替比夫定治疗HBeAgeAg阳性慢性乙型肝炎疗效的预测指标

目的探讨替比夫定治疗HBeAg阳性慢性乙型肝炎（CHB）48周的疗效及其预测指标。方法采用替比夫定（LdT）600 mg/d治疗78例HBeAg阳性CHB患者48周,从性别、年龄、ALT和HBV DNA基线、早期病毒学应答（治疗12周时HBV DNA转阴）为预测因素,分析其对治疗48周疗效的影响。结果性别、年龄与治疗8～48周时HBV DNA转阴无相关性（P〉0.05）;5 ULN≤ALT≤10 ULN组治疗24、36及48周时HBV DNA转阴率高于2 ULN≤ALT≤5 ULN组（P〈0.05,P〈0.01）;HBV DNA 106～105拷贝/ml组治疗48周时ALT复常率和HBV DNA转阴率高于HBV DNA〉107拷贝/ml组（P〈0.05）;早期病毒学应答组治疗48周时HBeAg阴转率ALT复常率和HBV DNA转阴率也高于非应答组（治疗12周时HBV DNA≥500拷贝/ml）（P〈0.05）。结论 ALT、HBV DNA基线、早期病毒学应答可能可以作为预测替比夫定抗HBV疗效的指标     

恩替卡韦治疗高ALT水平HBeAg阳性慢性乙型肝炎疗效观察

目的观察恩替卡韦治疗高ALT水平HBeAg阳性慢性乙型肝炎（CHB）患者的疗效。方法 60例HBeAg阳性的CHB患者以ALT为依据分为低ALT组（ALT在2倍ULN与10倍之间）和高ALT组（ALT在10倍ULN与20倍之间）,给予恩替卡韦0.5mg/d,观者治疗48周时的应答情况（HBV DNA阴转率,HBeAg/抗-HBe血清转换率,HBsAg/抗-HBs血清转换率和ALT复常率）。结果治疗48周时,高ALT组HBV DNA阴转率为95.0%,低ALT组为75.0%,差异有统计学意义（P=0.0225）;低ALT组HBeAg阴转率、HBeAg血清学转换率、HBsAg阴转率、HBsAg血清学转换率依次为25.0%、25.0%、0.0%、0.0%,均明显低于高ALT组的55.0%、45.0%、15.0%、15.0%,差异有统计学意义（P=0.0184,0.0302,0.0015,0.0012）;高ALT组中有3例出现HBsAg阴转,3例出现了HBsAb;低ALT组中没有出现HBsAg阴转及血清学转换。48周时两组患者ALT复常率、病毒学反弹、对恩替卡韦耐药及药物不良反应水平相似。结论高水平ALT是恩替卡韦治疗应答较好的预测因子。     

替比夫定治疗HBeAg阳性慢性乙型肝炎的疗效及相关预测因子的Logistic回归分析

目的观察替比夫定（LdT）治疗HBeAg阳性慢性乙型肝炎（CHB）患者3年的疗效,应用Logistic回归探讨HBeAg血清学转换的预测因子。方法收集58例采用LdT治疗的HBeAg阳性CHB患者,分析其性别、年龄、基线ALT水平、基线HBV DNA载量、基线HBeAg和HBsAg滴度与治疗3年时ALT复常率、HBV DNA阴转率、HBeAg阴转率和HBeAg血清转换率的相关性;采用Logistic回归分析HBeAg血清转换的相关因素。结果治疗3年时ALT复常率为84.48%,HBV DNA阴转率为70.69%,HBeAg阴转率为50.00%,HBeAg血清转换率为43.10%。与ALT≤2倍正常值上限（2×ULN）相比,基线ALT〉5×ULN的患者HBeAg转换率显著增高（P〈0.05）;与HBeAg≤100（S/CO）组相比,基线HBeAg〉200 S/CO的患者HBeAg的阴转率和血清转换率均显著下降（P〈0.05）;与HBV DNA≤6 log拷贝/ml组相比,HBV DNA〉7 log拷贝/ml的患者HBV DNA转阴率、HBeAg转阴率和HBeAg转换率下降显著（P〈0.05）;患者性别、年龄及基线HBsAg滴度对以上疗效指标无影响（P〉0.05）。多因素Logistic回归分析发现仅基线HBeAg滴度低的患者更易出现HBeAg血清学转换。结论 LdT能有效恢复肝功能,抑制HBV复制和提高HBeAg血清转换;基线HBeAg滴度可预测LdT治疗HBeAg阳性CHB患者的HBeAg血清转换率。     

