Hepatitis Monthly
Year:2013 | Volume:13 | Issue:1 |Papers Count:13

Background: Despite the advances in the treatment of chronic hepatitis B virus (HBV) infection, liver transplantation (LT) remains the only hope for many patients with end-stage liver diseases resulting from HBV.Objectives: The aim of this study was to investigate the rate of HBV recurrence in cases that had undergone LT due to the HBV related liver cirrhosis.Patients and Methods: Forty-nine patients who underwent LT due to HBV related cirrhosis since 2001 to 2009 in Shiraz Organ Transplantation Center were enrolled in the present study. They were asked to complete the planned questionnaire and also to sign the informed consent in order to take part in this study. Post-transplant prophylaxis protocol against HBV recurrence was based on a hundred milligrams of lamivudine daily plus intramuscular injections of hepatitis B immune globulin (HBIG) with appropriate dosage to keep anti-HBs antibody titer above 300 IU/L and 100 IU/L in the first six months and afterwards, respectively. Blood samples were obtained and checked for HBsAg, HBeAg, and the titers of Anti -HBsAb as well as Anti- HBeAb with ELISA. A quantitative HBV DNA assay was also done on all samples (GENE-RAD® Real-time PCR).Results: There were 91.8% males and 8.2% females enrolled in the study. The duration of post-transplant prophylaxis ranged from 3 months to 8 years (mean 18.9±19.3 months). HBsAg and HBeAg were positive in 24.5% and 2% of cases, respectively. Real-time PCR for HBV DNA were zero copies/mL in 91.8% of patients, none of which represented a positive value for HBV recurrence (Positive>10, 000 copies/mL). The mean Anti-HBs Ab titer was 231.7±135.9 IU/L; it was above 100 IU/L in 71.4% of patients. Thirty-seven (75.5%) of the patients were taking tacrolimus plus mycophenolate mofetil, 6 (12.2%) were on cyclosporine plus mycophenolate mofetil, and 6 (12.2%) were taking sirolimus plus mycophenolate mofetil. HBsAg was detectable in seven patients taking tacrolimus plus mycophenolate mofetil (18.9%), in four patients taking cyclosporine plus mycophenolate mofetil (66.7%), and in one patient among the six who were taking sirolimus plus mycophenolate mofetil (16.7%). There was no significant statistical correlation between the presence of a positive value for HBsAg and the immunosuppression regimen or Anti HBsAb titer (P>0.05). Presence of a positive value for HBsAg was not predictive of a positive HBV DNA or its level in blood (P>0.05).Conclusions: Post-transplant HBV prophylaxis with lamivudine and intramuscular HBIG with appropriate dosage to keep anti-HBs antibody titer above 300 IU/L in the first six months and above 100 IU/L afterwards is effective for prevention of HBV recurrence after LT.

Background: Hepatocytes are used as an in vitro model to evaluate drug metabolism. Human hepatocyte transplant has been considered as the temporary treatment of acute liver failure. Optimization freezing methods is very important to preserve both cell viability and function which are achieved by cryopreservation mostly always.Objectives: The present study aimed to investigate the cryoprotective effect of DTT and fructose on primary rat hepatocytes and HepG2 cells. Materials and Methods: Both fresh rat hepatocytes and HepG2 cell line were incubated with fructose (100 and 200 mM) and dithiothreitol (DTT) (25, 50, 100, 250, and 500 mM) at 37°C for 1 and 3 hours, respectively. The preincubated hepatocytes were cryopreserved for two weeks.Hepatocytes viability and function were determined post thawing and the results were compared with the control group.Results: The viability of both rat hepatocytes and HepG2 cells were significantly increased after one hour preincubation with fructose 200 mM. Preincubation with DTT (50 mM, 100 mM.250 mM and 500 mM) improved the viability and function upon thawing in both cell types (P< 0.001). In rat hepatocytes, no significant change was observed in albumin, urea production, and LDH leakage after preincubation with fructose or DTT. In HepG2 cells, albumin and urea production were significantly increased after preincubation with DTT (500 mM, 1 hour). The GSH content was significantly increased in DTT (250 and 500 mM, 1 hour) groups in both rat hepatocyte and HepG2 cells.Conclusions: Incubation of hepatocytes with fructose and DTT prior to the cryopreservation can increase the cell viability and function after thawing.

