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The aim of the study was to evaluate the characteristics of chronic hepatitis B with special reference to the geographical origin of the patients and to the prevalence of HBeAg and viral and non-viral co-factors of liver disease. A cross-sectional multicenter survey was undertaken, which enrolled 1,386 HBsAg chronic carriers observed consecutively in 21 referral centers over a 6-month period. The prevalence of HBeAg in patients was 11%; the presence of HBeAg was associated independently with a younger age and co-infection with HIV. Anti-HDV, anti-HCV, or anti-HIV antibodies were detected in 8.1%, 6.5%, and 2%, respectively. However, among the patients first diagnosed during the study period (incident cases), 14.3% were anti-HDV positive. Seven percent of the patients were immigrants; they were younger than Italian patients and 18% were HBeAg positive; no difference was observed in the prevalence of anti-HDV, anti-HCV, or anti-HIV antibodies. The presence of cirrhosis was associated independently with an age >52 years, the presence of anti-HDV or anti-HCV, alcohol use >4 drinks/day, and a high BMI. The clinical epidemiology of chronic hepatitis B virus (HBV) infection shows a dynamic profile, with the potential for re-emergence of cases with HBeAg or anti-HDV and an emerging impact of metabolic factors on the evolution of liver disease.

Treatment with peginterferon α-2a (PegIFN) for 48 weeks is the standard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus (HBV), but with limited treatment efficacy. A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population.128 HBeAg-negative patients (120 genotype D) were randomised to weekly 180 μg PegIFN for 48 weeks (group A, n=51), 180 μg PegIFN for 48 weeks followed by 135 μg weekly for an additional 48 weeks (group B, n=52) or 180 μg PegIFN plus lamivudine (100 mg/day) for 48 weeks then 135 μg PegIFN for 48 weeks (group C, n=25). Endpoints were alanine aminotransferase normalisation plus HBV DNA3400 IU/ml (primary), HBV DNA2000 IU/ml and HBsAg clearance at 48 weeks after treatment.Forty-eight weeks after treatment, six patients in group A and 13 in group B achieved alanine aminotransferase normalisation plus HBV DNA3400 IU/ml (11.8% vs 25.0%, p=0.08), 6 vs 15 patients had HBV DNA2000 IU/ml (11.8% vs 28.8%, p=0.03), 0 vs 3 achieved HBsAg clearance (0% vs 5.8%, p=0.24) and 0 vs 5 had HBsAg10 IU/ml (0% vs 9.6%, p=0.06). While extended PegIFN treatment was the strongest independent predictor of response, the combination with lamivudine did not improve responses. Discontinuation rates were similar among the groups (19.6%, 23.1%, 32.0%, p=0.81) and were mostly due to PegIFN-related adverse events.In HBeAg-negative genotype D patients with chronic hepatitis B, PegIFN treatment for 96 weeks was well tolerated and the post-treatment virological response improved significantly compared with 48 weeks of treatment.http://ClinicalTrials.gov registration number: NCT01095835.

OBJECTIVES: Antiviral treatment in chronic hepatitis C (CHC) involves ribavirin, a hemolytic agent. We planned a prospective study to evaluate whether drug-induced iron perturbation is clinically relevant as it relates to therapeutic outcome. METHODS: Iron variables were sequentially assessed in 206 CHC patients undergoing antiviral therapy and were correlated with pretreatment iron status and histology, hemolysis, and therapeutic outcome. RESULTS: At week 1 of therapy, serum iron (SI), transferrin saturation (TS), and serum ferritin (SF) increased markedly in all patients. All iron parameters correlated with hemolysis up to week 4; this correlation was lost for SF at later time points. SF rise during treatment was inversely related to baseline SF and iron deposits in hepatic mesenchymal/Kupffer cells. Both baseline SF and mesenchymal iron significantly correlated with fibrosis at multivariate analysis (P=0.015 and 0.008, respectively). Interestingly, baseline SF, despite good specificity (89%), had low sensitivity in predicting siderosis (25%). During therapy, SI, TS, and hemolysis parameters did not correlate with sustained virological response (SVR), whereas SF rise became an independent predictor of therapeutic response: a 2.5-fold increase of SF at week 12 associated with higher likelihood of SVR (odds ratio 1.91, P=0.032). Accordingly, lack of mesenchymal iron deposits at the baseline biopsy correlated with SVR (odds ratio 3.02, P=0.043). CONCLUSIONS: In CHC, SF is a useful marker for assessing disease duration and progression before starting treatment and for predicting therapeutic response while on therapy. SF rise during antiviral therapy is largely independent of hemolysis and likely indicates activation of macrophages in response to antivirals.

