HBeAg Status Research Articles

High HBV Viral Loads in HIV-Infected Pregnant Women at a Tertiary Hospital, South Africa

High HBV Viral Loads in HIV-Infected Pregnant Women at a Tertiary Hospital, South Africa

The cost-effectiveness of treating chronic hepatitis B patients in a median endemic and middle income country

Background/aimsChronic hepatitis B (CHB) infection is a serious public health problem due to its potential liver disease sequelae and highly expensive medical costs such as the need for liver transplantation. The aim of this study was to quantify the burden of active CHB in terms of mortality and morbidity, the eligibility of antiviral treatment and to assess various treatment scenarios and possible salvage combinations for cost-effectiveness.MethodsA population cohort from a large data base of chronic hepatitis B patients was constructed and stratified according to 10-year age groups, the prevalence of HBsAg, HBV DNA level, ALT level, HBeAg status and the presence of cirrhosis. An age-specific Markov model for disease progression and cost-effectiveness analysis was constructed and calibrated for the specific population setting.ResultsOf about 3.2 million estimated HBsAg carriers, 25 % are eligible for treatment. If the active cohort remains untreated, 31 % will die due to liver related complications. Within a 20-year period, 11 % will have developed decompensated cirrhosis, 12 % liver cancer and 6 % will need liver transplantation. Quality adjusted life years (QALYs) for the no treatment scenario ranged from 9.3 to 14.0. For scenarios with antiviral treatment, QALYs ranged from 9.9 to 14.5 for lamivudine, 13.0–17.5 for salvage therapy, and 16.6–19.0 for the third generation drugs entecavir and tenofovir.ConclusionIn a country with considerable amount of active CHB patients, monotherapy with a highly potent third generation drug has the most health-gain, and is cost-effective in both HBeAg-positive and negative in all stages of liver disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s10198-012-0413-8) contains supplementary material, which is available to authorized users.

Molecular characterization of hepatitis B virus X gene in chronic hepatitis B patients

BackgroundHBV-X protein is associated with the pathogenesis of HBV related diseases, specially in hepatocellular carcinomas of chronic patients. Genetic variability of the X gene includes genotypic specific variations and mutations emerging during chronic infection. Its coding sequence overlaps important regions for virus replication, including the basal core promoter. Differences in the X gene may have implications in biological functions of the protein and thus, affect the evolution of the disease. There are controversial results about the consequences of mutations in this region and their relationship with pathogenesis. The purpose of this work was to describe the diversity of HBV-X gene in chronic hepatitis patients infected with different genotypes, according to liver disease.MethodsHBV-X gene was sequenced from chronic hepatitis B patient samples, analyzed by phylogeny and genotyped. Nucleotide and aminoacid diversity was determined calculating intragenetic distances. Mutations at 127, 130 and 131 aminoacids were considered in relation to liver disease.ResultsThe most prevalent genotype detected in this cohort was F (F1 and F4), followed by D and A. Most of the samples corresponding to genotypes A and F1 were HBeAg(+) and for genotypes D and F4, HBeAg(−) samples were represented in a higher percentage. Intragenetic distance values were higher in HBeAg(−) than in positive samples for all genotypes, and lower in overlapped regions, compared to single codification ones. Nucleotide and aminoacid diversities were higher in HBeAg(−), than in HBeAg(+) samples.ConclusionsIndependently of the infecting genotypes, mutations at any of 127, 130 and/or 131 aminoacid positions and HBeAg(−) status were associated with mild liver disease in this cohort.

Molecular analysis of hepatitis B virus associated with vaccine failure in infants and mothers: A case–control study in Thailand

