Hepatitis Monthly
Volume:11 Issue: 11, Nov 2011

Context: Patients with end-stage renal disease can easily acquire a hepatitis C virus (HCV) infection via several ways. An HCV infection is difficult to treat after renal transplantation due to the conflicting actions of immunosuppressant therapy to maintain the function of the transplanted kidney and viricidal interferon (IFN) or ribavirin (RBV) treatment. Antiviral therapy requires great caution to avoid the complex and potentially fatal pharmacological effects. In this review, we examined clinical challenges and potential solutions for this specific scenario.Evidence Acquisitions: We searched Pubmed (NLM), LISTA (EBSCO), Web of Science (TS). The management of patients on waiting list, the indications and regimens about treatment were studied. More than forty papers about this topic were found, including seven small clinical trials. International consensus has been reached to test patients awaiting renal transplantation. HCV detection after renal transplantation warrants careful consideration of when to initiate antiviral therapy. Treatment will begin immediately if deteriorating liver function increases the risk for loss of renal function. The choice of regimen depends on the patient's renal function and is individualized under close observation. The immunosuppressive regimen will be adjusted accordingly before antiviral therapy is initiated. The effects of modified antiviral therapy on these patients varies because of individual characteristics and disease state, and also because of the difficulty associated with conducting a large clinical trial to obtain statistically sound conclusions. The management before transplantation is important and when antiviral therapy needs to start, careful consideration of risks and benefits is needed before initiating this type of treatment.

The human HFE gene (a key component of iron homeostasis in humans) is involved in hereditary hemochromatosis, a common autosomal recessive genetic disorder that is characterized by excessive intestinal iron absorption and progressive iron overload. In this study, we assessed the frequency of two common forms of hemochromatosis HFE gene mutation (C282Y and H63D) in patients suffering from cryptogenic cirrhosis.Patients and One hundred and fifty individuals were included in this study, in which 100 were patients with cryptogenic cirrhosis and 50 were from the normal population. All individuals were examined for common HFE gene mutations by amplification of nucleotide 845 C282Y and 187 H63D alleles and product analysis using the polymerase chain reaction method and restriction enzyme digestion. No case of either a homozygous or heterozygous C282Y mutation was found. For the H63D mutation, no homozygosity was detected but heterozygosity was detected in 22% of patients and in 28% of the normal population. Hereditary hemochromatosis is not a major cause of cryptogenic cirrhosis in the Iranian population.

Wilson disease (WD) is an autosomal recessive disorder. The WD gene, ATP7B, encodes a copper-transporting ATPase involved in the transport of copper into the plasma protein ceruloplasmin and in excretion of copper from the liver. ATP7B mutations cause copper to accumulate in the liver and brain. We examined the ATP7B mutation spectrum in Wilson disease patients in Iran.Patients and Genomic DNA was extracted from patients with Wilson disease. The entire coding region of the ATP7B gene was amplified using PCR and analyzed using direct sequencing. We identified five novel mutations in 5 Iranian patients with Wilson disease. The first was a transversion, c.2363C > T, which led to an amino acid change from threonine to isoleucine. The second mutation was a deletion, c.2532delA (Val845Ser), which occurred in exon 10. The third mutation was a transition mutation, c.2311C > G (Leu770Leu), which occurred in the TM4 domain of the ATP7B protein. The fourth mutation was a transversion, (c.3061G > A) (Lys1020Lys), in exon 14. Lastly, we identified a transversion, c.3206C > A (His1069Asn) in exon 14 which led to a change in function of the ATP loop domain of the ATP7B protein. The H1069Q mutation was identified as the most common mutation in our study population. Based on our findings, the H1069Q may be a biomarker that can be used in a rapid detection assay for diagnosing WD patients.

The World Health Organization (WHO) estimates that about 180 million people, 3% of the world population, are infected with the hepatitis C virus (HCV). In Italy, the prevalence in the general population is reported to be greater than 5% and 9% among households of HCV-positive patients. The aim of this study was to estimate the trends of HCV infection in Italy in the period 1996-2006. The formula ln (rate) = b × years was applied for logarithmic transformation of the incidence rates to obtain time trends of HCV infection, using the joinpoint regression program software version 3.3.1. Linear graphs representing trends and the annual percentage change (APC) were considered for each joinpoint. Time changes are expressed as expected annual percentage change (EAPC) with the respective 95% confidence intervals (CIs); significance levels of time trends are also reported. The null hypothesis was tested using a maximum of 3 changes in slope with an overall significance level of 0.05 divided by the number of joinpoints in the final model. Considering all age groups, the incidence rate decreased from 2.02 to 0.55 per 100,000. The joinpoint analysis showed a statistically significant decrease in the incidence rates of HCV infection. No joinpoints were found in any age groups. Our data show that the incidence rates of HCV infections have considerably decreased in each age group throughout the studied period (1996-2006). This decreasing trend in HCV infections is, in part, attributable to behavioral and social changes. Improved hygiene, use of precautions in medical settings, blood screening, and sexual educational campaigns seem to have contributed to reduce the transmission of infection during the last 10 years.

