Genotype rs8099917 near the IL28B gene and amino acid substitution at position 70 in the core region of the hepatitis C virus are determinants of serum apolipoprotein B-100 concentration in chronic hepatitis C

The life cycle of the hepatitis C virus (HCV) is closely related to host lipoprotein metabolism. Serum levels of lipid are associated with the response to pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy, while single nucleotide polymorphisms (SNPs) around the human interleukin 28B (IL28B) gene locus and amino acid substitutions in the core region of the HCV have been reported to affect the efficacy of PEG-IFN/RBV therapy in chronic hepatitis with HCV genotype 1b infection. The aim of this study was to elucidate the relationship between serum lipid and factors that are able to predict the efficacy of PEG-IFN/RB therapy, with specific focus on apolipoprotein B-100 (apoB-100) in 148 subjects with chronic HCV G1b infection. Our results demonstrated that both the aa 70 substitution in the core region of the HCV and the rs8099917 SNP located proximal to the IL28B were independent factors in determining serum apoB-100 and low-density lipoprotein (LDL) cholesterol levels. A significant association was noted between higher levels of apoB-100 (P = 1.1 × 10(-3)) and LDL cholesterol (P = 0.02) and the subjects having Arg70. A significant association was also observed between subjects carrying the rs8099917 TT responder genotype and higher levels of apoB-100 (P = 6.4 × 10(-3)) and LDL cholesterol (P = 4.2 × 10(-3)). Our results suggest that apoB-100 and LDL cholesterol are markers of impaired cellular lipoprotein pathways and/or host endogenous interferon response to HCV in chronic HCV infection. In particular, serum apoB-100 concentration might be an informative marker for judging changes in HCV-associated intracellular lipoprotein metabolism in patients carrying the rs8099917 responder genotype.     

Serum zinc as a factor predicting response to interferon-alpha2b therapy in children with chronic hepatitis B

Although it has been unclear why more than 50% of children with chronic hepatitis B virus infection do not respond to interferon therapy, in some instances resistance to interferon probably is caused by an inability to stimulate appropriately cellular immune responses to hepatitis B virus. It is known that immune integrity is tightly linked to zinc status. We examined the relationship between serum zinc levels and response to interferon (INF)-α therapy in children with chronic hepatitis B. Twenty-five children with chronic hepatitis B infection were injected with 5 × 10⁶ units/m² recombinant IFN-α 2b subcutaneously three times weekly for 9 mo. Children were followed for at least 9 mo after the end of therapy. Sustained response was obtained in eight (32%) patients. Although initial serum zinc and alanine aminotransferase levels were significantly higher; initial hepatitis B Virus (HBV)-DNA values, hepatic activity index, periportal necrosis, and fibrosis scores were significantly lower in sustained responders than in nonresponders. Mean baseline serum zinc, alanine aminotransferase and HBV-DNA values, histologic activity index, periportal necrosis, and fibrosis scores were predictive of response to IFN-α 2b therapy. These findings suggest that serum zinc levels might be used as a factor predicting response to interferon-α 2b therapy, and so may help in identifying those children with a better chance of response.     

Therapy for chronic hepatitis C.

BACKGROUND/AIMS: in Hungary, over the past 5 years more than 900 patients with chronic hepatitis C have been examined for treatment with interferon at 16 major hepatology centres, using unified diagnostic and therapeutical criteria. Authors give an account of their experiences on the clinical features of patients with chronic hepatitis C and report the results of the interferon therapy. METHODS: a total of 993 patients--virtually the entire Hungarian hepatitis C patient population who had been referred for interferon treatment--were included in the program. Actually, the sustained efficacy of the therapy was evaluated in 724 cases. Treatment protocols (dose of interferon and duration of therapy) have changed with time from a weekly dose of 3x3 MU IFN for 6 months in the first period, to 3x3-5 MU for 12 months in the second period, and finally in the third period a combination therapy with ribavirin has also been introduced. RESULTS: in the first period, the end-of-treatment response (ETR) was 35%, sustained response (SR) 13%, the second phase schedule resulted in 42% ETR and 22% SR, while in the third period, ETR was 49% and SR 36%, respectively. Fibrosis in histology and baseline pretreatment HCV-RNA level appeared as predictors of response. The duration of treatment and the total dose of interferon exerted a moderate effect on therapeutic efficacy. Neither age nor gender influenced the outcome. CONCLUSIONS: our results-obtained in a Central East European country-are in accordance with findings of suboptimal efficacy of traditional interferon monotherapy for chronic hepatitis C reported in the West, and suggest the benefit of the combination treatment of interferon with ribavirin.     

Immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) as a marker of interferon therapy in patients with persistent hepatitis B virus infection

Immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc) was measured by radioimmunoassay in the sera of 96 HBV carriers. IgM anti-HBc was detected in 17 of 66 patients with chronic active hepatitis and in 4 of 11 with liver cirrhosis. This antibody was not present in asymptomatic carriers or in patients with chronic persistent hepatitis. Testing of sequential samples revealed that the presence of IgM anti-HBc indicated active replication of HBV and at the same time an immune response to the virus. The relationship between IgM anti-HBc and the response to interferon (IFN) therapy was also studied. Results showed that IgM anti-HBc is a useful marker of the efficacy of interferon therapy.     

Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis C

A potent, long-lasting form of interferon alpha-2a mono-pegylated with a 40 kilodalton branched poly(ethylene glycol) was designed, synthesized, and characterized. Mono-pegylated interferon alpha-2a was comprised of four major positional isomers involving Lys31, Lys121, Lys131, and Lys134 of interferon. The in vitro anti-viral activity of pegylated interferon alpha-2a was found to be only 7% of the original activity. In contrast, the in vivo antitumor activity was severalfold enhanced compared to interferon alpha-2a. Pegylated interferon alpha-2a showed no immunogenicity in mice. After subcutaneous injection of pegylated interferon alpha-2a, a 70-fold increase in serum half-life and a 50-fold increase in mean plasma residence time concomitant with sustained serum concentrations were observed relative to interferon alpha-2a. These preclinical results suggest a significantly enhanced human pharmacological profile for pegylated interferon alpha-2a. Results of Phase II/III hepatitis C clinical trials in humans confirmed the superior efficacy of pegylated interferon alpha-2a compared to unmodified interferon alpha-2a.     

Pretransplant Serum Hepatitis C Virus RNA Levels Predict Response to Antiviral Treatment after Living Donor Liver Transplantation

Background

Given the limited efficacy and high adverse event rate associated with treatment of recurrent hepatitis C after liver transplantation, an individualized treatment strategy should be considered. The aim of this study was to identify predictors of response to antiviral therapy for hepatitis C after living donor liver transplantation (LDLT) and to study the associated adverse events.

Methods

A retrospective chart review was performed on 125 hepatitis C virus (HCV)-positive LDLT recipients who received interferon plus ribavirin and/or peginterferon plus ribavirin therapy at Kyoto University between January 2001 and June 2011.

Results

Serum HCV RNA reached undetectable levels within 48 weeks in 77 (62%) of 125 patients, and these patients were defined as showing virological response (VR). Of 117 patients, 50 (43%) achieved sustained VR (SVR). Predictive factors associated with both VR and SVR by univariate analysis included low pretransplant serum HCV RNA levels, a non-1 HCV genotype, and low pretreatment serum HCV RNA levels. In addition, LDLT from ABO-mismatched donors was significantly associated with VR, and white cell and neutrophil counts before interferon therapy were associated with SVR. Multivariate analysis showed that 2 variables–pretransplant serum HCV RNA level less than 500 kIU/mL and a non-1 HCV genotype–remained in models of both VR and SVR and that an ABO mismatch was associated with VR. No variables with a significant effect on treatment withdrawal were found.

Conclusions

Virological response to antiviral therapy in patients with hepatitis C recurring after LDLT can be predicted prior to transplant, based on pretransplant serum HCV-RNA levels and HCV genotype. LDLT from ABO-mismatched donors may contribute to more efficacious interferon therapy.