Context: We briefly reviewed the evidence on the association of hepatitis C (HCV) infection with several aspects of mental and psychosocial health.Evidence Acquisition: Medline was searched with appropriate keywords. The primary sources were the systematic reviews. If systematic reviews were not available for a subject, then the most relevant and methodologically sound original studies were selected.Results: HCV infection is associated with poorer health-related quality of life, and physical, mental, and social health. A part of impaired health of these patients is related to cirrhosis, intravenous drug use, co morbid psychiatric disorders, stigmatization, poor social support, alcohol abuse, and interferon treatment. However, HCV itself is also associated with poorer health status particularly in the physical and cognitive domains, which might be related to brain alterations induced by the virus. Interferon treatment is an important cause of depression in HCV patients and sometimes is associated with irritability, manic episode, or acute confusional state. Social health of HCV patients is significantly impaired by stigmatization, poor social support, psychiatric comorbidties, and impaired coping. Psychosocial impairment of HCV patients significantly impairs their treatment adherence. A supportive and nonjudgmental multidisciplinary team is required for optimal management of these patients.Conclusions: Patients with HCV infection had complex neuropsychiatric and psychosocial problems. These problems are challenges for management of HCV infection, affect the patient’s care significantly, and might alter the course of the disease. A multidisciplinary approach, a supportive environment, and a nonjudgmental healthcare team are required for optimal medical and psychosocial management of patients with HCV.

Background: Immunomodulators and Nucleotide analogues have been used globally for the dealing of chronic hepatitis B virus (HBV) infection. However, the development of drug resistance is a major limitation to their long-term effectiveness.Objectives: The aim of this study was to characterize the hepatitis B virus reverse transcriptase (RT) protein variations among Iranian chronic HBV carriers who did not receive any antiviral treatments.Materials and Methods: Hepatitis B virus partial RT genes from 325 chronic in active carrier patients were amplified and directly sequenced.Nucleotide/amino acid substitutions were identified compared to the sequences obtained from the database.Results: All strains belonging to genotype D.365 amino-acid substitutions were found. Mutations related to lamivudine, adefovir, telbivudine, and entecavir occurred in (YMDD) 4% (n=13), (SVQ) 17.23% (n=56), (M204I/V+L180M) 2.45% (n=8) and (M204I) 2.76% (n=9) of patients, respectively.Conclusions: RT mutants do occur naturally and could be found in HBV carriers who have never received antiviral therapy. However, mutations related to drug resistance in Iranian treatment-naïve chronic HBV patients were found to be higher than other studies published formerly. Chronic HBV patients should be monitored closely prior the commencement of therapy to achieve the best regimen option.

Dear Editor: Actually, in literature, it is known that HLA-DQ2 haplotype is over-represented in celiac population and since both HBsAg protein fragments and gliadin peptides bind to HLA-DQ2 molecules; their competition may favors a defective antibody response against the recombinant HBsAg vaccine in active celiac disease. On the other hand, some studies demonstrate that in celiac individuals, the gluten intake at the time of vaccination influences the vaccine-induced immune response.

background: Hepatitis D Virus (HDV) causes the most threatening form of chronic viral hepatitis. To date, there is no overall estimation of HDV prevalence in the Eastern Mediterranean Region Office of WHO (EMRO) countries.Objectives: To provide a clear estimation of HDV prevalence in the aforementioned region.Patients and Methods: In the current systematic review, databases such as PubMed, Embase, Web of sciences and Google scholar were searched Until December 2010. The summary estimate of HDV prevalence in the EMRO region was calculated as an average of the pooled infection prevalence of each country weighted by the ratio of the country’s HBV population to the study’s sample size in the survey data analysis.Results: We included 62 eligible studies. The weighted mean of HDV prevalence in the EMRO region was 14.74% (95% CI: 14.73-14.77), 27.8% (95% CI: 27.78-27.82), 36.57% (95% CI: 36.55-36.59) and 16.44%. (95% CI: 16.42-16.46) in asymptomatic HBsAg positive carriers, chronic hepatitis patients, cirrhosis/ hepatocellular carcinoma, and high risk group, respectively. Among the asymptomatic HBsAg positive group, HDV prevalence was increased by years in older patients in Saudi Arabia but its prevalence was decreased in Iran. No specific pattern was seen according to chronological analysis during years among the EMRO countries.Conclusions: HDV infection is endemic in the EMRO countries and it is more common among patients with severe forms of hepatitis. Due to the high HDV infection rates in the EMRO countries, we recommend blood screening for HDV infection in this region.