Background Pegylated interferon (PEG-IFN) and ribavirin is the most effective treatment for chronic hepatitis C virus (HCV) hepatitis, but the rate of sustained virological response (SVR) remains approximately 50%, and 15-20% of all treated patients have a virological relapse after completing the treatment. Studies on the SVR have failed to discriminate between non-responders and relapsers. Aims To identify the risk factors for relapse among patients with an end-of-treatment response (ETR). Methods We retrospectively analyzed 281 patients consecutively treated with PEG-IFN and ribavirin with a follow- up period of at least 24 weeks. The baseline details collected on each patient included demographic data, histological features, and biochemical profiles. Results Forty-six patients (16.4%) relapsed during the first 6 months of follow-up after discontinuing the therapy. Relapser patients were significantly older, had more steatosis, fibrosis, and showed significantly lower rapid virological response (RVR) rates compared with SVR patients. By logistic regression analysis, only the absence of RVR was found to be significantly associated with relapses in both subgroups of patients with genotypes 1 and 4 (p.004) and those with genotypes 2 and 3 (p.006). Severe fibrosis was also predictive of relapsing disease, but only for genotypes 2 and 3 patients (p.003). During the treatment, serum HCV-RNA decreased more rapidly in patients with SVR compared to non-responder and relapser patients (p.001). Interestingly, relapser patients exhibited an intermediate serum HCV-RNA decay during the first 4 weeks of therapy. Conclusion Among HCV patients treated with PEG-IFN and ribavirin, the absence of RVR was the most important independent predictor of relapse, independent of the HCV genotype. In the subgroup of genotypes 2 and 3 patients, the severity of fibrosis was also an important factor associated with the relapse rate.

In recent years, a worsening outcome of hepatitis C virus (HCV)-positive recipients and a faster progression of recurrent disease to overt cirrhosis have been reported. Our aims were to 1) assess patient survival and development of severe recurrent disease (Ishak fibrosis score > 3) in different transplant years; and 2) model the effects of pre- and post-liver transplantation (LT) variables on the severity of recurrent disease. A multicenter retrospective analysis was conducted on 502 consecutive HCV-positive transplant recipients between January 1990 and December 2002. Protocol liver biopsies were obtained at 1, 3, 5, 7, and 10 yr post-LT ir almost 90% of the patients. All 502 patients were included in the overall survival analysis, while only the 354 patients with a follow-up longer than 1 yr were considered for the analysis of predictors of disease progression. The overall Kaplan-Meier survival rates were 78.7%, 66.3%, and 58.6%, at 12, 60, and 120 months, respectively, and a trend for a better patient survival over the years emerged from all 3 centers. The cumulative probability of developing HCV-related recurrent severe fibrosis (Ishak score 4-6) in the cohort of 354 patients who survived at least 1 yr remained unchanged over the years. Multivariate analysis indicated that older donors (P = 0.0001) and female gender of recipient (P = 0.02) were the 2 major risk factors for the development of severe recurrent disease, while the adoption of antilymphocytic preparations was associated with a less aggressive course (P = 0.03). Two of these prognostic factors, donor age and recipient gender, are easily available before LT and their combination showed an important synergy, such that a female recipient not only had a much higher probability of severe recurrent disease than a male recipient but her risk increased with the increasing age of the donor, reaching almost 100% when the age of the donor was 60 or older. In conclusion, a trend for a better patient survival was observed in more recent years but the cumulative probability of developing severe recurrent disease remained unchanged. The combination of a female recipient receiving an older graft emerged as a strong risk factor for a severe recurrence. © 2007 AASLD

Lamivudine is a nucleoside analogue with a potent antiviral activity used as prophylaxis against hepatitis B virus reactivation in patients with chronic HBV infection receiving chemotherapy. No standard guidelines exist, however, for the duration of lamivudine treatment. We report a clinical case of a 56-year-old patient with HBeAg-negative cirrhosis who developed a multiple myeloma. He was treated with lamivudine for 1 year while receiving chemotherapy and a subsequent bone marrow transplant. Complete remission from multiple myeloma was achieved. Four months after lamivudine was withdrawn, he experienced HBV reactivation with jaundice, though no YMDD mutations were detected. The patient rapidly developed fatal decompensation with septicemia and renal failure. In conclusion, this case shows that physicians should avoid discontinuing nucleoside therapy in patients with HBV infection who undergo immunosuppression for concomitant neoplastic conditions.

Background & Aims: This study extends our previously reported observations that various immunological factors are associated with the occurrence of histologically proven recurrent hepatitis C. The two specific issues investigated were to confirm the associations of MHC alleles and donor/recipient mismatch with the occurrence of recurrent hepatitis C in an independent cohort of newly transplanted patients and to look for immunologic and nonimmunologic variables affecting the severity of the recurrent disease. Methods: Two separate cohorts of consecutive patients were studied: a look-back cohort (LC) of 120 patients and a cohort for studying the disease progression (CSDP) of 190 patients. Protocol liver biopsies were obtained at least 1, 3, 5, 7, and 10 years after liver transplantation (LT). Results: A fully mismatched donor/recipient pair at the DRB1 locus was confirmed to be associated with both the recurrence of histologic hepatitis in the LC (59% vs 23%, P = .0002) and its progression beyond stage 3 in the CSPD (71.4% vs 39.3%, P = .0003). Relevant immunologic and nonimmunologic variables were included into a multivariate Cox proportional model and three variables, namely, donor age, full HLA-DRB1 donor-recipient mismatch, and HLA B14, resulted in independent risk factors for the development of severe fibrosis. Conclusion: This study provides evidence that DRB1 donor-recipient mismatch affects both the occurrence and progression of recurrent hepatitis C disease. This information is clinically relevant as it may help to better allocate organs and to recognize patients at risk for progression so that specific interventions can be implemented. © 2006 by the American Gastroenterological Association Institute