Hepatitis research and treatment最新文献

Despite the success of postexposure prophylaxis (PEP) of the newborn in preventing mother-to-child transmission of hepatitis B virus), in non-US clinical trials, administering hepatitis B immune globulin (HBIG) to mothers at the end of pregnancy (in addition to passive-active PEP of the newborn) only partially improved outcomes. That is, a significant percentage of newborns became infected during their first year of life. We used a relevant animal model for human IgG transplacental transfer to study dose, time and subclass dependence of HBV neutralizing antibody (nAb) maternal, and fetal levels at the end of pregnancy. Pregnant guinea pigs received 50 or 100 IU/kg HBIGIV 2-5 days before delivery. Human total IgG, IgG subclasses, and nAb in mothers and their litters were measured. In vitro analyses of guinea pig Fc neonatal receptor binding to HBIGIV, as well as to all human IgG subclasses, were also performed. Our study showed that nAb transferred transplacentally from the pregnant guinea pigs to their litters; no transfer occurred during parturition. The amount of the transferred nAb was dose and time dependent. Thus, selection of an efficacious dose in the clinic is important: microdosing may be underdosing, particularly in cases of high viraemia.

The aim of the present study was to predict sustained virological response (SVR) to telaprevir with pegylated interferon (PEG-IFN) and ribavirin using viral response within 2 weeks after therapy initiation. Thirty-six patients with genotype 1 hepatitis C virus (HCV) and high viral load were treated by telaprevir-based triple therapy. SVR was achieved in 72% (26/36) of patients. Significant differences between the SVR group and non-SVR group were noted regarding response to prior PEG-IFN plus ribavirin, interleukin (IL)28B polymorphism, amino acid substitution at core 70, cirrhosis, hyaluronic acid level, and HCV-RNA reduction within 2 weeks. Setting 4.56 logIU/mL as the cut-off value for HCV-RNA reduction at 2 weeks, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for predicting SVR were 77%, 86%, 95%, 50%, and 79%, respectively, and for neither the IL28B minor allele nor core 70 mutant were 80%, 71%, 91%, 50%, and 78%, respectively. In conclusion, evaluation of viral reduction at 2 weeks or the combination of IL28B polymorphism and amino acid substitution at core 70 are useful for predicting SVR to telaprevir with PEG-IFN and ribavirin therapy.

Objectives. To empirically determine a categorization of people who inject drug (PWIDs) recently infected with hepatitis C virus (HCV), in order to identify profiles most likely associated with early HCV treatment uptake. Methods. The study population was composed of HIV-negative PWIDs with a documented recent HCV infection. Eligibility criteria included being 18 years old or over, and having injected drugs in the previous 6 months preceding the estimated date of HCV exposure. Participant classification was carried out using a TwoStep cluster analysis. Results. From September 2007 to December 2011, 76 participants were included in the study. 60 participants were eligible for HCV treatment. Twenty-one participants initiated HCV treatment. The cluster analysis yielded 4 classes: class 1: Lukewarm health seekers dismissing HCV treatment offer; class 2: multisubstance users willing to shake off the hell; class 3: PWIDs unlinked to health service use; class 4: health seeker PWIDs willing to reverse the fate. Conclusion. Profiles generated by our analysis suggest that prior health care utilization, a key element for treatment uptake, differs between older and younger PWIDs. Such profiles could inform the development of targeted strategies to improve health outcomes and reduce HCV infection among PWIDs.

We determined the prevalence and incidence of HBV and HCV infection in people who inject drugs (PWIDs) at high risk for HIV in China and Thailand and determined the association of HBV and HCV incidence with urine opiate test results and with short-term versus long-term buprenorphine-naloxone (B-N) treatment use in a randomized clinical trial (HPTN 058). 13.8% of 1049 PWIDs in China and 13.9% of 201 PWIDs in Thailand were HBsAg positive at baseline. Among HBsAg negative participants, the HBsAg incidence rate was 2.7/100 person years in China and 0/100 person years in Thailand. 81.9% of 1049 PWIDs in China and 59.7% of 201 in Thailand were HCV antibody positive at baseline. The HCV confirmed seroincidence rate among HCV antibody negative PWIDs was 22/100 person years in China and 4.6/100 person years in Thailand. Incident HBsAg was not significantly different in the short-term versus long-term B-N arm in China or Thailand. Participants with positive opiate results in at least 75% of their urines during the time period were at increased risk of incident HBsAg (HR = 5.22; 95% CI, 1.08 to 25.22; P = 0.04) in China, but not incident HCV conversion in China or Thailand.

Liver fibrosis and viremia are determinant factors for the treatment policy and its outcome in chronic hepatitis C virus (HCV) infection. We aimed to investigate serum level of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and its relation to liver fibrosis and viremia in children with chronic HCV. ITIH4 was measured by ELISA in 33 treatment-naive children with proved chronic HCV and compared according to different clinical, laboratory and histopathological parameters. Liver histopathological changes were assessed using Ishak score and compared with aspartate transaminase-to-platelet ratio (APRI) and FIB-4 indices as simple noninvasive markers of fibrosis. ITIH4 was measured in a group of 30 age- and sex-matched healthy controls. ITIH4 was significantly higher in patients than in controls (54.2 ± 30.78 pg/mL versus 37.21 ± 5.39 pg/mL; P = 0.021). ITIH4, but not APRI or FIB-4, had a significant direct correlation with fibrosis stage (P = 0.015, 0.961, and 0.389, resp.), whereas, the negative correlation of ITIH4 with HCV viremia was of marginal significance (P = 0.071). In conclusion, ITIH4 significantly correlated with higher stages of fibrosis indicating a possible relation to liver fibrogenesis. The trend of higher ITIH4 with lower viremia points out a potential antiviral properties and further studies in this regard are worthwhile.

