Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation

To update and extend a 2006 report on the clinical effectiveness and cost-effectiveness of adefovir dipivoxil (ADV) and pegylated interferon alpha (PEG-alpha) for the treatment of chronic hepatitis B (CHB). Thirteen bibliographic databases were searched including MEDLINE, EMBASE and the Cochrane Library. Searches were run from the beginning of 2005 to September 2007. For the clinical effectiveness review, randomised controlled trials (RCTs) comparing ADV, PEG-alpha-2a and PEG-alpha-2b with currently licensed treatments for CHB, including non-pegylated interferon alpha (IFN-alpha) and lamivudine (LAM), were included. Outcomes included biochemical, histological and virological response to treatment, drug resistance and adverse effects. A systematic review of economic evaluations of antiviral treatments for CHB was conducted. The economic Markov model used in the 2006 report was updated in terms of utility values, discount rates and costs. `

Entecavir for the treatment of chronic hepatitis B infection

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of entecavir for the treatment of chronic hepatitis B (CHB) in adults based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from five randomised controlled trials (RCTs), of good methodological quality and measuring a range of clinically relevant outcomes, comparing entecavir with lamivudine. After 1 year of treatment entecavir was statistically superior to lamivudine in terms of the proportion of patients achieving hepatitis B virus (HBV) DNA suppression, alanine aminotransferase (ALT) normalisation and histological improvement, but not in terms of the proportion of patients achieving hepatitis B e antigen (HBeAg) seroconversion. The incidence of adverse or serious adverse events was similar for both treatments. The results of the manufacturer's mixed treatment comparison (MTC) model to compare entecavir with the comparator drugs in nucleoside-naive patients were considered to be uncertain because of concerns over its conduct and reporting. For the economic evaluation the manufacturer constructed two Markov state transition models, one in HBeAg-positive and one in HBeAg-negative patients. The modelling approach was considered reasonable subject to some uncertainties and concerns over some of the structural assumptions. In HBeAg-positive patients the base-case incremental cost-effectiveness ratios (ICER) for entecavir compared with lamivudine and pegylated interferon alpha-2a were 14,329 pounds and 8403 pounds per quality-adjusted life-year (QALY) respectively. Entecavir was dominated by telbivudine. In HBeAg-negative patients the base-case ICERs for entecavir compared with lamivudine, pegylated interferon alpha-2a and telbivudine were 13,208 pounds, 7511 pounds and 6907 pounds per QALY respectively. In HBeAg-positive lamivudine-refractory patients entecavir dominated adefovir added to lamivudine. In one-way deterministic sensitivity analysis on all key input parameters for entecavir compared with lamivudine in nucleoside-naive patients, ICERs generally remained under 30,000 pounds per QALY. In probabilistic sensitivity analysis in nucleoside-naive HBeAg-positive patients the probability of the ICER for entecavir being below 20,000 pounds per QALY was 57%, 82% and 45% compared with lamivudine, pegylated interferon alpha-2a and telbivudine respectively. In nucleoside-naive HBeAg-negative patients the probabilities were 90%, 100% and 96% respectively. The manufacturer's lifetime treatment scenario for HBeAg-negative patients and the ERG's 20-year treatment scenario for HBeAg-positive patients increased the ICERs, particularly in the latter case. Amending the HBeAg-negative model so that patients with compensated cirrhosis would also receive lifetime treatment gave probabilities of entecavir being cost-effective at a willingness to pay of 20,000 pounds and 30,000 pounds of 4% and 40% respectively. The NICE guidance issued in August 2008 as a result of the STA states that entecavir is recommended as an option for the treatment of people with chronic HBeAg-positive or HBeAg-negative hepatitis B in whom antiviral treatment is indicated.

Nurse-led clinic: Effective and efficient delivery of assessment and review of patients with Hepatitis B and C

Hepatology and gastroenterology services are increasingly utilising the skills and experience of nurse practitioners and nurse specialists to help meet the increasing demand for health care. A new nurse-led assessment clinic has been established in the liver clinic at Geelong Hospital to utilise the expertise of nurses to assess and triage new patients and streamline their pathway through the health care system. The aim of this study is to quantitatively assess the first two years of operation of the nurse assessment clinic at Geelong Hospital, and to assess advantages and disadvantages of the nurse-led clinic. Data was extracted retrospectively from clinical records of new patients at the liver clinic. Quarterly one-month periods were recorded over two-years. Patients were categorised according to the path via which they saw a physician, including missed and rescheduled appointments. The number of appointments, the waiting time from referral to appointments and the number of ‘did-not-attend’ occasions were analysed before and after the institution of the nurse-led assessment clinic. The Mann-Whitney rank sum test of ordinal data was used to generate median wait times. There was shown to be a statistically significant longer waiting time for physician appointment if seen by the nurse first. The difference in waiting time was 10 days. However, there was also a reduction in the number of missed appointments at the subsequent physician clinic. Other advantages have also been identified including effective triage of patients, and organisation of appropriate investigations from the initial nurse assessment.

