (peginterferon and ribavirin). At 50% SVR, which might be expected with triple therapy, the estimated NNT was 43 (95% CI 38–71). The NNT to prevent clinical disease progression in one patient in 5 years was 302 (95% CI 271–407), 18 (95% CI 16–24) and 13 (95% CI 11–17) at 2%, 35% and 50% SVR, respectively. In conclusion, the NNT to prevent clinical endpoints among cirrhotic patients with HCV genotype 1 has declined enormously with the improvement of antiviral therapy.     

Impact of previous hepatitis B infection on the clinical outcomes from chronic hepatitis C? A population‐level analysis

Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is associated with adverse liver outcomes. The clinical impact of previous HBV infection on liver disease in HCV infection is unknown. We aimed at determining any association of previous HBV infection with liver outcomes using antibodies to the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The Scottish Hepatitis C Clinical Database containing data for all patients attending HCV clinics in participating health boards was linked to the HBV diagnostic registry and mortality data from Information Services Division, Scotland. Survival analyses with competing risks were constructed for time from the first appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver‐related mortality. Records of 8513 chronic HCV patients were included in the analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause‐specific proportional hazards models showed previous HBV infection (HBcAb positive and HBsAg negative) significantly increased the risks of decompensated cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01‐1.65) and HCC (HR: 1.64, 95% CI: 1.09‐2.49), but not liver‐related death (HR: 1.02, 95% CI: 0.80‐1.30). This is the largest study to date showing an association between previous HBV infection and certain adverse liver outcomes in HCV infection. Our analyses add significantly to evidence which suggests that HBV infection adversely affects liver health despite apparent clearance. This has important implications for HBV vaccination policy and indications for prioritization of HCV therapy.     

Hepatitis C Virus-Associated Primary Hepatocellular Carcinoma in Non-cirrhotic Patients

Background

There is limited literature on hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection in the absence of cirrhosis.

Aims

To investigate the relationship between HCV and HCC in the absence of cirrhosis and to characterize patients with HCV infection presenting with HCC in the absence of cirrhosis.

Methods

We identified all adult patients with histological confirmation of HCC between 1994 and 2007 (404 patients). A case?Ccontrol design (four controls for each case with non-cirrhotic HCC) was chosen to compare characteristics and survival of HCV in HCC patients without (cases) and with (controls) cirrhosis. Conditional logistic regression analysis was used to identify factors independently associated with HCV in non-cirrhotic HCC.

Results

Eighty-seven patients with non-cirrhotic HCC were identified, six (7?%) had HCV infection in comparison with 107 of 317 (55.7?%) with cirrhotic HCC (P?<?0.001). Compared with the HCV-associated HCC cirrhotic group, patients with HCV-associated HCC in the absence of cirrhosis were more likely to present with a single nodule (100 vs. 66.7?%), larger nodule size (>5?cm) (100 vs. 16.7?%), and macrovascular invasion (66.7 vs. 17.4?%) at time of diagnosis. Four of six patients with HCV-associated HCC in the absence of cirrhosis where alive at three years (all had resection), which was better survival than for HCC arising in cirrhotic livers of HCV-infected individuals (66.7 vs. 39.1?%).

Conclusion

We found that HCV is responsible for a small minority of non-cirrhotic HCC cases representing an uncommon and poorly defined subgroup of HCC.     

Hepatocellular carcinoma incidence post direct-acting antivirals in hepatitis C-related advanced fibrosis/cirrhosis patients in Australia

