Combination transcatheter hepatic arterial chemoembolization with thymosin alpha1 on recurrence prevention of hepatocellular carcinoma

BACKGROUND/AIMS: To observe recurrence prevention on hepatocellular carcinoma after hepatectomy by using TACE (transcatheter hepatic arterial chemoembolization) with thymosin alpha1 postoperatively. METHODOLOGY: From January 2000 to December 2002, 57 patients with hepatocellular carcinoma were randomly divided into three groups: Group A (n=18) received hepatectomy plus TACE and thymosin alpha1 postoperatively, group B (n=23) received hepatectomy plus TACE postoperatively and group C (n=16) received hepatectomy only. The recurrent rate, recurrent time and median survival period for the three groups were observed and measured. RESULTS: For group A, B and C, one-year recurrent rates were 83.3%, 87.0% and 87.5% (p=0.926), respectively. The recurrent time were 7.0, 5.0 and 4.0 months (p=0.039), respectively, and the median survival were 10.0, 7.0 and 8.0 months (p=0.002), respectively. CONCLUSIONS: Comprehensive therapy combining TACE plus Talpha1 postoperatively could not decrease the recurrent rate, but it might delay the recurrent time and prolong survival periods for hepatocellular carcinoma patients after hepatectomy.     

Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomised trial

BACKGROUND, AIM, AND METHODS: Alpha interferon is the generally approved therapy for HBe antigen positive patients with chronic hepatitis B, but its efficacy is limited. Lamivudine is a new oral nucleoside analogue which potently inhibits hepatitis B virus (HBV) DNA replication. To investigate the possibility of an additive effect of interferon-lamivudine combination therapy compared with interferon or lamivudine monotherapy, we conducted a randomised controlled trial in 230 predominantly Caucasian patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis B. Previously untreated patients were randomised to receive: combination therapy of lamivudine 100 mg daily with alpha interferon 10 million units three times weekly for 16 weeks after pretreatment with lamivudine for eight weeks (n=75); alpha interferon 10 million units three times weekly for 16 weeks (n=69); or lamivudine 100 mg daily for 52 weeks (n=82). The primary efficacy end point was the HBeAg seroconversion rate at week 52 (loss of HBeAg, development of antibodies to HBeAg and undetectable HBV DNA). RESULTS: The HBeAg seroconversion rate at week 52 was 29% for the combination therapy, 19% for interferon monotherapy, and 18% for lamivudine monotherapy (p=0.12 and p=0.10, respectively, for comparison of the combination therapy with interferon or lamivudine monotherapy). The HBeAg seroconversion rates at week 52 for the combination therapy and lamivudine monotherapy were significantly different in the per protocol analysis (36% (20/56) v 19% (13/70), respectively; p=0.02). The effect of combining lamivudine and interferon appeared to be most useful in patients with moderately elevated alanine aminotransferase levels at baseline. Adverse events with the combination therapy were similar to interferon monotherapy; patients receiving lamivudine monotherapy had significantly fewer adverse events. CONCLUSIONS: HBeAg seroconversion rates at one year were similar for lamivudine monotherapy (52 weeks) and standard alpha interferon therapy (16 weeks). The combination of lamivudine and interferon appeared to increase the HBeAg seroconversion rate, particularly in patients with moderately elevated baseline aminotransferase levels. The potential benefit of combining lamivudine and interferon should be investigated further in studies with different regimens of combination therapy.     