替比夫定和恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者早期疗效分析

目的比较替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者24周疗效及安全性。方法将60例HBeAg阳性慢性乙型肝炎患者随机分为替比夫定组和恩替卡韦组,比较两组治疗第12周和24周的疗效。结果在治疗12周时,两组患者HBV DNA低于检测水平和ALT复常率相比较,差异无统计学意义（P〉0.05）,替比夫定治疗组HBeAg阴转率和HBeAg血清学转换率高于恩替卡韦组（36.7%对14.3%,26.7%对6.7%,P〈0.05）;在治疗24周时,两组HBV DNA低于检测水平、ALT复常率、HBeAg血清学转换率相比较,差异均无统计学意义（P〉0.05）,而替比夫定组HBeAg阴转率高于恩替卡韦组（P〈0.05）;多因素Logistic回归分析发现仅基线ALT水平高的患者更易出现HBeAg血清学转换。结论替比夫定和恩替卡韦治疗CHB患者疗效相当,但替比夫定治疗患者HBeAg阴转率稍高于恩替卡韦治疗。     

替比夫定与恩替卡韦治疗e抗原阳性慢性乙型肝炎的近期疗效比较

目的 观察替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者近期疗效及安全性. 方法 80例患者随机分为替比夫定治疗组和恩替卡韦治疗组,分别在治疗前,治疗第12周和24周检测患者血清HBV DNA水平、ALT复常率、HBeAg阴转率和HBeAg/抗-HBe转换率,并比较不同基线血清HBV DNA水平患者治疗12周和24周时的血清HBV DNA下降值,HBV DNA低于检测值率,HBV DNA＜104拷贝/ml患者的比例.观察治疗过程中药物使用的安全性.结果 替比夫定和恩替卡韦组患者的基础人口学、临床和病毒学特征均具有可比性.治疗12周时,替比夫定组和恩替卡韦组患者HBV DNA低于检测值率均为50.0%,ALT复常率分别为52.5%和60.0%(P＞0.05),HBeAg阴转率分别为30.0%和5.0%(P＜0.01),HBeAg血清学转换率分别为20.0%和5.0%(P＜0.05);在治疗24周时,两组HBV DNA低于检测值率分别为80%和70%,(P＞0.05),ALT复常率分别为77.5%和75.0%(P＞0.05),HBeAg阴转率分别为45.0%和32.5%(P＞0.05),HBeAg血清学转换率分别为27.5%和17.5%(P＞0.05),两组均未发现明显不良反应.结论 替比夫定与恩替卡韦治疗HBeAg阳性的慢性乙型肝炎的近期HBV DNA水平低于检测值率,ALT复常率无明显差异;12周时替比夫定HBeAg血清学转换率高于思替卡韦组,但24周时两组间差异无统计学意义.     

替比夫定治疗HBeAg阳性慢性乙型肝炎48周疗效及其影响因素

目的观察替比夫定(LDT)治疗HBeAg阳性慢性乙型肝炎(CHB)患者48周疗效、HBeAg变化及可能的影响因素。方法检测46例HBeAg阳性CHB患者在LDT治疗前及治疗12周、24周、48周时ALT、HBVDNA定量、HBeAg定量、HBeAg阴转及血清转换率、HBsAg定量,以治疗48周时HBeAg阴转与否分A、B两组,观察两组在治疗前及治疗12周、24周、48周各项指标比较差异有无统计学意义。结果随治疗时间延长,HBVDNA定量、HBeAg定量、HBsAg定量呈逐步下降趋势,治疗48周时ALT复常率91.60%,HBVDNA阴转率89.13%,HBeAg阴转率34.78%,HBeAg血清学转换率26.09%,1例患者出现HBsAg阴转,HBsAg阴转率2.2%;治疗48周HBeAg阴转组患者在治疗前ALT水平较高,治疗12周HBVDNA阴转率100%,治疗12周、24周HBeAg定量较治疗前的下降更为明显,治疗24周、48周时HBsAg定量较治疗前的下降更为明显,与未阴转组比较差异有统计学意义。结论 LDT治疗HBeAg阳性CHB患者具有较强抑制病毒能力、较高HBeAg血清转换率,且伴有HBsAg定量的下降;治疗前ALT水平较高、12周HBVDNA阴转、治疗12周及24周HBeAg明显下降、治疗24周及48周HBsAg明显下降对治疗48周HBeAg阴转具有预测作用。     