Chronic hepatitis C infection is caused by the hepatitis C virus (HCV), and its clinical complications include liver cirrhosis, liver failure, and hepatocellular carcinoma. Transforming growth factor-β1 (TGF-β1) is an important cytokine in cell growth and differentiation, angiogenesis, extracellular matrix formation, immune response regulation, and cancer development and progression. The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in TGF-β1 and chronic HCV infection among patients referred to the Taleghani Hospital, Tehran, Iran between 2008 and 2010.Patients and In this case-control study, samples were collected using a convenience sampling method. We genotyped 164 HCV patients and 169 healthy controls for 3 SNPs in the TGF-β1 gene (-509 promoter, codon 10, and codon 25). We determined the SNP genotypes by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. To confirm the PCR-RFLP genotyping results, 10% of the samples were re-genotyped using a direct sequencing method. There were no significant differences in the allelic frequency distribution of SNPs at -509 C/T, +869 C/T, or +915 G/C between HCV patients and the healthy controls. Genotyping results for all three polymorphic sites were similar with no statistically significant differences between the groups. Most of the Iranian patients (over 85%), both healthy controls and HCV patients, had the GG genotype at the +915 G/C position, resulting in a high level of TGF-β1 production. Therefore, we concluded that the SNPs investigated by us cannot be considered as prognostic factors for HCV infection in our population, despite being reported as prognostic markers in other populations. Moreover, there is a possibility that most of the population is susceptible to HCV infection.

In recent years, the confidential unit exclusion (CUE) option has been used to increase blood safety at blood transfusion centers in several countries. The epidemiologic characteristics of diseases and demographic characteristics of patients vary in different countries; therefore, we investigated whether the CUE option is useful in Iran. In this study, we determined the prevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) in CUE-positive and CUE-negative units, as well as the efficacy of the CUE option. The aim of this study was to evaluate the efficacy of the CUE option in reducing the prevalences of HBV and HCV in blood units.Patients and All donors were tested for the HCV antibody (anti-HCV) and hepatitis B surface antigen (HBsAg). Supplemental tests were performed to confirm the presence of viruses in the units that tested positive. In total, 2000 units (1000 CUE-positive units and 1000 CUE-negative units) were tested using the nucleic acid testing (NAT) method. The prevalence of infectious markers was estimated in all demographic subgroups. The prevalences of HBV and HCV markers were higher in donors who opted for CUE than in those who did not. The CUE option had low sensitivity (21.5%) and positive predictive value (PPV; 20.9%) for the markers. Most of the donors who opted for CUE for the first time were men with low levels of education. The CUE option has low sensitivity and PPV, and its effectiveness in reducing the transmission of infectious diseases through window-period units is minimal. The CUE process can be continued in Iran because Iran is geographically located in a region where HBV is endemic; however, higher levels of education are necessary to make this process effective.

Hepatitis E virus (HEV) is a major causative agent of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. The lack of an efficient cell culture system for HEV has greatly limited our understanding of the mechanisms of infection, replication, and pathogenicity of this virus. The yeast two-hybridization system is considered to be an efficient method for determining protein-protein interactions and screening interactive proteins associated with host cells. In order to identify the host-cell proteins interacting with the HEV-capsid proteins, a fragment of the HEV-capsid protein p239 (amino acids 368-606) was used as bait; human liver cDNA library was used as a source of host-cell proteins, and the screening was performed using the CytoTrap yeast two-hybrid system. The CytoTrap yeast two-hybrid system, which is also called Sos Recruitment System (SRS), was used to analyze the interaction of the p239 fragment with host-cell proteins. We isolated 2 proteins, cytochrome P4502C8 (CYP4502C8) and retinol-binding protein 4 (RBP4) after 2 rounds of screening. Co-immunoprecipitation assays showed that both the proteins could bind in vitro to the HEV virion in HepG2 cells. CYP4502C8 and RBP4 screened from liver cDNA library using the CytoTrap yeast two-hybrid system interact with HEV capsid in vitro.

Xerostomia is a common adverse event of unknown etiology observed during pegylated interferon (PegIFN)/Ribavirin (Rbv) treatment. To assess the frequency and mechanisms of xerostomia during PegIFN/Rbv therapy.Patients and Thirty-one naïve patients with chronic hepatitis C consecutively received PegIFN-α2a (180 μg/week) plus Rbv (800-1200 mg/day). The controls were 10 patients with chronic hepatitis B who received PegIFN-α2a (180 μg/week). During treatment and follow-up, all patients underwent basal and masticatory stimulated sialometry, otorhinolaryngoiatric (ORL) examination, and a questionnaire survey to subjectively assess symptoms of oral dryness. Twenty-seven patients on PegIFN/Rbv and 4 on PegIFN (87% vs. 40%, P = 0.006) reported xerostomia. Thirty patients on PegIFN/Rbv combination therapy and 2 patients on monotherapy had ORL signs of salivary gland hypofunction (97% vs. 20%, P < 0.0001). Mean basal (A) and stimulated (B) salivary flow rates (mL/min) progressively decreased during PegIFN/Rbv treatment (A, 0.49 at baseline vs. 0.17 at the end of treatment, P < 0.0001; B, 1.24 at baseline vs. 0.53 at the end of treatment, P = 0.0004). At week 24 following PegIFN/Rbv treatment, salivary flow rates were similar to baseline (A, 0.53 at the end of follow-up vs. 0.49 at baseline; B, 1.19 at the end of follow-up vs. 1.24 at baseline). Salivary function was unaffected in monotherapy patients. Rbv causes salivary gland hypofunction in hepatitis C patients receiving PegIFN/Rbv therapy, which promptly reverts to normal upon cessation of treatment.