Viral genotype and baseline load predict the response to adefovir treatment in lamivudine-resistant chronic hepatitis B patients

BACKGROUND/AIMS: To determine the factors associated with virological response (VR), HBeAg loss or the emergence of adefovir (ADV)-related mutations in ADV-treated chronic hepatitis B (CHB) patients with lamivudine (LAM) resistance. METHODS: Fifty-four LAM-resistant CHB patients (46% HBeAg-positive) were treated with ADV monotherapy (n=28) or ADV plus LAM (n=26) for a mean of 30.4 months. RESULTS: Thirty-eight patients (70.4%) achieved VR defined as HBV-DNA levels <10(4)copies/ml within the first 12 months of treatment. Six (24%) of 25 HBeAg-positive patients exhibited HBeAg loss and 20% seroconverted to anti-HBe. Eight patients (14.8%) developed ADV-related mutations. In the multivariate analysis, female gender (HR=0.20, 95% CI: 0.05-0.76, p=0.018), HBeAg-negative (HR=0.37, 95% CI: 0.14-0.96, p=0.040) and low baseline HBV-DNA levels (HR=0.65, 95% CI: 0.45-0.95, p=0.027) were independent predictors of VR, whereas low HBV-DNA levels (HR=0.36, 95% CI: 0.11-1.20, p=0.095) and HBV-genotype D (HR=0.06, 95% CI: 0.004-0.84, p=0.037) independently predicted HBeAg loss. CONCLUSIONS: ADV therapy suppresses viral replication in more than 70% of LAM-R patients. Factors associated with virologic response are female gender, HBeAg-negative status and low baseline serum HBV-DNA levels. Genotype D HBV infection and low baseline HBV-DNA levels independently predict HBeAg loss.     

胸腺肽α1、α干扰素和拉米夫定联合治疗HBV慢性携带者的临床研究

观察胸腺肽α1、α干扰素和拉米夫定联合治疗HBV慢性携带者的临床疗效。选择HBsAg、HBeAg、抗- HBc、HBV DNA阳性,肝功能正常的HBV慢性感染者72例,分为联合治疗组42例:拉米夫定0．1／d,口服,疗程52 周;胸腺肽α1 1．6mg／次,皮下注射,2次／周,连续26周;α干扰素500万单位／日,肌注,疗程26周。单用拉米夫定组 30例:剂量、疗程同联合治疗组。联合治疗组HBV DNA阴转率在26周时76．2％,52周时81．0%,拉米夫定组为 50．0％和66．7％。联合治疗组HBeAg阴转率26周时33．3％,52周时38．1％,拉米夫定组为10％和13．3％。HBeAg 血清转换率两组无统计学差异。联合治疗对HBV DNA和HBeAg的抑制作用显著优于单用药。     

拉米夫定联合博尔泰力治疗慢性乙型肝炎临床研究

为探讨拉米夫定与博尔泰力联用对慢性乙型肝炎的临床治疗价值，将60例慢性乙肝患者随机分为两组，一组接受拉米夫定和博尔泰力联合治疗（LM组）。另一组单纯接受拉米夫定治疗（L组），结果两组HBVDNA阴转率分别为93．75％和89．29％，差异无显著性意义。但LM组HBeAg阴转率和ALT复常率均显著高于L组（50％对17．85％，P＜0．01和81．25％对50％，P＜0．05），两组不良反应发生率相近。拉米夫定联合博尔泰力治疗慢性乙型肝炎可有效地提高HBeAg阴转率和ALT复常率，且有希望缩短拉米夫定在慢性乙型肝炎治疗中的疗程。     

Combination therapy with lamivudine and famciclovir for chronic hepatitis B-infected Chinese patients: a viral dynamics study

