A comparison of 48-week treatment efficacy between clevudine and entecavir in treatment-naïve patients with chronic hepatitis B

Purpose  

Clevudine and entecavir are currently available in Korea as antiviral drugs against chronic hepatitis B (CHB). We aimed to compare the efficacy of clevudine and entecavir therapy.     

De novo combination of lamivudine and adefovir versus entecavir monotherapy for the treatment of naïve HBeAg-negative chronic hepatitis B patients

Purpose

Either combination treatment or monotherapy using agents with a high genetic barrier are recommended for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). The aim of this study was to compare effect of naïve HBeAg-negative CHB patients with either de novo combination of lamivudine (LAM) and adefovir dipivoxil (ADV) or entecavir (ETV) monotherapy.

Methods

HBeAg-negative CHB patients (n = 71) with ALT levels between 2 and 10 times the upper normal limit and HBV DNA levels >10⁴ copies/mL were enrolled. Patients were treated with either LAM 100 mg plus ADV 10 mg per day (n = 31) or ETV 0.5 mg per day (n = 40) for 48 weeks.

Results

The average reduction in HBV DNA level compared with baseline were 5.16 ± 1.69 log in the LAM + ADV group and 5.36 ± 1.70 log in the ETV group by week 48 (P = 0.624). The virological response (VR) rates were 80.65 and 77.5%, the biochemical response (BR) rates were 93.55 and 90.00% at week 48 in the LAM + ADV and ETV groups, respectively. There was no significant difference in the VR and BR between the two groups. During the 48-week treatment period, virological breakthrough and serious side effects were not noted in any patient.

Conclusions

Both LAM + ADV combination therapy and ETV monotherapy are effective in naïve HBeAg-negative CHB patients, but further studies are needed to obtain long-term results.     

恩替卡韦治疗慢性乙型肝炎和乙型肝炎肝硬化96周疗效观察

目的探讨恩替卡韦治疗慢性乙型肝炎和乙型肝炎肝硬化96周的临床疗效。方法应用恩替卡韦治疗HBV DNA阳性的34例慢性乙型肝炎患者和24例乙型肝炎肝硬化患者,观察96周。结果 34例慢性乙型肝炎患者治疗12周、24周、48周和96周时HBV DNA低于检测下限比率分别为61.76%（21/34）,82.35%（28/34）,94.12%（32/34）和94.12%（32/34,P〈0.05）;22例乙型肝炎肝硬化患者也分别为72.73%（16/22）,81.82%（18/22）,81.82%（18/22）和90.91%（20/22,P〈0.05）;治疗期间未发生与应用恩替卡韦相关的不良反应。结论恩替卡韦治疗慢性乙型肝炎和乙型肝炎肝硬化患者有明显的疗效,安全性较好。     

Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B

Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.     

Hepatitis B and liver transplantation: Molecular and clinical features that influence recurrence and outcome

Hepatitis B virus (HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people will develop hepatic cirrhosis with decompensation and/or hepatocellular carcinoma. For such patients, liver transplantation may be the only hope for cure or real improvement in quality and quantity of life. Formerly, due to rapidity of recurrence of HBV infection after liver transplantation, usually rapidly progressive, liver transplantation was considered to be contraindicated. This changed dramatically following the demonstration that hepatitis B immune globulin (HBIG), could prevent recurrent HBV infection. HBIG has been the standard of care for the past two decades or so. Recently, with the advent of highly active inhibitors of the ribose nucleic acid polymerase of HBV (entecavir, tenofovir), there has been growing evidence that HBIG needs to be given for shorter lengths of time; indeed, it may no longer be necessary at all. In this review, we describe genetic variants of HBV and past, present, and future prophylaxis of HBV infection during and after liver transplantation. We have reviewed the extant medical literature on the subject of infection with the HBV, placing particular emphasis upon the prevention and treatment of recurrent HBV during and after liver transplantation. For the review, we searched PubMed for all papers on the subject of “hepatitis B virus AND liver transplantation”. We describe some of the more clinically relevant and important genetic variations in the HBV. We also describe current practices at our medical centers, provide a summary and analysis of comparative costs for alternative strategies for prevention of recurrent HBV, and pose important still unanswered questions that are in need of answers during the next decade or two. We conclude that it is now rational and cost-effective to decrease and, perhaps, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection. Here we propose an individualized prophylaxis regimen, based on an integrated approach and risk-assessment.     