BackgroundDespite efficacy in HCV eradication, direct-acting antiviral (DAA) therapy has raised controversies around their impact on hepatocellular carcinoma (HCC) incidence. Herein we reported the first Australian data on HCC incidence in DAA-treated HCV patients with advanced fibrosis/cirrhosis.MethodsWe conducted a retrospective single center study of DAA-treated HCV patients with advanced fibrosis/cirrhosis from April 2015 to December 2017. Patients with prior HCC were included if they had complete response to HCC treatment.ResultsAmong 138 patients who completed DAA therapy, 133 (96.4%) achieved sustained virologic response (median follow-up 23.8 months). Ten had prior HCC and 5/10 (50.0%) developed recurrence, while de novo HCC developed in 7/128 (5.5%). Median time from DAA to HCC diagnosis was 34 weeks in recurrent HCC vs. de novo 52 weeks (P = 0.159). In patients with prior HCC, those with recurrence (vs. without) had shorter median time between last HCC treatment and DAA (12 vs. 164 weeks, P < 0.001). On bivariate analysis, failed sustained virologic response at 12 weeks (SVR12) (P = 0.011), platelets (P = 0.005), model for end-stage liver disease (MELD) score (P = 0.029), alpha fetoprotein (AFP) (P = 0.013), and prior HCC (P < 0.001) were associated with HCC post-DAA. On multivariate analysis, significant factors were prior HCC (OR = 4.80; 95% CI: 1.47–48.50; P = 0.010), failed SVR12 (OR = 2.83; 95% CI: 1.71–16.30; P = 0.016) and platelets (OR = 0.97; 95% CI: 0.95–0.99; P = 0.009).ConclusionsOur study demonstrates a high incidence of recurrent HCC in HCV patients with advanced fibrosis/cirrhosis treated with DAA. Factors associated with HCC development post-DAA were more advanced liver disease, failed SVR12 and prior HCC, with higher rates of recurrence in those who started DAA earlier.     

Hepatitis C virus genotype 3 was associated with the development of hepatocellular carcinoma in Korea

Although hepatitis C virus (HCV) genotype 3 infection is thought to be an important risk factor for hepatocellular carcinoma (HCC), current evidence is limited because only a few Western studies have evaluated the occurrence of HCC in patients with HCV genotype 3 infection. We evaluated the impact of genotype 3 and non‐3 on HCC incidence and on disease progression in chronic HCV patients; this is the first study reporting such findings in an Asian population. We performed a retrospective cohort study using the data of 1448 consecutive chronic HCV patients evaluated at three centres in Korea between January 2005 and December 2016. Of these, 604, 675 and 169 had genotype 1, genotype 2 and genotype 3 HCV infections, respectively. Over a mean follow‐up period of 53.2 months, 75 and 143 patients of all the patients developed HCC and experienced disease progression, respectively. The incidences of HCC were 1.10, 0.92 and 2.50 per 100 person‐years, and those of disease progression were 1.95, 1.62 and 6.72 per 100 person‐years for HCV genotypes 1, 2 and 3, respectively. In multivariate Cox regression analysis, genotype 3 was associated with an increased risk of HCC (hazard ratio [HR] = 4.26, 95% confidence interval [CI] = 2.02‐8.97) and an increased risk of disease progression (HR = 4.88, 95%; CI = 2.94‐8.08). Our study proposes that HCV genotype 3 is an independent risk factor for HCC and disease progression in chronic HCV patients.     

Minor Role of Hepatitis B and C Virus Infection in the Etiology of Hepatocellular Carcinoma in a Low-Endemic Area

Background: The etiologic role of hepatitis B (HBV) and C virus (HCV) for hepatocellular carcinoma (HCC) in a low-endemicity area is obscure. Methods: Patients suspected of having primary liver cancer (PLC) in Göteborg, Sweden (n = 113), were tested serologically for HBV surface antigen and antibodies to HBV surface and core antigens. The presence of HBV surface and core antigens in cancer and non-neoplastic liver tissue in HCC cases was investigated immunohistochemically. Antibodies to HCV were tested by third-generation tests. The prevalence of HBV and HCV infection was compared in 73 patients with HCC and 32 patients with a final diagnosis other than PLC. Results: No patient had signs of chronic HBV infection. Seven of 64 (11%) HCC patients were anti-HCV-positive, compared with 1 of 31 (3%) without PLC. All seven patients with HCC and HCV infection had liver cirrhosis, and two were alcoholics. Alcoholism was judged the commonest (42%) cause of cirrhosis. Conclusion: Contrary to areas with a high incidence of HCC, chronic viral hepatitis, particularly HBV, seems to play a minor etiologic role for HCC in Sweden compared with alcohol-related cirrhosis.     

