Hepatitis Monthly
Year:2014 | Volume:14 | Issue:1|Papers Count:14

Background: Portal hypertension is a common consequence of hepatic cirrhosis, which causes esophageal varices. Bleeding from varices has a high mortality rate. The present gold standard for diagnosing varices is endoscopy. Considering endoscopy side effects and patients' low acceptance, there have been always efforts for finding alternative diagnostic methods including Doppler ultrasonography (US).Objectives: The aim of the present study was to evaluate changes of Doppler indices in cirrhotic patients with and without esophageal varices.Patients and Methods: Sixty six patients with known cirrhosis entered this cross-sectional study. Gastroscopy was performed for patients, and the first questionnaire was filled based on the Japanese Portal Hypertension Society guidelines. Then patients were referred for Doppler US of splenoportal system, and information was documented in the second questionnaire.Results: Forty-four patients were male and 22 female. Forty six patients had esophageal varices, and 20 did not. There were no significant associations between splenoportal indices found by Doppler US, and presence of esophageal varices in patients. However, we found a negative association between platelet ratio to spleen diameter, and to splenic vein diameter.Conclusions: Neither of studied variables was perfect to differentiate cirrhotic patients with and without EVs. Endoscopy is still the gold standard diagnostic method for diagnosing esophageal varices in patients with cirrhosis. It seems that some of the splenoportal Doppler indices are promising, but more research and evaluation is necessary.

Background: Hepatitis C virus (HCV) infection as a worldwide health problem is associated with cirrhosis and hepatocellular carcinoma. With current treatment regimen, pegylated interferon (PEG-IFN) plus ribavirin, sustain virological response (SVR) is achieved in only 50% of infected individuals. In HCV infection, an inappropriate ratio of cytokines may affect the benefit of antiviral therapy. Given the polymorphisms in regulatory regions of cytokines genes may influence cytokines production.Objectives: We aimed to investigate both the frequency of genotypes and alleles of interferon gamma (IFN-g) gene at+874A/T, +2109A/G, and -183G/T loci in HCV-infected patients and their associations with response to therapy.Patients and Methods: A total of 158 patients were included and treated with PEG-IFN plus ribavirin. The presence of HCV infection in patients was confirmed by reverse transcription polymerase chain reaction, and genomic DNA was extracted from peripheral leukocytes using salting out method. IFN-g gene polymorphisms were identified by polymerase chain reaction using sequence specific primers and restriction fragment length polymorphism analysis on genomic DNA.Results: Of 158 patients, 110 (69.5%) subjects achieved SVR and 48 (30.5%) subjects did not respond to therapy. The frequency of AA genotype (P=0.001, OR: 11.2, CI: 2.26-63.21) and A allele (P=0.01, OR: 3.23, CI: 1.23 8.56) of IFN-g gene at+2109 locus were significantly different between the responder and non-responder subjects infected with genotype 1. Regardless of HCV genotype, the frequency of AG genotype was also higher in responder group than those who did not respond to therapy (P=0.041, OR: 05.05, CI: 1.05-33.25)). In case of IFN-g gene at+874 locus, there was no difference in genotypes and alleles frequencies between the responder and non-responder subjects infected with HCV genotypes 1 and 3. Haplotype analysis showed no association between haplotypes and response to therapy. All participants had G/T genotype at -183 locus.Conclusions: Our findings indicate that heterogeneity at+2109 locus of IFN-g gene but not at+874 locus could interfere with successful therapy in patients infected with HCV genotype 1.

Background: Mutations in the polymerase (P) gene of hepatitis B virus are often associated with drug resistance. The pattern of mutations varies geographically, thus giving rise to genotypes diversity.Objectives: This study was carried out to detect mutations in P gene of hepatitis B virus isolated from Malaysian HBV carriers.Materials and Methods: A total of 58 sera samples were analyzed by PCR and sequencing, of which the P gene of isolated HBV was successfully amplified and sequenced from 40 samples.Results: Genotyping of these samples revealed that the predominant genotype was genotype C (22.40, 55.0%), followed by genotype B (17.40, 42.5%), and only 1 sample showed genotype D (2.5%). A number of significant drug resistant mutations were found in five patients including S202I, N236T, M250L, L180M/V, M204I, A181T, T184G, M250V, and V173L. Of these, L180M/V and M204I were most frequently detected (80%) and associated with lamivudine in combination with emtricitabine and telbivudine drug resistance. Association with age, sex, and clinical symptoms revealed that these patients were all male, mid to elderly age and almost all hadcirrhotic liver disease.Conclusions: Detection and surveillance of the significant sites of mutations in HBV is crucial for clinicians to decide on the choice of antiviral treatment and further management of hepatitis B carriers.

