The impact of hepatitis B virus (HBV) superinfection in hepatitis C virus (HCV) chronic carriers was evaluated in a longC hronic hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is characterized by a reciprocal inhibition of the viral genomes, a severe clinical presentation, and an infrequent response to antiviral treatment. [1][2][3][4][5][6][7][8][9] This reciprocal inhibition was observed also in acute HBV/HCV coinfection. 10,11 Models of HBV and HCV superinfection have also been investigated. A marked inhibition of the preexisting viral replication has been observed both in HBV chronic carriers with superimposed acute hepatitis C 12-15 and in HCV chronic carriers with HBV superinfection, [16][17][18] both models being frequently characterized by a severe clinical course. 15,18 In a study on HBV superinfection in HCV chronic carriers, the inhibition exerted by HBV on the HCV genome persisted during a follow-up of 1 year in half of the patients, 18 but a comprehensive evaluation of the virus interaction and clinical outcome was hampered by the lack of information on HCV replication before HBV superinfection by the low sensitivity of the HBV-DNA assay used and the short follow-up period.The present article describes a case-control study performed on 29 HCV chronic carriers with HBV superinfection and 29 anti-HCV negative pair-matched controls who developed acute hepatitis B in the same period. Most of the patients with HBV superinfection had been observed for at least 1 year before the onset of acute hepatitis

The aim of the study was to evaluate clinical and virological differences in HBV reactivation between patients with overt and occult HBV infection. Twenty-three consecutive patients with symptomatic HBV reactivation occurring during or after immunosuppressive therapy were enrolled in a retrospective study: 10 with reactivation of overt HBV infection (overt group) and 13 of occult HBV infection (occult group). Twenty-one patients were treated with nucleot(s)ide analogues after HBV reactivation. Regimens including rituximab or fludarabine were administered more frequently in the occult group (61% vs. 31%, respectively). HBV reactivation was severe frequently in the overt (40%) and occult groups (38.4%). Patients in the overt group showed higher HBV-DNA titers (1.1 × 10(8) ± 1.4 × 10(8) vs. 5.1 × 10(5) ± 6.8 × 10(5) IU; P < 0.005). Seven patients died during HBV reactivation, two in the overt and five in the occult group. Of these seven patients, two remained untreated and five had been treated with Lamivudine; of the 16 patients showing remission of HBV reactivation, four had been treated with Lamivudine, four with Entecavir, two with Telbivudine, and six with Lamivudine plus Adefovir. It is concluded that HBV reactivation is life-threatening in patients with diseases inhibiting the immune response and/or receiving immunosuppressive drugs. Supportive therapy without antiviral drugs or Lamivudine monotherapy may not be effective for treating patients with HBV reactivation.

To study in HBsAg chronic carriers the expression of liver hsa-miR-125a-5p and its correlation with liver HBV-DNA values and clinical presentation, 27 consecutive Caucasian, HBsAg/anti-HBe/HBV-DNA-positive patients who were naive to nucleos(t)ide analogues and interferon therapy and had no marker of HCV, HDV or HIV infection and no history of alcohol intake were enrolled. For each patient, liver HBV DNA and liver hsa-miR-125a-5p were quantified by real-time PCR in relation to β-globin DNA or RNU6B, respectively. Liver fibrosis and necroinflammation were graded by applying Ishak's scoring system. Liver hsa-miR-125a-5p was detected in all patients enrolled and a correlation between its concentration and liver HBV DNA was demonstrated (p<0.0001). Higher liver hsa-miR-125a-5p concentrations were observed in patients with HBV-DNA plasma level >103 IU/ml (p<0.02), in those with HAI >6 (p = 0.02) and those with fibrosis score >2 (p<0.02) than in patients with lower scores. Higher HBV-DNA liver concentrations were found in patients with abnormal AST (p = 0.005) and ALT serum levels (p = 0.05), in those with serum HBV DNA higher than 10E3 IU/mL (p = 0.001) and those with fibrosis score >2 (p = 0.02) than in patients with a lower load. By multivariate logistic regression analysis, liver hsa-miR-125a-5p was identified as an independent predictor of disease progression: O.R. = 4.21, C.I. 95%  = 1.08–16.43, p<0.05, for HAI >6; O.R. = 3.12, C.I. 95%  = 1.17–8.27, p<0.05, for fibrosis score >2. In conclusion, in HBsAg/anti-HBe-positive patients, the liver hsa-miR-125a-5p level correlated with liver and plasma HBV-DNA values and was associated to a more severe disease progression.

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A female patient with non-Hodgkin lymphoma who tested positive for surface antigen of the hepatitis B virus and negative for hepatitis B core antibody experienced a reactivation of occult HBV infection 20 months after rituximab discontinuation despite lamivudine prophylaxis covering the 4 months of rituximab administration and the subsequent 12 months.

