Hepatitis Monthly
Volume:11 Issue: 10, Oct 2011

Non-alcoholic fatty liver disease (NAFLD) is becoming as an important health problem in the pediatric age group. In addition to the well-documented role of obesity on the fatty changes in liver, there is a growing body of evidence about the role of environmental factors, such as smoking and air pollution, in NAFLD. Given that excess body fat and exposure to air pollutants is accompanied by systemic low-grade inflammation, oxidative stress, as well as alterations in insulin/insulin-like growth factor and insulin resistance, all of which are etiological factors related to NAFLD, an escalating trend in the incidence of pediatric NAFLD can be expected in the near future. This review focuses on the current knowledge regarding the epidemiology, diagnosis and pathogenesis of pediatric NAFLD. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for broadening efforts in prevention and control of the main risk factors. The two main universal risk factors for NAFLD, obesity and air pollution, have broad adverse health effects, and reducing their prevalence will help abate the serious health problems associated with pediatric NAFLD.

Chronic infection with hepatitis B virus (HBV) is a global public health problem because of its worldwide distribution and its potential to cause sequelae. HBV is most prevalent in China, South East Asia, sub-Saharan Africa, and the Amazon basin of South America where health care resources are most limited. Numerous challenges exist for effective management of chronic HBV infection, particularly in resource-limited regions. These challenges include lack of accurate prevalence data, absence of a surveillance program, and poor political will of governments in resource-poor countries to enforce effective measures to control the disease. There is a lack of understanding regarding HBV infection by both the general public and health care providers. A better understanding of the pathogenesis and treatment of this condition is necessary. The acute shortage of trained medical manpower necessary for accurate diagnosis and treatment of chronic hepatitis B (CHB) in resource-poor countries is a formidable challenge. The condition is complicated by the continuing efflux of medical graduates from low-income economies to richer countries.The most critical problem in the management of CHB is the high cost of laboratory tests and drugs. Drugs are also not readily available. Other challenges in the management of CHB include stigmatization of patients, co-infection with other viruses, lack of management guidelines, and absence of an effective patient referral system. To address these challenges, governments of resource-poor nations must be committed to budgetary allocation for the implementation of health programs. It is necessary to provide awareness campaigns, health education, proper screening of blood and blood products for transfusion, active screening, intensification of existing childhood immunization, technical and financial assistance from wealthier nations, and implementation of the recommendations outlined in the Global Hepatitis Policy (2010).

The small delta antigen protein of hepatitis delta virus (HDV) has been shown to be important for replication of the virus and essential for the viral life cycle. Therefore, it may be an appropriate target for designing biological experiments for drug development to identify the potential inhibitors of hepatitis D. To identify a novel molecule as possible drug candidate for the treatment of Hepatitis D. In the present study, a computational approach was used for the identification of novel small-molecule inhibitors against HDV replication using docking studies. An Autodock tool was used for docking and identifying the active binding sites in target proteins. The Lipinski filter and preADMET program were also used for determining the pharmacokinetic properties in order to filter out potential ligand molecules to restrain virus replication. Our results suggest that pyridinone (3-[(4,7-dichloro-1,3-benzoxazol-2-yl) methylamino]-5-ethyl-6-methyl-pyridin-2(1H)-one) is a validated potential inhibitor of HDV replication and could be as a novel antiviral drug for the treatment of hepatitis D. Counclusions: We have identified a novel antiviral drug by using innovative computational approaches. The results provide a basis to experimentally develop into drug which can be used for the treatment of delta hepatitis.

