Hepatitis Monthly
Year:2011 | Volume:11 | Issue:10 (39)|Papers Count:15

Despite the use of hepatitis B virus (HBV) vaccines and preventive measures, infection with HBV remains a major global health problem. Patients with chronic kidney disease (CKD) are at an increased risk of acquiring HBV infections from shared dialysis equipment, increased exposure to blood products, and immunodeficiency associated with CKD (1, 2). In addition, they may be more likely to develop chronic infections on exposure to HBV (1, 2), and HBV infection among CKD patients is associated with high rates of morbidity and mortality (3, 4). Vaccination is important both for preventing susceptible patients from acquiring HBV and for reducing the pool of HBVinfected patients. HBV infection remains a concern in dialysis populations, because the vaccination programs have been less successful in these populations than in the general population. The causes of poor seroconvertsion in CKD patients include malnutrition, uremia, and immunosuppression due to renal failure (5).

Hepatitis B virus (HBV) is an important threat to global public health. Despite the availability of safe and effective prophylactic vaccines, the existence of a large reservoir of chronic carrier patients impedes the eradication of this virus, therefore, HBV-related diseases still rank ninth on the global ranking of causes of mortality. Moreover, HBV is considered the fifth most important infectious agent leading to death, with approximately 1 million HBV-related deaths occurring per year. Previous studies showed that the infectivity rate of HBV is higher than those of other blood-borne viruses. The risk of infection after percutaneous exposure to the 3 major blood-borne viruses—HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) —varies greatly, and the risk of infection in non-immune individuals exposed to HBV may be over 30% if the source is hepatitis B e antigen (HBeAg) positive. The average infection rate for HCV and HIV is 1.8% and 0.3%, respectively.

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).

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.

Background: 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.Objectives: To identify a novel molecule as possible drug candidate for the treatment of Hepatitis D.Materials and Methods: 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.Results: 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.

Background: It is difficult to predict what type of chronic hepatitis B (CHB) progresses to chronic severe hepatitis B.Objectives: 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 Methods: 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.Results: 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).Conclusions: 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.

Background: 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 endstage 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).Objectives: 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 Methods: 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 mg 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.Results: 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.

Background: Hypoxia-inducible factor-1 (HIF-1) is a ubiquitously expressed oxygen-regulated transcription factor composed of a and b subunits. HIF-1 activates the transcription of various genes including those involved in the formation and metastatic growth of hepatocellular carcinoma (HCC).Objectives: To investigate the levels of hepatic and circulating HIF-1a 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 Methods: Total RNA was extracted from a self-controlled HCC and paracancerous specimen. HIF-1a mRNA was amplified by nested RT-PCR and confirmed by sequencing. Tissue HIF-1a was analyzed by immunohistochemistry. The levels of HIF-1a, 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.Results: The positive staining of liver HIF-1a 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-1a expression in relation to tumor number, degree of differentiation, or hepatitis B surface antigen (HBsAg) positivity, but with some correlation between HIF-1a and tumor size. HIF-1a 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 patients’ gender, age, or alpha-fetoprotein (AFP) levels.Conclusions: Hepatic HIF-1a expression is associated with the development and prognosis of HCC, and circulating HIF-1a level is a useful marker for HCC diagnosis and prognosis.

Background: Hepatitis B virus (HBV) infection is highly endemic in many Asian countries.Objectives: We examined whether prior contraceptive methods and sexual behavioral factors impact maternal HBV carriage in an obstetric population.Patients and Methods: 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.Results: 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.Conclusions: Contraceptive use played only a minimal role in preventing sexual transmission of HBV infection within the sexually active female population in an endemic area.

Background: 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)].Objectives: 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 Methods: 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.Results: 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.Conclusions: 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.

Background: 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.Objectives: 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.Discussion: 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.

We read with interest the article by Arababadiet al. which highlights different and important areas of concern in the management of occult hepatitis B (OBI).There are two relevant issues worthy of discussion. First, the authors described the variable prevalence of OBI in different geographical regions worldwide. The laboratory assay used to detect OBI is an important determinant of its prevalence. Because of the low viremic state of patients, OBI may not be detected even when sensitive polymerase chain reaction (PCR) assays are employed.Results of a recent population study in our locality involving 13, 034 blood donors showed the prevalence of OBI to be between 0.11% and 0.13%. We used nucleic acid testing to detect hepatitis B virus (HBV) DNA, which has a detection limit (3.7 IU/mL) lower than that of most available PCR assays. Only studies using sensitive assays should be considered when implementing policies for screening blood donors.

First, we agree with Setoet al. regarding the impacts of the sensitivity of the detection methods of OBI (occult hepatitis B infection) prevalence but disagree regarding their idea on the lack of usefulness of anti-HBc screens.They have referred to Seoet al., who reported that the prevalence of anti-HBc positivity in Korea was 13.5%, whereas the prevalence of OBI was 0.016%. Anti-HBc is the first antibody that is produced against HBV and is the most stable antibody, hence, the presence of the antibody in individuals demonstrates introduction of HBV to the immune system via several mechanisms, including transfusion.

The article by Ertekinet al. published in Hepatitis Monthly indicates that a new hepatitis B virus (HBV) vaccine schedule should be created for children with celiac disease (CD), and the response of all children with CD to the HBV vaccine should be routinely investigated.The authors investigated a group of children with CD vaccinated against HBV and found that the anti-HBs titer was not detected in a significant percentage (38.5%) of children. In addition, the clinical presentation of the disease and dietary compliance of the patients seemed to play a role in nonresponsiveness to the HBV vaccine.Therefore, the authors suggest a different immunization schedule. Most studies indicate that major histocompatibility complex (MHC) and human leukocyte II antigens (HLA-II) are responsible for nonresponsiveness to HBV vaccine. However, Nemeset al.

One of the five known hepatitis viruses that can infect humans is hepatitis E virus (HEV). The first documented infection that was caused by HEV occurred in 1955 during an outbreak in New Delhi, India (1). HEV is a small nonenveloped particle that belongs to the familyHepeviridae and the genusHepevirus. Its single-stranded RNA genome has approximately 7200 base pairs (2). By genomic sequence analysis, there are four genotypes (1-4) and at least 24 subgenotypes (1a-1e, 2a-2b, 3a-3j, and 4a-4g) of HEV in humans and other mammals (4). Avian isolates of HEV were initially proposed to constitute the fifth genotype of HEV; but, due to their shorter genome and low homology with mammalian isolates, they have been categorized as a member of a separate genus (3).