Trial Registration

UMIN-CTR UMIN000003286     

Interferon alfa with or without ribavirin for chronic hepatitis C: systematic review of randomised trials

ObjectiveTo assess the efficacy and safety of interferon alfa with or without ribavirin for treatment of chronic hepatitis C.DesignSystematic review of randomised trials on interferon alfa plus ribavirin combination therapy versus interferon alfa. Patients were naive (not previously treated with interferon), relapsers (transient response to previous interferon therapy), or non-responders (no response to previous interferon therapy).ResultsCompared with interferon, combination therapy reduced the risk of not having a sustained virological response for 6 months by 26% in naive patients (relative risk 0.74, 95% confidence interval 0.70 to 0.78), 33% in relapsers (0.67, 0.57 to 0.78), and 11% in non-responders (0.89, 0.83 to 0.96). Morbidity and mortality showed a non-significant trend in favour of combination therapy (Peto odds ratio 0.45, 0.19 to 1.06). Combination therapy significantly reduced the risk of not having improvement in results of histology by 17% in naive patients (0.83, 0.74 to 0.93) and by 27% in relapsers and non-responders (0.73, 0.66 to 0.82). The risk of treatment discontinuations was significantly higher after combination therapy (1.28, 1.07 to 1.52).ConclusionTreatment with interferon alfa plus ribavirin has a significant beneficial effect on the virological and histological responses of patients with chronic hepatitis C, irrespective of previous treatment. Combination therapy may therefore also be considered appropriate for relapsers and non-responders.

What is already known on this subject

Interferon alfa was the recommended treatment for chronic hepatitis C until the late 1990sCombination therapy is recommended for previously untreated patients with chronic hepatitis C, but the benefit of treating relapsers and non-responders to previous treatment with interferon remains controversialThe effect of treatment on liver related morbidity and mortality has not been established

What this study adds

Combination therapy is more effective in treating hepatitis C than interferon alfa alone in naive patients, relapsers, and non-respondersCombination therapy significantly reduced the risk of not having a sustained virological or histological response irrespective of previous treatment and may therefore also be considered in relapsers and non-responders to previous treatmentThe data indicate a non-significant trend towards a beneficial effect on morbidity plus mortality rates     

Treatment of chronic hepatitis C

Chronic hepatitis C entails a life-long risk of developing cirrhosis and hepatocellular carcinoma and eradication of the hepatitis C virus (HCV) is the only realistic approach for lowering the risk of disease progression. Treatment is indicated for patients with high transaminases and histologic signs of chronic hepatitis: 6-12 month therapy with 3-6MU interferon alfa thrice weekly combined with 1-1.2 grams ribavirin yielded up to 30% sustained virological responses (SVR). SVR raised up to 50% with pegylated interferons combined with ribavirin. Favourable predictors of response to the former treatment are genotype 2 or 3, less than 2 million copies of HCV, no or portal fibrosis at biopsy, age less than 40 yr and female gender. The same was true for the latter treatment, however, with body weight less than 82 kg replacing female gender. Six month treatment is enough for treating genotype 2 or 3 patients whereas 12-month therapy is indicated for the more resistant patients with genotype 1 or 4.98% cure of community-acquired acute hepatitis C was achieved with early treatment with daily doses of 5MU interferon, compared to a calculated 30% virus clearance occurring in untreated patients. Cost-effective stopping rules based upon early clearance of serum HCV-RNA, are under investigation. A cut-off equal or more than 2 log decrease in serum HCV-RNA at week 12, has 97% negative predictive value and 60% positive predictive value. Treatment could be optimized also by retreatment with combination therapy of relapsers and non-responders to monotherapy, with SVR rates of 50% and 25%, respectively. Difficult-to-treat patients include patients who have high genotype 1 and 4 viremia or coinfection with HIV or hepatitis B virus as well as patients who carry an organ graft. Extended treatment of virological non responders with pegylated interferons might slow down progression of hepatic fibrosis and prevent hepatocellular carcinoma.     

Treatment of genotype 1b HCV-related chronic hepatitis: efficacy and toxicity of three different interferon alfa-2b/ribavirin combined regimens in naive patients

This prospective open-label randomized trial of chronic hepatitis C genotype-1b patients compared compared the efficacy and safety of peg-interferon alfa-2b administered once-weekly versus interferon alfa-2b thrice-weekly or daily, both in combination with ribavirin. Seventy-eight previously untreated patients, with biopsy-documented genotype 1 chronic HCV and persistently elevated ALT levels and detectable HCV RNA, were randomized (26 subjects each) to receive: interferon alfa-2b at 6MIUs.c./three-times-weekly (group A) or interferon alfa-2b, 3MIUs.c./daily (group B) or peg-interferon alfa-2b 1.5mcg/Kg s.c./once-weekly (group C). All regimens included standard weight-based doses of ribavirin (800, 1,000 or 1,200 mg/day) administered for 52-weeks. Patients in the three groups were comparable for age, sex, viral load, ALT value and histological-activity-index (HAI). Therapy was completed by 22, 20 and 23 patients in groups A, B and C, respectively. At the end of treatment, a complete (biochemical and virological) response was observed in 50.0% patients of group A, 57.7% of group B and 65.4% of group C. After an additional 24-weeks of follow-up, a sustained response was observed in 26.9%, 46.1% and 50.0% of patients in groups A, B or C, respectively. Therapy was discontinued by 4, 6 and 2 patients because of adverse events in the above three groups. In naive patients with chronic genotype-lb hepatitis C, a 48 week therapy with peg-interferon or interferon at daily doses combined with ribavirin were both more effective than treatment with thrice-weekly interferon in inducing end of treatment and sustained response. Peg-interferon treatment was better tolerated and provoked significantly fewer therapy discontinuations.     

