Antigen-positive Chronic Hepatitis Research Articles

Serum Hepatitis B Surface Antigen Quantitation Can Reflect Hepatitis B Virus in the Liver and Predict Treatment Response

We aimed to evaluate serum hepatitis B surface antigen (HBsAg) quantitation as a surrogate marker for covalently closed circular DNA (cccDNA) and intrahepatic hepatitis B virus (HBV) DNA, and as a predictor of sustained virologic response to peginterferon and lamivudine combination therapy. Twenty-six hepatitis B e antigen-positive chronic hepatitis B patients receiving combination treatment of 32-week peginterferon alfa-2b and 2-year lamivudine were studied. All patients had liver biopsy before and after treatment for cccDNA and intrahepatic HBV DNA measurement. Sustained virologic response was defined as sustained hepatitis B e antigen seroconversion and HBV DNA less than 10,000 copies/mL at the end of treatment until 1 year posttreatment. Seven patients developed sustained virologic response. At baseline, HBsAg correlated well with both log (cccDNA) (r = 0.54, P = .004) and log [total intrahepatic HBV DNA] (r = 0.43, P = .028). The median reduction of HBsAg was 1287 IU/mL (range, 12,223-26,763 IU/mL). Reduction of HBsAg has good correlation with reduction in log [cccDNA] (r = 0.68, P < .0001) and reduction in log [total intrahepatic HBV DNA] (r = 0.65, P < .0001). Patients with lower baseline cccDNA, intrahepatic HBV DNA, and HBsAg level but not serum HBV DNA level tend to develop sustained virologic response. A baseline HBsAg level of less than 10,000 IU/mL had sensitivity, specificity, and positive and negative predictive values for sustained virologic response of 86%, 56%, 43%, and 92%, respectively. Serum HBsAg levels correlate well with the cccDNA and intrahepatic HBV DNA. Low pretreatment HBsAg is better than HBV DNA to predict good response to peginterferon and lamivudine treatment.

Low Resistance to Adefovir Combined With Lamivudine: A 3-Year Study of 145 Lamivudine-Resistant Hepatitis B Patients

Adefovir monotherapy is an established treatment modality for lamivudine-experienced patients with chronic hepatitis B, but it carries a significant risk of resistance in the long term. We assessed whether this risk could be overcome by adefovir-lamivudine combination therapy. A total of 145 lamivudine-resistant patients with chronic hepatitis B (73% cirrhotics, 86% hepatitis B e antigen negative, 92% genotype D) were treated with adefovir 10 mg in addition to lamivudine 100 mg. Liver function tests and hepatitis B virus (HBV) DNA (Versant 3.0) were assessed bimonthly, whereas adefovir-related mutations were searched by INNO-LiPA assay at baseline and at yearly intervals. During 42 months (range, 12-74), 116 patients (80%) cleared serum HBV DNA, 67 (84%) had normalized alanine aminotransferase levels, and 145 (100%) remained free of virologic and clinical breakthroughs, independently of the degree of HBV suppression. The rtA181V/T was the only adefovir-related mutation detected, which occurred in 6 patients at baseline (4%; 1 rtA181V and 5 rtA181T) and in an additional 3 patients (2%; all rtA181T) during treatment. In all these 9 patients, HBV DNA levels progressively declined during therapy to become undetectable in 7 (78%). The 1-, 2-, 3-, and 4-year cumulative rates of de novo rtA181T were 1%, 2%, 4%, and 4%, respectively. None of the cirrhotic patients clinically decompensated, but 11 (12%) developed hepatocellular carcinoma. Under prolonged adefovir-lamivudine therapy, patients with lamivudine-resistant hepatitis B were unlikely to develop genotypic resistance to adefovir and had durable prevention of virologic and clinical breakthrough.

Long-term outcome of chronic hepatitis B in Caucasian patients: mortality after 25 years

Objective:To assess risk factors for liver-related death, we re-evaluated, after a median follow-up of 25 years, a cohort of 70 Caucasian patients with hepatitis B e antigen (HBeAg) positive chronic...

