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Background: We investigated the patterns and predictors for virological relapse (VR), clinical relapse (CR), and sustained clinical response (SCR) and the outcomes of retreatment after nucleos(t)ide analogue (NUC) therapy discontinuation.Methods: Patients with chronic hepatitis B who were discontinuing NUC therapy were prospectively enrolled. Viral and host predictors of relapse were evaluated, including hepatitis B virus (HBV) surface antigen (HBsAg) level, anti-HBV core antibody level, and presence of single-nucleotide polymorphisms in the genes encoding the receptors NTCP (rs2296651) and CTLA4 (rs231775) and in the 3' untranslated regions of the genes encoding HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277535); posttherapy predictors of relapse were also investigated. Information about NUC retreatment and outcomes were recorded.Results: Overall, 100 patients discontinuing 3-year entecavir (ETV) or tenofovir (TDF) therapy were enrolled. Patients discontinuing TDF exhibited significantly higher rates of VR (52.9% vs 6.1%; P < .001) and CR (15.2% vs. 1.5%, P = .007) at 3 months than those discontinuing ETV, but relapse rates at 12 months were comparable. The end-of-therapy HBsAg levels predicted VR (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.19-2.21), CR (HR, 1.78; 95% CI, 1.13-2.81), and SCR (OR, 0.57; 95% CI, .35-.94). The CTLA4 (rs231775) non-GG genotype predicted VR (HR, 1.74; 95% CI, 1.01-3.00) and CR (HR, 2.06; 95% CI, 1.04-4.11), while the HLA-DPA1 (rs3077) AA genotype predicted SCR (OR, 10.84; 95% CI, 1.12-105). The HBV DNA 1 month after NUC treatment cessation was an early predictor of subsequent relapse.Conclusions: Discontinuation of tenofovir disoproxil fumarate treatment rather than entecavir treatment is associated with earlier relapse, and NUC-specific posttherapy monitoring is necessary. [ABSTRACT FROM AUTHOR]

Background. Clinical implications of persistent alanine aminotransferase (ALT) elevation and associated factors in chronic hepatitis C (CHC) patients who achieved undetectable hepatitis C virus (HCV) RNA during pegylated interferon plus ribavirin (peg-IFN/RBV) therapy remain unknown. Methods. A total of 1113 CHC patients with undetectable HCV RNA during peg-IFN/RBV therapy were enrolled. Baseline characteristics associated with persistent on-treatment ALT elevation (POAE), and its impact on treatment outcomes, were investigated. Results. Of 1113 CHC patients, 254 (22.8%) had POAE. Among patients with HCV genotype 1 (HCV-1) who had complete early virologic response (EVR) and received 48 weeks of therapy, patients with POAE had a lower rate of sustained virologic response (SVR) than those without POAE (44.1% vs 74.0%; P = .0002). Multivariate analyses showed that body mass index ⩾ 27 kg/m2, ALT level ⩾3 times the upper limit of normal, aspartate aminotransferase to platelet ratio index score ⩾1.5, hepatic fibrosis ⩾F3, and hepatic steatosis ⩾S2 were independent factors associated with POAE after viral clearance. Conclusions. POAE is common in CHC patients during therapy. HCV-1 patients with POAE have a lower SVR rate to 48-week therapy if they achieve complete EVR. Advanced hepatic fibrosis, obesity, and steatosis are factors associated with POAE in these patients. [ABSTRACT FROM AUTHOR]

