Hepatitis Monthly
Year:2014 | Volume:14 | Issue:10|Papers Count:8

Context: Our objective was to evaluate the effect of gene polymorphisms of apolipoprotein C3 (APOC3) on the development of non-alcoholic fatty liver disease (NAFLD) in different populations.Evidence Acquisition: We performed a meta-analysis of all relevant studies published in the literature. A total of 115 clinical trials or reports were identified, but only seven trials met our inclusion criteria. A meta-analysis was performed according to the Cochrane Reviewers’ Handbook recommendations.Results: Five hospital-based and two population-based case-control studies were included in the final analysis. The overall frequency of APOC3 gene polymorphisms was 67.5% (1177.1745) in NAFLD and 68.8% (988/1437) in controls. The summary odds ratio for the association of gene polymorphisms of APOC3 and the risk of NAFLD was 1.03 (95% CI: 0.89-1.22), which was not statistically significant (P>0.05).Conclusions: Our meta-analysis, while not ruling out possible publication bias, showed no association between gene polymorphisms of APOC3 and the risk of NAFLD development in different populations in the world.

Background: Some reports revealed that rapamycin could reactivate HBV infection. However, the mechanism has not been clearly explained.Objectives: In this report, we studied the mechanism by which rapamycin enhances HBV replication and expression by inducing cellular autophagy.Materials and Methods: HepG2.2.15 cells were treated with rapamycin to induce autophagy. Autophagosomes were observed by fluorescence microscopy and transmission electron microscopy. Autophagy marker protein LC3-II/LC3-Iwas detected by Western blotting. HBV DNA and mRNA were determined by real time PCR and Southern blotting. HBsAg was evaluated by ELISA.Results: In HepG2.2.15 cells, HBV DNA and HBsAg increased when host cells were treated with rapamycin and the effect was reversed by autophagy inhibitor, 3-methyladenine (3-MA).Conclusions: These results indicated a potential explanation for reactivation of HBV infection when patients with hepatitis receive rapamycin

Background: Accurate and personalized molecular virological diagnosis of hepatitis B virus (HBV) infection is crucial for individualized selection of patients for antiviral therapy in Romania.Objectives: We aimed to investigate HBV mutations in Romanian patients with chronic HBV infection, also to match HBV genotypes with HBV mutations identified and clinical outcomes.Patients and Methods: This was a cross-sectional study. A total of 484 Romanian patients with chronic HBV infection and hepatocellular carcinoma (HCC) were investigated. This was performed in Fundeni Clinical Institute, Bucharest, Romania during January 2005 to August 2010. HBsAg positive patients with chronic HBV infection admitted to Fundeni Clinical Institute were randomly enrolled in the study. Analysis was performed in the Centre for Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania. Indirect diagnosis was performed with enhanced chemiluminescence method using Architect i2000SR and HBV-DNA was quantified with COBAS TaqMan HBV PCR. Direct sequencing of the PCR-products was performed with the PCR-product sequencing kit. HBV genotyping was performed with INNO-LiPA DR Amplification and INNO-LiPA HBV precore-core.Results: We detected two HBV genotypes, A (8.1%) and D (60.5%), and a mixture of genotypes A and D (31.4%) (P<0.001). Basal core promoter (BCP) A1762T/G1764A and precore (PC) G1896A mutations were detected in these Romanian patients with chronic HBV infection. HBV chronic carriers had mainly genotype D (54.4%) and HBV WT (64.0%). BCP A1762T, G1764A and PC G1896A were significantly associated with HCC-tissue HBV sequencing (75.3%) (P<0.001). PC G1896A alone was detected in HCC-serum HBV sequencing group (66.7%).Conclusions: Genotype D was the main genotype detected in Romanian patients with chronic HBV infection. Genotype D presented both BCP and PC mutations more frequently.

Context: Pain management in cirrhotic patients is a major clinical challenge for medical professionals. Unfortunately there are no concrete guidelines available regarding the administration of analgesics in patients with liver cirrhosis. In this review we aimed to summarize the available literature and suggest appropriate evidence-based recommendations regarding to administration of these drugs.Evidence Acquisition: An indexed MEDLINE search was conducted in July 2014, using keywords "analgesics", "hepatic impairment", "cirrhosis", "acetaminophen or paracetamol", "NSAIDs or nonsteroidal anti-inflammatory drugs", "opioid" for the period of 2004 to 2014. All randomized clinical trials, case series, case report and meta-analysis studies with the above mentioned contents were included in review process. In addition, unpublished information from the Food and Drug Administration are included as well.Results: Paracetamol is safe in patients with chronic liver disease but a reduced dose of 2-3 g/d is recommended for long-term use. Non-steroidal anti-inflammatory drugs (NSAIDs) are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Most opioids can have deleterious effects in patients with cirrhosis. They have an increased risk of toxicity and hepatic encephalopathy. They should be administrated with lower and less frequent dosing in these patients and be avoided in patients with a history of encephalopathy or addiction to any substance.Conclusions: No evidence-based guidelines exist on the use of analgesics in patients with liver disease and cirrhosis. As a result pain management in these patients generates considerable misconception among health care professionals, leading under-treatment of pain in this population. Providing concrete guidelines toward the administration of these agents will lead to more efficient and safer pain management in this setting.