Cost‐effectiveness of peginterferon alfa‐2a compared to lamivudine treatment in patients with hepatitis B e antigen positive chronic hepatitis B in Taiwan

Peginterferon alpha-2a (40KD), a new treatment option for patients with chronic hepatitis B (CHB), offers improved efficacy with a defined treatment duration compared with lamivudine, but at a higher cost. We undertook an economic evaluation of peginterferon alpha-2a from the perspective of the Taiwan Bureau of National Health Insurance to assess the clinical outcomes and costs of 48 weeks of peginterferon alpha-2a for the treatment of patients with hepatitis B e antigen (HBeAg)-positive CHB, compared to lamivudine treatment for 48 weeks. We performed a cost-effectiveness analysis using a state-transition Markov model simulating the natural history of HBeAg-positive CHB. Efficacy data were obtained from a randomized clinical trial of 820 patients (87% were Asian) comparing peginterferon alpha-2a to lamivudine. We modeled a hypothetical cohort of 32-year-old patients with HBeAg-positive CHB. Life expectancy, quality-adjusted life expectancy, lifetime costs ($NTD) and incremental cost-effectiveness ratios (ICER) were estimated. One-way sensitivity analyses were performed on all parameters in the model to evaluate uncertainty. Treatment with peginterferon alpha-2a compared to lamivudine resulted in higher total costs, but longer quality-adjusted life expectancy, yielding an ICER of $NTD 381 000 ($US 12,000) per quality-adjusted life year (QALY) gained. Although there is uncertainty associated with the prognosis of HBeAg-positive CHB, the ICER did not exceed $NTD 485,000 ($US 15,000) per QALY gained despite variation in the parameters used in the analysis. Our analysis suggests that 48-week treatment with peginterferon alpha-2a compared to 48-week treatment with lamivudine in HBeAg-positive patients offers life expectancy and quality of life benefits at a favorable cost-effectiveness ratio.

Comparison of interferon and lamivudine treatment in Japanese patients with HBeAg positive chronic hepatitis B

The aim of this study was to elucidate the long-term outcome after interferon (IFN) or lamivudine (LMV) treatment in Japanese patients with hepatitis B e antigen (HBeAg) positive chronic hepatitis B. Inclusion criteria were biopsy proven chronic hepatitis or liver cirrhosis, no history of IFN or LMV treatment. Three hundred twenty-seven patients satisfied above criteria were treated with IFN or LMV. The primary end point of our study was serum clearance of HBeAg and decrease of serum HBV-DNA to < or =5 LEG/ml after the initiation of treatment. This study was a retrospective cohort study. Attainment of serum clearance of HBeAg and decrease of serum HBV-DNA to < or =5 LEG/ml was regarded as response. Two hundred eighty-six patients had got response after the initiation of treatment. The cumulative rate of response was 28.0% in the first year, 56.2% at the 5th year and 82.5% at the 10th year. Response occurred when HBV-DNA load was high level of more than 7 LEG/ml, and serum ALT level was more than 100 IU/L, HBV genotype was B. IFN and LMV were the similar effect on response (P = 0.410). On IFN therapy, cumulative rate of response in patients of <35 years was higher than that in patients > or =35 years (P = 0.002). Our results suggest that (1) IFN and LMV are the similar effect on response, (2) IFN therapy is more effective for younger patients.

Profound suppression of chronic hepatitis C following superinfection with hepatitis B virus

Hepatitis B virus (HBV) and hepatitis C virus (HCV) share similar transmission routes; thus, coinfection is frequent. The consequences of acute HBV infection in patients with chronic hepatitis C are unknown. We describe a 47-year-old male with chronic hepatitis C who acquired HBV and then spontaneously and apparently completely cleared HCV but developed chronic hepatitis B. Five serum samples collected over 14 months and lymphoid cells obtained after acquiring HBV were tested for HCV and HBV by both standard assays and ultra-sensitive polymerase chain reaction/nucleic acid hybridization (PCR/NAH) (sensitivity approximately 2 IU/ml). After superinfection with HBV, HBV surface antigen-positive chronic hepatitis developed with readily detectable HBV DNA. All sera collected after acquisition of HBV, which tested negative for HCV RNA by standard laboratory assay, were positive for HCV genomes when analysed by PCR/NAH. Peripheral lymphoid cells carried HBV DNA and covalently closed circular DNA, but were negative for HCV. This is the first reported case of profound suppression of chronic hepatitis C after superinfection with HBV and establishment of chronic hepatitis B. It is hypothesized that HBV infection precipitated generalized and/or virus-specific cellular immune responses that profoundly suppressed HCV replication and yet failed to inhibit progression to chronic hepatitis B.