We read with great interest the article by Martinot-Peignoux et al. 1 In this report from France, undetectable serum hepatitis C virus (HCV) RNA at 12 weeks (Wþ12) (409 patients) post-treatment follow-up was as relevant as undetectable serum HCV RNA at 24 weeks (Wþ24) (sustained virological response [SVR]; 408 patients) after the end of treatment.Current standard therapy is based on a combination of pegylated interferon (PEG-IFN) and ribavirin, but it leads to only $50% SVR in patients with HCV genotype 1 and high viral loads. 2 IFN reduced the risk for HCC, especially among patients with SVR. 3,4 Then, we need to accurately judge whether the patient is SVR or non-SVR, applying the present standard for the judgment of SVR with the undetectability of serum HCV RNA at post-treatment Wþ24.We investigated 102 patients with chronic hepatitis C genotype 1 treated with PEG-IFN-alfa 2a plus ribavirin for 48 weeks. Some of these patients had already been included in previous reports. 5,6 Serum HCV RNA was measured using the COBAS TaqMan HCV test with a detection limit of 1.2 logIU/mL. At the Wþ24 posttreatment follow-up, 40 (39.2%) patients had SVR, and 31 (48.4%) and 9 (23.6%) were treatment naïve and previously treated patients, respectively. At Wþ12, serum HCV RNA was undetectable in 42 patients, and 40 patients were SVR (PPV, 95.2%). We found two relapsers at Wþ24 (undetectable at Wþ12).In the case of using direct-acting antivirals, earlier knowledge of treatment outcome would be useful for retreatment for the same patient. Taken together, our findings show that Wþ12 undetectable serum HCV RNA is not suitable for predicting persistent virological response. Further understanding of the mechanism of relapse could be useful in reducing the posttreatment follow-up period from the current standard of 24 weeks. Reply:We read, with interest, the letter by Kanda et al. regarding our article. As you know, the primary end-point of antiviral therapy for chronic hepatitis C virus (HCV) is achieving sustained virological response (SVR), defined as undetectable HCV-RNA in serum 24 weeks after stopping antiviral therapy. SVR is equivalent to viral eradication and is associated with a reduction in the risk of cirrhosis and hepatocellular carcinoma. 1 Recently, it has been proposed that a 12-week post-treatment follow-up might be as relevant as 24 weeks to determine the SVR in patients with HCV receiving pegylated-interferon (PEG-IFN) and ribavirin. 2 In our study, 573 patients who received combination PEG-IFN and ribavirin and had a virological response at the end of treatment were evaluated. Serum HCV-RNA was measured, using a new assay based on transcription-mediated amplification (TMA), with a lowest detection limit of 5-10 IU/mL, at week (W)þ12 and Wþ24 after the end of treatment. At the Wþ24 post-treatment follow-up, 408 (71%) patients had an SVR, 181 (71.2%) were treated with PEG-IFN alpha-2a and ribavirin, and 227 (71.1%) were treated with PEG-IFN alpha-2b and ribavirin. At Wþ12, serum HCV-RNA was undetectable in 409 pati...

BackgroundTwo formulations of Pegylated interferon (Peg-IFN) are on the market for treatment of chronic hepatitis C virus (HCV) infection. The purpose of this meta-analysis was to assess the efficacy of Peg-IFN α-2a versus Peg-IFN α-2b in combination with ribavirin in anti-human immunodeficiency virus (HIV)-negative patients with genotype 1 chronic HCV infection.MethodsThe following criteria were to be met for inclusion in the meta-analysis: (a) original data from randomized and non-randomized clinical trials; (b) study on the efficacy of conventional doses of Peg-IFN α-2a (180 μg/week) versus Peg-IFN α-2b (1.5 μg/kg of body weight/week), both in combination with ribavirin, in antiviral therapy-naïve HCV-genotype 1 subjects; (c) at least one of these primary outcomes: Rapid Virological Response (RVR); Early Complete Virological Response (EVR); End of Treatment Response (ETR); Sustained Virological Response (SVR); (d) odds ratio estimates of relative risk (RR) and associated 95% confidence intervals (CIs) or at least data enabling them to be computed; (e) English language; and (f) published as a full paper up to December 2011.ResultsSeven published studies met the inclusion criteria, allowing a meta-analysis on 3,026 patients. Peg-IFN α-2a and Peg-IFN α-2b showed similar rate of RVR (RR = 1.05; 95% CI = 0.87-1.27, p = 0.62) and SVR (RR = 1.08; 95% CI = 0.99-1.18, p = 0.098). Peg-IFN α-2a more frequently than Peg-IFN α-2b achieved EVR (RR = 1.11; 95% CI = 1.02-1.21, p = 0.013) and ETR (RR = 1.22; 95% CI = 1.14-1.31, p < 0.0001).ConclusionThe standard schedules of Peg-IFN α-2a and Peg-IFN α-2b, both in combination with ribavirin, can be used indifferently for patients with chronic HCV genotype 1 who are anti- to eliminate HIV-negative and antiviral treatment-naïve.

To explore changes in molecular epidemiology of acute viral hepatitis B (AVH-B), hepatitis B virus (HBV) genotypes were determined by direct sequencing of the Pre-S-S region in 123 consecutive patients, with AVH-B observed in Naples or its surroundings in the last decade (group AVH-B) and in 123 HBV chronic carriers [chronic carrier of HBV (CC-B) group] from the same areas, who had been hepatitis B surface antigen-positive for more than 10 years. Genotype D was less frequently detected in patients with AVH-B than in those in the CC-B group (76.4%vs 97.5%, P < 0.0001). In the AVH-B group, intravenous drug addiction (IVDA) was the prevalent risk factor (55.3%) for acquiring HBV in the 94 patients with HBV genotype D, but it was rarely recorded (6.9%) in the 29 patients with genotypes non-D (P < 0.0001); unsafe sexual intercourse was prevalent in patients with genotype non-D (72.3%) and less frequent in those with genotype D (28.8%, P < 0.005). In the AVH-B group, the prevalence of non-D genotypes increased during the observation period from 11.1% in 1999-2003 to 41.1% in 2004-2008 (P < 0.0005), paralleling the increase in the prevalence of patients with unsafe sexual intercourse; similarly, the progressive decrease in IVDA paralleled the decrease in the prevalence of genotype D (from 88.3% in 1999-2003 to 11.7% in 2004-2008). The prevalence of HBV non-D genotypes recorded in the last 10 years in AVH-B in this area shows a progressive increase, most probably because of recent changes in HBV epidemiology, namely, the HBV mass vaccination campaign and increased immigration from areas with high HBV endemicity.