Background: About 30% of individuals with hepatitis C virus (HCV) infection are able to clear HCV spontaneously. Differences in host genetics affect the outcome of HCV infection. Single nucleotide polymorphisms (SNPs) of the Interferon lambda (IFNL) genes were associated with spontaneous and treatment-induced clearance of HCV infection.Objectives: The aim of this study was to evaluate the association between the IFNL4 rs12979860 SNP and spontaneous clearance of HCV infection in Iranian population.Materials and Methods: A case-control study was designed on 91 cases with spontaneous HCV infection clearance and 259 patients with persistent HCV infection as the control group. The rs12979860 SNP was assessed as the most common IFNL polymorphism by PCR-RFLP method.Results: Distribution of rs12979860 CC genotype in the spontaneous clearance group was around two folds of its distribution in chronic hepatitis C group (P<0.001, OR=4.09, 95% CI=2.44-6.86).Conclusions: The rs12979860 SNP was observed as a strong host genetic factor associated with spontaneous clearance of hepatitis C infection.

Background: Distribution of Hepatitis C Virus (HCV) genotypes may be changed over time. Epidemiological Studies on distribution patterns of HCV genotypes in Pakistani population might assist for better treatment options and preventive strategies.Objectives: This study was conducted to determine distribution patterns of HCV genotypes in different geographical regions of Pakistan.Patients and Methods: In this cross-sectional study, 1818 randomly selected patients from different geographical regions of Pakistan, diagnosed with HCV infection by the third generation Enzyme Linked Immunosorbent Assay (ELISA), were included between April 2011 and December 2013. HCV RNA was detected in serum samples of patients by Reverse Transcription Polymerase Chain Reaction (RT- PCR) of the core region. Qualitative PCR was performed to determine viral load. HCV genotyping was performed by RT-nested PCR using type-specific primers of the core region. Frequency of different genotypes among patients was assessed according to gender, age and geographical region at the time of sampling.Results: Of 1818 HCV RNA positive samples, HCV genotypes PCR fragments were detected in 1552 (85.5%) samples. HCV genotype 3a was the predominant genotype (39.4%) followed by genotype 2a (24.93%). HCV genotype 3 was the predominant genotype in Punjab and Sindh regions, while genotype 2 was the most predominant genotype in Khyber Pakhtunkhwa region and the second predominant genotype after genotype 3 in Sindh region. The incidence of genotype 2a is increasing in our country with decrease in the incidence of genotype 3a. A higher incidence of HCV various genotypes were observed among male patients and those younger than 45 years.Conclusions: This study may facilitate treatment options and preventive strategies in Pakistan.

Background: Hypervariability of HCV proteins is an important obstacle to design an efficient vaccine for HCV infection. Multi-epitope vaccines containing conserved epitopes of the virus could be a promising approach for protection against HCV.Objectives: Cellular and humoral immune responses against multi-epitope DNA and peptide vaccines were evaluated in BALB/c mice.Materials and Methods: In this experimental study, multi-epitope DNA- and peptide-based vaccines for HCV infection harboring immunodominant CD8+T cell epitopes (HLA-A2 and H2-Dd) from Core (132-142), NS3 (1073-1081) and NS5B (2727-2735), a Th CD4+epitope from NS3 (1248-1262) and a B-cell epitope from E2 (412-426) were designed. Multi-epitope DNA and peptide vaccines were tested in two regimens as heterologous DNA/peptide (group 1) and homologous peptide/peptide (group 2) prime/boost vaccine in BALB/c mice model. Electroporation was used for delivery of the DNA vaccine. Peptide vaccine was formulated with Montanide ISA 720 (M720) as adjuvant. Cytokine assay and antibody detection were performed to analyze the immune responses.Results: Mice immunized with multi-epitope peptide formulated with M720 developed higher HCV-specific levels of total IgG, IgG1 and IgG2a than those immunized with multi-epitope DNA vaccine. IFN-γ levels in group 2 were significantly higher than group 1 (i.e.3 weeks after the last immunization, 37.61±2.39 vs.14.43±0.43, P<0.05). Moreover, group 2 had a higher IFN-Y/IL-4 ratio compared to group 1, suggesting a shift toward Th1 response. In addition, in the present study, induced immune responses were long lasting and stable after 9 weeks of the last immunization.Conclusions: Evaluation of multi-epitope DNA and peptide-vaccines confirmed their specific immunogenicity in BALB/c mice. However, lower Th1 immune responses in mice immunized with DNA vaccine suggests further investigations to improve the immunogenicity of the multi-epitope DNA vaccine through immune enhancers.

Background: Liver transplantation is a critical survival point for patients with end stage liver diseases. It can dramatically increase patients’ survival if the donor liver is intact. One aspect of liver health is absence of steatosis. Nonalcoholic Steato Hepatitis (NASH) and Nonalcoholic Fatty Liver Disease (NAFLD) are increasing among young adults and patients living with chronic liver diseases.Objectives: In this study, we determined the prevalence of NALFD in livers of brain-dead donors in Imam-Khomeini hospital Complex, Tehran, Iran. We assumed that the calculated prevalence would represent NAFLD prevalence in Iranian population in the age range of 20-60 years.Materials and Methods: All eligible brain dead liver transplant donors were enrolled in the survey from March 21, 2011 to March 21, 2013 in Imam-Khomeini hospital Complex. Eligible participants were donors aged 20 to 60 years without any obvious history of liver disease. Liver needle biopsy was performed at the end of the transplant operation, time zero biopsy. We calculated the prevalence of NAFLD among brain-dead donors. Moreover, the frequency of NASH was calculated based on the NAS (NAFLD Activity Score).Results: Among 116 cases, two were diagnosed as probable NASH. There was a significant association between NAFLD and male gender (P=0.04). Moreover, we found a higher steatosis level in male gender. There was a significant association between NAFLD and BMI (P=0.05). Those with BMI more than 27 had severe steatosis.Conclusions: Our comprehensive literature review showed that our study was the first investigation in Iran and the region, which determined the prevalence of NAFLD based on tissue diagnosis. We believe that the prevalence of NAFLD/NASH in our donors can represent the overall prevalence in this age group in Iran.