Perinatal transmission of hepatitis B virus (HBV) has been controlled incompletely despite adequate immunoprophylaxis in infants. The aim of this study was to characterize virological factors of HBV associated with vaccine failure in Thailand. Sera of 14 infected infants (13 HBeAg-positive and one HBeAg-negative) with vaccine failure and their respective mothers (group M1) were tested quantitatively for HBV DNA by real-time PCR, HBV genotypes and mutations were characterized by direct sequencing. Sera collected from 15 HBeAg-positive (group M2) and 15 HBeAg-negative (group M3) mothers whose infants had been vaccinated successfully served as controls. The results showed that group M1 and group M2 mothers had equal titers of HBV DNA but higher titers than group M3. All infected infants and their respective mothers had the same HBeAg status and HBV genotypes. DNA analysis in a pair of HBeAg-negative infant and mother revealed that both were infected with an HBV precore mutant (G1896A). Escape mutants in the "a" determinant region (residues 144 and 145) were detected in two (14%) infected infants. The prevalence of BCP mutations/deletions in groups M2 and M3 was higher significantly than in group M1 (P = 0.022 and P < 0.001, respectively). In conclusion, instead of the HBeAg status, a high titer of HBV DNA in mothers was the major contributor to perinatal transmission of HBV. Escape mutants might be associated with vaccine failure in some infants. BCP mutations/deletions in mothers might contribute to the prevention of mother-to-infant transmission of HBV.

Patterns of hepatitis B viral load level (HBV DNA), hepatitis B e antigen (HBeAg) status and risk factors of cirrhosis and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients in Thailand

Background: There is a strong relationship between HBeAg sero-status, HBV DNA level and CHB-associated complications, especially cirrhosis and HCC. However, the distribution of HBV DNA and HBeAg seroprevalence and risk factors of cirrhosis among Thai CHB patients have not been adequately described. We aim to determine the patterns of HBV DNA level, HBeAg status, and risk factors of cirrhosis and HCC in Thai CHB patients. Methods: A cross-sectional study was conducted at Chulabhorn Hospital in 2010. CHB patients, aged 20-65 years, were tested for liver function test , HBeAg, HBV DNA, alpha fetoprotein and ultrasound upper abdomen. Results: 2,293 CHB patients (1,086 (47.36%) males) with the mean age (SD) of 41.25 (10.95) years were included. Mean HBV DNA was 3.62(2.22) log 10 IU/ml, and 47.71% had HBV DNA > 2,000 IU/ml. HBeAg positivity was present in 17.2% and most cases (96.19%) had high HBV-VL > 2,000 IU/ml. The majority of CHB (82.8%) were HBeAg negative, and only 37.6% of them had HBV DNA > 2,000 IU/ml. ALT level was 35.5(40.1) IU/L, of which 22.5% had ALT > 40 IU/ml. Higher HBV DNA and increased ALT levels were significantly associated with male gender, HBeAg-seropositivity and cirrhosis (p< 0.001). Liver cirrhosis by liver biopsy, transient elastography and US was found in 180 (7.8%) cases. HBeAg-seropositivity was more frequently found in cirrhosis patients than HBeAg-seronegativity (23.33% vs 16.67%, p=0.023). High prevalence of cirrhosis was found in HBV DNA level 2-3 and 5-6 log 10 IU/ml in 18.33% and 18.89%, respectively (p<0.001). Multivariate analysis showed factors associated with cirrhosis, including male gender, age > 50 years and HBV DNA> 2000 IU/ml. Logistic regression analysis revealed HBV DNA level of 200,000-1,999,999 IU/ml, which significantly associated with cirrhosis (OR 5.84). Conclusion: Higher HBV DNA level, HBeAg-seropositivity and risk factors for cirrhosis were commonly found in Thai CHB patients. HBeAg negative with 39.34% viremic regardless of ALT were observed in most CHB cases. The predominant trend towards HBeAg –seronegativity CHB has also been observed as in western countries. Hence, the active national surveillance policy should be implemented in those with high HBV DNA and HBeAg-seropositivity to provide effective treatment and prevent complications.