Serologic profile in hepatitis B virus and hepatitis C virus in a Brazilian liver transplant waiting list

Chronic viral hepatitis is currently the most common indication for liver transplantation (OLT). Knowing the serological profile of patients on the liver transplant waiting list (LTWL) is essential to manage prophylactic and therapeutic strategies pre- and post-OLT. The aim of this study was to determine the hepatitis B virus (HBV) and hepatitis C virus (HCV) serological profile on the LTWL.Methods. Serological data were collected from 44 candidates included on, the LTWL from May 2003 to November 2004. HBV and HCV serological profiles were performed by microenzyme immunoassay.Results. Twenty-eight patients (66.7%) lacked H13V serological markers. Anti-HBs was detected in 9.5% and was positive for HBsAg, anti-HBc, IgM anti-HBc, or HbeAg in 4.8% of patients, probably related to reactivation of chronic infection. In 7.1% of patients, the markers demonstrated serological cure of infection. In HCV patients, 41.5% were positive. There was H13V and HCV co-infection in 12.2% of patients.Conclusion. HBV infection in 21.4% of the patients corroborates the need to use more efficient protocols for prophylactic and therapeutic management pre- and post-OLT. The high prevalence of HCV infection reinforces the need to follow adequate protocols to avoid related complications and guarantee rational and universal use of more efficient drugs.

Liver HLA-G expression is associated with multiple clinical and histopathological forms of chronic hepatitis B virus infection

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da prevalência de imunização contra a hepatite B nos profissionais da secretaria de saúde de Maringá

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

A possible correlation between the host genetic background in the epidemiology of Hepatitis B virus in the Amazon region of Brazil

ABSTRACT: The Amazon region of Brazil is an area of great interest because of the large distribution of hepatitis B virus in specific Western areas. Seven urban communities and 24 Indian groups were visited in a total of 4,244 persons. Each individual was interviewed in order to obtain demographic and familial information. Whole blood was collected for serology and genetic determinations. Eleven genetic markers and three HBV markers were tested. Among the most relevant results it was possible to show that (i) there was a large variation of previous exposure to HBV in both urban and non-urban groups ranging from 0 to 59.2%; (ii) there was a different pattern of epidemiological distribution of HBV that was present even among a same linguistic Indian group, with mixed patterns of correlation between HBsAg and anti-HBs and (iii) the prevalence of HBV markers (HBsAg and anti-HBs) were significantly higher (P=0.0001) among the Indian population (18.8%) than the urban groups (12.5%). Its possible that the host genetic background could influence and modulate the replication of the virus in order to generate HB carrier state.

Hepatitis B and C virus infection among Brazilian Amazon riparians

INTRODUÇÃO: As hepatites virais constituem um importante problema de saúde pública no mundo. No Brasil existem poucos estudos sobre esta questão, especialmente entre as comunidades ribeirinhas. O objetivo deste estudo foi determinar a soroprevalência das hepatites B e C virais na comunidade ribeirinha da Ilha do Pacuí, no Estado do Pará, Brasil, e investigar os principais fatores de risco principal a que está comunidade está exposta. MÉTODOS: O presente estudo avaliou amostras de sangue de 181 voluntários que responderam a um questionário epidemiológico. Análises de marcadores sorológicos foram testados com kits comerciais de ELISA para detecção de HBsAg, anti-HBc total, anti-HBs e anti-VHC. Nos pacientes reagentes para VHC, RT-PCR e um line probe assay foi realizado para identificar o genótipo viral. RESULTADOS: Na análise dos marcadores sorológicos para hepatite B, observou-se taxas de 1,1% para anti-HBc total e 19,3% para anti-HBs, o marcador sorológico HBsAg não foi encontrado nesta população. Para a hepatite C foi encontrada um soroprevalência de 8,8%, destes 62,5% tinham RNA viral. Entre os fatores de risco estudados se destacaram: a não-utilização de preservativos, o compartilhamento de instrumentos cortantes, uso de drogas ilícitas e relatos de doença na família com VHB ou VHC. CONCLUSÕES: Observamos que a cobertura de vacinação contra o VHB é baixa e uma alta prevalência da hepatite C nesta comunidade.