In vitro studies have shown that lamivudine and penciclovir (the active metabolite of famciclovir) act synergistically to inhibit hepatitis B virus (HBV) replication. We compared the effectiveness of HBV viral suppression by lamivudine monotherapy versus lamivudine plus famciclovir combination therapy in Chinese patients with chronic HBV infection. Twenty-one Chinese hepatitis B e antigen (HBeAg)-positive patients, with detectable HBV DNA (Digene Hybrid Capture II), were randomized to receive either lamivudine 150 mg/d orally (group 1, 9 patients) or lamivudine 150 mg/d plus famciclovir 500 mg 3 times a day orally (group 2, 12 patients) for 12 weeks, with a follow-up period of at least 16 weeks. Serial serum HBV-DNA levels were determined and a mathematical model with provision for incomplete inhibition of virus production during therapy was applied to analyze the dynamics of viral clearance. The mean antiviral efficacy was significantly greater in group 2 than in group 1 (0.988 +/- 0.012 vs. 0.94 +/- 0.03, P =.0012). HBV DNA returned to pretreatment level within 16 weeks after the end of initial treatment in 4 patients (66.7%) in group 1 and none in group 2 (P =.08), who remained HBeAg positive and received no further treatment after week 12. Hence, in Chinese chronic HBeAg-positive patients, combination therapy using lamivudine and famciclovir was superior to lamivudine monotherapy in inhibiting HBV replication. Further studies of longer duration are needed to define whether combination therapy will increase the HBeAg seroconversion rate and decrease the rate of emergence of lamivudine-resistant variants.     

Clinical outcomes of chronic hepatitis B patients with persistently detectable serum hepatitis B virus DNA during lamivudine therapy

BACKGROUND AND AIM: A small proportion of chronic hepatitis B patients have persistently detectable serum hepatitis B virus (HBV) DNA despite lamivudine therapy. The incidence and clinical outcomes of patients who persistently have detectable serum HBV-DNA during lamivudine therapy was investigated. METHOD: We enrolled 221 chronic hepatitis B patients who underwent lamivudine therapy for more than 6 months. Among them, 180 were HBeAg positive. Serum HBV-DNA, HBeAg, anti-HBe and alanine aminotransferase (ALT) levels were serially monitored. The study groups were defined, using a hybridization assay, as patients with reductions in serum HBV-DNA below the detectable level (group I) or patients with persistently detectable serum HBV-DNA (group II) during the initial 6 months of lamivudine therapy. RESULTS: The incidence of patients who had persistently detectable HBV-DNA was 7.7%. After the first year, the rates of viral breakthrough, HBeAg loss and serum ALT normalization of group I versus group II were 21% versus 63%, 38% versus 0%, and 71% versus 28%, respectively (P < 0.001). The log(10) reduction of serum HBV-DNA at 6 months was -4.58 log(10) for group I and -1.97 log(10) for group II (P < 0.001, bDNA assay). There were no pretreatment lamivudine-resistant mutants in group II. CONCLUSION: Lamivudine had little effect on serum HBV-DNA suppression, viral breakthrough suppression and rate of HBeAg loss and ALT normalization in chronic hepatitis B patients with persistently detectable serum HBV-DNA during the initial 6 months of therapy. Early termination of lamivudine therapy is advocated for these patients.     

Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group

BACKGROUND & AIMS: One-year lamivudine therapy significantly suppressed hepatitis B virus (HBV) replication, improved hepatic necroinflammatory activity, and prevented progression of fibrosis. However, the effects of prolonged therapy are unknown. METHODS: A total of 334 Asian patients with chronic hepatitis B from a previously reported 1-year study were randomized to receive either lamivudine (100 or 25 mg) or placebo for another year. The effects of treatment on serum HBV-DNA suppression, alanine transaminase (ALT) normalization, and hepatitis B e antigen (HBeAg) seroconversion were measured. The presence of YMDD variant HBV and its effect were also determined. RESULTS: A significantly greater proportion of patients achieved sustained HBV-DNA suppression and ALT normalization with 100 mg lamivudine daily for 2 years compared with lamivudine for 1 year followed by placebo for the second year (P<0.001). Daily lamivudine therapy for 2 years was safe and resulted in incremental HBeAg seroconversion from 17% at week 52 to 27% at week 104. HBeAg seroconversion during continued lamivudine therapy increased linearly with increasing pretherapy ALT levels (P< 0.001). Despite the emergence of YMDD mutant in 38% of the patients, they continued to clear serum HBeAg and maintain lower median serum HBV-DNA and ALT levels than baseline values. In contrast, ALT levels increased 8-12 weeks after switching from lamivudine to placebo, but returned to normal once lamivudine treatment was resumed. CONCLUSIONS: Treatment with lamivudine for 2 years is both well tolerated and efficacious in patients with chronic hepatitis B.     