Comparison of the efficacy of tenofovir and entecavir for the treatment of nucleos(t)ide-naive patients with chronic hepatitis B

Chronic hepatitis B virus infection is an important cause of morbidity and mortality. Tenofovir disoproxil fumarate and entecavir were licensed for the treatment of hepatitis B virus infection. We evaluated the first 12 months of chronic hepatitis B treatments with tenofovir and entecavir and compared their efficiencies. The study enrolled 94 chronic hepatitis B patients with compensated liver disease. The entecavir group consisted of 29 patients who received entecavir 0.5 mg/day and the tenofovir group consisted of 65 patients who received tenofovir 245 mg/day. There was no statistically significant demographic or HBeAg status difference between the groups. Patients returned to the clinic every four weeks for laboratory assessments of serum chemical and hematologic values, liver function and for documentation of any adverse events. Hepatitis B serologic markers and HBV-DNA levels were assessed every 12 weeks. The primary efficacy endpoint was a plasma HBV-DNA level of less than 400 copies/ml over 48 weeks. At the end of 48 weeks, treatment with either tenofovir or entecavir resulted in clinically important suppression of HBV-DNA, as 71.3%. There was no statistical difference in inducing undetectable levels of HBV-DNA between the entecavir (69%) and tenofovir (72.3%) groups. Furthermore, no side effect as an increase in creatinine was seen. HBeAg seroconversion was seen in only one patient in the entecavir group, but in no patients of the tenofovir group. In the first year of treatment for chronic hepatitis B, virologic response and tolerability did not differ significantly between tenofovir and entecavir. Both drugs are safe and efficacious for patients infected with HBV.

Characteristic of liver pathology in HBeAg-positive and HBeAg-negative chronic hepatitis B patients with mildly elevated ALT

To analyse the live pathology characteristics in mild ALT-elevated (1 x ULN less than ALT less than 2 x ULN ) HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB) patients, and to explore the influence of the age and HBV DNA level to liver pathology in different HBeAg status patients. All the patients who met the inclusion criteria form "eleventh five-year plan" National Science and Technology Major Project, the treatment program of integrative traditional and western medicine for CHB were enrolled in this study between October 2009 and March 2011 .B type ultrasound-guided liver biopsy was carried out in all patients and hepatitis B surface antigen (HBsAg) , HBeAg titer as well as HBV DNA level were detected at the same time. Hepatic tissue inflammation and fibrosis degree of patients according to HBeAg-positive and negative, age ( more than or equal to 40 years and less than 40 years), HBV DNA level (more than or equal to 10^5copy/ml and less than l0^5 copy/ml) were compared respectively. Chi-square test was used to compare the constitute percentage between the two samples. Multivariate logistic regression analysis was also performed to evaluate the correlation between different factors. There were no significant difference in the grade of liver inflammation and the stage of liver fibrosis between 389 HBeAg positive and 126 HBeAg-negative patients (X2=4.326 and X2=3.464, respectively, P values were all more than 0.05). In the group of patients with age less than 40 years, the distribution of different liver inflammation and fibrosis had no significant difference between HBeAg-positive and negative patients (X2=2.543 and X2=5.024, respectively, P values were all more than 0.05). In the group of patient with age more than or equal to 40 years, the percentage of moderate and severe inflammation (G3, G4) HBeAg-positive patients(32.9%) owned is much higher than that of HBeAg-negative patients(16.4%), X2=8.777, P less than 0.05.But the stage of liver fibrosis in HBeAg-positive patients was not significantly different than that of HBeAg-negative ones (X2=0.977, P more than 0.5). In the group of patients with HBV DNA more than or equal to 10^5copy/ml, the percentage of mild inflammation in HBeAg-positive patients (17.5%) was much high than that of HBeAg-negative patients(7.3%), X2=8.851, P less than 0.05. The stage of liver fibrosis between HBeAg-positive and negative patients was no significant difference (X2=8.227, P more than 0.05).In the patients with HBV DNA less than 10^5 copy/ml, The percentage of HBeAg-negative patients(29.6%) with mild inflammation(G1) was much higher than HBeAg-positive patients (6.9%), X2=6.357, P less than 0.05. There was no significant difference in the stage of liver fibrosis between HBeAg-positive and negative patients (X2=4.061, P more than 0.05). The results of multivariate logistic regression analysis showed that age was the independent risk factor for different degree of liver inflammation and fibrosis seriousness. The status of HBeAg has no association with the grade of liver inflammation and the stage of liver fibrosis in CHB patients with mildly elevated ALT. The percentage of moderate and severe inflammation in the HBeAg-positive patients with age more than or equal to 40 years was significantly elevated. The grade of liver inflammation has significant difference between HBeAg-positive and negative patients with different HBV DNA levels as well.

