Evaluation of TyG index and TG/HDL-C ratio in HBeAg negative chronic hepatitis B infected patients.

Patients with hepatitis B e antigen (HBeAg) negative chronic HBV infection are regularly followed up. This study investigates the presence of insulin resistance and the relationship between hepatosteatosis and insulin resistance in patients with HBeAg negative chronic HBV infection using the TyG index and TG/HDL-C ratio. Patients with HBeAg negative chronic HBV infection who applied to the Infectious Diseases and Clinical Microbiology outpatient clinic between January 2019 and December 2020 were included in the study. Glucose, lipid panel, alanine amino transferase (ALT), acetyl amino transferase (AST), body mass index (BMI), TyG index, TG/HDL-C and hepatobiliary ultrasonography (USG) results were evaluated. The data were compared with the control group consisting of 308 HBsAg negative individuals. The study included 132 patients with a median age of 52 years. There was no significant difference between the patient and control groups regarding age, gender and BMI. Glucose, total cholesterol, TG, LDL, AST, ALT, TyG index and TG/HDL-C ratio were significantly higher in patient than in the control group. At the same time, the HDL value was significantly lower in the patients. There was a strong positive correlation between the TG and BMI, and a strong negative correlation between HDL levels and both TyG index and TG/HDL-C ratio. Our findings showed that the TyG index and TG/HDL-C ratio are helpful in the diagnosis of insulin resistance and hepatosteatosis in patients with HBeAg negative chronic HBV infection.

The association between obesity with serum levels of liver enzymes, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transferase in adult women.

BACKGROUND: Obesity-induced inflammation may independently disturb the function of critical organs such as liver. This study aimed to investigate the association of obesity with serum levels of biomarkers of liver function including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) in adult women. METHODS: This cross-sectional study was carried out on 360 adult women in the summer of 2020 in Tehran, Iran. The participants were categorized into two groups based on their body mass index (BMI≤29.9 and BMI > 30). The serum levels of ALT, AST, ALP and GGT were measured. Logistic regression method was used to assess the association between BMI and liver enzymes after adjusting for the confounders. RESULTS: The mean BMI in non-obese and obese groups was 26.32 ± 2.61 and 33.40 ± 2.80 kg/m2 , respectively (p = .01). A significant association was found between BMI with ALT (ß = .16, p = .002) and GGT (ß = .19, p = .01) enzymes after adjustment for age. The association between BMI and GGT remained significant after further adjustments for smoking, alcohol use, physical activity and educational status. There was no significant association between BMI and liver enzymes after adjustment for dietary intake. CONCLUSIONS: Obesity was associated with the level of serum liver enzymes. However, adjustment for dietary intake disappeared the significant results. Further studies are needed to determine the independent effects of obesity on the liver function.

A combined association of serum uric acid, alanine aminotransferase and waist circumference with non-alcoholic fatty liver disease: a community-based study.

Background: Increasing evidence has supported that serum uric acid (SUA), alanine aminotransferase (ALT) and waist circumference (WC) are associated with the occurrence of non-alcoholic fatty liver disease (NAFLD). However, the combined role of these factors in early screening of NAFLD has not been investigated. We aimed to de lineate this role in a community-based population. Methods: Binary logistic regression was used to explore the correlations of SUA, ALT and WC with NAFLD risk. The goodness of fit and discriminative ability of the model were evaluated by the Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUROC), respectively. Results: Logistic regression analysis indicated that elevated SUA (adjusted odds ratio (OR) = 2.44, 95% confidence interval (CI) [1.76-3.38]), ALT (adjusted OR = 4.98, 95% CI [3.41-7.27]) and WC (adjusted OR = 3.22, 95% CI [2.01-5.16]) were facilitating factors for incident NAFLD after fully adjusted for related confounders. In addition, the risk of NAFLD followed linear trend s with increasing levels of these three indicators (all P trend < 0.001). The risk assessment model consisting of SUA, ALT, WC and demographics showed useful discrimination by AUROC being 0.825 (95% CI [0.811-0.838]) and good performance of calibration (P = 0.561). Conclusions: SUA, ALT and WC were all associated with NAFLD, independent of known risk factors. The simple model composed of these indicators showed good performance in the Chinese population, which may be applicable for appraisal of NAFLD risk in primary healthcare.