An open-label study of lamivudine for chronic hepatitis B in six patients with chronic renal failure before and after kidney transplantation

OBJECTIVE: The course of hepatitis B virus (HBV) infection after kidney transplantation is aggressive, with a high mortality rate from liver disease mainly in patients who were serum hepatitis B e antigen (HBeAg) or HBV DNA-positive before transplantation. Lamivudine has been shown to be a potent inhibitor of HBV replication. The aim of the study was to examine the efficacy and safety of lamivudine therapy in patients with chronic renal failure and chronic HBV infection. METHODS: The study population consisted of six potential candidates for kidney or combined kidney and liver transplantation aged 25-49 yr (four patients had already undergone a kidney transplantation and developed chronic rejection). All were serum HBeAg and/or HBV DNA-positive and had been maintained on hemodialysis for 3 months to 3 yr. The duration of HBV infection was 7 months to 14 yr. Serum alanine aminotransferase (ALT) levels ranged from 72 to 610 U/L (median, 158 U/L). Liver histological evaluation showed mild to moderate chronic hepatitis (n = 4) or liver cirrhosis (n = 2). None of the patients was infected with hepatitis C or D viruses. In four patients, treatment consisted of 10 mg of oral lamivudine per day. In the other two patients, a virological and biochemical response could be achieved only when the dose was increased to 40 mg/day. RESULTS: Lamivudine treatment was associated with 1) normalization of serum ALT levels and rapid disappearance of serum HBV DNA (by hybridization) (five patients, one of whom died from sepsis); 2) seroconversion: disappearance of HBeAg (three patients) and HBsAg (two patients); 3) minor side effects: abdominal pain and nausea (one patient); 4) clinically asymptomatic lamivudine resistance 8 months after treatment (one patient); and 5) successful combined kidney and liver transplantation with no evidence of recurrent HBV infection at 6-8 months postoperatively (two patients with cirrhosis). CONCLUSIONS: Lamivudine therapy is effective as an HBV replication inhibitor in patients with chronic renal failure and HBV infection. Prospective studies of lamivudine pharmacokinetics and dosing in renal failure are needed to be able to treat patients appropriately. Although our study is small and further follow-up is needed, our data suggest that lamivudine therapy may enable selected patients with chronic hepatitis B to undergo kidney or combined kidney and liver transplantation in patients with established cirrhosis.     

Treatment of chronic hepatitis B with the sequential administration of interferon and lamivudine

BACKGROUND/AIMS: Interferon monotherapy has been shown to induce a sustained viral response in 30-40% of patients with HbeAg-positive chronic hepatitis B infection. Similarly, lamivudine monotherapy causes HBeAg seroconversion in less than 20% of patients treated for one year. This study aims to assess the efficacy and safety of the sequential administration of interferon alfa-2a plus lamivudine to patients with chronic hepatitis B in comparison to lamivudine monotherapy. METHODOLOGY: Sixty-one patients with HbeAg-positive chronic hepatitis B infection and raised ALT were randomized to receive either interferon Alfa-2a, 4.5 million units daily for 16 weeks plus lamivudine 100 mg daily starting from week 5 and continuing for 48 weeks (Group A, n = 32) or lamivudine monotherapy for 48 weeks (Group B; n = 29). Patients were followed for 48 weeks after completion of therapy. RESULTS: HBeAg seroconversion to anti-HB +ve was observed in 2 (6.2%) patients in Group A. Both patients remained HBeAg negative and HBV-DNA negative throughout the follow-up phase. None of the group B patients seroconverted at the end of therapy or during follow-up (P = NS). All group A patients experienced at least one side effect and as a result, one dropped out. All group B patients completed the study without side effects. CONCLUSIONS: The sequential administration of interferon plus lamivudine was not superior to lamivudine monotherapy for the treatment of chronic hepatitis B and was associated with more side effects.     