肝纤维化程度及自身抗体表达对熊去氧胆酸单药治疗自身免疫性肝病重 叠综合征患者临床疗效的影响

目的:肝纤维化程度及自身抗体表达对熊去氧胆酸单药治疗自身免疫性肝病重叠综合征患者临床疗效的影响。方法:回顾性收集2007年-2011年住院的20例做过肝穿活检的经熊去氧胆酸单药治疗达到满意效果的自身免疫性肝炎和原发性胆汁性肝硬化重叠综合征患者的临床资料。结果:20例患者中,12例患者(60%)的肝穿标本活检评估处于肝纤维化S3或S4期,其初诊时基线特征与肝纤维化处于S0-S2期的患者基线特征无统计学差异。此外,该20例患者的血清抗平滑肌抗体的阳性率较低(1/20)。结论:肝脏纤维化程度不会引起熊去氧胆酸治疗效果的下降。     

Serum malondialdehyde: possible use for the clinical management of chronic hepatitis C patients

Serum lipid peroxidation products are increased in inflammatory liver disease and, as we previously reported, also in chronic hepatitis C. We have performed a specific assay of malondialdehyde, the reported most abundant product of lipid peroxidation, in serum of twenty four chronic hepatitis C patients, before, during, and after interferon treatment. Liver biopsies were performed in each patient before and after interferon treatment. The results show higher serum malondialdehyde values in chronic hepatitis C patients than healthy subjects (n = 68) before interferon treatment (p < .001). Mean value of serum malondialdehyde levels after interferon treatment was significantly lower than before it (p < .002). Associating the histopathological findings in each of the 48 biopsies performed, with serum malondialdehyde and alanine aminotransferase activity levels, of the sample obtained the same day of biopsy, a much better correspondence with the histopathological severity was observed for malondialdehyde concentration than for alanine aminotransferase activity. These levels decreased significantly after interferon treatment. However, when the patients were grouped in responding (group I; n = 9) and non-responding (group II; n = 15) to interferon treatment, according to the histopathological findings before and after interferon, the values of group I before interferon treatment were significantly higher than group II (p < .03). Thus, a potential predictive value could be ascribed to the serum malondialdehyde levels before interferon treatment in these patients. We propose the utility of the specific assay of malondialdehyde for the clinical management of chronic hepatitis C patients.     

Modeling the dynamics of Hepatitis C virus with combined antiviral drug therapy: Interferon and Ribavirin

A mathematical modeling of hepatitis C virus (HCV) dynamics and antiviral therapy has been presented in this paper. The proposed model, which involves four coupled ordinary differential equations, describes the interaction of target cells (hepatocytes), infected cells, infectious virions and non-infectious virions. The model takes into consideration the addition of ribavirin to interferon therapy and explains the dynamics regarding a biphasic and triphasic decline of viral load in the model. A critical drug efficacy parameter has been defined and it is shown that for an efficacy above this critical value, HCV is eradicated whereas for efficacy lower this critical value, a new steady state for infectious virions is reached, which is lower than the previous steady state value.     