Dear Editor: A recent report by Shakeri et al. (March, 2013) published in Hepatitis Monthly showed that HCV prevalence is 0.2% in Mashad, Iran (1). Moreover, Previous report from Iran showed the similar prevalence of HCV in voluntaries blood donors (2). Pakistan, a neighboring country of Iran, is a low socioeconomic country having more than 10 million HCV infected people (3). Recently we have published the prevalence of HCV among 62, 251 healthy blood donors from North West Province of Pakistan. The study showed that 2.6% of healthy individuals were HCV antibody positive (4). We also concluded that the HCV prevalence is increasing with time when the results were compared with other previous reports.

Background: Hepatitis E virus (HEV) is a major causative agent of acute clinical hepatitis in adults through much of Asia, the Middle East and Africa. Open reading frame 3 (ORF3) encodes around 120 amino acids of phosphorylation protein that associates with the cytoskeleton, while its precise biological function is still unknown.Objectives: In order to understand the function of ORF3 protein (pORF3) in depth, HEV ORF3 interacting proteins were screened in human hepatocytes cDNA library using two-hybrid system techniques and further verification of the interactions were carried out through co-immunoprecipitation (Co-IP).Materials and Methods: The Cyto-Trap two-hybrid system technology, a classical method for analyzing protein interactions, was used to screen the pORF3 interacting proteins from human hepatocytes cDNA library.Results: Through the Cyto-Trap two-hybrid system, eight proteins interacting with pORF3 were winnowed. The Co-IP results confirmed that hepsin which is reported to function as the inhibitor of several tumors reacted with pORF3.Conclusions: Out of eight screened proteins interacting with pORF3, hepsin was confirmed to have specific interactions with pORF3.

Background: During antiviral therapy for chronic hepatitis B, renal function impairment could be a critical concern when oral nucleot (s) ide analogues were used. Paradoxically, long-term telbivudine treatment was associated with an increase of estimated glomerular filtration rate (eGFR) through unknown mechanisms.Objectives: We aimed to investigate changes in serum protein abundances associated with renal function in response to antiviral treatments.Materials and Methods: Primarily, a transcriptomic assay was performed to identify differentially expressed genes in peripheral blood cells caused by the telbivudine treatment. Two genes coding angiotensin converting enzyme (ACE) and complement factor H (CFH) were screened from 14 candidate renal function-related genes. ACE and CFH production were further investigated using enzyme-linked immunoassays.Results: Verification studies showed no significant change of serum CFH levels, but there was a significant reduction of serum ACE levels by continuous telbivudine treatment for 330.00±0.85 days (34 patients, paired t-test, P=0.022). Serum HBV DNA and ALT levels also decreased (P=0.008 and<0.001, respectively). A significant increase in eGFR was found (33 patients, paired t-test, P=0.002) at 708.64±31.63 days. Patients’ eGFRs were negatively correlated with serum ACE levels (r=-0.375, P=0.002) but not with serum HBV DNA and ALT levels (P=0.241 and 0.088 respectively). Significant decreases of the ACE levels were also observed upon entecavir treatment (20 patients, paired t-test, P=0.020) at 412.88±36.92 days. No significant correlation was found between serum ACE levels and eGFRs (r=-0.239, P=0.138) in entecavir-treated patients.Conclusions: We discovered a consistent reduction of serum ACE levels by two oral antiviral monotherapies, entecavir and telbivudine. Serum ACE levels were negatively correlated with eGFRs in telbivudine treated patients.

Dear Editor: Hepatitis C virus (HCV) with around 180 million infected patients worldwide is the leading cause of mortality and morbidity (1). The prevalence of HCV in Iran is about 0.2% (2). Geographically, HCV genotype has specific distribution pattern in the world. However, in many countries it is currently observed that the genotype pattern is going to change. Changing HCV clade pattern is mainly due to world globalization, and traveling to other countries especially to the neighboring ones.