苦参素与贺普丁、迈普新联合序贯治疗慢性乙型肝炎59例临床观察

目的 了解苦参素与贺普丁、迈普新（胸腺肽a1）联合治疗慢性乙型肝炎的临床疗效.方法 将118例HBeAg阳性的慢性乙型肝炎患者随机分为治疗组和对照组.治疗组59例,同时使用苦参素、贺普丁、迈普新13周,随后使用贺普丁及迈普新13周,最后单用贺普丁26周;对照组59例单用同样剂量贺普丁52周.疗程中定期检测血常规、谷丙转氨酶（ALT）、HBeAg、抗-HBe、HBV DNA、透明质酸酶（HA）.结果 全部患者完成1年治疗.治疗组ALT、HA复常率,HBeAg/抗-HBe血清转换率、HBV DNA阴转率明显高于对照组（分别为81.6%和53.1%,P＜0.005;44.9%和22.4%,P＜0.025;42.9%和20.4%,P＜0.025;79.6%和51.0%,P＜0.005）.结论 苦参素与贺普丁、迈普新联合治疗慢性乙型肝炎疗效优于单用贺普丁.     

Efficacy of antiviral therapy with lamivudine after initial treatment for hepatitis B virus-related hepatocellular carcinoma

AIM: The aim of this study was to determine whether antiviral therapy with lamivudine is beneficial in patients after initial treatment for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: Forty-nine consecutive patients with HBV-related HCC completely treated by hepatic resection or radiofrequency ablation were retrospectively enrolled in this study. Comparison was made between 16 patients who received lamivudine therapy at a dose of 100 mg/day after treatment for HCC (lamivudine group) and 33 patients who did not (control group) in terms of changes in remnant liver function, HCC recurrence and survival. RESULTS: Cumulative recurrence rates of HCC did not significantly differ between the two groups (P = 0.622). However, median Child-Pugh score at the time of HCC recurrence was significantly different; 5 (range 5-6) in the lamivudine group versus 7 (range 5-12) in the control group (P = 0.005). All patients in the lamivudine group were able to receive curative treatment for recurrent HCC. In contrast, 10 of 15 patients in the control group were unable to receive curative optimal therapy for recurrent HCC due to deterioration of remnant liver function. The cumulative survival rates of patients in the lamivudine group tended to be higher than those of patients in the control group (P = 0.063). CONCLUSION: It is suggested that lamivudine therapy is beneficial for patients after initial treatment for HBV-related HCC because it contributes to improving remnant liver function, thus decreasing the risk of liver failure and increasing the chances of receiving available treatment modalities for recurrent HCC.     

Changes in serum hepatitis B e antigen (HBeAg) levels associated with the emergence of YMDD mutants in HBeAg non-seroconverted patients during lamivudine therapy.

Background: To elucidate the associations between the changing patterns of hepatitis B e antigen (HBeAg) levels and the emergence of tyrosine–methionine–aspartate–aspartate (YMDD) mutants in HBeAg non‐seroconverted patients undergoing lamivudine therapy. Methods: This study analysed 76 HBeAg‐positive naïve chronic hepatitis B patients treated with lamivudine. The median duration of therapy was 52 weeks. The YMDD mutants were detected in 35 patients. The changing patterns of HBeAg levels were categorized into three groups: Descending, Descending–Ascending and Fluctuation. HBeAg breakthrough was defined as progressive HBeAg decreasing to <10% of pretreatment levels, followed by increases exceeding 50 S/Co [the ratio of the sample (S) to the cut‐off (Co)] above nadir levels. Results: Of 76 patients, the sensitivity and specificity for predicting YMDD mutants by the Descending–Ascending pattern were 66 and 100% respectively. Of 17 patients with YMDD mutants in the Descending–Ascending group, hepatitis B virus (HBV) DNA first increased, followed by increased HBeAg levels and finally by biochemical breakthrough. The median intervals between virological breakthrough and HBeAg breakthrough, between HBeAg breakthrough and biochemical breakthrough and between virological breakthrough and biochemical breakthrough were 4, 24 and 33 weeks respectively. Conclusions: Serial HBeAg levels are useful in predicting YMDD mutant emergence in HBeAg non‐seroconverted patients during lamivudine therapy.     