Validation of Dynamic Aspartate-to-Alanine Aminotransferase Ratio for Predicting Liver Disease Mortality.

The dynamic aspartate-to-alanine aminotransferase ratio (dAAR) was developed recently to predict the risk of incident chronic liver disease among the Nordic adult population; however, the dAAR has not been externally validated in other ethnic cohorts. Therefore, we aimed to examine the predictive ability of dAAR for liver disease mortality in the South Korean adult population. As a population-based cohort study, we used the National Health Screening Cohort database, which included adult individuals who underwent standardized medical examinations between 2002 and 2003 in South Korea. The primary endpoint was liver disease mortality, defined as death due to liver disease. Liver disease mortality was evaluated between 2004 and 2015 (12 years). Analysis of data from 512,749 adults showed that 4,052 (0.8%) individuals died due to liver disease. On receiver operating characteristic (ROC) analyses, the area under curve for alanine aminotransferase (ALT), aspartate-to-ALT ratio (AAR), and dAAR for liver disease mortality were 0.74, 0.55, and 0.81, respectively. The cutoff point of dAAR was determined to be 0.72 on ROC analysis, using the Youden index method. On competing risk analysis using the Fine and Gray model, the dAAR > 0.72 group demonstrated a 4.43-fold higher rate of liver disease mortality (subdistribution hazard ratio: 4.43, 95% confidence interval: 4.11, 4.77; P < 0.001) after adjustment for covariates. Conclusion: The performance of dAAR in predicting liver disease mortality was better than that of AAR or ALT in South Korea. Our study suggests that dAAR scores can potentially be used for screening and predicting liver disease mortality among the general Korean population.

Overexpression of a newly identified d-amino acid transaminase in Mycobacterium smegmatis complements glutamate racemase deletion.

Glutamate racemase (MurI) has been proposed as a target for anti-tuberculosis drug development based on the inability of ΔmurI mutants of Mycobacterium smegmatis to grow in the absence of d-glutamate. In this communication, we identify ΔmurI suppressor mutants that are detected during prolonged incubation. Whole genome sequencing of these ΔmurI suppressor mutants identified the presence of a SNP, located in the promoter region of MSMEG_5795. RT-qPCR and transcriptional fusion analyses revealed that the ΔmurI suppressor mutant overexpressed MSMEG_5795 14-fold compared to the isogenic wild-type. MSMEG_5795, which is annotated as 4-amino-4-deoxychorismate lyase (ADCL) but which also has homology to d-amino acid transaminase (d-AAT), was expressed, purified and found to have d-AAT activity and to be capable of producing d-glutamate from d-alanine. Consistent with its d-amino acid transaminase function, overexpressed MSMEG_5795 is able to complement both ΔmurI deletion mutants and alanine racemase (Δalr) deletion mutants, thus confirming a multifunctional role for this enzyme in M. smegmatis.

[Biomarkers of alcohol abuse. Part I. Traditional biomarkers and their interpretation]. / Biomarkery naduzywania alkoholu. Czesc I. Biomarkery tradycyjne i ich interpretacja.

Approximately 15% of the Polish population abuse alcohol. Early detection of alcohol problems may prevent their further development and progression. The study reviews traditional biomarkers associated with alcohol abuse. The nature of biomarkers, their practical application and limitations in alcohol abuse detection, in assessment and monitoring of drinking, are reviewed. Despite the limited sensitivity and specificity in alcohol abuse detection, traditional biomarkers remain useful in alcohol abuse detection. They are widely available and relatively inexpensive, providing valuable data on complications of drinking and prognosis as well as on concurrent conditions affected by drinking.

Genome-scale model for Clostridium acetobutylicum: Part II. Development of specific proton flux states and numerically determined sub-systems.