Collagen vascular diseases (CVDs) like systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjogren syndrome (SS), and scleroderma are immunologically mediated disorders that typically have multisystem involvement. Although clinically significant liver involvement is rare, liver enzyme abnormalities are common in these patients. The reported prevalence of hepatic involvement in SLE, histopathologic findings, and its significance is very variable in the existing literature. It is important to be familiar with the causes of hepatic involvement in SLE along with histomorphological features which aid in distinguishing hepatitis of SLE from other hepatic causes as they would alter the patient management and disease course. Histopathology of liver in SLE shows a wide morphological spectrum commonly due to a coexisting pathology. Drug induced hepatitis, viral etiology, and autoimmune overlap should be excluded before attributing the changes to SLE itself. Common histopathologic findings in SLE include fatty liver, portal inflammation, and vascular changes like hemangioma, congestion, nodular regenerative hyperplasia, arteritis, and abnormal vessels in portal tracts.

Hepatitis B (HBV) and hepatitis C (HCV) viruses are the most important causes of chronic liver disease in patients with end stage renal disease on hemodialysis. The prevalence of hepatitis infection among hemodialysis patients is high and varies between countries and between dialysis units within a single country. This case-control study was undertaken to estimate the occurrence of HBV and HCV infections in patients undergoing hemodialysis in our tertiary care center. All patients receving hemodialysis at our centre with HCV or HBV infection were included in the study. The total number of patients admitted for hemodialysis during the study period was 1710. Among these, 26 patients were positive for HBV, 19 were positive for HCV, and 2 were positive for both HCV and HBV. Mean age of the infected cases in our study was 48.63 years. Mean duration of dialysis for infected cases was 4.8 years while that of the noninfected controls was 3.18 years. The mean dialysis interval was twice a week. Interventions to reduce the occurrence of these infections are of utmost need to reduce the risk of long-term complications among hemodialysis patients.

Of 168 patients with chronic hepatitis B virus (HBV) infection-related liver disease, 20 patients who had received 100 mg of lamivudine plus 10 mg/day of adefovir dipivoxil (ADV) (ADV group) and 124 patients who had received 0.5 mg/day of entecavir or 100 mg/day of lamivudine (non-ADV group) for >1 year were enrolled. For comparative analyses, 19 well-matched pairs were obtained from the groups by propensity scores. At the time of enrollment, serum creatinine and phosphate concentrations were similar between the ADV and non-ADV groups; however, urinary phosphate (P = 0.0424) and serum bone-specific alkaline phosphatase (BAP) (P = 0.0228) concentrations were significantly higher in the ADV group than in the non-ADV group. Serum BAP was significantly higher at the time of enrollment than before ADV administration in the ADV group (P = 0.0001), although there was no significant change in serum BAP concentration in the non-ADV group. There was a significant positive correlation between the period of ADV therapy and ΔBAP (R (2) = 0.2959, P = 0.0160). Serum BAP concentration increased before increase in serum creatinine concentration and was useful for early detection of adverse events and for developing adequate measures for continuing ADV for chronic HBV infection-related liver disease.

Occult HBV infection (OBI) is defined as HBV DNA detection in serum or in the liver by sensitive diagnostic tests in HBsAg-negative patients with or without serologic markers of previous viral exposure. OBI seems to be higher among subjects at high risk for HBV infection and with liver disease. OBI can be both a source of virus contamination in blood and organ donations and the reservoir for full blown hepatitis after reactivation. HBV reactivation depends on viral and host factors but these associations have not been analyzed thoroughly. In OBI, it would be best to prevent HBV reactivation which inhibits the development of hepatitis and subsequent mortality. In diverse cases with insufficient data to recommend routine prophylaxis, early identification of virologic reactivation is essential to start antiviral therapy. For retrieving articles regarding OBI, various databases, including OVID, PubMed, Scopus, and ScienceDirect, were used.

Background. HCV infection is associated with musculoskeletal manifestations such as chronic widespread pain, sicca syndrome, polyarthritis, and a reduced HRQOL. Little data is available on the effect of treatment on these manifestations. This study measured changes in extrahepatic symptoms and HRQOL before and after antiviral treatment in a large UK patient cohort. Methods. 118 patients completed HQLQ and rheumatological questionnaires before and after treatment with pegylated interferon- α and ribavirin, with specific regard to chronic widespread pain, sicca syndrome, and sustained virological response. Results. There was significant improvement in HQLQ domains of physical functioning, physical disability, social functioning, limitations and health distress due to hepatitis, and general health. There was significant deterioration in domains of positive well-being, health distress, and mental health. There was a significant decline prevalence of CWP (26.3% versus 15.3%, P = 0.015). Sicca syndrome prevalence fell insignificantly (12.7% versus 11%). SVR was associated positively with all HRQOL changes and significantly with CWP remission. Conclusions. HCV antivirals significantly improve poor HRQOL scores and CWP. Before treatment, both were common, coassociated, and unaccounted for through mixed cryoglobulinemia alone. Although a role of the hepatitis C virus in CWP cannot be deduced by these results, symptomatic improvement via antiviral treatment exists for this subset of patients.