The effect of pegylated interferon-alpha on the treatment of lamivudine resistant chronic HBeAg positive hepatitis B virus infection

BACKGROUND/AIMS: To determine the response to pegylated interferon-alpha treatment of HBeAg-positive hepatitis B patients with proven lamivudine resistance. METHODS: Sixteen HBeAg-positive HBV patients with YMDD mutations were treated with pegylated interferon. Median treatment duration was 52 weeks (range 20-53), with a 26-week follow-up. RESULTS: Two of 16 (12.5%) patients seroconverted to HBeAg negative and achieved sustained virological (HBV-DNA levels below 10log 5 copies/ml) together with biochemical (normalization of serum ALT levels) responses. Compared with the strong signal in all other patients, only these two patients had a faint signal in the lamivudine resistance assay. For all patients, the median viral load decreased from 10log 9.4 to 7.9 copies/ml (P = 0.001) during treatment but rebounded to a median of 10log 8.7 copies/ml after treatment cessation. Similarly, elevated median ALT levels at baseline decreased with treatment but rebounded after the end of treatment. CONCLUSIONS: In the largest cohort study to date, pegylated interferon-alpha therapy showed marginal efficacy in the presence of lamivudine resistance but such therapy may be beneficial in patients with only small amounts of mutant virus. In our opinion, an analysis of the patient subgroup harbouring an YMDD-mutation should be included in all future studies of pegylated interferon-alpha in chronic hepatitis B.     

Disappearance of serum hepatitis B virus DNA by polymerase chain reaction after adenine arabinoside 5‘-monophosphate therapy in chronic hepatitis B

ABSTRACT— The aim of antiviral therapy in chronic hepatitis B is the cessation of viral replication, which may be demonstrated by the loss of hepatitis B “e” antigen (HBeAg) and serum hepatitis B virus DNA (HBV-DNA) detected by dot-blot hybridization. With the development of the sensitive polymerase chain reaction (PCR) technique for detecting HBV-DNA, it has become apparent that many HBeAg negative patients may still have small amounts of circulating viral DNA. We assessed 19 of 25 patients with chronic hepatitis B who seroconverted from HBeAg to anti-HBe after adenine arabinoside 5′-monophosphate therapy (5 mg ·kg^-1 · day^-1 for 7 weeks) to determine whether serum HBV-DNA became undetectable. Sixteen of the 19 HBeAg negative patients remained hepatitis B surface antigen (HBsAg) positive, and the other three lost HBsAg during follow-up. All of them were HBV-DNA negative by dot-blot hybridization. Using the PCR technique, HBV-DNA became negative in 13 (81.2%) of the 16 patients who seroconverted to anti-HBe without losing HBsAg, and in all the patients who lost HBsAg. These data suggest that the majority of patients who respond to adenine arabinoside 5′-monophosphate show a complete inhibition of hepatitis B virus replication, as demonstrated by the absence of viral DNA by PCR. This inhibition was present in all patients who, at the same time, lost HBsAg.     

Lamivudine versus Entecavir for Newly Diagnosed Hepatitis B Virus-Related Hepatocellular Carcinoma