Background: Hepatitis B virus (HBV) infection has remained a significant public health problem. Generating a large-scale, community-based profile of HBV infection in China is essential to prevention of the disease.Objectives: The current study was designed to investigate HBV-infected individuals at the community level and determine the age distribution, hepatitis B e antigen (HBeAg) positivity and its related risk factors, relationship among serological markers.Patients and Methods: A cross-sectional, community-based survey was carried out without age restriction, in 12 communities of two counties. The study population was selected by random multistage cluster sampling. Serological samples and demographic information were collected from 8439 HB surface antigen (HBsAg) -positive individuals.Results: The constituent ratio of individuals with HBsAg-positive infections was lowest among persons aged<20 years (0.4%) and the highest among persons aged 40-49 years (33.2%). The HBeAg-positive rate among infected individuals was 18.5%, and the constituent ratio decreased with increasing of age. The HBeAg-positive rate in males (21.9%) was significantly higher than in females (14.7%), and was higher among coastland inhabitants (22.9%) than among plains inhabitants (12.9%). Among the 1561 HBeAg-positive individuals, 91.0% were HBV DNA-positive. However, of the 6878 HBeAg-negative individuals, only 45.4% were HBV DNA-positive, and the HBeAg-positive rate was significantly different at different levels of HBV DNA expression. The proportion of detectable HBV DNA levels was significantly higher in individuals with elevated ALT, compared to those with normal ALT, regardless of HBeAg-positivity.Conclusions: The HBV prevalence remained high in the>20 age group. The positivity of HBeAg was related to age, region, and sex. Testing HBeAg and serum ALT levels were effective ways to assess HBV infectiousness in community-level hospitals in China.

Background: Epidemiological evidence has clearly indicated that chronic infection with the hepatitis B virus (HBV) is the major risk factor for developing hepatocellular carcinoma (HCC). Nonetheless, the mechanisms by which HBV contributes to the pathogenesis of HCC have not been fully elucidated. Objectives: Our aim was to characterize differential gene expression profiles related to the Wnt signaling pathway between primary tumor and adjacent normal tissues in HCC patients with concomitant HBVinfection. Materials and Methods: An oligoGEArrayÒ (an oligonucleotide-based gene expression array platform) containing 126 Wnt signaling pathway-related genes was used to compare gene expressions between primary HCC and adjacent non-tumorous liver tissues from 10 patients with HCC. Selected differential genes were identified with real-time RT-PCR and immunohistochemistry (IHC). In particular, the protein of the differential gene DVL3 (disheveled, dsh homolog 3 [Drosophila]) was chosen to investigate whether it is up regulated in primary tumor correlated with the clinic pathological characteristics of HCC patients. For this purpose we examined 56 HCC tissue samples via IHC for the presence of DVL3 protein.Results: Sixteen genes were identified with significant differential expression between HCC and adjacent non-tumorous liver tissue. These genes have been previously associated with the Frizzled signaling pathway, cell cycle, transcription, or protein degradation. All (100%) of the tumor samples results from 56 HCC patients tested were positive for DVL3 via IHC. Based on the intensity of DVL3 immunoreactivity, 25 (44.6%) and 31 (55.4%) of the patients were classified aslow and high-DVL3, respectively, which correlated with tumor stage (P=0.029). Conclusions: This study clarified a number of Wnt pathway-related genes which are dysregulated in HBV-associated HCC. These genes may be contributedto the frequent activation of the Wnt signaling pathway. Our results promote the role of the Wnt signaling pathway in HBV- associated HCC.

Background: Clinical observations have shown that patients infected with chronic hepatitis B virus (HBV) genotype C versus genotype B had a higher load of the virus, more serious illness, and poorer responses to antiviral therapy and prognosis. However, the disparity between the two has not been clarified.Objectives: To explore possible relationship between HBV genotypes B and C and peripheral blood follicular helper T cells (Tfh) and its significance in treating chronic hepatitis B (CHB) patients.Patients and Methods: One hundred and fifty CHB patients were enrolled into this study, including 70 cases infected with HBV genotype C and 79 cases with genotype B. One patient had suffered from both genotypes B and C. The levels of Tfh, also known as interleukin-21 (IL-21), HBV specific cytotoxic T lymphocytes (CTL), HBV DNA and alanine transaminase (ALT) were evaluated and compared in patients infected with genotype B and C.Results: Levels of Tfh, IL-21 and HBV specific CTL of patients infected with HBV genotype C were significantly lower than those of patients infected with HBV genotype B, P<0.01. Levels of HBV DNA and ALT of patients infected with genotype C were significantly higher than those of the patients infected with HBV genotype B, P<0.01.Conclusions: Compared with chronic hepatitis B (CHB) patients infected with genotype B, higher levels of serum HBV DNA, ALT and TBil of patients infected with HBV genotype C may be related to their lower level of peripheral blood Tfh, which may result in lower IL-21, and it may result in lower HBV specific CTL.