Prevalence of hepatitis B virus infection and carriage after nineteen years of vaccination program in the Western Brazilian Amazon

Introduction: Reductions in the prevalence of hepatitis B virus (HBV) infection and carriage, decreases in liver cancer incidence, and changes in patterns of liver dysfunctions are described after hepatitis B vaccination. Methods: We conducted a population-based seroprevalence study aimed at estimating the HBV prevalence and risk of infection in the rural area of Labrea following nineteen years of HBV vaccination. Results: Half of the subjects showed total anti-HBc of 52.1% (95% CI 49.6-54.7). The HBsAg prevalence was 6.2% (95% CI 5.1-7.6). Multivariate analysis showed an inverse association between HBV infection and vaccination (OR 0.62; 95% CI 0.44-0.87). HBsAg remained independently associated with past hepatitis (OR 2.44; 95% CI 1.52-3.89) and inversely to vaccination (OR 0.43; 95% CI 0.27-0.69). The prevalence of HBeAg among HBsAg-positive individuals was 20.4% (95% CI 12.8-30.1), with the positive subjects having a median age of 11 years (1-46) p=0.0003. Conclusions: We demonstrate that HBV infection is still an important public health issue and that HBV vaccination could have had better impact on HBV epidemiology. If we extrapolate these findings to other rural areas in the Brazilian Amazon, we can predict that the sources of chronic infected patients remain a challenge. Future studies are needed regarding clinical aspects, molecular epidemiology, surveillance of acute cases, and risk groups.

Hepatitis B virus genotypes from European origin explains the high endemicity found in some areas from southern Brazil

Southern Brazil is considered an area of low Hepatitis B endemicity, but some areas of higher endemicity have been described in the Southwest of Parana and Santa Catarina states. The aim of this study was to evaluate viral genotypes circulating throughout Parana state. PCR amplification and partial sequencing of the S gene was carried out in 228 samples from HBsAg positive candidate blood donors. Samples have been collected in seven different counties (Cascavel, Curitiba, Foz do Iguacu, Francisco Beltrao, Matinga Londrina and Paranagua). The most common HBV genotype in Parana state was D (82.9%; 189/228), followed by A (14.1%; 32/228). Genotypes F (1.3%; 3/228), C (1.3%; 3/228) and H (0.4%; 1/228) were also found. Distribution of genotypes was different in the studied counties, but genotype D was the most frequent in all of them. In Francisco Beltrao, all studied samples belonged to genotype D. The high prevalence of HBV genotype Din South of Brazil is explained by the intense migration of settlers from Europeans countries. Subgenotypes A1 and A2 were identified circulating in all cities where HBV/A was found. As observed in other areas of Brazil, HBV/A1 is more frequent than the HBV/A2 in Parana state and its presence was significantly larger in black and mulatto individuals. Genotype C was found only in individuals with Asian ancestry from Londrina and Maringa. Most HBV/F sequences identified in this study were classified as subgenotype F2a that was previously described in Brazil. The sole case of subgenotype F4 was from Foz do Iguacu city, near to Northern Argentina, where F4 is highly prevalent. The single genotype H sample was from Curitiba. This is the first case of this genotype described in Brazil. Further studies should be carried out to determine if more genotype H samples can be found in other populations from Brazil. (C) 2012 Elsevier B.V. All rights reserved.

Phylogenetic analysis of complete genome sequences of hepatitis B virus from an Afro-Colombian community: presence of HBV F3/A1 recombinant strain

Background: Hepatitis B virus (HBV) infection is one of the most prevalent viral infections in humans and represents a serious public health problem. In Colombia, our group reported recently the presence of subgenotypes F3, A2 and genotype G in Bogota. The aim of this study was to characterize the HBV genotypes circulating in Quibdo, the largest Afro-descendant community in Colombia. Sixty HBsAg-positive samples were studied. A fragment of 1306 bp (S/POL) was amplified by nested PCR. Positive samples to S/POL fragment were submitted to PCR amplification of the HBV complete genome. Findings: The distribution of HBV genotypes was: A1 (52.17%), E (39.13%), D3 (4.3%) and F3/A1 (4.3%). An HBV recombinant strain subgenotype F3/A1 was found for the first time. Conclusions: This study is the first analysis of complete HBV genome sequences from Afro-Colombian population. It was found an important presence of HBV/A1 and HBV/E genotypes. A new recombinant strain of HBV genotype F3/A1 was reported in this population. This fact may be correlated with the introduction of these genotypes in the times of slavery.