错位双链RNA,丙氧鸟苷和原核细胞DNA促旋酶B对鸭乙肝病毒的抑制作用

人工合成错位双链ＲＮＡ（ａｍｐｌｉｇｅｎ）是一种已知的干扰素诱导剂。单独和／或与其它抗病毒药物联合使用治疗鸭乙型肝炎病毒（ＤＨＢＶ）阳性鸭。这些药物包括丙氧鸟苷（ｇａｎｃｉｃｌｏｖｉｒ）和原核细胞ＤＮＡ促旋酶Ｂ抑制物（ｃｏｕｍｅｒｍｙｃｉｎＡｌ）。单独和／或联合该两种药物时,对鸭血清和肝组织内ＤＨＢＶ均有抑制作用,但以三种药物联合时抑制效果最好。上述下种方案治疗结束后肝内松弛环状ＤＮＡ（ＲＣ）和超螺旋ＤＮＡ（ＳＣ）持续存在,而且不能消除血中鸭乙肝表面抗原（ＤＨＢｓＡｇ）。对治疗的大多数鸭血清干扰素,测定结果表明,ａｍｐｌｉｇｅｎ能诱生鸭干扰素,但其出现时间与抗病毒效果产生没有平行关系。本研究为人慢性乙型肝炎治疗合理使用抗病毒药物和免疫诱导剂提供了参考。     

Successful interferon alpha therapy in atopic dermatitis of Besnier's prurigo pattern with normal serum IgE and blood eosinophil fraction: randomized case-controlled study

A randomized case-controlled study was carried out to investigate for interferon alpha therapy in atopic dermatitis (AD) of Besnier's prurigo pattern with normal serum IgE and normal blood eosinophil fraction. Interferon alpha therapy was conducted on 14 non-responders to interferon gamma and subsequent thymopentin therapy among 100 atopic dermatitis patients. Eight patients who improved significantly, showed skin lesions of the Besnier's prurigo pattern with normal serum IgE and normal blood eosinophil fraction. For the randomized prospective case-controlled study, 44 patients with the above characteristics were selected. Thirteen Besnier's prurigo patients were treated with interferon alpha therapy, ten with interferon gamma, ten with thymopentin, and the remaining 11 were untreated as the control group. With interferon alpha therapy, 11 out of 13 Besnier's prurigo patients with normal IgE and normal blood eosinophil fraction improved significantly, two out of ten improved with interferon gamma therapy, and none improved with thymopentin therapy or in the untreated control group. Interferon alpha therapy was effective on AD of Besnier's prurigo pattern with normal serum IgE and normal blood eosinophil fraction. These results suggest the possibility of non-IgE-mediated AD and the heterogeneity of atopic dermatitis.     

IL28B Polymorphism Cannot Predict Response to Interferon Alpha Treatment in Patients with Melanoma

Background

Recent genome-wide association studies revealed the rs12979860 single nucleotide polymorphism (SNP) of the IL28B gene (CC genotype) to be the strongest pre-therapeutic predictor of therapy response to interferon alpha in patients with chronic hepatitis C infection. The favorable CC genotype is associated with significantly higher rates of sustained virologic response. No data exist on the role of IL28B polymorphism in interferon therapy of diseases other than viral hepatitis.

Methods

A retrospective study involving 106 patients with melanoma who received low- or high-dose interferon therapy was performed. The CC and non-CC genotype of IL28B rs12979860 SNP were correlated with progression-free and overall survival.

Results

44 (41.5%) patients were CC and 62 (58.5%) non-CC. There was no statistically significant difference in age at diagnosis, melanoma type or localization, Breslow level or AJCC stage between CC and non-CC patients. During the observation period (6.43±4.66 years) disease progression occurred in 36 (34%) patients after 5.5±4.3 years. 43.2% (19) of patients with CC and 27.4% (17) of patients with non-CC genotype were affected (p = 0.091). Disease progression was more frequent in patients on high dose interferon therapy and with a worse AJCC stage.

Conclusion

In contrast to classical risk factors like tumor thickness and clinical stage, IL28B polymorphism was not associated with progression-free or overall survival in patients with melanoma treated with interferon alpha.     

Interferon-based treatment of chronic hepatitis C

The treatment of patients with chronic hepatitis C has rapidly evolved in the past 10 years centered on the use of interferon alpha 2 as an antiviral and immunomodulatory agent against hepatitis C virus. Firstly used as a monotherapy associated with a deceiving long-term efficacy, interferon alpha was then combined with ribavirin, a nucleoside analog with large antiviral properties. Combination of both drugs dramatically improved the efficacy of treatment with 50% of patients reaching a sustained viral response, characterized by the final eradication of the virus from the infected individual. Surprisingly, this synergistic effect remains greatly unexplained. The third step consisted in the use of pegylated interferon in order to adapt its pharmacokinetics and to allow a better efficacy with a more tolerable dosing schedule: once weekly subcutaneous injection instead of thrice weekly. Pegylated interferon combined with ribavirin during 24-48 weeks of treatment is the current standard of care with nearly 60% of sustained virologic response, overall. Development of new forms of interferon alpha are on the way with promising preliminary results.     

