Hepatitis Monthly
Volume:13 Issue: 10, Oct 2013

Nucleus(t)ide analogs (NAs), containing Lamivudine (LMV), adefovir dipivoxil (ADV), endeavor (ETV), telbivudine (LdT), and tenofovir (TDF) are widely used for the treatment of chronic hepatitis B (CHB), but long term anti-Hepatitis B virus (HBV) therapy with NAs may give rise to the emergence of drug-resistant viral mutants.. This study aimed to find and identify some new resistance mutations of HBV from the patients accepted anti-HBV therapy..Patients and The reverse transcriptase (RT) coding region of HBV was PCR-amplified using HBV DNA extracted from patients'' blood samples and sequenced.. Nineteen substitution mutations were detected. Among them, rtQ267H was often observed in patients receiving LMV administration. This LMV therapy-related mutation was introduced into HBV replication-competent plasmids. The in vitro susceptibility of both wild-type (WT) and mutant-type (MT) HBV to NAs was analyzed by Southern blot, and/or quantitative real-time PCR (qRT-PCR). The rtQ267H substitution enhanced HBV replication not merely in single-site mutation, but also in multisite mutations. The in vitro susceptibility analysis showed that the existence of rtQ267H in WT and LMV-resistant (LMVr) HBV were responsible for the reduced susceptibility to LMV to varying degrees, and enhanced HBV replication capacity. However, HBV harbored this substitution retained normal susceptibility to ADV, LdT, ETV, and TDF.. The result suggested that rtQ267H is a potential adaptive mutation of HBV to LMV..

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in western world. However, NAFLD shows an increasing trend in China every year, which has attracted the attention of national health authorities. The previous studies have shown that NAFLD caused severe gastrointestinal motor disorders, but little is known about the interstitial cells of Cajal role in gastrointestinal motor disorders.. The aim of this study was to observe the ICC in jejunum of nonalcoholic fatty liver mice by immunohistochemistry and assessed the relationship between intestinal motility and ICC.. Thirty five Sprague-Dawley (SD) rats were randomly divided into nonalcoholic fatty liver (n = 25) and control groups (n = 10), rats were housed individually in cages and had free access to food and water, nonalcoholic fatty liver group was duplicated by high-fat diet (consisted of ordinary food, 20g/kg cholesterol and 100g/kg fat) feeding. Dextran blue-2000 was used to monitor the intestinal motility. The proximal small intestine was harvested to investigate the C-kit positive ICC. The hepatic tissue slices were used for pathological observation.. Nonalcoholic fatty liver disease was successfully established. The intestinal motility in nonalcoholic fatty liver group (49.5 ± 10.9) was weaker compared to the control group (57.3 ± 8.9), P < 0.05. The rate of ICC also have shown statistically significant differences between nonalcoholic fatty liver (4.87 ± 2.97/mm 2) and control groups (6.54 ± 3.13/mm 2), P < 0.05.. ICC may be related to the intestinal motility in nonalcoholic fatty liver mice..

Liver transplantation is a life-saving intervention for many patients with end-stage liver disease. In the past, evaluation of successful liver transplantation was based on patients’ survival rate. However, in recent years this evaluation has been based on patients’ quality of life. Various instruments have been developed to evaluate patients’ quality of life. Nonetheless, scholars still believe that it is crucial to develop a standardized and disease specific instrument for evaluating the quality of life in liver transplant recipients.. The aim of this paper was to describe the development and psychometric testing process of a quality of life instrument specific to liver transplant recipients.. Initial items of this instrument were extracted from a conventional content analysis study, and then were completed with findings of related international literature. The face validity was assessed by interviewing with four liver transplant recipients, and the content validity was evaluated by eleven experts in the field of transplantation. The construct validity was achieved by involving 250 liver transplant recipients through exploratory factor analysis method, and reliability was calculated by Cronbach''s alpha.. Three main factors with 40 items were extracted from the exploratory factor analysis: Health Satisfaction, Concerns, and Complications. Reliability of the instrument was confirmed (alpha = 0.922).. Given the special considerations regarding liver transplant recipients, this questionnaire is more accurate in evaluating the success of liver transplantation..

Viral hepatitis B (VHB) is an occupational risk for dentists. It is necessary that dental students start clinical practice immunized with the vaccine, response monitored and informed about the means of transmission of the disease. Rarely, there are studies, which evaluate concomitantly knowledge of these academics and their vaccine situation?. To evaluate the knowledge about Hepatitis B, the vaccine situation and the immunization status of dental students and to investigate the probable correlation between the status of immunization, vaccination membership and adherence to the test of seroconversion and associated factors..Patients and 189 students from the dentistry course at the Federal University of Piaui (UFPI) who attended from the 3rd to 9th period were invited to participate in the research. Their knowledge about HBV, attitude regarding protection and their vaccine situation were assessed through a self-administered form. Antibodies against surface antigens of Hepatitis B virus (Anti-HBs) and against the antigens of the virus nucleous of Hepatitis B (Anti-HBc total) were measured qualitatively using the enzyme-linked immunosorbent assay (ELISA).. Of the 179 students surveyed, 58.1% knew about the degree of virulence of the Hepatitis B virus (HBV). As to the means of transmission, 98.3% considered blood transmission, 82.6% plates and cutlery, 15.6% cough and 12.3% vertical transmission. Most students (87.4%) knew that they should take 3 doses of the vaccine and 62.2% completed the immunization schedule. A minority of students (48.6%) knew the about the Anti-HBs test and 5.6% took the test. Among the students who reported having taken three doses of the vaccine, 12.5% were not seroconverted. There was no significant correlation between the variables.. Dental academics were unsure about the means of infection and prevention against HBV. Many of them had not completed the immunization scheme and did not have the test of seroconversion. The serological analysis revealed unprotection, even after students completed the vaccination schedule..