De novo combined lamivudine and adefovir dipivoxil therapy vs entecavir monotherapy for hepatitis B virus-related decompensated cirrhosis

AIM:To compare efficacy of combined lamivudine(LAM)and adefovir dipivoxil(ADV)therapy with that of entecavir(ETV)monotherapy for hepatitis B virus(HBV)-related decompensated liver cirrhosis.METHODS:A total of 120 na ve patients with HBVrelated decompensated cirrhosis participated in this study.Sixty patients were treated with combined LAM and ADV therapy(LAM+ADV group),while the other60 were treated with ETV monotherapy(ETV group)for two years.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time(PT),and ultrasonography or computed tomography scan of the liver were performed every1 to 3 mo.Repeated measure ANOVA and theχ2test were performed to compare the efficacy,side effects,and the cumulative survival rates at 48 and 96 wk.RESULTS:Forty-five patients in each group were observed for 96 wk.No significant differences in HBV DNA negative rates and alanine aminotransferase(ALT)normalization rates at weeks 48(χ2=2.12 and 2.88)and96(χ2=3.21 and 3.24)between the two groups were observed.Hepatitis B e antigen seroconversion rate in the LAM+ADV group at week 96 was significantly higher in the ETV group(43.5%vs 36.4%,χ2=4.09,P<0.05).Viral breakthrough occurred in 2 cases(4.4%)by week 48 and in 3 cases(6.7%)by week 96 in the LAM+ADV group,and no viral mutation was detected.In the ETV group,viral breakthrough occurred in 1 case(2.2%)at the end of week 96.An increase in albumin(F=18.9 and 17.3),decrease in total bilirubin and in ALT(F=16.5,17.1 and 23.7,24.8),reduced PT(F=22.7 and 24.5),and improved Child-Turcotte-Pugh and the model for end-stage liver disease scores(F=18.5,17.8,and 24.2,23.8)were observed in both groups.The cumulative rates of mortality and liver transplantation were 16.7%(10/60)and 18.3%(11/60)in the LAM+ADV and ETV groups,respectively.CONCLUSION:Both LAM+ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,and decrease mortality.     

Choice of drugs in the treatment of chronic hepatitis B in pregnancy

The selection of antiviral drugs for chronic hepatitis B(CHB) treatment in pregnancy is very difficult since none of the drugs have been approved for use in pregnancy.Transmission from mother to newborn remains the most frequent route of infection in mothers with high viral load and positive hepatitis B e antigen status,even with the use of appropriate prophylaxis with hepatitis B virus(HBV) immunoglobulin and HBV vaccination.We read from the article written by Yi et al that lamivudine treatment in early pregnancy was safe and effective.However,we could not understand why adefovir dipivoxil(ADV) was used in three pregnancy cases,since ADV has been classified as pregnancy category C.In pregnancy,telbivudine or tenofovir should be selected when the treatment of CHB is necessary,since these drugs have been classified as Food and Drug Administration pregnancy risk category B.     