Liver-specific alpha 2 interferon gene expression results in protection from induced hepatitis

The current therapy for hepatitis B and C is based on systemic administration of recombinant human alpha interferon (r-hIFN-alpha). However, systemic delivery of r-hIFN-alpha is associated with severe side effects, but more importantly, it is effective in only a small percentage of patients. In an effort to maximize IFN-alpha antiviral efficacy, we have explored the therapeutic potential of murine IFN-alpha2 (mIFNalpha2) selectively expressed in the liver. To this end, we have developed a helper-dependent adenovirus vector (HD) containing the mIFN-alpha2 gene under the control of the liver-specific transthyretin promoter (HD-IFN). Comparison with a first-generation adenovirus carrying the same mIFN-alpha2 expression cassette indicates that at certain HD-IFN doses, induction of antiviral genes can be achieved in the absence of detectable circulating mIFN-alpha2. Challenge of injected mice with mouse hepatitis virus type 3 showed that HD-IFN provides high liver protection. Moreover, liver protection was also observed in acute nonviral liver inflammation hepatitis induced by concanavalin A at 1 month postinfection. These results hold promise for the development of a gene therapy treatment for chronic viral hepatitis based on liver-restricted expression of IFN-alpha2.     

Osteopontin gene polymorphisms as predictors for the efficacy of interferon therapy in chronic hepatitis C Egyptian patients with genotype 4

This study aimed to determine the relationship between osteopontin gene polymorphisms and its protein level and the efficacy of interferon‐based therapies in Hepatitis C virus (HCV) patients. Hundreds HCV patients genotype 4, treated with pegylated interferon alfa‐2b plus ribavirin and 60 healthy subjects were enrolled. All individuals were subjected to clinical and laboratory parameters, including hepatitis markers and HCV quantitation by real‐time polymerase chain reaction. Single nucleotide polymorphisms (SNPs) of osteopontin (OPN) gene (nucleotide ?155, ?443 and ?1748) were analysed by direct sequencing in addition to estimation of serum level of OPN. SNP at ?443 (C/C versus C/T, T/T) was found to represent predictors for treatment response by univariate logistic regression analysis. OPN serum level was independent predictors for treatment response by both univariate and multivariate logistic regression analysis. SNP at nucleotide ?443 and serum OPN protein levels could be used as useful markers to predict the efficacy of treatment. Copyright © 2013 John Wiley & Sons, Ltd.     

Use of an in vitro allergy test for the differential diagnosis of human brucellosis and yersiniosis

The degree of the allergic reorganization in the body of brucellosis and yersiniosis patients was determined by the study of their blood and serum samples in the in vitro allergy test (the direct and indirect leukocytolysis test). The allergy test is highly specific and recommended as a differential diagnostic method in brucellosis and yersiniosis infections.     

Pegylated interferon alpha-2a (40 kDa) in the treatment of chronic hepatitis B

Chronic hepatitis B virus (HBV) is a serious and life-threatening disease afflicting 350 million of the world's population. So far, current monotherapy with conventional interferon-alpha, lamivudine, and adefovir dipivoxil remains unsatisfactory. In addition, the use of conventional interferon-alpha needs to be administered subcutaneously daily or thrice weekly and is associated with frequent adverse events. Although nucleoside-nucleotide analogs such as lamivudine and adefovir dipivoxil are well tolerated and can normalize serum alanine aminotransaminase rapidly, 1-year therapy with either lamivudine or adefovir dipivoxil results in low hepatitis B e antigen (HBeAg) seroconversion rates. In HBeAg negative patients, most of the patients would relapse after lamivudine has been discontinued. Pegylated interferon alpha-2a, an immunomodulatory agent, is a new drug that has just completed phase III clinical trials for the treatment of both HBeAg positive and HBeAg negative chronic HBV infection. The advantage of pegylated interferon alpha-2a in achieving sustained virological response over nucleoside-nucleotide analogs is particularly obvious in the HBeAg negative group. In both of these phase III studies, sustained off-treatment response is superior to the use of lamivudine. These recent data put pegylated interferon alpha-2a as the first choice of anti-HBV therapy, especially in young and motivated patients with chronic HBV infection.