Background/AimsAntiviral therapy is a key component in the management of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. However, whether the potent drug entecavir is more effective than a less potent drug, such as lamivudine, in HBV-related HCC is not clear.MethodsA retrospective cohort of 451 newly diagnosed, HBV-related HCC patients without antiviral therapy at diagnosis, who started antiviral therapy with either entecavir (n=249) or lamivudine (n=202), were enrolled.ResultsThe median survival was longer for the entecavir group than for the lamivudine group, and lamivudine use (vs entecavir) was an independent factor for mortality (hazard ratio [HR], 1.49; p=0.002). Lamivudine use (vs entecavir) was an independent risk factor for new-onset hepatic decompensation (HR, 1.67; p=0.010) in 318 patients without previous hepatic decompensation, and it was also an independent risk factor for recurrence after curative therapy (HR, 1.84; p=0.002) in 117 patients who received curative therapy. The findings were similar in a propensity score-matched cohort.ConclusionsOverall survival, decompensation-free survival, and recurrence-free survival were better in the entecavir-treated patients than in the lamivudine treated-patients, indicating that the potent antiviral drug should be the preferred choice in HBV-related HCC patients.     

Combination therapy of thymosin alpha-1 and lamivudine for HBeAg positive chronic hepatitis B: A prospective randomized, comparative pilot study

Background and Aim: Monotherapy of lamivudine, interferon‐alpha (IFN‐α), and thymosin alpha‐1 (Tα1) is unlikely to be sufficient for the eradication of a chronic hepatitis B virus (HBV) infection. The aim of our study is to elucidate whether the combination of Tα1 and lamivudine is superior to lamivudine monotherapy in hepatitis B e antigen (HBeAg) positive naïve patients with chronic hepatitis B. Methods: Sixty‐seven patients were assigned to two different groups in a randomized manner. The combination group (n = 34) received Tα1 (1.6 mg subcutaneously, twice a week) and lamivudine (100 mg orally, daily) for 24 weeks, followed by continuous lamivudine therapy. The monotherapy group (n = 33) received lamivudine monotherapy continuously. Results: The incidence of HBeAg seroconversion at 24 weeks was 26.5% (9/34) in the combination group and 6.1% (2/33) in the monotherapy group (P = 0.024). However, there was no statistically significant difference between 26.5% (9/34) in the combination group and 12.1% (4/33) in the monotherapy group at 52 weeks (P = 0.138). The emergence of viral breakthrough gradually increased to 35.3% (12/34) in the combination group, and to 21.2% (7/33) in the monotherapy group at 52 weeks (P = 0.201). Conclusions: The combination treatment of Tα1 and lamivudine did not have an obvious benefit of virological and biochemical response as compared to the lamivudine monotherapy during the combination period. In addition, after the cessation of Tα1 treatment, the combination therapy did not prevent the occurrence of viral and biochemical breakthroughs.     

Experience with lamivudine therapy for hepatitis B virus infection before and after liver transplantation,and review of the literature

OBJECTIVES: To analyse the results of lamivudine therapy on suppression of hepatitis B virus (HBV) replication before transplantation and on preventing graft reinfection postoperatively. DESIGN: Long-term clinical study. SETTING: Liver Institute and Department of Transplantation of a tertiary-care university-affiliated centre. SUBJECTS: (1) 14 candidates for liver transplantation with decompensated liver disease caused by active replication of HBV; (2) six patients with recurrent HBV infection after transplantation. INTERVENTION: Lamivudine 100 mg daily; administered in group 1 before surgery and continued after in nine patients who underwent transplantation; administered in group two postoperatively only. anti-hepatitis B surface antigen immunoglobulin (HBIg) was administered postoperatively in both groups. MAIN OUTCOME MEASURES: Immunoassay evaluation of serum hepatitis B surface antigen, serum hepatitis Be antigen and serum HBV DNA (hybridization and PCR); sequencing through the tyrosine-methionine-aspartate-aspartate locus of the HBV polymerase gene in patients with lamivudine breakthrough; inflammation and fibrosis scoring on liver biopsy before and at least 2 years after lamivudine therapy in group 2. RESULTS: Pretransplantation therapy (group 1) significantly suppressed HBV replication and enabled nine patients (64.2%) to undergo transplantation. Only one patient (7.1%) had lamivudine breakthrough, and one (7.1%) had recurrent HBV. Lamivudine administration begun after transplantation (mean 48.0 months, range 30-60 months) because of graft reinfection (group 2) was associated, over the long-term, with the emergence of high mutation rates (83.3%), histological disease progression (66.6%), and hepatic failure (33.3%). CONCLUSIONS: In patients with chronic HBV infection and active viral replication, lamivudine therapy is effective when started before transplantation. However, its long-term administration after transplantation for recurrent HBV leads to high resistance rates. Combination therapy with lamivudine and HBIg immunoglobulin can substantially reduce the recurrence rate. Further studies on combination antiviral therapy are needed in this patient population.     