Background: Biliary complications are significant source of morbidity after liver transplantation (LT). Cholangiography is the gold standard for diagnosis and specification of biliary complications.Objectives: Detailed analyses of ultrasound (US) as a safe imaging method in this regard are still lacking. Therefore we analyzed systematically the diagnostic value of US in these patients.Patients and Methods: Retrospectively, 128 liver graft recipients and their clinical data were analyzed. All patients had a standardized US examination. The findings of US were compared to cholangiographic results in 42 patients. Following statistical analyses were performed: descriptive statistics, sensitivity, specificity, positive and negative predictive values (PPV, NPV).Results: 42 patients had 54 different biliary complications (Anastomotic stenosis (AS) n=33, ischemic type biliary lesions (ITBL) n=18 and leakage n=3). US detected n=22.42 (52%) patients with biliary complications. The sensitivity, specificity, PPV and NPV of US were: 61%, 100%, 100%, 79% (95CI, 36-86%) for ITBL and 24%, 100, 100%, 31% (95CI, 9-46 %) for AS, respectively Conclusions: US examination had no false positive rate. Therefore, it may be helpful as a first screening modality. But for the direct diagnosis of the biliary complication US is not sensitive enough.

Background: Hepatitis C virus (HCV) has different genotypes throughout the world. Since the determination of which antiviral treatment to be applied is related to HCV genotypes, identification of an individual’s HCV genotypes prior to antiviral therapy is critical.Objectives: The purpose of this study was to investigate the distribution of HCV genotypes in a large population of Iranian HCV infected patients.Patients and Methods: Eleven thousand, five hundred and sixty one patients with chronic HCV infection which referred to hospitals related to the Tehran University of Medical Sciences and Tehran Hepatitis Center-Clinical Department of Baqiyatallah Research Center for Gastroeneterology and Liver Disease from March 2003 to December 2011 were enrolled. Following extraction of viral RNA of the serum, HCV-RNA was detected using reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) and then HCV genotypes analyzed by restriction fragment length polymorphism (RFLP) assay.Results: The mean age of patients was 37.6±14.2 years (range: 1-87). The highest frequency was noted for subtype 1a (44.9%) followed by subtype 3a (39.6%), and 1b (11.3%). Mixed HCV genotypes were also found in 2.5% of the total cases. Subtype 1a was the most frequent genotype in patients over 40 years of age (46.1% versus 42.4%) and subtype 3a was the most frequent in patients under 40 years old (41.5% versus 38.9%).Conclusions: This study suggested that the dominant HCV subtype among Iranian patients was 1a followed by subtype 3a.

Background: Hepatitis C is prevalent among thalassemia patients in Iran. It is mainly transfusion mediated, in particular among patients treated before 1996 when blood screening was introduced.Objectives: The current study aimed to investigate why patients still seroconvert to anti-HCV in Iranian thalassemia centers.Patients and Methods: During 2006-2007 sera were sampled from 217 anti-HCV positive thalassemia patients at nine thalassemia centers in Tehran and Amol city, where 34 (16%) patients had been infected after 1996. The HCV subtype could be determined by sequencing and phylogenetic analysis of partial NS5B and/or 5 ׳NCR-core region in 130 strains.1a (53%) was predominant followed by 3a (30%), 1b (15%), and one strain each of 2k, 3k and 4a. Phylogenetic analysis revealed 19 clades with up to five strains diverging with less than six nucleotides from each other within subtypes 1a and 3a. Strains in seven clades were from nine patients infected between 1999 and 2005 and similar to strains from eight patients infected before 1996, indicating ongoing transmission at the centers. Further epidemiological investigation revealed that 28 patients infected with strains within the same clade had frequently been transfused at the same shift sitting on the same bed. An additional eight patients with related strains had frequently been transfused simultaneously in the same room.Conclusions: The results suggest nosocomial transmission at these thalassemia centers both before and after the introduction of blood screening. Further training of staff and strict adherence to preventive measures are thus essential to reduce the incidence of new HCV infections.

Background: Hepatitis C is one of the common infectious diseases throughout the world. About 170 million people worldwide are infected with Hepatitis C virus. The most common route of transmission is direct blood-to-blood contacts.Objectives: This study conducted to compare the amount of contamination might be found in ultra-filtered liquid passed through 2 kinds of filters ps10 (Mediatex, Iran) and Lups (Bio brand, Germany).Patients and Methods: To achieve the goal, infected dialysis patients in which hepatitis C virus infection was detected by Elisa and PCR were selected.Results: As shown in data the first stage of PCR test using ps10 filters all samples were negative. In the second step performed in later dialysis steps (with Lups filters), no infection was recorded, too.Conclusions: Our results showed that dialysis machines do not have an important role in transmission of hepatitis C infection and sanitation control in the environment of dialysis should be emphasized.