A regulated genome-scale model for Clostridium acetobutylicum ATCC 824 was developed based on its metabolic network reconstruction. To aid model convergence and limit the number of flux-vector possible solutions (the size of the phenotypic solution space), modeling strategies were developed to impose a new type of constraint at the endo-exo-metabolome interface. This constraint is termed the specific proton flux state, and its use enabled accurate prediction of the extracellular medium pH during vegetative growth of batch cultures. The specific proton flux refers to the influx or efflux of free protons (per unit biomass) across the cell membrane. A specific proton flux state encompasses a defined range of specific proton fluxes and includes all metabolic flux distributions resulting in a specific proton flux within this range. Effective simulation of time-course batch fermentation required the use of independent flux balance solutions from an optimum set of specific proton flux states. Using a real-coded genetic algorithm to optimize temporal bounds of specific proton flux states, we show that six separate specific proton flux states are required to model vegetative-growth metabolism and accurately predict the extracellular medium pH. Further, we define the apparent proton flux stoichiometry per weak acids efflux and show that this value decreases from approximately 3.5 mol of protons secreted per mole of weak acids at the start of the culture to approximately 0 at the end of vegetative growth. Calculations revealed that when specific weak acids production is maximized in vegetative growth, the net proton exchange between the cell and environment occurs primarily through weak acids efflux (apparent proton flux stoichiometry is 1). However, proton efflux through cation channels during the early stages of acidogenesis was found to be significant. We have also developed the concept of numerically determined sub-systems of genome-scale metabolic networks here as a sub-network with a one-dimensional null space basis set. A numerically determined sub-system was constructed in the genome-scale metabolic network to study the flux magnitudes and directions of acetylornithine transaminase, alanine racemase, and D-alanine transaminase. These results were then used to establish additional constraints for the genome-scale model.

Degradation of pyrimidines in Saccharomyces kluyveri: transamination of beta-alanine.

Beta-alanine is an intermediate in the reductive degradation of uracil. Recently we have identified and characterized the Saccharomyces kluyveri PYD4 gene and the corresponding enzyme beta -alanine aminotransferase ((Sk)Pyd4p), highly homologous to eukaryotic gamma-aminobutyrate aminotransferase (GABA-AT). S. kluyveri has two aminotransferases, GABA aminotransferase ((Sk)Uga1p) with 80% and (Sk)Pyd4p with 55% identity to S. cerevisiae GABA-AT. (Sk)Pyd4p is a typical pyridoxal phosphate-dependent aminotransferase, specific for alpha-ketoglutarate (alpha KG), beta-alanine (BAL) and gamma-aminobutyrate (GABA), showing a ping-pong kinetic mechanism involving two half-reactions and substrate inhibition. (Sk)Uga1p accepts only alpha KG and GABA but not BAL, thus only (Sk)Pydy4p belongs to the uracil degradative pathway.

D-alanylation of lipoteichoic acid contributes to the virulence of Streptococcus suis.

We generated by allelic replacement a DeltadltA mutant of a virulent Streptococcus suis serotype 2 field strain and evaluated the contribution of lipoteichoic acid (LTA) d-alanylation to the virulence traits of this swine pathogen and zoonotic agent. The absence of LTA D-alanylation resulted in increased susceptibility to the action of cationic antimicrobial peptides. In addition, and in contrast to the wild-type strain, the DeltadltA mutant was efficiently killed by porcine neutrophils and showed diminished adherence to and invasion of porcine brain microvascular endothelial cells. Finally, the DeltadltA mutant was attenuated in both the CD1 mouse and porcine models of infection, probably reflecting a decreased ability to escape immune clearance mechanisms and an impaired capacity to move across host barriers. The results of this study suggest that LTA D-alanylation is an important factor in S. suis virulence.

Verapamil modulates LPS-induced cytokine production via inhibition of NF-kappa B activation in the liver.

OBJECTIVE: To investigate the effect of verapamil on Lipopolysaccharide (LPS)-induced cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-10 (IL-10)] and nuclear factor kappa B (NF-kappa B) in the liver. METHODS AND MATERIALS: Adult male Sprague-Dawley rats were randomly divided into seven groups of eight rats each: control rats treated with saline (0.9 % NaCl); rats treated with saline and then challenged intraperitoneally with LPS (10 mg/kg); rats treated intraperitoneally with different levels of verapamil (1, 2.5, 5, 10 mg/kg) and then challenged with LPS (10 mg/kg); and rats treated only with verapamil (10 mg/kg). TNF-alpha, IL-6, IL-10 and NF-kappa B in the liver tissues were investigated as well as the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) one hour after LPS injection. RESULTS: LPS alone stimulated production of TNF-alpha, IL-6 and IL-10, and activated NF-kappa B in the liver. Pretreatment with verapamil before LPS challenge reduced acute liver injury, down-regulated production of LPS-induced pro-inflammatory cytokines (TNF-alpha and IL-6), up-regulated production of anti-inflammatory cytokines (IL-10) and inhibited NF-kappa B activation in the liver in a dose-dependent manner. CONCLUSION: Verapamil can attenuate acute liver injury by down-regulating the production of TNF-alpha and IL-6 and up-regulating IL-10 in the liver, possibly via inhibition of NF-kappa B.