Efficacy of lamivudine on hepatitis B viral status and liver function in patients with hepatitis B virus‐related hepatocellular carcinoma

Background/Aims: Treatment of patients with hepatocellular carcinoma (HCC) depends on the tumour extent and underlying liver function. Antiviral therapy with nucleoside/nucleotide analogues has been shown to be effective in improving the liver function of chronic hepatitis B (CHB) patients. We assessed whether lamivudine could induce biochemical and virological improvements in patients with hepatitis B virus‐related HCC. Patients/Methods: Of 148 CHB patients treated with 100 mg/day lamivudine for at least 6 months, 80 had HCC (CHB/HCC group) and 68 did not (CHB group). Biochemical and virological parameters were serially monitored. Results: Compared with the CHB group, the CHB/HCC group was older, had higher male predominance, bilirubin levels and liver cirrhosis rate, and lower albumin and hepatitis B virus (HBV) DNA levels and hepatitis B e antigen (HBeAg) positivity (P<0.05 each). The two groups showed similar cumulative rates of alanine aminotransferase normalization, HBV DNA seroconversion, HBeAg loss and viral breakthrough during 12 months of lamivudine treatment. After 12 months, the CHB/HCC group showed, relative to baseline, increased albumin levels (3.51±0.5 vs. 3.72±0.5 mg/ml) and decreased ascites scores (1.63±0.7 vs. 1.45±0.6) and Child–Pugh scores (6.92±1.9 vs. 6.02±1.38) (P<0.05 each). Conclusion: Lamivudine had comparable antiviral effects both in patients with CHB and CHB/HCC, and improved underlying liver function in the latter group. Treatment of HBV may increase the chance of curative treatments in patients with HBV‐related HCC.     

Profile of chronic hepatitis B virus in children in India: experience with 116 children

BACKGROUND: Hepatitis B virus (HBV) infection in children is mostly asymptomatic and therefore the disease burden is likely to be under appreciated. There is limited information on the profile of chronic HBV infection in children from the Indian subcontinent. METHOD: In 116 (male:female 89:27) children, aged <15 years, with persistent HBsAg positivity for more than 6 months, a clinical, biochemical, virological and histological assessment was carried out. RESULTS: At presentation, 21.6% of children were symptomatic, with icterus in 12%. Features of decompensation such as ascites (7%) and gastrointestinal (GI) bleed (5%) were noted uncommonly. Five (4.3%) children had hepatocellular carcinoma (HCC) at presentation. Elevated alanine aminotransferase (ALT) was observed in 76% of subjects (median 61; range 14-815). A significantly higher proportion of children with hepatitis B early antigen (HbeAg) positive status had higher histological activity index (HAI) (84% vs 16%, P < 0.001) and fibrosis score (80% vs 20%, P = 0.007). A strong positive correlation was noted between aspartate aminotransferase (AST), ALT, HBV-DNA and histological severity of the disease (HAI > or =4, fibrosis > or =2). Median HBV-DNA levels were significantly higher in the HBeAg positive compared to the HBeAg negative group (25.6 vs 0.7 pg/mL, P = 0.004). Seventy-four percent of the mothers had evidence of past or present HBV infection. CONCLUSIONS: Majority of the children with chronic HBV infection are asymptomatic at presentation. HBeAg positive status reflects histologically more severe disease, and a higher level of HBV-DNA. Almost two-thirds of the children may have acquired their HBV infection perinataly.