It is difficult to predict what type of chronic hepatitis B (CHB) progresses to chronic severe hepatitis B. This study aimed to observe changes in the HBV-specific and -nonspecific cellmediated immune responses after CHB deteriorates into severe hepatic disease and explore the significance of such changes.Patients and This study aimed to observe changes in the HBV-specific and -nonspecific cell-mediated immune responses after CHB deteriorates into severe hepatic disease and explore the significance of such changes. In 49 of 255 CHB patients (19.22%), the disease developed into chronic severe hepatitis (early stage) an average of 10.06 ± 1.73 days after admission. CD4+ and NK cells levels in Group A were lower after progression into severe hepatitis than on the second day of admission (baseline) (P < 0.01). CD8+ cells and nonspecific CTL levels in Group A were higher after progression than at baseline (P < 0.01), and latter was higher than in Group B at baseline (P < 0.01); the levels of CD8+ cells and nonspecific CTLs in Group A after progression were significantly higher than those of Group B 10 days after admission (P < 0.01). There were no significant differences in HBV-specific CTL levels in Group A before and after progression to severe hepatitis (P > 0.05). Our results suggest that the immunological pathogenesis of chronic severe hepatitis B is related to significant rises in CD8+ and nonspecific CTL levels and that such increases predict that the disease will deteriorate into severe hepatitis.

Despite improvement in hepatitis B infection prevention through national vaccination programs, implementation of compulsory and thorough blood donor screening, and reduction of transfusion numbers due to erythropoietin administration, hepatitis B remains a major concern in hemodialysis (HD) centers (1). Compared to a response rate of over 90% in the normal population, only 50 to 60% of those with end-stage renal disease (ESRD) achieve protective antibody levels following immunization against hepatitis B (2, 3). Various strategies have been developed to overcome the low seroconversion rate in ESRD patients, including co-administering zinc, gamma-interferon, thymopentin, interleukin-2, and levamisole as immunostimulants or adjuvants (3, 4), changing the injection mode (intradermal versus intramuscular), or doubling the vaccine dose (5). Previous studies demonstrated that renal failure patients benefit from HBV vaccination; however, not all studies have demonstrated this. Therefore, we compared the rates of seroconversion (hepatitis B surface antibody [HBsAb] titer > 10 IU/mL) in patients at various stages of chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) who received HBV vaccination.Patients and A total of 167 patients in 3 different stages of CKD were vaccinated against HBV. Each patient received the vaccine according to a standardized vaccination schedule consisting of 40 μg of the recombinant vaccine "Engerix" at 0, 1, and 6 months. Eight to 12 weeks after the last dose of vaccination, anti-HBsAb levels were measured. Mean age and eGFR were 57.4 ± 16.5 years and 26.7 ± 14.7 mL/min/1.73 m2, respectively. The overall seroconversion rate was 78%. Although a significant correlation between HBsAb titer and eGFR (r = 0.265, P = 0.001) was observed, in the multivariate analysis using age, CKD stage, diabetes mellitus, and gender as independent variables, the degree of renal function did not significantly contribute to seroconversion. In contrast, higher age (> 60 years) showed a significant negative correlation to seroconversion (odds ratio = 0.22; P = 0.004).Conclousions: CKD patients of advanced age should be vaccinated against HBV. Although higher eGFR was not associated with improved seroconversion, the persistence of seroconversion was not evaluated; future studies should be conducted to develop recommendations for earlier or later vaccination.

Hypoxia-inducible factor-1 (HIF-1) is a ubiquitously expressed oxygen-regulated transcription factor composed of α and β subunits. HIF-1 activates the transcription of various genes including those involved in the formation and metastatic growth of hepatocellular carcinoma (HCC). To investigate the levels of hepatic and circulating HIF-1α expression in a range of patients with liver disease in order to determine how it can be used in the diagnosis of HCC and in establishing prognosis.Patients and Total RNA was extracted from a self-controlled HCC and paracancerous specimen. HIF-1α mRNA was amplified by nested RT-PCR and confirmed by sequencing. Tissue HIF-1α was analyzed by immunohistochemistry. The levels of HIF-1α, vascular endothelial growth factor (VEGF), and angiopoietin-2 (Ang-2) expression in the sera of 220 patients with liver disease were quantitatively detected by ELISA. The positive staining of liver HIF-1α was brown and granule-like and was mainly present in the cytoplasm, with lower levels in the nucleus of hepatocytes. Its incidence was 80% in HCC cells and 100% in paracancerous tissues, with no significant difference in HIF-1α expression in relation to tumor number, degree of differentiation, or hepatitis B surface antigen (HBsAg) positivity, but with some correlation between HIF-1α and tumor size. HIF-1α expression was detected in the sera of HCC patients at a significantly higher level than in cases of benign liver disease, with pathological characteristics associated with the levels of circulating VEGF and Ang-2 expression, the size of the tumor, and the level of extrahepatic metastasis, but not with patient's gender, age, or alpha-fetoprotein (AFP) levels. Hepatic HIF-1α expression is associated with the development and prognosis of HCC, and circulating HIF-1α level is a useful marker for HCC diagnosis and prognosis.