Antiviral therapy against chronic hepatitis B in Brazil: high rates of lamivudine resistance mutations and correlation with HBV genotypes

The effectiveness of antiviral treatments of chronic hepatitis B has been poorly studied in Brazil. Here, hepatitis B virus (HBV) DNA positivity, drug resistance mutations and their association with HBV genotypes were evaluated in chronically HBV-infected patients under different drug regimens in Brazil. The study involved 129 patients under interferon or nucleos(t)ide analogue therapy for a median treatment time of 12 months. One hundred and five (81%) of these patients were treated with lamivudine (LAM), either in monotherapy or in combination with newer drugs, such as entecavir (ETV) or tenofovir (TDF). High (37.5-100%) rates of HBV DNA positivity were observed with all but one drug regimen (LAM + ETV). However, patients that were treated with ETV alone, TDF alone or with LAM combination therapies had a mean viral load that was 3-4 log lower than patients treated with LAM monotherapy. Of the patients treated with LAM, 47% developed resistance mutations. HBV genotypes A (59.1%), D (30.3%) and F (9.1%) were found. There was no association between the presence of LAM resistance mutations and genotypes, HBeAg status or treatment duration. Nevertheless, the rtM204V mutation was observed more frequently (12/13, 92%) in genotype A than in the others (p = 0.023). Six out of nine isolates that contained the rtM204I mutation belonged to genotype D and half of them displayed a single mutation. Genotype D isolates with the rtM204V variant preferentially displayed a triple mutation, while genotype A preferentially displayed a double mutation (p = 0.04).

Is there an association between the measurement of qualitative HBsAg and virologic response in chronic HBV infection?

Background. In the follow up of chronic hepatitis B infection (HBV), a significant correlation between quantitative HBsAg titer measurement and HBV DNA level, and moreover with intrahepatic covalently closed circular DNA was already shown. However, besides their impact on long-term follow up, they are really expensive methods, and not available widespread. We aimed to investigate the utility of qualitative measurement of HBsAg titer in prediction of virologic response at the end of the first year of anti-viral treatment in chronic HBV infection.Material and methods. A total of 70 patients receiving anti-viral therapies for chronic HBV infection were included into the study. The patients were evaluated according to Hbe Ag status and response to treatment. The determinations used in the study (biochemical, virologic responses, primary non-response) were accepted as it was described in AASLD.Results. Qualitative HBsAg titer increased significantly in both HBeAg positive and negative patients (p values 0.002 and < 0.000). Increasing of HBsAg titer in first three months is more dramatic in responder group, however the difference was disappeared at the sixth and twelve moths on follow up. Similarly, a fast increasing in anti-HBe titer in HBeAg negative chronic HBV patients was related with higher response at the end of first year therapy. However, the changings at the 12th month of anti-viral treatment were similar in both responder and non-responder groups.Conclusion. In conclusion, the fast increase in qualitative measurement of HBsAg titer seemed to be a predictor of higher anti-viral medication success in chronic HBV patients. However, this meaningful increasing was disappeared on the follow up, particularly after the six months examination.

Correlation of the occurrence of YMDD mutations with HBV genotypes, HBV-DNA levels, and HBeAg status in Chinese patients with chronic hepatitis B during lamivudine treatment