慢性乙型肝炎优化治疗疗效评价

目的根据基线ALT及HBV DNA水平评价乙型肝炎e抗原（HBeAg）阳性慢性乙型肝炎（CHB）患者优化治疗疗效。方法观察不同基线ALT水平患者,行拉米夫定抗病毒治疗12周、24周及52周时的HBeAg阴转率,不同基线HBV DNA患者抗病毒治疗24周后HBV DNA阴转率。结果基线ALT〈2 ULN组患者12周和52周HBeAg阴转率分别为2.1%和29.27%;基线ALT〉5 ULN组12周和52周HBeAg阴转率分别为22.5%和63.89%。24周治疗结束,单纯ALT≥2 ULN组和ALT≥2 ULN组且HBV DNA〈8log10拷贝/mL组病毒学应答分别为56.88%和73.22%。结论基线ALT水平较高患者抗病毒治疗HBeAg阴转率更高。较低病毒载量时病毒学应答更优。     

替比夫定联合双环醇治疗HBeAg阳性慢性乙型肝炎患者的疗效分析

目的研究替比夫定联合双环醇片治疗HBeAg阳性慢性乙型肝炎(CHB)患者的疗效和安全性。方法选择133例未应用其他抗病毒药物的HBeAg阳性CHB患者,随机分两组接受治疗。试验组67例,每日口服替比夫定600 mg,同时每日服用双环醇片75 mg;对照组66例,仅给予每日口服替比夫定600 mg,两组均连续用药104周。观察治疗前后血清ALT水平及病毒学指标方面的改变。结果两组血清均明显下降,试验组更为显著(P<0.01)。治疗12周时,两组患者在HBeAg转阴率及血清学转换方面比较,差异均无统计学意义,随治疗时间延长,在治疗24、52、104周各时间点,实验组HBeAg转阴率及血清学转换均高于对照组,差异均有统计学意义。两组HBV DNA水平均出现明显下降,但各治疗时间点HBV DNA下降水平及检测不到比率比较,差异无统计学意义(P>0.05)。治疗52周时,治疗组和对照组各出现2例和3例耐药,耐药率分别为4.69%和7.81%,两组比较,差异无统计学意义(P>0.05),治疗104周时,治疗组耐药5例,对照组耐药13例,耐药率分别为7.81%和20.31%,两组比较,差异有统计学意义(P<0.05)。2组均未发生与研究药物相关的不良反应。结论替比夫定与双环醇片联合应用治疗HBeAg阳性CHB在肝功能及病毒学方面取得较好疗效且安全。     

HBeAg阳性慢性乙型肝炎患者替比夫定相关耐药的临床特点

目的探究HBeAg阳性慢性乙型肝炎(CHB)患者替比夫定治疗导致耐药变异的临床特点。方法对62例接受单一替比夫定抗病毒治疗出现相关耐药的HBeAg阳性CHB患者的抗病毒治疗基线、治疗过程和发生病毒学突破时的资料进行分析,探究替比夫定耐药突变的临床特点。结果替比夫定耐药患者病毒学突破的中位时间为78周,其血清HBV DNA、ALT水平在发生病毒学突破时与基线水平相比,差异有统计学意义;单一位点耐药突变和多位点耐药突变血清HBV DNA水平在发生病毒学突破时相比,差异有统计学意义(u=315.50,P=0.03);检测到8个耐药突变位点、11种组合模式,均含有M204I位点突变。替比夫定耐药组较对照组,年龄、性别、HBeAg、ALT基线水平,差异有统计学意义;替比夫定耐药组12周、24周的HBV DNA阴转率、HBeAg阴转率、HBeAg转换率换均低于对照组患者,差异有统计学意义。结论高龄、男性、HBeAg、ALT基线水平低患者易出现替比夫定耐药;早期实现病毒学转阴及血清学转阴、转换的患者不易耐药。     

