Newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with DAAs: A prospective population study.

BACKGROUND & AIMS: Direct-acting antiviral agents (DAAs) are safe and effective in patients with hepatitis C. Conflicting data were reported on the risk of hepatocellular carcinoma (HCC) during/after therapy with DAAs. The aim of this study was to evaluate the incidence of newly diagnosed HCC and associated risk factors in patients with advanced hepatitis C treated with DAAs. METHODS: The study is based on the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C receiving DAAs in the Veneto region of Italy. The inclusion criteria were: fibrosis stage ≥F3. The exclusion criteria were: Child-Turcotte-Pugh (CTP)-C, liver transplantation before DAAs, history or presence of HCC, follow-up <4 weeks after starting DAAs. A total of 3,917 out of 4,234 consecutive patients were included, with a mean follow-up of 536.2 ±â€¯197.6 days. RESULTS: Overall, HCC was diagnosed in 55 patients. During the first year, HCC incidence was 0.46% (95% CI 0.12-1.17) in F3, 1.49% (1.03-2.08) in CTP-A and 3.61% (1.86-6.31) in CTP-B cirrhotics; in the second year, HCC incidences were 0%, 0.2%, and 0.69%, respectively. By multivariate analysis, HCC was significantly associated with an aspartate aminotransferase to platelet ratio ≥2.5 (hazard ratio [HR] 2.03; 95% CI 1.14-3.61; p = 0.016) and hepatitis B virus infection (HR 3.99; 1.24-12.91; p = 0.021). Failure to achieve a sustained virological response was strongly associated with development of HCC (HR 9.09; 5.2-16.1; p = 0.0001). A total of 29% of patients with HCC had an aggressive tumor, often seen in the early phase of treatment. CONCLUSIONS: These data, obtained in a large, prospective, population-based study, indicate that in patients with advanced hepatitis C receiving DAAs, the risk of "de novo" hepatocarcinoma during the first year is not higher, and might be lower, than that of untreated patients. The risk further declines thereafter. Early hepatocarcinoma appearance may reflect pre-existing, microscopic, undetectable tumors. LAY SUMMARY: Hepatocellular carcinoma is one of the complications of hepatitis C related cirrhosis. Treating patients with advanced hepatitis C with the new interferon-free direct-acting antiviral agents has been associated with improvement in liver function and survival, while more conflicting data have been reported regarding the risk of hepatocellular carcinoma. We report the results of a prospective population study on the incidence of newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with direct-acting antiviral agents, clearly indicating that the residual hepatocellular carcinoma risk is reduced and declines progressively with time after a sustained virological response. Development of a liver tumor during/after therapy was associated with known risk factors and with virological failure.

Therapy of chronic hepatitis C with PEG-IFN α-2b plus ribavirin in patients with genotype 2 or 3: 16 versus 24 weeks, clinical outcome and direct cost analyses.

INTRODUCTION: Short antiviral therapy has been proposed for patients with chronic hepatitis C, easy genotypes, low fibrosis score, low viral load at baseline, and rapid virological response (RVR). However, this approach is not completely accepted. OBJECTIVES: The aims of this study were (a) to evaluate the sustained virological response (SVR) in noncirrhotic patients with genotype 2 or 3, achieving an RVR, randomized to receive pegylated-interferon (IFN) α-2b plus ribavirin for either 16 or 24 weeks and (b) to carry out direct cost analysis comparing patients treated for 16 versus 24 weeks. RESULTS: Of the 142 initially evaluated patients, 130 were enrolled according to the selection criteria, but independent of the viral load. According to the intention-to-treat analysis, SVR was achieved in 104 patients (80%). Logistic regression analysis showed that RVR (P<0.001) and genotype 2 (P<0.03) were the most important factors independently associated with SVR. Among patients with RVR, SVR was comparable between patients treated for 16 weeks and those treated for 24 weeks (86.2 vs. 89.7%, P=NS). The mean direct costs were €4003.7 for patients treated for 16 weeks and €5676.7 for those treated for 24 weeks, with a 30% difference between the two arms. CONCLUSION: In patients achieving an RVR, a 16-week treatment with pegylated-interferon plus ribavirin was comparable to a 24-week treatment. Short treatment in patients with RVR allows us to save 30% of the direct costs, independent of the viral load at baseline.