Continuous lamivudine therapy is associated with high rates of YMDD mutations, which are the main causes of drug resistance. The current study explores the association of the emergence of YMDD mutations with pretherapy HBV genotype, HBV-DNA levels, HBeAg status, and serum alanine aminotransferase (ALT) levels in Chinese patients receiving lamivudine therapy for chronic hepatitis B. A total of 319 chronic hepatitis B patients who received lamivudine therapy for more than a year were enrolled in this study. YMDD mutations, HBV genotype, HBV-DNA levels, HBeAg status, and ALT levels were determined prior to their lamivudine treatment and every three months for a year of this therapy. Among the 319 patients, 137 (42.95%) were infected with genotype B and 182 (57.05%) with genotype C. Up to 94 patients (29.47%) developed YMDD mutations within one year of lamivudine therapy. Furthermore, 50 patients with HBV genotype B and 44 patients with genotype C developed YMDD mutations (36.50% vs 24.18%, P<0.05). Logistic regression analysis showed that pretherapy HBV genotype, HBV-DNA levels, and HBeAg status are independent factors for the emergence of YMDD mutations (HBV genotype: OR=2.159, 95% CI 1.291-3.609, P=0.003; HBV-DNA: OR=1.653, 95% CI 1.231-2.218, P=0.001; HBeAg: OR=2.021, 95% CI 1.201-3.399, P=0.008). HBV genotype, HBV-DNA levels, and HBeAg status at baseline are the independent factors associated with the emergence of YMDD mutations among Chinese patients receiving lamivudine therapy for chronic hepatitis B. These findings are helpful to the development of therapeutic strategies for these patients.

480 ANTIVIRAL THERAPY CAN LEAD TO FIBROSIS REGRESSION IN ANTIHBE-POSITIVE CHRONIC HEPATITIS B PATIENTS TREATED IN CLINICAL PRACTICE

of patients according to various guidelines and liver histology of these patients. Patients andMethods: 574 HBV patients (353; 61.5% male – median age 46; range 19–78) without clinical or laboratory evidence of cirrhosis were included in the study. Patients were grouped into treatment, follow-up (no treatment) and borderline sub-groups according to age, gender, HBeAG status, serum ALT, HBVDNA levels defined in HBV guidelines published by AASLD, EASL, APASL and WGO. Liver histologies of all patients were evaluated and were grouped as treatment and follow-up groups according to the degree of histologic activity or stage of fibrosis. Results: Of the 574 patients 54(9.4%) had no inflammation, 206(35.9%) had minimal (HAI: 1–4), 141 (24.6%) had mild, 138 (24.1%) had moderate and 35 (6.1%) had severe inflammation. Fibrosis stages were 0 (no fibrosis) in 211 (36.8%), 1–2 in 303 (52.7%) and >2 in 60 (10.45%) patients according to modified Ishak’s method. Treatment was indicated in 157 (27.4%) of the patients according to liver biopsy. Distributions of patients according to treatment guidelines and histopathologic findings (Treatment indicated according to biopsy/treatment indicated according to serum markers) in liver biopsy is shown in table 1. Among the 347 patients with minimal-mild histologic activity 76 (21.9%) had HBVDNA between 2000–20,000 IU/ml and 134 (38.6%) had HBVDNA >20,000 IU/ml.

The naturally occurring YMDD mutation among patients chronically infected HBV and untreated with lamivudine: a systematic review and meta-analysis.

BackgroundSeveral recent reports have demonstrated that tyrosine (Y)-methionine (M)-aspartic acid (D)-aspartic acid (D) (YMDD) motif mutations can naturally occur in chronic HBV patients without antiviral treatment such as lamivudine therapy. This paper aims to assess the overall spontaneous incidence and related risk factors of YMDD-motif mutations among lamivudine-naïve chronic HBV carriers, so as to provide some clue for clinical treatment of hepatitis B.Methodology/Principal FindingsChinese and English literatures were searched for studies reporting natural YMDD mutations among untreated chronic HBV patients from 2001 to 2010. The incidence estimates were summarized and analyzed by meta-analyses. Forty-seven eligible articles from eight countries were selected in this review (13 in English and 34 in Chinese). The pooled incidence of YMDD-motif mutation among untreated chronic HBV patients from eight countries was 12.21% (95% CI: 9.69%–14.95%). China had an incidence of 13.38% (95% CI: 10.90%–16.07%) and seven other countries had an incidence of 9.90% (95% CI: 3.28%–19.55%), respectively. Lamivudine therapy would increase the risk of mutations 5.23 times higher than the untreated patients. A higher HBV DNA copy number was associated with increased incidence of natural YMDD mutation. No significant difference was found in YMDD mutation incidence between groups of different gender, age, HBeAg status, patients' ALT (alanine aminotransferase) level, and between the groups of HBV genotype B and C.ConclusionsThe YMDD-motif mutations can occur spontaneously with a relatively high incidence in CHB patients untreated with lamivudine. These mutations might be the consequence of accumulated base mismatch due to the nature of viral polymerase. More fundamental and clinical studies are needed to clarify the influence of YMDD mutations in hepatitis B progression and antiviral treatment.