Background: Detectable HCV-specific cellular immune responses in HCV antibody and RNA negative people who inject drugs (PWID) raise the question of whether some are resistant to HCV infection. Immune responses from people who have been exposed to hepatitis C virus (HCV) and remain anti-HCV negative are of interest for HCV vaccine development, however, limited research addresses this area.Objectives: In a cohort of HCV antibody and RNA negative PWID, we assessed whether the presence of HCV-specific IFN-g responses or genetic associations provide any evidence of protection from HCV infection.Patients and Methods: One hundred and ninety-eight participants were examined longitudinally for clinical, behavioral, social, environmental and genetic characteristics (IFNL3 genotype [formally IL-28B] and HLA type). Sixty-one of the 198 participants were HCV antibody and RNA negative, with 53 able to be examined longitudinally for HCV-specific IFN-g ELISpot T cell responses.Results: Ten of the 53 HCV antibody and RNA negative participants had detectable HCV-specific IFN-g responses at baseline (18%). The magnitude of IFN-g responses averaged 131+/-96 SFC/106 PBMC and the breadth was mean 1+/-1 pool positive. The specificity of responses were mainly directed to E2, NS4b and NS5b. Participants with (10) and without (43) HCV-specific IFN-g responses did not differ in behavioral, clinical or genetic characteristics (P>0.05). There was a larger proportion sharing needles (with 70%, without 49%, P=0.320) and a higher incidence of HCV (with 35.1 per 100 py, 95% CI 14.6, 84.4, without 16.0 per 100 py, 95% CI 7.2, 35.6, P=0.212) in those with IFN-g responses, although not statistically significant. Half the participants with baseline IFN-g responses became HCV RNA positive (5.10), with one of these participants spontaneously clearing HCV. The spontaneous clearer had high magnitude and broad Th1 responses, favorable IFNL3 genotype and favorable HLA types.Conclusions: This study demonstrated the detection of HCV-specific IFN-γ responses in HCV antibody and RNA negative individuals, with a tendency for HCV-specific IFN-g responses to be associated with HCV exposure. The potential role of HCV-specific IFN-g responses in those who remained HCV RNA negative is of value for the development of novel HCV therapeutics.

Background: Hepatitis B virus (HBV) infection significantly contributes to the onset of liver disease and hepatocellular carcinoma. Understanding the pathogenesis of HBV infection susceptibility could help us to control HBV infection effectively.Objectives: This study investigated single nucleotide polymorphisms (SNPs) of the tripartite motif-containing 22 (TRIM22) gene associated with HBV infection outcome.Patients and Methods: A total of 765 Chinese Han subjects were enrolled: 293 patients were presented with chronic hepatitis B (CHB), 224 were asymptomatic HBV carriers, 248 had self-limited HBV infection, and all of them were recruited for TRIM22 SNPs genotyping. RING and SPRY domains of TRIM22 gene were DNA-sequenced, and HBV serum markers and HBV DNA were measured quantitatively in all subjects.Results: 243 (31.76%) of 765 Chinese Han patients showed genetic variation in the TRIM22 gene. TRIM22 SNPs were mainly in RING area -364T/C site, accounting for 98.35% of the population. There were no significant differences (P>0.05) in the RING domain -364T/C SNP and allele frequencies between patients with chronic hepatitis and asymptomatic HBV carriers. The CC genotype of TRIM22 gene RING domain -364T/C locus (rs10838543) was associated with chronic HBV infection (OR=2.30, 95% CI=1.24-3.97, P=0.0012, OR=2.26, 95% CI=1.08-3.74, P=0.002) and a mutant allele C carrier of the TRIM22 gene was associated with HBV chronic infection (OR=1.97, 95% CI=1.10-3.75, P=0.0049, OR=2.12, 95% CI=1.17-3.89, P=0.0038).Conclusions: TRIM22 gene RING domain -364T/C polymorphism is associated with chronic HBV infection in Chinese Han population.

Background: In the living donor liver transplant setting, the preoperative assessment of potential donors is important to ensure the donor safety.Objectives: The aim of this study was to identify causes and costs of living liver-donors rejection in the donation process.Materials and Methods: From June 2010 to June 2012, all potential living liver donors for 66 liver transplant candidates were screened at the Ain Shams Center for Organ Transplantation. Potential donors were evaluated in 3 phases, and their data were reviewed to determine the causes and at which phase the donors were rejected.Results: One hundred and ninety two potential living liver donors, including 157 (81.7%) males, were screened for 66 potential recipients. Of these, 126 (65.6%) were disqualified for the donation. The causes of rejection were classified as surgical (9.5 %) or medical (90.5 %). Five donors (3.9 %) were rejected due to multiple causes. Factor V Leiden mutation was detected in 29 (23 %) rejected donors (P=0.001), 25 (19.8 %) donors had positive results for hepatitis serology (P=0.005), and 16 (12.7 %) tested positive for drug abuse. Portal vein trifurcation (n=9, 7.1%) and small size liver graft estimated by CT volumetric analysis (n=6, 4.8 %) were the main surgical causes which precluded the donation.Conclusions: Among potential Egyptian living liver donors, Factor V Leiden mutation was a significant cause for live donor rejection. A stepwise approach to donor assessment was found to be cost-effective.