Targeted screening for genetic haemochromatosis: a combined phenotype/genotype approach.

OBJECTIVE: To evaluate the clinical utility of a targeted screening approach for the detection of genetic haemochromatosis. METHODS: Screening by measuring fasting serum transferrin saturation (TS) and gene testing was carried out in patients in whom a raised serum alanine amino transferase (ALT) activity and raised random serum TS had been found on routine blood testing. RESULTS: During the 29 month study period, 32 patients homozygous for the C282Y genotype were detected from a catchment population of 330,000 by screening blood samples referred initially for routine laboratory liver function tests. By comparison, during the same period of time and within the same population, only seven patients were found by clinical suspicion alone. The patients in the study, after treatment by venesection, have shown both clinical and biochemical improvement. CONCLUSIONS: The study shows that from a population of patients in whom a routine liver function profile had been requested, it is possible to detect subjects homozygous for the C282Y HFE genotype who have clinical or biochemical markers of iron overload.

Dose-dependent liver regeneration in chloroform, trichloroethylene and allyl alcohol ternary mixture hepatotoxicity in rats.

The present study was designed to examine the hypothesis that liver tissue repair induced after exposure to chloroform (CF) + trichloroethylene (TCE) + allyl alcohol (AA) ternary mixture (TM) is dose-dependent similar to that elicited by exposure to these compounds individually. Male Sprague Dawley (S-D) rats (250-300 g) were administered with fivefold dose range of CF (74-370 mg/kg, ip), and TCE (250-1250 mg/kg, ip) in corn oil and sevenfold dose range of AA (5-35 mg/kg, ip) in distilled water. Liver injury was assessed by plasma alanine amino transferase (ALT) activity and liver tissue repair was measured by (3) H-thymidine incorporation into hepatonuclear DNA. Blood and liver levels of parent compounds and two major metabolites of TCE [trichloroacetic acid (TCA) and trichloroethanol (TCOH)] were quantified by gas chromatography. Blood and liver CF and AA levels after TM were similar to CF alone or AA alone, respectively. However, the TCE levels in blood and liver were substantially decreased after TM in a dose-dependent fashion compared to TCE alone. Decreased plasma and liver TCE levels were consistent with decreased production of metabolites and elevated urinary excretion of TCE. The antagonistic interaction resulted in lower liver injury than the summation of injury caused by the individual components at all three-dose levels. On the other hand, tissue repair showed a dose-response leading to regression of injury. Although the liver injury was lower and progression was contained by timely tissue repair, 50% mortality occurred only with the high dose combination, which is several fold higher than environmental levels. The mortality could be due to the central nervous system toxicity. These findings suggest that exposure to TM results in lower initial liver injury owing to higher elimination of TCE, and the compensatory liver tissue repair stimulated in a dose-dependent manner mitigates progression of injury after exposure to TM.

Constitutive production of human leptin by fed-batch culture of recombinant rpoS- Escherichia coli.

High-level production of human leptin by fed-batch culture of recombinant Escherichia coli using constitutive promoter system was investigated. For the constitutive expression of the obese gene encoding human leptin, the strong constitutive HCE promoter cloned from the D-amino acid aminotransferase gene of Geobacillus toebii was used. To develop an optimal host-vector system, several different recombinant E. coli strains were compared for leptin production. In flask cultures, E. coli FMJ123, which is a rpoS mutant strain, showed the highest level of leptin production (41% of total proteins). By comparing the expression levels of leptin in several different rpoS- and rpoS+ strains, it could be concluded that rpoS mutation positively affected constitutive production of leptin. For the large-scale production of human leptin, fed-batch cultures of recombinant E. coli FMJ123 were carried out using three different feeding solutions--chemically defined, yeast extract-containing, and casamino acid-containing feeding solutions. Among these, the use of casamino acid-containing feeding solution allowed production of leptin up to 2.1 g/L, which was 2.1- and 1.8-fold higher than that obtained with chemically defined and yeast extract-contained feeding solutions, respectively. These results suggest that the HCE promoter can be used for the efficient production of leptin, and most likely other recombinant proteins, in a constitutive manner.

Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life.

BACKGROUND AND AIM: Obesity is a risk factor for progression of fibrosis in chronic liver diseases such as non-alcoholic fatty liver disease and hepatitis C. The aim of this study was to investigate the longer term effect of weight loss on liver biochemistry, serum insulin levels, and quality of life in overweight patients with liver disease and the effect of subsequent weight maintenance or regain. PATIENTS: Thirty one patients completed a 15 month diet and exercise intervention. RESULTS: On completion of the intervention, 21 patients (68%) had achieved and maintained weight loss with a mean reduction of 9.4 (4.0)% body weight. Improvements in serum alanine aminotransferase (ALT) levels were correlated with the amount of weight loss (r = 0.35, p = 0.04). In patients who maintained weight loss, mean ALT levels at 15 months remained significantly lower than values at enrollment (p = 0.004), while in regainers (n = 10), mean ALT levels at 15 months were no different to values at enrollment (p = 0.79). Improvements in fasting serum insulin levels were also correlated with weight loss (r = 0.46, p = 0.04), and subsequent weight maintenance sustained this improvement. Quality of life was significantly improved after weight loss. Weight maintainers sustained recommended levels of physical activity and had higher fasting insulin levels (p = 0.03) at enrollment than weight regainers. CONCLUSION: In summary, these findings demonstrate that maintenance of weight loss and exercise in overweight patients with liver disease results in a sustained improvement in liver enzymes, serum insulin levels, and quality of life. Treatment of overweight patients should form an important component of the management of those with chronic liver disease.

Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study.

A study was performed in 10 European health care centers in which 914 patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) who had elevated serum alanine aminotransferase (ALT) levels underwent liver biopsy during the period of 1992 through 2002. Overall, the METAVIR liver fibrosis stage was F0 in 10% of patients, F1 in 33%, F2 in 22%, F3 in 22%, and F4 in 13%. Predictors of severe liver fibrosis (METAVIR stage, F3 or F4) in multivariate analysis were age of >35 years (odds ratio [OR], 2.95; 95% confidence interval [CI], 2.08-4.18), alcohol consumption of >50 g/day (OR, 1.61; 95% CI, 1.1-2.35), and CD4+ T cell count of <500 cells/mm3 (OR, 1.43; 95% CI, 1.03-1.98). Forty-six percent of patients aged >40 years had severe liver fibrosis, compared with 15% of subjects aged <30 years. The use of antiretroviral therapy was not associated with the severity of liver fibrosis. In summary, severe liver fibrosis is frequently found in HCV-HIV-coinfected patients with elevated serum ALT levels, and its severity increases significantly with age. The rate of complications due to end-stage liver disease will inevitably increase in this population, for whom anti-HCV therapy should be considered a priority.

A prospective comparison of the effect of interferon-alpha and interferon-beta treatment in patients with chronic hepatitis C on the incidence of hepatocellular carcinoma development.

To investigate differences in the effect of interferon (IFN) -alpha and IFN-beta treatment for hepatitis C on hepatocellular carcinoma (HCC) development, we prospectively followed 351 consecutive patients (median age, 56.6 years; mean follow-up, 5.7 +/- 2.6 years) with chronic hepatitis C virus (HCV) viremia. Of 260 IFN-alpha and 91 IFN-beta treated patients, 17 (6.5%) and 4 (4.4%), respectively, developed HCC. Virological response (VR) was defined as persistent HCV RNA disappearance from serum, and biochemical response (BR) as persistent alanine aminotransferase (ALT) normalization after treatment. No significant between-group differences in HCC development were found between those with and without VR. Although the HCC development rate in patients without BR was significantly higher than that in patients with BR in the IFN-alpha group (11.4% and 0.8%; P << 0.05), no significant difference was found in the IFN-beta group (6.3% and 2.3%). Similar rates of HCC development were found in patients with chronic HCV viremia treated with either IFN-alpha or IFN-beta.

[Analysis on quality control of blood in blood banks in a five-year program in Hunan province].