Saudi Guidelines for the Diagnosis and Management of Hepatocellular Carcinoma: Technical Review and Practice Guidelines

Recognizing the significant prevalence of hepatocellular carcinoma (HCC) in Saudi Arabia, and the difficulties often faced in early and accurate diagnoses, evidence-based management, and the need for appropriate referral of HCC patients, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) formed a multi-disciplinary task force to evaluate and update the previously published guidelines by the Saudi Gastroenterology Association. These guidelines were later reviewed, adopted and endorsed by the Saudi Oncology Society (SOS) as its official HCC guidelines as well. The committee assigned to revise the Saudi HCC guidelines was composed of hepatologists, oncologists, liver surgeons, transplant surgeons, and interventional radiologists. Two members of the task force served as guidelines editors. A wide based search on all published reports on all aspects of the epidemiology, natural history, risk factors, diagnosis, and management of HCC was performed. All available literature was critically examined and available evidence was then classified according to its strength. The whole document and the recommendations were then discussed in details by members and consensus was obtained. All recommendations in these guidelines were based on the best available evidence, but were tailored to the patients treated in Saudi Arabia. We hope that these guidelines will improve HCC patient care and enhance the multidisciplinary care needed for these patients.

Detection of HBV-DNA and Its Correlation with the HBeAg/Anti-HBe Serological Status in HBsAg-positive Patients

Background : In the past years, HBeAg and anti-HBe status in individuals with positive HBsAg were often correlated to viral replication. This study was aimed to find correlation between the HBV viremia and HBeAg/anti-HBe serological status in HBsAg-positive individuals. Method : An observational-analytic design was performed in this study. The sera of all positive HBsAg patients at Biomedika Hospital Laboratory were collected and examined for HBeAg and anti-HBe using immunochromatography technique between January and April 2012. The sampling method was purposive sampling. Afterwards, the sera were examined for HBV-DNA by polymerase chain reaction (PCR). Results: Sufficient amount of sera were collected from 44 patients consisting of 33 males and 11 females. The mean age was 15-68 years. Positive HBeAg and negative anti-HBe status was found in 11 (42%) patients. Negative HBeAg and positive anti-HBe was found in 26 (59.1%) patients. Both HBeAg and anti-HBe were negative in 7 (16.3%) patients. HBV-DNA was detected in all 11 (100%) patients with positive HBeAg and negative anti-HBe. HBV-DNA was also detected in 11 (42%) patients with negative HBeAg and positive anti-HBe. However, there was only one patient (14.3%) with both negative HBeAg and anti-HBe status, who had detectable HBV-DNA. Conclusion: Positive HBeAg can be used as an indicator of viremia, but negative HBeAg cannot be used as an indicator of the absence of viremia without further HBV-DNA testing. Patients with negative HBeAg and positive HBV-DNA were suspected for having pre-core mutant. Keywords : HBV-DNA, positive HBsAg, HBeAg, anti-HBe, pre-core mutant

Laboratory Evaluation of Three Regimens of Treatment of Chronic Hepatitis B: Tenofovir, Entecavir and Combination of Lamivudine and Adefovir