Higher risk of hepatocellular carcinoma in chronic hepatitis B vs chronic hepatitis C after achievement of virologic response

It is unclear whether the achievement of virologic response modifies the risk of hepatocellular carcinoma (HCC) differently in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). Our aim was to compare the risk of HCC between patients with CHB and CHC who achieved virological response. We analysed data from patients with CHB treated with entecavir (n=2000) or CHC treated with peg‐interferon and ribavirin (n=733) at a tertiary hospital from 2004 to 2011. Virological response was defined as serum HBV DNA<15 IU/mL at 1 year of treatment for CHB or the achievement of sustained virologic response for CHC. Virological response was achieved in 1520 patients with CHB (76.0%) and 475 patients with CHC (64.8%). During the median follow‐up period of 6 years, 228 patients with CHB (11.4%) and 59 patients with CHC (8.0%) developed HCC. Among patients with virological response, CHB was independently associated with a significantly higher incidence of HCC (hazard ratio, 2.17; 95% CI, 1.30‐3.63; P=.003) than CHC. Among patients without virological response, there were no differences in HCC incidence between the two cohorts (P=.52). In patients with cirrhosis at baseline, the incidence of HCC did not differ between the two cohorts even after achieving virological response (P>.99). In conclusion, patients with CHB treated with entecavir were associated with a higher risk of HCC compared to patients with CHC treated with peg‐interferon and ribavirin after achieving virological response. However, the risk of HCC did not differ between the two cohorts if the patients had cirrhosis at baseline, even if virological response was achieved.     

恩替卡韦治疗肺结核合并HBV携带者抗结核药物所致肝损伤临床初步研究

目的 探讨恩替卡韦预防性治疗HBV携带者合并肺结核（PTB）患者抗结核药物所致肝损伤（ATDH）的作用。方法 　171例HBV携带者合并PTB患者接受2HRZE/4HR方案抗结核治疗,57例B组患者同时接受甘草酸二铵肠溶胶囊口服,54例C组患者接受恩替卡韦治疗。结果 在治疗早期,C组患者ATDH发生率显著低于A组或B组（P＜0.05）,但在治疗3个月时,由于临床干预,3组ATDH发生率无显著性相差（P>0.05）;在治疗6 m末,C组血清HBV DNA、ALT和TBIL水平分别为（2.4±0.8） copies/ml、（35.2±5.8）U/L和（13.0±4.2） μmol/L,与A组［分别为（5.4±0.9） copies/ml、（65.4±9.0）U/L和（32.4±7.6） μmol/L］或B组［分别为（4.9±1.1） copies/ml、（50.6±8.0）U/L和（25.5±8.0） μmol/L］比,差异显著（P＜0.05）。结论 HBV携带者合并PTB患者在抗结核开始时,给予恩替卡韦抗病毒治疗可抑制HBV DNA复制,防止HBV再激活,降低ATDH的发生。     

恩替卡韦治疗失代偿期乙型肝炎肝硬化3年疗效观察

目的 探讨恩替卡韦治疗失代偿期乙型肝炎肝硬化患者的疗效及其对血清肝纤维化指标的影响。方法 按照住院时间顺序编号,将190例失代偿期乙型肝炎肝硬化患者随机分为观察组95例和对照组95例,给予观察组口服恩替卡韦治疗,给予对照组水飞蓟等综合治疗。应用SPSS 17.0统计软件进行分析。结果 在治疗3年末,观察组血清HBV DNA载量为（2.01±1.1） lg copies/ml,显著低于对照组的（5.93±1.3） lg copies/ml（P<0.05）;观察组ALT为32.3±4.6 U/L、TBIL为13.2±3.3 μmol/L、ALB为35.1±4.6 g/L和INR为0.9±0.1,与对照组的（262.5±25.5 U/L、29.5±4.1 μmol/L、28.5±4.1 g/L和1.6±0.1）比,差异显著（P<0.05）;观察组血清HA、LN、IV-C和PCⅢ分别为180.7±20.6 ng/ml、190.8±23.4 ng/ml、153.7±19.3 ng/mL和31.21±5.62 ng/ml,显著低于对照组的（310.7±20.8 ng/ml、410.5±20.9 ng/ml、214.7±20.2 ng/ml和79.56±8.23 ng/ml,P<0.05）。结论 恩替卡韦治疗失代偿期乙型肝炎肝硬化可以显著降低血清HBV DNA水平,改善肝功能和阻断肝纤维化进展,且安全性高,延长了生存期。