Impact of occult HBV infection in HIV/HCV co-infected patients: HBV-DNA detection in liver specimens and in serum samples.

Prevalence and impact of occult HBV infection in HIV positive patients is controversial. The aims of this study were to determine the prevalence of occult HBV infection and its impact on histological and virological parameters. 52 HIV/HCV (but HBsAg-negative) co-infected patients, 29 HBsAg and anti-HCV negative chronic hepatitis, and 20 HBsAg positive chronic hepatitis controls were studied. DNA was extracted from frozen biopsies and amplified with primers for S, C and X regions, and for (ccc) HBV-DNA. Sera were tested for HBV-DNA with two quantitative assays (Cobas Amplicor HBV Monitor, and the real-time COBAS (r) Taqman HBV Test, Roche Diagnostics, UK). Occult HBV infection was detected in 7 (13.4%) liver biopsies of the study group, and in none case of the non viral chronic hepatitis group (p=0.04). All serum samples were HBV-DNA negative with Cobas Amplicor HBV monitor assay, while 3 cases were found positive with real time PCR. Statistical analysis didn't show any impact of occult HBV infection on liver histology, CD4+ cells count, HIV and HCV load, and ALT levels. Occult B infection is relatively frequent in HIV/HCV co-infected patients, and is underestimated by common HBV-DNA serological assays. However, it doesn't seem to exert a relevant impact.

Alcohol is an important co-factor for both steatosis and fibrosis in Northern Italian patients with chronic hepatitis C.

BACKGROUND/AIMS: Steatosis in patients with chronic hepatitis C (CHC) may be the result of both viral and host factors. To evaluate: (1) the relationship between steatosis and either host or viral factors; (2) the correlation between steatosis and fibrosis in patients with CHC. METHODS: A consecutive series of 349 patients were evaluated for steatosis. At liver biopsy, patients were tested for virological, and laboratory analysis and questioned for alcohol consumption. RESULTS: Logistic regression analysis demonstrated that steatosis was independently associated with genotype 3a (odds ratio, OR 3.5), alcohol intake at the time of biopsy (OR 2.6) and age >35 years (OR 2.7). In multivariate analysis the presence of fibrosis was associated with past alcohol abuse (OR 3.7), and age older than 44 years (OR 2.2). Overall, a weak correlation was found between grade of steatosis and fibrosis score (r=0.861, P=0.05), which disappeared excluding patients without past or current alcohol intake. A direct correlation emerged between grade of steatosis and both 'grading' and 'staging' only in patients with genotypes other than 3a. CONCLUSIONS: Genotype 3a is the main risk factor for steatosis in patients with CHC. The grade of steatosis correlated with both grading and staging only in patients with genotypes other than 3a and this relationship is strictly linked to alcohol consumption.

A randomized trial of consensus interferon in combination with ribavirin as initial treatment for chronic hepatitis C.

BACKGROUND/AIMS: The aim of the present, open-labeled, randomized study was to determine the efficacy and safety of different doses of consensus interferon plus ribavirin in the initial treatment of chronic hepatitis C. METHODS: One hundred and one genotype 2/3 patients were randomized to receive 9 mcg (group A, n=48) or 18 mcg (group B, n=53) of consensus interferon thrice weekly plus ribavirin (1000/1200 mg/daily) for 24 weeks and 92 genotype 1 patients to receive 9 mcg (group C, n=47) or 18 mcg (group D, n=45) of consensus interferon plus ribavirin for 48 weeks. RESULTS: In an intention-to-treat analysis, the sustained virologic response at 24-week follow-up was 69% and 66% for group A and B (P=0.77) and 40% and 36% for group C and D (P=0.63). The overall sustained response was 67% and 38% in patients with genotype 2/3 and 1, respectively. Among genotype 1 patients the sustained virologic response was 39% and 41% for high or low baseline viremia levels. CONCLUSIONS: Higher consensus interferon dose does not increase sustained virologic response. Naive genotype 1 patients may achieve significant response rate of approximately 40% if treated with 9 mcg of consensus interferon plus ribavirin for 48 weeks.