Background. Hemodialysis patients are at risk of hepatitis C virus (HCV) infection. However, little is known about the efficacy and safety of pegylated interferon (IFN) therapy for hemodialysis patients with acute hepatitis C. Methods. From 2005 through 2008, 35 hemodialysis patients with acute hepatitis C who did not have spontaneous clearance of HCV by 16 weeks were treated with pegylated IFN alfa-2a at a dosage of 135 mg weekly for 24 weeks. In contrast, 7 patients with clearance of HCV by 16 weeks were under observation only. Thirty-six hemodialysis patients from 2002-2005 who had acute hepatitis C but did not receive treatment served as historical controls. The primary efficacy and safety end points were sustained virologic response (undetectable HCV RNA levels at 24 weeks after therapy) by intention-to-treat analysis and treatment-related withdrawal. Results. The rate of sustained virologic response in the treatment group was significantly higher than the rate of spontaneous HCV clearance in the control group (88.6% vs 16.7%; P ! .001). Two patients (5.7%) prematurely terminated treatment at 8 and 10 weeks because of constitutional symptoms, and both did not have sustained virologic response. All but one patient had rapid virologic response (undetectable HCV RNA levels at 4 weeks of therapy), and all patients who received 112 weeks of therapy had early and end-of-treatment virologic responses. All patients who had clearance of HCV by 16 weeks had undetectable HCV RNA levels until the end of follow-up. Conclusions. Pegylated IFN alfa-2a monotherapy is safe and efficacious for hemodialysis patients with acute hepatitis C. It is suggested that patients without spontaneous clearance of HCV by week 16 should receive therapy. [ABSTRACT FROM AUTHOR]

Background. With use of peginterferon alfa-2a and ribavirin combination therapy in patients with dual chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, 11.2% of patients achieved clearance of hepatitis B surface antigen (HBsAg) at 6 months after treatment; however, reactivation of HBV DNA was observed in 36.3%. We investigated the predictive potential of HBsAg quantification. Methods. HBsAg quantification was performed in 120 e antigen-negative patients dually infected with HBV and hepatitis C virus and treated with peginterferon alfa-2a/ribavirin for 48 weeks (HCV genotype 1; np74) or 24 weeks (HCV genotype 2/3; np46). HBsAg was quantified at baseline, week 4, week 12, end of treatment, and 24 weeks after treatment. Results. The baseline median serum HBsAg level was 120 IU/mL and decreased gradually during treatment. Low baseline HBsAg was significantly associated with HBsAg clearance (40% for HBsAg level ⩽20 IU/mL vs 2.2% for HBsAg level 120 IU/mL; P < .05). A decrease in HBsAg level from baseline to week 12 of 50% was associated with a reduced likelihood of HBV DNA reactivation in patients with baseline undetectable serum HBV DNA (positive predictive value, 89.5%). Conclusions. HBsAg quantification appears to be a useful indicator of posttreatment outcome in patients dually infected with HBV and hepatitis C virus. [ABSTRACT FROM AUTHOR]

Background. Expression of intrahepatic hepatitis B core antigen (HBcAg) is related to the immunopathogenesis of hepatitis B virus (HBV) infection. This study investigated the role that HBV genotype and basal core promoter (BCP) mutation play in the expression of HBcAg. Methods. A total of 70 hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis (genotype B in 52 patients and genotype C in 18 patients; BCP mutation T1762/A1764 in 16 patients) were enrolled. Clinical, virologic, and histologic features were compared with regard to localization and expression of intrahepatic HBcAg. The effects that HBV genotype and BCP mutation T1762/A1764 had on expression of HBcAg were further evaluated by in vitro assays. Results. Cytoplasmic, mixed cytoplasmic/nuclear, and nuclear localization of intrahepatic HBcAg was found in 38 (56.7%), 25 (37.3%), and 4 (6.0%) patients, respectively; HBcAg was not discernible in 3 patients. A total of 58 (82.9%) of these patients expressed a high level of HBcAg. In multivariate analysis, cytoplasmic localization of HBcAg correlated only with a low HBV load in serum (P = .045) and BCP mutation (P = .04). A high expression level of HBcAg also correlated with a high HBV load in serum (P = .015) and with BCP wild-type sequence (P = .037). In vitro assays indicated that the HBV BCP mutant strain had lower subcellular expression of HBcAg than did the BCP wild-type strain. Conclusions. HBV BCP mutation and HBV load, but not genotype, contribute to the expression of intrahepatic HBcAg. [ABSTRACT FROM AUTHOR]