Hepatitis C infection and hepatocellular carcinoma in liver transplantation: a 20-year experience

Background: Hepatitis C infection (HCV) and hepatocellular carcinoma (HCC), the two main causes of liver transplantation (LT), have reduced survival post-LT. The impact of HCV, HCC and their coexistence on post-LT survival were assessed.Methodology: All 601 LT patients from 1992 to 2011 were reviewed. Those deceased within 30 days (n = 69) and re-transplants (n = 49) were excluded. Recipients were divided into four groups: (a) HCC-/HCV-(n = 252) (b) HCC+/HCV-(n = 58), (c) HCC-/HCV+ (n = 106) and (d) HCC+/HCV+ (n = 67). Demographics, the donor risk index (DRI), Model for End-Stage Liver Disease (MELD) score, survival, complications and tumour characteristics were collected. Statistical analysis included anova, chi-square, Fisher''s exact tests and Cox and Kaplan–Meier for overall survival.Results: Groups were comparable with regards to baseline characteristics, but HCC patients were older. After adjusting for age, MELD, gender and the donor risk index (DRI), survival was lower in the HCC+/HCV+ group (59.5% at 5 yrs) and the hazard ratio (HR) was 1.90 [95% confidence interval (CI),1.24–2.95, P = 0.003] and 1.45 (95% CI, 0.99–2.12, P = 0.054) for HCC-/HCV+. HCC survival was similar to controls (HR 1.18, 95% CI, 0.71–1.93, P = 0.508). HCC+/HCV-patients exceeded the Milan criteria (50% versus 31%, P < 0.04) and had more micro-vascular invasion (37.5% versus 20.6%, P = 0.042). HCC+/HCV+ versus HCC+/HCV-survival remained lower (HR 1.94, 95% CI, 1.06–3.81, P = 0.041) after correcting for tumour characteristics and treatment.Conclusion: HCV patients had lower survival post-LT. HCC alone had no impact on survival. Patient survival decreased in the HCC+/HCV+ group and this appears to be as a consequence of HCV recurrence.     

Should we continue surveillance for hepatocellular carcinoma and gastroesophageal varices in patients with cirrhosis and cured HCV infection?

Hepatocellular carcinoma (HCC) and variceal bleeding are among the most common causes of liver-related mortality in patients with hepatitis C virus (HCV)-induced cirrhosis. Current guidelines recommend HCC and gastroesophageal varices (GEV) surveillance in patients with HCV infection and cirrhosis. However, since the recent introduction of direct-acting antivirals, most patients with cirrhosis are now cured of their chronic HCV infection. As virological cure is considered to substantially reduce the risk of cirrhosis-related complications, this review discusses the current literature concerning the surveillance of HCC and GEV in patients with HCV-induced cirrhosis with a focus on the setting following sustained virological response.     

Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients

OBJECTIVES: The aim of this study was to compare the prognosis of patients with hepatitis B surface antigen (HBsAg) positive and those with antibody to hepatitis C (anti-HCV) positive cirrhosis. METHODS: This was a retrospective cohort study of 297 untreated Western European patients with compensated viral cirrhosis (Child class A; 161 patients with hepatitis type B and 136 with type C) who were followed for a median period of 6.6 yr. RESULTS: At diagnosis, median age was lower (48 vs 58 yr, respectively) in HBsAg-positive cirrhotic patients. The Kaplan-Meier 5-yr probability of hepatocellular carcinoma (HCC) was 9% and 10% in HBsAg and anti-HCV-positive cirrhotic patients, respectively; the corresponding figures for decompensation unrelated to HCC were 16% and 28% and for survival were 86% and 84%, respectively. After adjustment for clinical and serological differences at baseline, the relative risk (95% CI) for HCC, decompensation and mortality was 1.53 (CI = 0.81-2.89), 0.59 (CI = 0.37-0.94), and 1.44 (CI = 0.85-2.46) respectively, in HBsAg-positive patients compared with anti-HCV-positive cirrhotic patients. Among HBsAg-positive cirrhotic patients, the relative risk for HCC, decompensation, and mortality was 0.89 (CI = 0.30-2.63), 4.05 (CI = 1.09-15.1), and 5.9 (CI = 1.64-21.3), respectively, in HBV-DNA positive (HBeAg positive or negative) compared with HBV-DNA negative (HBeAg negative) patients at entry. CONCLUSIONS: Patients with HBV infection may present with cirrhosis about 10 yr earlier than those with HCV infection. HCV infection tends to be associated with a higher risk of decompensation, but these data should take into consideration the heterogeneity of HBV-related cirrhosis in terms of viremia levels and risk of hepatic failure. Survival shows no significant differences according to HBV or HCV etiology in Western European cirrhotic patients.     

Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: a seventeen-year prospective cohort study

Hepatocellular carcinoma (HCC) is the most frequent cause of death in patients with hepatitis C virus (HCV)-induced cirrhosis. Despite a number of studies in different populations worldwide suggesting an association between HCV genotype 1 and the risk of HCC, no consensus has emerged yet on this matter, which is still controversial. In an attempt to clarify this issue, a prospective study of 163 consecutive HCV-positive patients with cirrhosis, who were enrolled between January 1989 and December 1990, was carried out. HCC occurrence was detected by ultrasound surveillance every 6 months. Independent predictors of HCC were assessed with a Cox regression analysis. After a median follow-up of 10.7 years, 44 [4.26/100/year, confidence interval (CI) = 3.11-5.68/100/year] of 104 patients infected with genotype 1b developed HCC versus 10 (1.69/100/year, CI = 0.82-3.09/100/year) of 52 patients infected with genotype 2a/c (P = 0.0001). Multivariate analysis showed that HCV genotype 1b was independently associated with HCC development [hazard ratio (HR) = 3.02, 95% CI = 1.40-6.53]. Other predictors of HCC were esophageal varices (HR = 2.15, 95% CI = 1.03-4.47), male gender (HR = 2.12, 95% CI = 1.10-4.11), and age over 60 years (HR = 5.96, 95% CI = 1.23-28.8). Conclusion: HCV genotype 1b is associated with a statistically significant higher risk of developing HCC. Patients with cirrhosis that are infected with this genotype require more intensive surveillance for the early detection and aggressive management of neoplasia.     

Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection.

Non-insulin-dependent diabetes mellitus (NIDDM) may be associated with chronic hepatitis C virus (HCV) infection. This was studied further in two parts. First, 1,151 patients with HCV-related cirrhosis and 181 patients with hepatitis B virus (HBV)-related cirrhosis, well matched for age, sex, and severity of cirrhosis, were reviewed retrospectively. The prevalence of diabetes mellitus was higher in HCV-related cirrhosis (23.6%) than in HBV-related cirrhosis (9.4%; odds ratio [OR], 2.78; 95% confidence interval [CI], 1.6-4.79; P =.0002). The prevalence of diabetes mellitus was associated closely with the Child-Pugh score (OR, 3.83; 95% CI, 2. 38-6.17; P <.0001) and increasing age (OR, 1.02; 95% CI, 1.00-1.03; P =.0117). Second, 235 patients with biopsy confirmed chronic HBV or HCV underwent an oral glucose tolerance test. Only 1 of 70 patients with chronic viral hepatitis without cirrhosis was diabetic. However, 31 of 127 patients with HCV-related cirrhosis (24.4%) were diabetic compared with 3 of 38 patients with HBV-related cirrhosis (7.9%, P =.0477). The major variables associated with NIDDM were cirrhosis (OR, 14.39; 95% CI, 1.91-108; P =.0096) and male sex (OR, 4.64; 95% CI, 1. 32-16.18; P =.0161). Fasting insulin levels in 30 patients with HCV-related cirrhosis and diabetes mellitus were elevated significantly, which was consistent with insulin resistance. However, acute insulin responsiveness was reduced in all patients with HCV infection and diabetes suggesting concomitant B-cell dysfunction. This study confirms an association between HCV and NIDDM.     