Navigating the Maze of Hepatitis B Treatments

Navigating the Maze of Hepatitis B Treatments

Efficacy and safety of adefovir dipivoxil 20 mg daily in HBeAg-positive patients with lamivudine-resistant hepatitis B virus and a suboptimal virological response to adefovir dipivoxil 10 mg daily

Some patients receiving adefovir at the approved dose of 10 mg daily for chronic hepatitis B have a "suboptimal" virological response characterized by a slow and moderate decrease in viral replication. We assessed the efficacy and safety of adefovir 20 mg daily in patients with hepatitis B e antigen-positive chronic hepatitis B resistant to lamivudine and a suboptimal virological response to adefovir 10 mg daily add-on. No amino acid substitutions known to confer adefovir resistance were found in these patients. In the five treated patients, the switch from 10 mg to 20 mg of adefovir daily significantly improved antiviral efficacy (-1.78+/-0.28 log international units/mL versus -3.73+/-0.51 log international units/mL, respectively, p=0.0039), and alanine aminotransferase levels normalized in all but one of the patients. No signs of renal dysfunction occurred. These results suggest: (i) that suboptimal responses to adefovir 10 mg daily are due to underdosing; and (ii) that increasing the adefovir dose to 20 mg daily is beneficial and safe in patients with lamivudine-resistant HBV and a suboptimal response to adefovir 10 mg daily, especially when alanine aminotransferase levels are elevated and/or the liver disease is severe or rapidly progressive. Careful monitoring of renal function is necessary.

Natural course of hepatitis B e antigen positive chronic hepatitis B: Mortality after 25 years

Background and aim. Data regarding the long-term prognosis of chronic hepatitis (CH) B in untreated Caucasian adults are scarse. To assess the long-term survival of patients with hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive CH, according to virologic status.

Management of hepatitis B

Chronic hepatitis B is caused by persistent infection with the hepatitis B virus (HBV), a unique DNA virus that replicates through an RNA intermediate produced from a stable covalently closed circular DNA molecule. Viral persistence appears to be due to inadequate innate and adaptive immune responses. Chronic infection has a variable course after several decades resulting in cirrhosis in up to one-third of patients and liver cancer in a proportion of those with cirrhosis. Sensitive assays for HBV DNA levels in serum have been developed that provide important insights into pathogenesis and natural history. Therapy of hepatitis B is evolving. Peginterferon induces long-term remissions in disease in one-third of patients with typical hepatitis B e antigen (HBeAg) positive chronic hepatitis B, but a lesser proportion of those without HBeAg. Several oral nucleoside analogues with activity against HBV have been shown to be effective in suppressing viral levels and improving biochemical and histological features of disease in a high proportion of patients with and without HBeAg, at least in the short term. What is uncertain is which agent or combination of agents is most effective, how long therapy should last, and which criteria should be used to start, continue, switch or stop therapy. Long-term therapy with nucleoside analogues may be the most appropriate approach to treatment, but the expense and lack of data on long-term safety and efficacy make recommendations difficult. Clearly, many basic and clinical research challenges remain in defining optimal means of management of chronic hepatitis B.

Relationship Between Viral Load and Genotypes of Hepatitis B Virus in Children With Chronic Hepatitis B

We evaluated the prevalence and clinical significance of hepatitis B virus (HBV) genotypes in children with chronic hepatitis B. Hepatitis B virus genomes of 249 hepatitis Be antigen-positive chronic hepatitis B surface antigen carriers were genotyped based on restriction fragment length polymorphism. Genotypes were correlated with corresponding values for alanine aminotransferase levels, quantitative HBV DNA and histological findings. One hundred and sixty-two boys and 87 girls (mean age, 7.2 years) were studied. Ninety-six percent were attributed to HBV genotypes A (32.5%) or D (63.5%). The remaining were classified as genotypes B, C, E and F. There was no significant difference in both alanine aminotransferase levels and histological findings among different genotypes. However, there was a clear association between very high HBV DNA levels and individuals with genotype D (P = 0.006). Mean time follow-up of 3.6 years showed later anti-HBe seroconversion in patients with genotype D than in those with genotype A (58% vs 37%). Compared with children with genotype A, children with genotype D showed a significantly higher viral load. Inasmuch as a relationship exists between viral load and response to treatment in children infected through vertical transmission, children with genotype D have to be carefully monitored. Long-term studies are needed to determine whether these patients are at risk of a poorer outcome.