Background. Comparable sustained virologic response (SVR) rates have been documented between Asian patients who received 24 weeks of pegylated interferon (IFN) plus ribavirin and white patients who received 48 weeks of combination therapy for hepatitis C virus genotype 1 (HCV-1) infection. Whether a 48-week course of combination therapy shows a better SVR rate than a 24-week course of such therapy among Asian patients with HCV-1 infection has not been confirmed in multicenter, randomized studies. Methods. In this multicenter, randomized trial, 308 treatment-naive HCV-1-infected Asian patients were randomly assigned to receive either 24 or 48 weeks of pegylated IFN-α-2a (180 μg per week) plus ribavirin (1000-1200 mg/day) therapy. The primary end point was SVR, defined as an undetectable serum HCV RNA level 24 weeks after discontinuation of therapy. In addition, rapid virologic response (RVR) was defined as an undetectable serum HCV RNA level at week 4 of therapy, and complete early virologic response was defined as an undetectable serum HCV RNA level at 12 weeks of therapy in the absence of RVR. Results. By intention-to-treat analysis, patients who received 48 weeks of therapy had a significantly higher SVR rate than did those who received 24 weeks of therapy (76% vs. 56%; P < .001). Among patients with a baseline serum HCV RNA level < 800,000 IU/mL and RVR, SVR rates were comparable between 24- and 48-week courses of therapy (94% vs. 100%; Pp.13). In contrast, 48 weeks of therapy was associated with a significantly higher SVR rate than was 24 weeks of therapy among patients without RVR (39% vs.16%; P < .01) and among those who achieved a complete early virologic response (44% vs. 20%; P = .02). Conclusions. In treatment-naive Asian patients with HCV-1 infection, 48 weeks of pegylated IFN-a-2a plus ribavirin therapy is associated with a higher SVR rate, compared with 24 weeks of such therapy. Patients with a baseline serum HCV RNA level < 800,000 IU/mL and who have achieved an RVR can receive a 24-week course of therapy without compromising the SVR rates; however, those who have not achieved an RVR but who have achieved a complete early virologic response should receive a 48-week course of therapy. Clinical trials registration. NCT00495131. [ABSTRACT FROM AUTHOR]

Background. Little is known about the transmission of variant hepatitis C virus (HCV) genome through needlestick injuries. Methods. To demonstrate how HCV quasi species are transmitted and adapt to the new host in acute resolving infection, we analyzed the nucleotide and deduced amino acid sequences of the hypervariable region 1 (HVR-1) in the E2 domain of HCV in both the source of the virus ("donor") and the person who received the virus through a needlestick accident ("recipient"). In addition, we also performed phylogenetic analysis of HCV quasi species in these patients to document the viral transmission. Results. We obtained a total of 33 clones at different time points by using polymerase chain reaction amplification and cloning and sequencing of HVR-1. A predominant HVR-1 variant (in 4 of 10 isolates) in the donor was not present in the recipient 6 and 14 weeks after the accident. In contrast, a minor variant (in 1 of 10 isolates) in the donor became the predominant strain in the recipient 6 weeks (in 10 of 12 isolates) and 14 weeks (in 6 of 11 isolates) after the accident. Additional phylogenetic analysis showed high homology of nucleotide sequences between isolates obtained from the donor and isolates obtained from the recipient. In addition, the variants in the recipient's virus showed substantial genetic preservation in the course of acute resolving hepatitis. Conclusions. These data suggested that a minor HCV variant from a donor was transmitted to the recipient through a needlestick injury and that it prevailed as the dominant species. The preserved genetic homogeneity of the transmitted viral variants in patients with acute HCV infection may account for their clinical outcomes of resolving hepatitis. [ABSTRACT FROM AUTHOR]