OBJECTIVE: To investigate the blood quality of blood banks. METHODS: HBsAg, Anti-HCV, Anti-HIV were detected by enzyme linked immunoadsorbent assay (ELISA). Treponema pallidum was detected by Trust or rapid plasma regain card test (RPR) before August 2001 and ELISA was used afterwards. Alanine aminotransferase (ALT) was detected by Reitman-Frankel before December 1999 and by continuous monitoring assay afterwards. Results were compared between (1) sampling and spot check, (2) different determent methods, (3) two kinds of reagents with different antigen coating. RESULTS: Seventy-two (8.28 per thousand ) of the 8,699 plasma samples were found unqualified with levels of anti-HCV, ALT, HBsAg, Treponema pallidum and anti-HIV 24 (2.76 per thousand ), 19 (2.18 per thousand ), 16 (1.84 per thousand ), 7 (0.80 per thousand ), 6 (0.69 per thousand ), respectively. There were significant differences between different determent methods and different reagents, but only ALT showed significant difference in the sampling and spot check. CONCLUSION: The unqualified samples were associated with testing methods, quality of reagents as well as ability and responsibility of the staff.

Increasing serum levels of IgM anti-HCV are diagnostic of recurrent hepatitis C in liver transplant patients with ALT flares.

Recurrent hepatitis and acute rejection share common features which make difficult for diagnosis in liver transplant hepatitis C virus (HCV) positive patients. We studied the usefulness of quantitative monitoring of HCV RNA and immunoglobulin (Ig)M anti-HCV in the differential diagnosis between recurrent hepatitis and acute rejection in 98 consecutive anti-HCV positive liver transplant patients. Aminotransferase levels, serum HCV RNA and IgM anti-HCV were measured at the time of transplantation and monthly thereafter. A liver biopsy (LB) was obtained when serum aminotransferase levels increased to twice or more than normal. During a mean follow-up of 16 months 86 aminotransferase flares were observed. Histology was compatible with recurrent hepatitis C in 44 cases and with acute rejection in 28, doubtful in 14. The fluctuations of HCV RNA serum levels were not significantly different in the three groups. Serum IgM anti-HCV levels increased (from negative to positive or with value variations > or = 0.18) in 36 of 44 cases with recurrent hepatitis C at the time of alanine aminotransferase (ALT) flare. IgM anti-HCV remained unchanged in all rejection cases (P < 0.001), but increased in 10 of 11 histologically doubtful cases that were diagnosed as hepatitis at the second LB. Increasing serum levels of IgM anti-HCV at the time of ALT flares are significantly associated with recurrent hepatitis C in liver transplant patients. The quantitative monitoring of IgM anti-HCV appears to be an additional diagnostic tool for distinguishing recurrent hepatitis C from acute graft rejection with a 100% specificity; 100% positive predictive value and 88.9% diagnostic accuracy.

Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase.

BACKGROUND AND AIMS: Interferon (IFN) induced hepatitis B e antigen (HBeAg) seroconversion is durable in 80-90% of chronic hepatitis B patients. Preliminary reports on the durability of HBeAg seroconversion following lamivudine are contradictory. We investigated the durability of response following IFN, lamivudine, or IFN-lamivudine combination therapy in a meta-analysis of individual patient data. PATIENTS AND METHODS: Twenty four centres included 130 patients in total with an HBeAg seroconversion (HBeAg negative, antibodies to hepatitis B e antigen positive) at the end of antiviral therapy: 59 with lamivudine, 49 with interferon, and 22 with combination therapy. Relapse was defined as confirmed reappearance of HBeAg. RESULTS: The three year cumulative HBeAg relapse rate by the Kaplan-Meier method was 54% for lamivudine, 32% for IFN, and 23% for combination therapy (p=0.01). Cox regression analysis identified pretreatment hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT), sex, and therapy as independent predictive factors of post-treatment relapse; Asian race, previous therapy, centre, and type of study were not predictive of relapse. The relative HBeAg relapse risk of lamivudine compared with IFN therapy was 4.6 and that of combination therapy to IFN therapy 0.7 (p(overall)=0.01). CONCLUSIONS: The durability of HBeAg seroconversion following lamivudine treatment was significantly lower than that following IFN or IFN-lamivudine combination therapy. The risk of relapse after HBeAg seroconversion was also related to pretreatment levels of serum ALT and HBV DNA, but independent of Asian race.