Hepatitis Monthly
Year:2015 | Volume:15 | Issue:5|Papers Count:11

Background: While Roux-en-Y hepaticojejunostomy (RYH) is the common anastomotic technique for liver transplantation (LT) in patients with primary sclerosing cholangitis (PSC), duct-to-duct (DD) reconstruction may be used if the recipient common bile duct is normal. There are conflicting observational data on the rate of success of DD reconstruction versus RYH, in PSC.Objectives: The aim of this study was to assess the safety and efficacy of DD anastomosis, compared to RYH reconstruction, among adults transplanted for PSC.Patients and Methods: All adult patients, who underwent primary LT for PSC between 1990 and 2012, were evaluated, according to type of biliary reconstruction. Recipient and graft survival, postoperative medical and surgical complications, and postoperative resource utilization rates were compared between the two groups.Results: Totally, 73 patients fulfilled the inclusion criteria. Of them, 58 had RYH and 15 had DD reconstruction. A total of 53 subjects (73%) were male, with the mean age±standard deviation at LT of 43.3±14.4 years. Rates of recipient mortality, graft failure, biliary complications, acute cellular rejection, and reoperation were similar in both groups. Postoperative cholangiography was used more frequently in patients with DD reconstruction (33.3% vs. 8.6%, P=0.026).Conclusions: In selected recipients with PSC, DD reconstruction is a safe and efficacious technique, with long-term clinical outcomes comparable to RYH.

Background: Chronic Hepatitis B (CHB) infection is common in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). The replication level of Hepatitis B Virus (HBV) was inversely correlated with hepatic steatosis. Toll-Like Receptor (TLR) 4-mediated innate immunity plays a pivotal role in the occurrence of NAFLD and controls HBV replication.Objectives: This study aimed to investigate whether the TLR4-mediated innate immunity stimulates the pathogenesis of CHB in patients with NAFLD and to determine whether TLR4 plays a role in inhibiting HBV replication.Materials and Methods: The HBV transgenic mice were randomized into the HBV and HBV/NAFLD groups. HepG2.2.15 cells were treated with different concentrations (0-200 mM) of Stearic Acid (SA) to induce steatosis. The total RNA of the liver tissue was extracted for Real-Time Polymerase Chain Reaction (RT-PCR) detection, and immunohistochemistry or western blot was conducted for further validation. The Enzyme-Linked Immunosorbent Assay (ELISA) analysis was applied to evaluate the production of Interleukin 6 (IL-6), Tumor necrosis factor a (TNF-a) and Interferon b (IFN- b). Moreover, viral dynamics were analyzed using HBV DNA and HBV-related antigens (HBsAg and HBeAg).Results: Non-alcoholic fatty liver disease was induced in HBV-transgenic mice fed with High Fat Diet (HFD) for 8 - 24 weeks. Oil red-O staining positive droplets and the content of Triglyceride (TG) were increased in HepG2.2.15 cells treated with SA. TLR4, Myeloid differentiation factor 88 (MyD88), IL-6 and TNF-a expression levels were significantly higher in the HBV/NAFLD group and the steatotic HepG2.2.15 cells than those in their respective controls. Compared to the HBV group, significant reductions in serum levels of HBsAg, HBeAg, and HBV DNA titers occurred in the HBV/NAFLD group at 24 weeks, but the IFN- b level was remarkably increased. Similar data were also obtained from the steatoric HepG2.2.15 cells.Conclusions: Saturated Fatty Acids (SFAs) served as a potential ligand for TLR4 and activated TLR4 signaling pathway, which might be involved in the pathogenesis. Thus, SFAs can accelerate the mechanism of inhibiting HBV replication in CHB with NAFLD.

Background: Blood is frequently involved in dental treatment procedures, which increases the exposure of dentists to a variety of blood-borne pathogens and microorganisms such as Hepatitis B Virus.Objectives: The current study aimed to assess Chinese dental and medical interns’ knowledge, attitude and behavior (KAB) towards Hepatitis B Virus (HBV) infection and to evaluate which exact KAB phase respondents were involved in.Patients and Methods: A self-administered questionnaire survey was conducted on 313 fifth to eighth year students. Descriptive statistics and bivariate analyses were used to identify correlations between KAB and the results obtained from different grades.Results: Despite the fact that Chinese dental interns had good general knowledge level, they lacked the experience with active and artificial immunities against HBV. Graduates forgot basic knowledge and applied the methods without understanding the terms. Compared with the medical interns, dental interns were less willing to treat patients with HBV infection. All three required vaccination doses were received by a significant number of dental interns. However the frequency of antibody titer status check and the use of eye wear or face mask were not satisfying.Conclusions: It is therefore recommended that Chinese dental interns continue improving knowledge level, assume more positive attitude by accumulating clinical experience, and pay more attention to the overlooked procedures. The results of the current study can help the Chinese dental interns on theoretical studies and clinical practices regarding HBV.