Sofosbuvir plus ribavirin in treatment‐naïve patients with chronic hepatitis C virus genotype 1 or 3 infection in India

Until 2014, pegylated interferon plus ribavirin was the recommended standard of care for the treatment of chronic hepatitis C virus (HCV) infection in India. This open‐label phase 3b study, conducted across 14 sites in India between 31 March 2014 and 30 November 2015, evaluated the efficacy and safety of sofosbuvir plus ribavirin therapy among treatment‐naïve patients with chronic genotype 1 or 3 HCV infection. A total of 117 patients with genotype 1 or 3 HCV infection were randomized 1:1 to receive sofosbuvir 400 mg and weight‐based ribavirin (1000 or 1200 mg) daily for 16 or 24 weeks. Among those with genotype 1 infection, the primary efficacy endpoint of sustained virologic response at 12 weeks post‐treatment (SVR12) was reported in 90% (95% confidence intervals [CI], 73‐98) and 96% (95% CI, 82‐100) of patients following 16 and 24 weeks of treatment, respectively. For patients with genotype 3 infection, SVR12 rates were 100% (95% CI, 88‐100) and 93% (95% CI, 78‐99) after 16 and 24 weeks of therapy, respectively. Adverse events, most of which were mild or moderate in severity, occurred in 69% and 57% of patients receiving 16 and 24 weeks of treatment, respectively. The most common treatment‐emergent adverse events were asthenia, headache and cough. Only one patient in the 24‐week group discontinued treatment with sofosbuvir during this study. Overall, sofosbuvir plus ribavirin therapy achieved SVR12 rates ≥90% and was well tolerated among treatment‐naïve patients with chronic genotype 1 or 3 HCV infection in India.     

Long-term survival and clinical outcomes following direct-acting antiviral (DAA) treatment in HCV decompensated cirrhosis in Brazil: a real-world study

IntroductionThe outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario.Patients and methodsThis was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method.ResultsOne hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p < 0.001).ConclusionsDecompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.     

Association of interferon lambda-4 rs12979860 polymorphism with hepatocellular carcinoma in patients with chronic hepatitis C infection

BACKGROUND Hepatitis C virus(HCV) infection is a public health concern worldwide.Several factors,including genetic polymorphisms,may be evolved in the progression of HCV infection to liver diseases.Interferon lambdas(IFNLs) modulate the immune response during viral infections.IFNLs induce antiviral activity,interfering in the viral replication by promoting the expression of several genes that regulate immunological functions.The interferon lambda-4(IFNL4) rs12979860 polymorphism,which is characterized by a C to T transition in intron 1,is associated with spontaneous and treatment-induced clearance of HCV infection and may play a role in the development of HCV-associated liver diseases,including hepatocellular carcinoma(HCC).AIM To investigate the association of IFNL4 rs12979860 polymorphism with fibrosis,cirrhosis,and HCC in patients with chronic HCV infection.METHODS This study was comprised of 305 chronic HCV-infected patients(53 fibrosis,154 cirrhosis,and 98 HCC cases).The control group was comprised of 260 HCVnegative healthy individuals.The IFNL4 rs12979860 polymorphism was genotyped using the TaqMan assay.Fibrosis was diagnosed based on liver biopsy findings,while cirrhosis was diagnosed through clinical,laboratory,anatomopathological,and/or imaging data.HCC was diagnosed through imaging tests,tumor,and/or anatomopathological markers.RESULTS The T allele was observed in the three groups of patients(fibrosis,cirrhosis,and HCC) at a significantly higher frequency when compared with the control group(P=0.047,P 0.001,and P=0.01,respectively).Also,genotype frequencies presented significant differences between the control group and cirrhosis patients(P 0.001) as well as HCC patients(P=0.002).The risk analysis was performed using the codominant and dominant T allele models.In the codominant model,it was observed that the CT genotype showed an increased risk of developing cirrhosis in comparison with the CC genotype [odds ratio(OR)=2.53;95%confidence interval(CI):1.55-4.15;P 0.001] as well as with HCC(OR=2.54;95%CI:1.44-4.56;P=0.001).A similar result was observed in the comparison of the TT vs CC genotype between the control group and cirrhosis group(OR=2.88;95 % CI:1.44-5.77;P=0.001) but not for HCC patients.In the dominant T allele model,the CT+TT genotypes were associated with an increased risk for progression to cirrhosis(OR=2.60;95%CI:1.63-4.19;P 0.001) and HCC(OR=2.45;95%CI:1.42-4.31;P=0.001).CONCLUSION These findings suggest that the T allele of IFNL4 rs12979860 polymorphism is associated with the development of cirrhosis and HCC in chronic HCV-infected patients.