Background:Chronic hepatitis B is a disease of concern due to its life-threatening complications like cirrhosis, and hepatocellular carcinoma (HCC) in 20-40% of patients. There are about 400 million people affected worldwide with HBV, and over 300,000 die every year from HBV-related diseases. Oral antivirals like lamivudine, adefovir, entecavir, and tenofovir are commonly used to treat chronic hepatitis B. In this study, we tried to evaluate the comparative efficacy of these drugs alone and in combination.Materials and Methods:Chronic hepatitis B patients with HBV-DNA more than 104 Copies/mL irrespective of their HBeAg status (n = 60) were enrolled in a prospective study. 21, 20, and 19 patients were treated with lamivudine (100 mg/day) plus adefovir (10 mg/day) combination entecavir monotherapy (0.5 mg/day) and tenofovir monotherapy (300 mg/day), respectively and were followed up for 24 weeks with their virological, serological, and biochemical markers measured at 12 and 24 weeks.Results:After 24 weeks of treatment, there was no significant difference between the 3 groups in suppressing HBV-DNA to undetectable levels. The median decrease in HBV-DNA levels from baseline was better with tenofovir and entecavir monotherapies than lamivudine and adefovir combination, which was statistically significant. There was no significant difference between the 3 groups in HBsAg and HBeAg seroconversion and normalization of biochemical parameters.Conclusion:Entecavir and tenofovir monotherapy were found to be more effective than lamivudine plus adefovir combination in reducing the HBV-DNA levels. However, lamivudine plus adefovir combination was not too inferior, especially when cost of treatment was taken into consideration.

Management of hepatitis B virus infection in the pre-transplant setting

Liver transplantation remains the ultimate cure for patients with hepatitis B virus-related end-stage liver disease. Clinical Practice Guidelines currently recommend that patients with decompensated HBV cirrhosis should be treated without delay with nucleos(t)ide analogues regardless of the patient's serum ALT, HBV DNA level, and HBeAg status. The main goal of pre-transplantation antiviral therapy is to achieve a rapid and prolonged suppression of viral replication and thus decrease the risk of hepatitis B virus reinfection of the graft. In addition, sustained negativization of serum HBV DNA may also result in clinical stabilization which can decrease the mortality rate while on the waiting list and delay or avoid liver transplantation in some cases. Clinical improvement may take from 3 to 6 months to become evident. Lamivudine and adefovir are no longer considered first-line therapy in these patients. Potent nucleos(t)ide analogues with good resistance profiles such as entecavir or tenofovir should be used instead. Preliminary data suggest that these agents are effective and have a good safety profile in patients with decompensated cirrhosis. More safety data, however, are needed, particularly in patients with severe impairment of liver function. More data are needed to determine which of the newer antiviral agents offer the best risk–benefit ratio in this challenging patient population. Although a tenofovir-based regimen may be preferred in decompensated patients with lamivudine-resistant hepatitis B virus, there are some concerns about the long-term safety of tenofovir including nephrotoxicity and metabolic bone disease.

Predictors of Histologic Severity in Chronic Hepatitis B-infected Patients

The role of liver biopsy in chronic Hepatitis B treatment guidelines remains incompletely defined. Our aim was to correlate histologic disease severity with demographic, biochemical and virologic parameters as currently used in Hepatitis B treatment guidelines. We conducted an Institutional Review Board (IRB) approved retrospective cross-sectional study of chronic Hepatitis B patients between January 2001 and July 2009. Patients with at least two Alanine Aminotransferase (ALT) values (6 months apart), with detectable Hepatitis B DNA quantitative levels at the time of initial evaluation, unchanged HBeAg status over a minimum of 6 months but no prior history of antiviral therapy, alcohol abuse, co-infection, hepatocellular carcinoma, iron overload or liver decompensation were reviewed. Advanced histological disease was defined as a METAVIR score of greater than or equal to stage and/or grade 3 (≥S/G 3). Multivariable binary logistic regression was used to determine the independent predictors of advanced histology. One hundred and twenty-eight patients met inclusion criteria. On multivariate logistic regression analysis, viral load was not an independent predictor. However, age ≥40, abnormal ALT and HBeAg(+) were independent predictors of ≥S/G3. Controlling for ALT and HBeAg status, patients ≥40 years old had 14.5 times the adjusted odds of ≥S/G3 (95% CI, 4.24–49.54) while 31% of HBeAg(-) /Low Viral load patients had ≥S/G3. Current HBV-treatment guidelines do not fully predict advanced histological disease. In the group where all the current guidelines recommend observation without treatment, one third had advanced histology on liver biopsy.