Background: As an important intermediate filament protein within liver cells, cytokeratin-18 (CK-18) has been confirmed as a potential indicator in various hepatitis progressions.Objectives: We sought to clarify the connection between serum CK-18 levels and hepatitis pathogenesis in the present meta-analysis.Materials and Methods: With the application of various computerized databases, including PubMed, Embase, Cochrane Library, Google Scholar, Web of Science, China BioMedicine (CBM), China National Knowledge Infrastructure (CNKI), published papers that assessed the relationship between serum CK-18 levels and hepatitis were obtained. The main key words used are “Hepatitis”, “hepatitides”, “Cytokeratin-18”, “Keratin-18” and “CK-18”. Statistical analysis was conducted using the STATA software (version 12.0).Results: Eight case-control studies published between 2010 and 2014 were confirmed eligible, according to our selection criteria. The results of the meta-analysis showed that serum levels of CK-18 in hepatitis patients were higher compared to healthy controls (standardized mean difference (SMD) = 3.71, 95%CI: 2.27-5.14, P<0.001). Subgroup analysis by ethnicity and disease implicated that high serum CK-18 levels might be a risk factor for non-alcoholic steatohepatitis (NASH), chronic hepatitis C (CHC), and chronic hepatitis B (CHB) (all P<0.05) among Asians (SMD=2.89, 95%CI: 2.35-3.43, P<0.001), Africans (SMD=0.69, 95%CI: 0.12-1.26, P=0.017), and Caucasians (SMD=4.86, 95%CI: 1.82-7.89, P=0.002).Conclusions: Serum CK-18 levels in hepatitis patients were higher, compared with healthy controls. Our results revealed the clinical values of CK-18, in combination with other apoptosis markers, in identifying the development of hepatitis.

Background: Hepatitis C virus infection is one of the leading causes of end stage liver diseases. The innate immune response slows down viral replication by activating cytokines such as type I interferon (IFN-a/ b), which trigger the synthesis of antiviral proteins and modulate the adaptive immune system. Recently, leucine-rich repeat (in Flightless I) interacting protein-1 (LRRFIP1) was reported contributing to the production of interferon- b in macrophages.Objectives: The aim of this study was to assess the role of LRRFIP1 in induction of IFN- b and inhibition of HCV infection in hepatocytes.Materials and Methods: Induction of IFN-β by LRRFIP1 in Huh7 and Huh7.5.1 was determined by real-time PCR and western blotting in vitro. Inhibition of HCV replication by LRRFIP1 overexpression in hepatocytes was assessed.Results: LRRFIP1 increased the expression of IFN-b in hepatocytes with or without HCV infection. Induction of IFN- b by LRRFIP1 was enhanced with the presence of hepatitis C virus. Overexpression of LRRFIP1 in hepatocytes inhibited HCV replication. However, HCV infection did not regulate intracellular expression of LRRFIP1.Conclusions: LRRFIP1 and its mediated production of type I interferon play a role in controlling HCV infection. The findings of this study provide new target for HCV treatment and contribute to development of anti-HCV drugs.

Context: Hepatitis B Virus expanded program on immunization (EPI) started on 1993 in Iran. Most surveys have assessed the level of response to vaccine by measuring the titers of anti-HBs. This meta- analysis aimed to summarize the Iranian published data on the rate of vaccine-responders versus non-responders. Moreover, the impact of variables such as age, gender, type of vaccine, etc. on the levels of responsiveness was evaluated.Evidence Acquisition: All published papers on this topic in Iranian and international journals with affiliation of “Iran” were reviewed using standard keywords up to 2014. We included our study to healthy participants with no previous HBV infection and who had already received a complete course of HB vaccine. The estimated prevalence and 95% confidence intervals in 28 eligible articles for HBV vaccine responders (anti-HBs>10 IU/mL) and non-responders (10<) were analyzed by random effect method due to between-study heterogeneity.Results: The age of subjects was between 6 months and 15 years old. Overall, 5991 (51.5%) were male and 4571 (48.5%) females. Overall, 80% were responders to vaccine versus 20% nonresponders. With increase in age, the number of responders to vaccine decreased significantly (P = 0.001). There was no strong difference between responders versus nonresponders to vaccine for gender, types of vaccine, ethnicity and living area.Conclusions: The results arose from this meta-analysis highlighted the safety of vaccine and its effectiveness in stimulating immune response of vaccines, despite being different in generation, manufacturers and types. Moreover, there was no substantial difference between Iranian and other international investigations in the rate of nonresponsiveness to HBV vaccine.

Dear Editor, We read the article by Garjani et al. with great interest. In this study, they demonstrated that patients with moderate or severe fatty liver disease on ultrasonography had higher platelet counts than those with mild fatty liver and concluded that platelet counts could be used as a clue to steatosis grade of nonalcoholic fatty liver disease (NAFLD).