Patients with chronic hepatitis C (CHC) often have elevated serum iron markers, which may worsen liver injury.. The aim of this study was to investigate the possible correlations between iron metabolism serum markers, HCV viral load, and liver disease severity in treatment-naive patients with chronic hepatitis C infection..Patients and Eighty five patients with untreated hepatitis C chronic infection were investigated.. . Twenty one patients (24.7%) had elevated serum iron levels, and 29 subjects (34.1%) had severe liver fibrosis. Significantly elevated levels of serum iron (P < 0.05) and ferritin (P < 0.001), associated with lower levels of TIBC (P < 0.05) were detected in patients with severe fibrosis compared tono/mild fibrosis. Severe necroinflammatory activity was also significantly correlated with serum iron (P < 0.001), TIBC (P < 0.05), and ferritin levels (P < 0.001). Using multiple linear regression analysis, serum levels of ferritin and transferrin were the independent variables selected as being good predictors for advanced fibrosis and severe necroinflammatory activity. No significant correlations were detected between HCV viral load and iron markers.. This study revealed that serum iron markers (especially ferritin and transferrin) might be used as surrogate markers for both liver fibrosis and necroinflammatory activity..

A supreme vaccine for Hepatitis C virus (HCV) infection should elicit strong Th1-oriented cellular responses. In the absence of a Th1-specific adjuvant, immunizations by protein antigens generally induce Th2-type and weak cellular responses.. To evaluate the adjuvant effect of BCG in comparison with nonionic copolymer-Pluronic F127 (F127) as a classic adjuvant in the formulation of HCV core protein (HCVcp) as a candidate vaccine for induction of Th1 immune responses.. Expression of N-terminally His-Tagged HCVcp (1-122) by pIVEX2.4a-core vector harboring the corresponding gene under the control of arabinose-inducible (araBAD) promoter was achieved in BL21-AI strain of E.coli and purified through application of nitrilotriacetic acid (Ni-NTA) chromatography. Mice were immunized subcutaneously (s.c.) in base of the tail with 100 μl of immunogen (F127+HCVcp or BCG+HCVcp; 5 μgHCVcp/mouse/dose) or control formulations (PBS, BCG, F127) at weeks 0, 3, 6. Total and subtypes of IgG, as well as cellular immune responses (Proliferation, In vivo CTL and IFN-γ/IL-4 ELISpot assays against a strong and dominant H2-d restricted, CD8+-epitopic peptide, core 39-48; RRGPRLGVRA of HCVcp) were compared in each group of immunized animals.. Expression and purification of core protein around the expected size (21 kDa) was confirmed by Western blotting. The HCVcp + BCG vaccinated mice showed significantly higher lymphocyte proliferation and IFN-γ production but lower levels of cell lysis (45% versus 62% in CTL assay) than the HCVcp+F127 immunized animals. “Besides, total anti-core IgG and IgG1 levels were significantly higher in HCVcp + F127 immunized mice as compared to HCVcp + BCG vaccinated animals, indicating relatively higher efficacy of F127 for the stimulation of humoral and Th2-oriented immune responses”.. Results showed that HCVcp + BCG induced a moderate CTL and mixed Th1/Th2 immune responses with higher levels of cell proliferation and IFN-γ secretion, indicating that BCG may have a better outcome when formulated in HCVcp-based subunit vaccines..

Context: Celiac disease (CD) is defined as a permanent intolerance to ingested gluten. The intolerance to gluten results in immune-mediated damage of small intestine mucosa manifested by villous atrophy and crypt hyperplasia. These abnormalities resolve with initiationa gluten-free diet..Evidence Acquisition: PubMed, Ovid, and Google were searched for full text articles published between 1963 and 2012. The associated keywords were used, and papers described particularly the impact of celiac disease on severity of liver disorder were identified.. Recently evidence has emerged revealingthat celiac disease not only is associated with small intestine abnormalities and malabsorption, but is also a multisystem disorder affecting other systems outside gastrointestinal tract, including musculo-skeletal, cardiovascular, and nervous systems. Some correlations have been assumed between celiac and liver diseases. In particular, celiac disease is associated with changes in liver biochemistry andlinked to alter the prognosis of other disorders. This review will concentrate on the effect of celiac disease and gluten-free diets on the severity of liver disorders.. Although GFD effect on the progression of CD associated liver diseases is not well defined, it seems that GFD improves liver function tests in patients with a hypertransaminasemia..