Genetic polymorphisms of interleukin‐1‐beta in association with sustained response to anti‐viral treatment in chronic hepatitis B in Chinese

Interleukin-1beta is a pro-inflammatory cytokine that may influence host defence against viral infection. To investigate the impact of interleukin-1beta gene polymorphism on the response to anti-viral treatment. Hepatitis B e antigen-positive chronic hepatitis B patients who have completed a randomized study of peginterferon alpha-2b and lamivudine combination vs. lamivudine monotherapy were included. Sustained responders were patients who had persistent hepatitis B e antigen loss and less than two occasions with hepatitis B virus DNA >100 000 copies/mL at any time up to week 76 post-treatment. Polymorphisms at interleukin-1beta-511, -31 and -3954 and interleukin-1 receptor antagonist (RN) were studied. Eighty-eight patients were studied and 18 (20%) patients developed sustained response. Near complete linkage disequilibrium was observed between interleukin-1beta-511 and -31 loci. After adjustment for the potential confounding effects of treatment allocation, hepatitis B virus genotype, pre-treatment alanine aminotransferase and hepatitis B virus DNA levels, genotype C/T at interleukin-1beta-511 was found to be associated with higher sustained response than genotype C/C (adjusted odds ratio 10.4, 95% CI 1.1, 96.9, P = 0.040). The proportion of sustained responders tend to be higher among patients with allele T at interleukin-1beta-511 (83%) than those without (70%) (P = 0.058). High interleukin-1beta production genotype at position -511 has a favourable response to anti-viral treatments.

Interferon α‐2b with and without ribavirin in the treatment of hepatitis B e antigen–positive chronic hepatitis B

To study whether interferon (IFN) alpha and ribavirin combination therapy has a beneficial effect for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, we enrolled 119 such patients in a randomized study. Fifty-nine patients received 5 million units of IFN-alpha2b daily for 4 weeks followed by 5 million units three times a week for 28 weeks, plus 1,200 mg ribavirin daily. Sixty patients received the same dosage of IFN plus placebo. They were followed up for 24 weeks posttreatment, and 105 patients (88%) completed the entire course of 56 weeks. By intention-to-treat analysis, the rate of combined response (serum hepatitis B virus [HBV] DNA <2.5 pg/mL and HBeAg seroconversion) was 17% versus 25% between the IFN/ribavirin and IFN/placebo group, respectively, at the end of treatment (P = .35) and 25% vs. 20% at the end of follow-up (P = .32). Using quantitative real-time polymerase chain reaction assay, the log10 reduction of serum HBV DNA was 1.05 +/- 1.72 (mean +/- SD) versus 1.29 +/- 1.91 between the two groups at the end of treatment (P = .49) and was 2.15 +/- 2.15 versus 1.21 +/- 2.48 at the end of follow-up (P = .04). Prolonged observations in 83 patients suggested that the combined response was 29% (n = 17) versus 20% (n = 12) at 48 weeks after the end of treatment, respectively (P = .17). The safety profile was similar, except that the IFN/ribavirin group had a higher risk of anemia (15% vs. 0%; P = .002). In conclusion, for the treatment of HBeAg-positive chronic hepatitis B, adding ribavirin does not seem to increase the efficacy of IFN.

Sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone for HBeAg-positive chronic hepatitis B.