Searching for chronic hepatitis B patients in a low prevalence area – role of racial origin

Abstract Background Clinical studies for testing new drugs against hepatitis B ought to be carried out in low prevalence areas despite difficulties on patient recruitment. In such areas, relatives of chronic hepatitis B patients are considered to be at risk of acquiring the hepatitis B virus (HBV). The aim of this study was to evaluate the prevalence of HBV markers (anti-HBc, HBsAg and anti-HBs) in familial members of chronic hepatitis B (CHB) patients according to their origin (Asian or Western) in a low prevalence area, the city of São Paulo, Brazil. Methods Twenty three Asian CHB probands and their 313 relatives plus 31 CHB probands of Western origin and their 211 relatives were screened for HBV serological markers; the study was carried out in the outpatient clinic of the University of São Paulo School of Medicine. Results Mother to child transmission was greater in the Asian group whereas sexual transmission was more frequent in the Western group (p < 0.0001). Anti-HBc was positive in 90% and 57% of the Asian and Western parents (p = 0.0432) and in 97% and 33% of the Asian and Western brothers (p = 0.0001), respectively. HBsAg was more frequent among the Asian (66%) than the Western (15%) mothers (p = 0.0260) as well as among the Asian (81%) than the Western (19%) brothers (p = 0.0001). We could detect 110 new HBsAg-positive subjects related to the 54 index patients, being the majority (81%) of Asian origin. Conclusion In low prevalence area of hepatitis B, family members and household contacts of chronic HBV carriers are at high risk for acquiring hepatitis B.

Hepatitis B virus infection in Haemodialysis Centres from Santa Catarina State, Southern Brazil. Predictive risk factors for infection and molecular epidemiology

Abstract Background Patients under haemodialysis are considered at high risk to acquire hepatitis B virus (HBV) infection. Since few data are reported from Brazil, our aim was to assess the frequency and risk factors for HBV infection in haemodialysis patients from 22 Dialysis Centres from Santa Catarina State, south of Brazil. Methods This study includes 813 patients, 149 haemodialysis workers and 772 healthy controls matched by sex and age. Serum samples were assayed for HBV markers and viraemia was detected by nested PCR. HBV was genotyped by partial S gene sequencing. Univariate and multivariate statistical analyses with stepwise logistic regression analysis were carried out to analyse the relationship between HBV infection and the characteristics of patients and their Dialysis Units. Results Frequency of HBV infection was 10.0%, 2.7% and 2.7% among patients, haemodialysis workers and controls, respectively. Amidst patients, the most frequent HBV genotypes were A (30.6%), D (57.1%) and F (12.2%). Univariate analysis showed association between HBV infection and total time in haemodialysis, type of dialysis equipment, hygiene and sterilization of equipment, number of times reusing the dialysis lines and filters, number of patients per care-worker and current HCV infection. The logistic regression model showed that total time in haemodialysis, number of times of reusing the dialysis lines and filters, and number of patients per worker were significantly related to HBV infection. Conclusions Frequency of HBV infection among haemodialysis patients at Santa Catarina state is very high. The most frequent HBV genotypes were A, D and F. The risk for a patient to become HBV positive increase 1.47 times each month of haemodialysis; 1.96 times if the dialysis unit reuses the lines and filters ≥ 10 times compared with haemodialysis units which reuse < 10 times; 3.42 times if the number of patients per worker is more than five. Sequence similarity among the HBV S gene from isolates of different patients pointed out to nosocomial transmission.

Characterization of Hepatitis B virus (HBV) genotypes in patients from Rondônia, Brazil

Abstract Background Hepatitis B virus (HBV) can be classified into nine genotypes (A-I) defined by sequence divergence of more than 8% based on the complete genome. This study aims to identify the genotypic distribution of HBV in 40 HBsAg-positive patients from Rondônia, Brazil. A fragment of 1306 bp partially comprising surface and polymerase overlapping genes was amplified by PCR. Amplified DNA was purified and sequenced. Amplified DNA was purified and sequenced on an ABI PRISM® 377 Automatic Sequencer (Applied Biosystems, Foster City, CA, USA). The obtained sequences were aligned with reference sequences obtained from the GenBank using Clustal X software and then edited with Se-Al software. Phylogenetic analyses were conducted by the Markov Chain Monte Carlo (MCMC) approach using BEAST v.1.5.3. Results The subgenotypes distribution was A1 (37.1%), D3 (22.8%), F2a (20.0%), D4 (17.1%) and D2 (2.8%). Conclusions These results for the first HBV genotypic characterization in Rondônia state are consistent with other studies in Brazil, showing the presence of several HBV genotypes that reflects the mixed origin of the population, involving descendants from Native Americans, Europeans, and Africans.