Hepatitis B virus (HBV) infection is a public health problem in developing countries. HBV genotypes play major role in the evolution of infection since they were involved in different clinical presentations and response to treatment.. This study was conducted to determine circulating HBV genotypes in the country and to evaluate the efficiency of restriction fragment length polymorphism (RFLP) analysis for HBV genotyping..Patients and We investigated 98 samples collected from patients chronically infected with HBV. HBV genotypes were determined by analysis of patterns obtained after amplification in Pre-S region and digestion of the amplicon by two endonucleases AvaII and DpnII. Obtained results were confirmed by partial sequencing in the same region.. Two different HBV genotypes were detected in this study, Genotype D (in 95. 9%) and Genotype A (in 4.1%). Seventy-four samples (75.5%) were successfully genotyped with RFLP analysis and all classified as genotype D. The remaining 24 samples (24.5%) which were un-genotyped by RFLP analysis, were classified by partial sequencing of the pre-S region as HBV genotype D (20 samples, 20.4%) and genotype A (4 samples, 4.1%). Atypical profiles were significantly associated with advanced liver disease (P = 0.001) as well as older age (P < 0.05).. Several previous studies used PCR-RFLP to genotype HBV; however, we showed the high risk to obtain atypical profiles, especially in advanced stages of chronic infection, with as results difficulties to genotype the virus. These profiles resulted from the accumulation of mutations during natural course of infection resulting in a modification in restriction sites for enzymes. So, we recommended completing the investigation by partial sequencing to confirm obtained results..

Normal or elevated values of serum alanine aminotransferase level (ALT) vary in different studies mostly related to characteristics of reference population including age, gender, body mass index, nonalcoholic fatty liver disease (NAFLD), and metabolic syndrome prevalence.. To measure upper normal limit (UNL) for serum ALT in an apparently healthy Iranian old population (which we had not sufficient data before this study), and its modulating factors..Patients and All inhabitants (> 50 years old) of Kalaleh, Golestan, Iran (N = 1986) were invited to the study. ALT measurements were performed for all subjects using the same laboratory method. Upper limit of normal (ULN) ALT was calculated based on its 95th percentile in normal weight subjects. Modulating factors of ALT were determined by multivariate analysis.. A total of 1309 subjects, with the mean age of 61.5 ± 7.5 years were included. UNL of ALT was 18.8 U/L and 21.4 U/L in women and men, respectively. Based on univariate analysis, waist circumference (r = 0.124, P = 0.01), body mass index (r = 0.118, P = 0.01), triglyceride (r = 0.143, P = 0.01), and having metabolic syndrome (OR = 2.04) modulate ALT levels in men. Also triglyceride (r = 0.119, P = 0.01) modulates ALT levels in women.. The calculated level for UNL of ALT is considerably far lower than previous accepted value. Age, gender, ethnicity, and metabolic factors should be accounted in future studies to determine normal ALT level..

Rapid virological response (RVR) strongly predicts sustained virological response (SVR) in patients with chronic hepatitis C (CHC), and abbreviates antiviral therapy in some patients.. To identify factors predicting virological relapse (VR) in CHC patients who attained RVR..Patients and Medical records of 133 CHC patients with an RVR after completing 24 weeks of antiviral therapy (a combination of pegylated interferon-α and ribavirin) were analyzed. Baseline characteristics and on-treatment responses were compared between the patients with an SVR and those with VR. Patients with normal alanine aminotransferase (ALT) levels at weeks 4 and 12 and at the end-of-treatment (EoT) and patients with elevated, but constantly decreasing, ALT levels were classified as having favorable patterns of ALT change. A trend of increasing ALT levels either between weeks 4 and 12 or between weeks 12 and EoT was classified as unfavorable. A high viral load (HVL) was defined as a baseline HCV RNA ≥ 600000 IU/mL.. In total, 116 (87.2%) patients had a SVR and 14 (10.5%) had VR. The VR rates were comparable between patients with genotype-1 (13.1%) and genotype-2 infection (8.7%) (P = 0.572). Multivariate analysis revealed that HVL (P = 0.015; odds ratio [OR] = 14.754; 95% confidence interval (CI) = 1.671–130.240), and unfavorable ALT patterns (P = 0.039; OR = 4.397; 95% CI = 1.078–17.930) independently predicted VR. In subgroup analysis, low viral load (LVL) patients had a minimal VR rate (1.8%). Among the HVL patients, the VR rate of those using peg-IFN-α-2a was relatively low (9.1%). Patients using peg-IFN-α-2b had a slightly higher VR rate (23.8%; P = 0.128), and patients with favorable patterns of ALT changes had a lower VR rate (10.3%) compared to the 53.8% in patients with unfavorable ALT patterns (P = 0.005).. In southern Taiwan, 24 weeks of antiviral therapy achieved a high SVR rate in patients with CHC attaining RVR, except in the subgroup of patients treated with peg-IFN-α-2b with HVL and on-treatment unfavorable ALT patterns..