Significant hepatic histopathology in chronic hepatitis B patients with serum ALT less than twice ULN and high HBV‐DNA levels in Indonesia

To study the prevalence of significant hepatic histopathology in chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) ≤ twice upper limit of normal (ULN) and its association with age, HBeAg status, hepatitis B virus (HBV)-DNA level and viral genotype. A prospective study was conducted over a 3-year period in treatment-naive CHB patients with ALT ≤ twice ULN. Patients with a history of acute flare hepatitis, use of alcohol and hepatotoxic drugs, hepatitis C, hepatitis D and human immunodeficiency virus (HIV) co-infection were excluded from the study. Hepatic histopathology was assessed according to the METAVIR scoring system. A total of 145 patients were recruited, 81 (55.9%) of whom were male. The patients' mean age was 41.50 ± 10.74 years (range 16-70 years). Significant hepatic inflammation was found in 59.3% of these patients, and significant hepatic fibrosis was found in 62.1%, the latter being associated with hepatitis B e antigen status, ALT levels and serum HBV-DNA, but not with their age group or viral genotype. Significant hepatic fibrosis was found in 24 of 35 CHB patients (68.6%) who were previously considered in an immunotolerance phase. The prevalence of significant hepatic histopathology in CHB patients with serum ALT levels ≤ twice ULN is high. Delayed antiviral treatment can be harmful.

Observation of genotype C infected chronic hepatitis B patients in clinical practice

Hepatitis B virus (HBV) genotype C is prevalent in many areas of the world including Thailand and Southeast Asia. It is a strong risk for hepatocellular carcinoma (HCC) by evidence. We aimed to describe the baseline clinical information of treatment naïve genotype C infected chronic hepatitis B (CHB) patients and to describe the treatment response by surrogate outcome markers in genotype C infected CHB patients after one year of nucleos(t)ide analogues (NA) treatment Thirty-four genotype C CHB patients were studied at the Hospital for Tropical Diseases, Bangkok, including 12 patients treated with lamivudine, 11 with telbivudine, 8 with adefovir, and 3 with entecavir. Serum HBV DNA levels, serum alanine amino transferase ( ALT ) levels, HBeAg status, and alpha-feto protein (AFP) levels were recorded at the start and after twelve months of ongoing treatment. HBV genotyping was performed by line-probe assay. About half of the patients (58.8%) were HBeAg positive. Mean HBV viral load was 6.53 + 1.15 log10 copies per ml at baseline and reduced to 3.63 + 1.3 log10 copies per ml after one year of NA treatment. Serum HBV DNA levels became undetectable in 47.1 % of the patients and serum ALT was normalized in 23.5 % of the patients. Most of the genotype C patients were aged above 40 years. More than half of the genotype C infected patients did not achieve virological response and biochemical remission. Among the CHB patients, genotype C infected patients are a high priority group for intervention.

The Role of Liver Fibrosis Assessment in the Management of Patients with Chronic Hepatitis B Infection: Lessons Learned from a Single Centre Experience

Background & Aims. Assess the clinical utility of the Prati criteria and normal ALT (<40 IU/L) in a cohort of patients with chronic hepatitis B infection (CHB). Methods. Serology, radiology, and histology were obtained in 140 patients with CHB. Results. HBeAg+ group: 7 patients (7/56−12% HBeAg+ group) misclassified as “immunotolerant”, with HBV DNA > 6 log copies/ml and normal ALT, who in fact had moderate/severe fibrosis on liver biopsy. HBeAg− group: 10 patients with normal ALT and moderate/severe fibrosis on liver biopsy; 4 of these patients had >3 log copies/ml HBV DNA levels and 6 patients misclassified as “inactive carriers” with negative HBV DNA levels normal ALT and moderate/severe fibrosis (6/84−7% HBeAg− group). Two male HBeAg+ and three male HBeAg− patients with ALT between 20 and 30 IU/L and moderate/severe fibrosis on liver biopsy would have been further mischaracterised using the Prati criteria for normal ALT. Age and ethnic group were more important predictors of moderate/severe fibrosis in multivariate analysis. Conclusion. HBeAg status, age, ethnic origin with longitudinal assessment of LFTs and viral load should be studied in patients with “normal ALT” at the upper end of normal range (ALT 20–40 IU/L) to appropriately classify patients and identify patients for liver fibrosis assessment to inform treatment decisions.