Hepatitis B virus (HBV) infection is highly endemic in many Asian countries. We examined whether prior contraceptive methods and sexual behavioral factors impact maternal HBV carriage in an obstetric population.Patients and For this study, pregnant women were considered to be representative of the sexually active and fertile female population. Contraceptive methods used prior to the index pregnancy were examined in 1283 pregnant Chinese women attending an antenatal clinic using a self-administered questionnaire, and correlated with the maternal HBV status determined using routine antenatal screening. In our study, 111 (8.7%) women were infected with HBV and there was no difference in the incidence of male condom usage between HBV-positive (88.3%) and HBV-negative (83.5%) women. No contraceptive method was associated with a reduced incidence of maternal HBV carriage, except for coitus interruptus. In multivariate analysis, only multiparity (adjusted odds ratio [aOR], 1.62) and more than 1 sexual partner (aOR, 1.57) were independent factors associated with maternal HBV carriage. Contraceptive use played only a minimal role in preventing sexual transmission of HBV infection within the sexually active female population in an endemic area.

Treatment for chronic hepatitis B (CHB) has improved over the last 10 years mainly due to the development of effective oral antiviral agents [nucleoside/nucleotide analogs (NUCs)]. The aim of the present study is to identify the frequency and major patterns of resistance to the hepatitis B virus (HBV) in a Turkish population of CHB patients treated with NUCs using add-on and switch therapy strategies.Patients and The investigation involved a total of 194 patients (88 were treated using add-on therapy, and 106 were treated using switch therapy). We analyzed the HBV polymerase gene by amplification and direct sequencing procedures. Primary drug-resistance mutations were detected in 84 patients (43%; 42 in add-on therapy, and 42 in switch therapy) taking lamivudine (LAM), 10 patients (5%; 6 in add-on therapy, and 4 in switch therapy) taking entecavir (ETV), and 16 patients (8%; 8 in add-on therapy, and 8 in switch therapy) taking adefovir (ADV). The most common LAM and ETV resistance mutations were rtM204I/V, rtL180M and rtT184A/I/S, respectively, while rtA181T/V and rtN236T substitutions were the most frequently observed ADV resistance mutations. Patients with CHB who developed NUC resistance were managed using 2 different rescue strategies. The frequency and mutation pattern of resistance were similar in patients treated with add-on and switch strategies. These findings may be helpful in the management of rescue strategies in LAM-resistant patients.

Itraconazole is believed to carry a low risk of hepatic toxicity owing to its low affinity for the human P-450 enzyme. Therefore, hepatic failure caused by itraconazole is exceedingly rare. We report the case of a 46-year-old woman who developed hepatic failure related to itraconazole that was administered for the treatment of onychomycosis. Her condition deteriorated after withdrawal of the drug, followed solely by supportive care initially.Case Report: Treatment with corticosteroids was started 10 days after her admission, and her condition gradually improved. Unfortunately, her condition worsened when the dosage of corticosteroids was abruptly decreased. Ultimately, her condition improved with appropriate adjustments of corticosteroid dosage. We conclude that corticosteroid therapy may be effective for itraconazole-induced hepatitis, especially in those patients who do not respond to conservative treatment. Notably, any decrease in the dosage should be performed with caution. We also recommend that close monitoring of liver function is mandatory during the use of itraconazole.