Chronic hepatitis B has serious effects on morbidity and mortality. Alfa interferon has been shown to increase the rates of HBeAg-clearance as well as seroconversion to anti-HBe, but response rates are unsatisfactory. Glucocorticosteroid pretreatment may increase the response to alfa interferon. The objectives were to assess the effects of the sequential combination of glucocorticosteroids and alfa interferon versus alfa interferon alone in hepatitis B 'e' antigen positive chronic hepatitis B on mortality, virological response, biochemical response, liver histology, quality of life, and adverse events. Eligible trials were identified through searches of The Cochrane Hepato-Biliary Controlled Trials Register (May 2005), The Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 2, 2005), MEDLINE (1950 to May 2005), EMBASE (Excerpta Medica Database) (1980 to May 2005), BIOSIS (1969 to May 2005), and reference lists of relevant articles. Further trials were sought through correspondence with authors of trials and pharmaceutical companies. Randomised clinical trials comparing identical alfa interferon treatment regimens with and without glucocorticosteroid pretreatment for hepatitis B 'e' antigen positive chronic hepatitis. We included trials irrespective blinding, publication status, or language. Three authors selected the trials independently and one extracted the data, which were then validated. We performed assessments of the outcome measures at the end of treatment and at six months and at maximal follow-up after the end of treatment with alfa interferon. We included a total of 13 randomised trials with 790 patients. Loss of hepatitis B 'e' antigen (OR 1.41, 95% confidence interval 1.03 to 1.92, P = 0.03) and hepatitis B virus DNA (OR = 1.51, 95% confidence interval 1.12 to 2.05, P = 0.008) were significantly more frequent among patients treated with the sequential combination of glucocorticosteroids and alfa interferon than among patients treated with alfa interferon alone. Glucocorticosteroid pretreatment did not significantly influence seroconversion from hepatitis B 'e' antigen to antibodies to hepatitis B 'e' antigen, loss of hepatitis B surface antigen, normalisation of alanine aminotransferase/aspartate aminotransferase activities, and severity of adverse events. Glucocorticosteroid pretreatment did not significantly affect mortality and adverse events. The effect of glucocorticosteroid pretreatment on liver histology and quality of life could not be assessed due to insufficient data. Pretreatment with glucocorticosteroids before treatment with alfa interferon in patients with hepatitis B 'e' antigen positive chronic hepatitis B may be more effective than treatment with alfa interferon alone with regard to loss of hepatitis B 'e' antigen and hepatitis B virus DNA, but evidence for effect on clinical outcomes is lacking.

The safety of pegylated interferon alpha‐2b in the treatment of chronic hepatitis B: predictive factors for dose reduction and treatment discontinuation

Treatment with interferon-alpha has been shown to be effective in one-third of hepatitis B e antigen-positive chronic hepatitis B patients, but is clinically associated with relevant adverse events. To investigate the safety of pegylated interferon alpha-2b in 300 hepatitis B e antigen-positive patients with compensated liver disease. Patients were treated with pegylated interferon alpha-2b for 52 weeks combined with either lamivudine 100 mg/day or placebo. Pegylated interferon alpha-2b was administered for 100 microg once a week for 32 weeks; thereafter, the dose was reduced to 50 microg once a week. Adverse events and their effect on study medication were reported at monthly visits in a standardized way. The most frequently reported side-effects were flu-like syndrome (68%), headache (40%), fatigue (39%), myalgia (29%) and local reaction at the injection site (29%). These symptoms typically occurred within the first month of therapy and subsided during the course of therapy. Neutropenia and thrombocytopenia induced by pegylated interferon alpha-2b increased the risk of infections and bleeding complications, but these complications were rare and mild. The frequency of all side-effects was not different between patients treated with pegylated interferon alpha-2b combined with lamivudine or placebo. In 69 (22%) patients the dose of pegylated interferon alpha-2b was reduced prematurely. Of these dose reductions, 36 (52%) were because of neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent reasons for early discontinuation were psychiatric side-effects (depression, psychosis) and flu-like symptoms. Multivariate Cox regression analysis showed that low neutrophil count at baseline and cirrhosis were independent predictors of dose reduction or therapy discontinuation. We conclude that in patients with chronic hepatitis B and compensated liver disease prolonged pegylated interferon alpha-2b therapy is safe, and that pre-existent cirrhosis and neutropenia are the most important predictors of dose reduction or early treatment discontinuation.

Haemolytic anaemia after nucleotide antiretroviral treatment discontinuation in a chronic hepatitis B-virus co-infected AIDS patient

Haemolytic anaemia after nucleotide antiretroviral treatment discontinuation in a chronic hepatitis B-virus co-infected AIDS patient

Lamivudine for chronic hepatitis B

Lamivudine (Epivir®, GlaxoSmithKline) was approved by the US Food and Drug Administration for the treatment of adult patients with chronic hepatitis B in 1998, and has since been shown to be of benefit to selected patients with chronic hepatitis B. Drug resistance is the main issue encountered during therapy, with lamivudine resistant mutants emerging at a rate of approximately 15 to 30% per year of therapy. These mutants are associated with relapse of hepatitis, and occasionally hepatic decompensation. Despite this, therapeutic indications and guidelines for lamivudine therapy have now been drawn up, which indicate that lamivudine will be the first line therapy for hepatitis B e antigen-positive chronic hepatitis B patients, although its role in hepatitis B e antigen-negative patients remains controversial.

The predictive value of liver fibrosis in determining the effectiveness of interferon and lamivudine therapies for chronic hepatitis B.