Context: Attaining a sustained virological response with antiviral therapy is a sign of clinical cure for chronic hepatitis C patients. The aim of this meta-analysis was to evaluate the long-term efficiency and outcome of antiviral therapy in patients with hepatitis C who attained a sustained virological response.Evidence Acquisition: A literature search was performed on published articles between January 2008 and February 2014. Patients with Hepatitis C who received interferon with or without ribavirin therapy were enrolled. Relative risks were estimated using either fixed or random effect models.Results: Patients who attained sustained virological response had a less risk (85%) for all-cause mortality and about 63% reduced risk of hepatocellular carcinoma incidence than those who did not achieve sustained virological response. Based on deeply analysis, the stage of liver fibrosis was a risk factor at baseline for the incidence of hepatocellular carcinoma.Conclusions: Sustained virological response can reduce all-cause mortality and the incidence of hepatocellular carcinoma of patients with hepatitis C. Advanced liver fibrosis is still a risk factor for the incidence of hepatocellular carcinoma, in spite of hepatitis C patients attained a sustained virological response.

Background: Tenofovir disoproxil fumarate (TDF) is a new effective treatment option for patients with chronic hepatitis B (CHB).Objectives: To evaluate TDF efficacy in nucleos (t)ide analogues (NAs)-naive Iranian patients with CHB.Patients and Methods: The NA-naive patients received TDF for at least six months. The primary endpoint was the proportion of patients achieving a complete virological response (CVR) during the treatment. Multivariate Cox regression analysis determined predictive factors independently associated with the time to CVR. The secondary endpoints were biochemical and serological responses, frequency of virological breakthrough, genotypic resistance development, safety and tolerability.Results: In all, 93 patients (64.5% hepatitis B e antigen [HBeAg]-negative) were eligible. Of these, 70 patients completed 24 months of treatment. The cumulative CVR rates in HBeAg-negative and HBeAg-positive patients were 87% versus 53% at 24 months, respectively. The multivariate Cox regression model showed only HBeAg positivity at baseline and a high baseline HBV DNA level were independent factors predicting a CVR. No patient achieved hepatitis B surface antigen (HBsAg) and HBeAg loss or seroconversion and no virologic breakthrough occurred. A new amino acid substitution (rtD263E) was observed to develop in 60% of patients with viremia.Conclusions: The cumulative CVR rates showed that patients with HBeAg-negative have better virologic respond than those with HBeAg-positive during the same period. The rtD263E mutation might be associated with partial resistance to TDF.

Background: Alcoholic hepatitis (AH) is an acute manifestation of alcoholic liver disease with high mortality rates.Objectives: Our aim was to study the molecular mechanisms of AH.Materials and Methods: The differentially expressed genes (DEGs) in liver between AH and control cases were identified by analyzing the GSE28619 microarray data using t-test. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) enrichment analyses were performed using DAVID online tool. The protein-protein interaction (PPI) network was constructed using Search Tool for the Retrieval of Interacting Genes (STRING) and the subnetwork was identified by BioNet. Both PPI network and subnetwork were visualized using the Cytoscape software.Results: Total 908 DEGs (551 up- and 357 down-regulated DEGs) were obtained. The up-regulated DEGs were significantly enriched in 15 pathways and 112 GO biological processes. The down-regulated DEGs were significantly enriched in 22 pathways and 84 GO biological processes. The PPI network with 608 nodes and 2878 interactions was constructed and the subnetwork with 53 nodes and 131 interactions was also identified. The hub DEGs (TSPO, PPIB, NME1 and NME2) were extracted in this subnetwork.Conclusions: TSPO might contribute to the liver damage and AH progression induced by mitochondrial dysfunction through oxidative stress of liver. TSPO interacted with PPIB might play important roles in liver damage in AH. The interaction between NME1 and NME2 might contribute to the transformation from AH to hepatocellular carcinoma.

Background: Previous studies have documented a high prevalence of hepatitis E among patients undergoing maintenance hemodialysis. Available studies reporting on the seroprevalence of hepatitis E in hemodialysis patients in Iran, an endemic region for the disease, are sparse.Objectives: The present study aimed to determine the prevalence rate of anti-hepatitis E antibody in hemodialysis patients in Hamadan, Iran.Patients and Methods: In this cross-sectional study, all 153 consecutive patients undergoing hemodialysis in two centers were enrolled. Patients’ demographic and clinical data were collected, using a standard questionnaire and from medical records. Serum immunoglobulin G concentrations against hepatitis E were determined using the enzyme linked immunosorbent assay method.Results: Thirty patients (19.2%), were seropositive. Seropositive patients were not significantly different from seronegative patients, with regard to age, sex, level of education, access to filtered water, and duration and frequency of hemodialysis. The proportions of patients with hepatitis B, C, and HIV infection were comparable between the two groups.Conclusions: One in five patients undergoing maintenance dialysis in Hamadan is seropositive for hepatitis E immunoglobulin G antibody. Future studies are needed to investigate the factors contributing to the observed high prevalence rate and the possibility of parenteral transmission of hepatitis E.