Background: Hepatocellular carcinoma (HCC), a major fatal cancer worldwide, is induced by different etiological factors in the liver.Objectives: To gain insight into serum protein profiling of HCC with different etiologies.Patients and Methods: We subjected the sera of HBV-HCC, HCV-HCC, non-B non-C-HCC patients, and healthy volunteers to two-dimensional gel electrophoresis (2-DE) and liquid chromatography tandem mass spectrometry (LC-MS/MS).Results: We found 30 differentially expressed protein spots (³1.5 fold P<0.05) between these two analyses, of them 17 protein spots corresponding to 8 proteins were identified by MS. Transthyretin, leucine rich a-2-glycoprotein, and ficolin 3 were differentially expressed between HBV-related HCC and non-B non-C-HCC sera. Moreover, haptoglobin a-2 isoforms were decreased in HCV-HCC compared to non-B non-CHCC.Conclusions: Serum proteome analyses of HCC with different origins showed a differential protein pattern, presumably related to different hepatopathogenesis in liver induced by different agents. Further studies are required to clarify the importance of identified proteins for early diagnosis of HCC with different origins.

Background: Histopathologic assessment of liver tissue is an essential step in management and follow-up of non-alcoholic fatty liver disease (NAFLD) while inter- and intra-observer variations limit the accuracy of these assessments.Objectives: The aim of this study was to assess the inter- and intra-observer reproducibility of histopathologic assessment of liver biopsies based on NAFLD activity score (NAS) scoring system.Materials and Methods: The anonymous liver biopsy samples of 100 consecutive NAFLD suspected adults were randomly assigned to four pathologists. Then, the samples were randomly reassigned to the pathologists for the second time in a way that each sample would be evaluated by two different pathologists. Biopsies were revisited by their first evaluator after two months. The results were reported based on NAS scoring system.Results: Inter-observer agreement of the pathology scores based on NAS scoring system was acceptable for steatosis, lobular inflammation, and fibrosis, but not for hepatocyte ballooning. The intra-observer agreement was acceptable in all scales, with lowest intra-class correlation observed for lobular inflammation.Conclusions: NAS scoring system has good overall inter- and intra-observer agreement, but more attention should be given to defining the hepatocyte ballooning and lobular inflammation, and training the pathologists to improve the accuracy of pathology reports.

Introduction: In general, the hepatitis E virus (HEV) causes acute, self-limiting hepatitis. Prolonged and chronic infections caused by HEV genotype 3 have been found in some immunosuppressed patients in developed countries.Case Presentation: Here we report a Chinese boy with acute lymphoblastic leukemia, who developed hepatitis E during a period of intensive chemotherapy. Twenty months after the initial infection, HEV viremia was reappeared in the patient, with detectable anti-HEV IgM and IgG and modestly elevated serum transaminases. Sequence analysis of the viral RNAs revealed the reactivation of the HEV genotype 4d strain, indicating viral persistence in the patient.Conclusions: To our knowledge, this is the first chronic case confirmed by the prolonged presence of HEV RNA in china. It is also the first reported persistent hepatitis E infection caused by HEV genotype 4.

Background: The duration of protection following primary series vaccination against hepatitis B is unknown in children and adolescents. It has been shown that the level of anti-hepatitis B surface antigen antibodies (anti HBs Ab) declines over years after vaccination.Objectives: The aim of this study was to estimate the long-term immunity against hepatitis B virus infection among children and adolescents who had received a complete hepatitis B vaccination series during infancy.Patients and Methods: In a cross-sectional study, the-anti-HBsAb levels of 840 vaccinated children and adolescents were determined by enzyme-linked immunosorbent assay.Results: Hepatitis B seroprotection rates (anti HBsAb³10 IU/L) among vaccinated children and adolescents aged 1 and 18 years were 90% and 48.9%, respectively. The declining trend of geometric mean titer of anti-HBsAb levels was observed as changed from 272.3 IU/L to 94.1 IU/L in 1 and 18-year-old population, respectively. A significant negative correlation was found between age and anti-HBsAb levels (r=-0.220, P=0.0001).Conclusions: The results showed a declining trend in anti-HBsAb titers over the time after vaccination against hepatitis B virus in our region. Further studies are warranted to establish the need for a booster dose in cases that are at risk of hepatitis B virus infection.