To determine the best indicator of the effective use of interferon and lamivudine for the treatment of hepatitis B e antigen-positive chronic hepatitis, we retrospectively analyzed histologic and virologic status in 200 patients who were treated with interferon and 45 patients who were treated with lamivudine. Histological grading and staging scores were determined by international criteria and the METAVIR scoring system. The YMDD motif associated with lamivudine resistance was analyzed by the sequencing of hepatitis B virus (HBV) DNA. Of 200 interferon-treated patients, 62 (31%) seroconverted to anti-hepatitis B e (anti-HBe). Multivariate analysis showed that the significantly important predictors of response were a higher grading score (P = 0.0056) and lower staging score (P = 0.0010). Twenty (44%) of the 45 lamivudine-treated patients seroconverted to anti-HBe, and multivariate analysis showed that the significantly important predictors of response were a higher alanine aminotransferase (ALT) level (P = 0.0034) and lower hepatitis B e antigen levels ( P = 0.0128). YMDD mutations occurred during therapy in 12 patients (27%). The significantly important predictor of the development of mutation was a higher staging score (P = 0.0226). Both interferon and lamivudine were effective for patients with high ALT levels, but interferon's efficacy appeared to be limited by the degree of fibrosis. Lamivudine appeared to be effective irrespective of the degree of fibrosis, but YMDD mutations seemed to develop sooner in patients with advanced liver fibrosis.

Therapy of viral hepatitis

Chronic viral hepatitis is a leading cause of chronic hepatitis, liver cirrhosis, hepatic decompensation and hepatocellular carcinoma worldwide. Here, we will briefly review common indications and current therapies for chronic hepatitis B and C and discuss practical aspects of these therapies. Current therapies for hepatitis C aim at viral eradication. With the introduction of pegylated interferon and ribavirin viral eradication is successful in about 55% of treated patients. The goal of therapy of HBe antigen positive chronic hepatitis B is seroconversion to anti-HBe which can be achieved with interferon alpha in 25-45% of patients. A loss of HBs can be achieved in approximately 10%. Responders proceed significantly less to cirrhosis or hepatocellular carcinoma. Anti-HBe positive patients can be treated with interferon alpha or lamivudine. The former requires longer treatment and the results are disappointing. Lamivudine is a promising agent in the treatment of chronic hepatitis B, but the success is hampered by a high relapse rate and the emergence of viral resistance.

Long-term outcomes of thymosin-α1 and interferon α-2b combination therapy in patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B

Hepatitis B e antibody (HbeAb) and hepatitis B virus (HBV) DNA positive chronic hepatitis is a clinical entity, distinct from classical hepatitis B e antigen (HbeAg) positive chronic hepatitis B. Our aim was to evaluate the long-term therapeutic efficacy of the combination of interferon alpha-2b and thymosin-alpha1 compared with lamivudine plus interferon alpha-2b and interferon alpha-2b alone. Fifty-two patients with HbeAg-negative chronic hepatitis B were assigned to three different groups in a nonrandomized manner. Group 1 (n = 27) received thymosin-alpha1 [1.6 mg subcutaneously (sc), twice a week] and interferon alpha-2b (10 MIU sc, three times per week) for 26 weeks, subsequently followed by interferon alpha-2b monotherapy at the same dosage for an additional 26 weeks. Group 2 (n = 10) received interferon alpha-2b (10 MIU sc, three times per week) for 52 weeks. Group 3 (n = 15) received interferon alpha-2b (10 MIU sc, three times per week) and lamivudine [100 mg orally (po), q.d.] for 52 weeks, followed by continuous lamivudine (100 mg po, q.d.) therapy. By the end of 78 weeks, a sustained response (SR-6 mo) was seen in 74% (20/27) of the patients within Group 1. On the contrary, Groups 2 and 3 had sustained response rates of 40 (4/10) and 53.3% (8/15), respectively (p = 0.13). At the end of 12 months post-treatment in Group 1, a virological and biochemical response rate was seen in 70.3% of patients (19/27); in contrast, Groups 2 and 3 had response rates of 20 (2/10) and 26.6% (4/15), respectively (p = 0036). At the end of the 18-month post-treatment follow-up period, 71.4% (19/27) of patients in Group 1, 10% of patients in Group 2 (1/10), and 20% of patients in Group 3(3/15) preserved their sustained response (p = 0.0003). Interferon alpha-2b and thymosin-alpha1 combination therapy results in significant virological and biochemical response rates compared with standard therapeutic regimens and is well tolerated.