HBeAg阳性和阴性慢性乙型肝炎患者肝组织学与血清学关系的比较

目的 研究慢性乙型肝炎(CHB)患者(1×ULN≤ALT≤2×ULN)肝组织学与血清学的关系.方法 对全国多中心516例CHB患者(1×ULN≤ALT≤2×ULN)行血清学及肝穿刺病理检查,依据血清HBeAg表达水平将患者分为HBeAg阳性组和HBeAg阴性组,分析两组肝组织病理学与血清学指标的相关性.结果 HBeAg阳性患者肝组织炎症分级和肝纤维化分期与血清HBsAg和HBeAg表达水平呈负相关(P＜0.01),与血清透明质酸(HA)和α2-巨球蛋白水平呈正相关(P＜0.01),与血清HBVDNA水平无明显相关性;HBeAg阴性患者肝组织炎症分级和肝纤维化分期与血清HBV DNA水平呈正相关(P＜0.01),与HBsAg、HA和α2-巨球蛋白等无明显相关性.结论 血清HBV DNA可做为HBeAg阴性CHB患者肝脏病变程度的有效预测指标,HBsAg、HBeAg、HA和α2-巨球蛋白均可做为HBeAg阳性CHB患者肝组织损伤的预测指标.     

Efficacy of telbivudine in HBeAg-positive chronic hepatitis B patients with high baseline ALT levels

AIM:To evaluate the efficacy and safety of telbivudine(LDT) in hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) patients who have high baseline alanine aminotransferase(ALT) levels between 10 and 20 times the upper limit of normal.METHODS:Forty HBeAg-positive CHB patients with high baseline ALT levels between 10 and 20 times the upper limit of normal were enrolled and received LDT monotherapy for 52 wk.Another forty patients with baseline ALT levels between 2 and 10 times the upper limit of no...     

Revisiting the natural history of chronic hepatitis B: impact of new concepts on clinical management

Appropriate treatment for chronic hepatitis B (CHB) to prevent disease progression and clinical complications requires an accurate knowledge of the natural history of this disorder. In patients who acquire the disease in early life, as is the situation in Asian CHB patients, complications of CHB continue to develop because of the prolonged insidious damage to the liver, even in the low viremic phase. Hepatitis B e antigen seroconversion with hepatitis B virus (HBV) DNA levels just below 10(5) copies/mL may not be an adequate treatment endpoint for Asian CHB patients. Furthermore, it has been shown that patients with mild elevation of alanine aminotransferase (ALT) levels are already at considerable risk of development of complications. More recent studies have shown that in order to move towards a better disease outcome, CHB patients should have HBV DNA levels at least less than 10(3) copies/mL, with ALT levels preferably in the range of less than 0.5 times the upper limit of the normal range. Therefore, prolonged, adequate suppression of viral replication should be the practical goal for the treatment of CHB disease in the Asian population.     

阿德福韦酯治疗HBeAg阴性慢性乙型肝炎疗效与HBV基因型的关系

目的探讨阿德福韦酯（ADv）治疗HBeAg阴性慢性乙型肝炎（chronic hepatitis B,CHB）的疗效与HBv基因型的关系。方法选择71例HBVDNA〉1×10^4copies／ml、ALT〉2倍正常值上限、TBIL正常的HBeAg阴性cHB患者,其中B基因型40例,C基因型31例,所有患者均口服ADV 10mg,1／d,治疗52周,动态观察治疗过程中HBV DNA和ALT水平的变化。结果在治疗12、24、52周时,B基因型患者ALT变化、血清HBVDNA水平下降≥2log。完全抑制比例与C基因型患者相比差异无统计学意义（P〉0．05）。结论ADV能有效抑制HBeAg阴性CHB患者HBV复制,促进肝功能好转,其疗效与HBV基因型B或C型无关。     

Assessment of chronic hepatitis B: the importance of hepatitis B virus DNA testing

Background: Chronic hepatitis B (CHB) has an estimated prevalence of 90 000 to 160 000 in Australia. Cirrhosis and hepatocellular carcinoma are important complications of CHB and appropriate evaluation of hepatitis B surface antigen (HBsAg)‐positive individuals is vital to identify treatment candidates. Methods: A review of the database of a tertiary hospital was performed and 348 HBsAg‐positive individuals with baseline demographic, virological, serological and biochemical variables were identified and evaluated cross‐sectionally. A small subgroup of hepatitis B e antigen (HBeAg)‐negative patients with normal alanine aminotransferase (ALT) at baseline were identified and followed longitudinally. Results: 175/348 (50%) of patients were in the HBeAg‐negative, chronic hepatitis phase of disease, 22% in the HBeAg‐positive immune clearance and 6% in the immune tolerant phases. HBeAg‐negative patients were older and more likely to be male than HBeAg‐positive patients. The correlation between hepatitis B virus (HBV) DNA and ALT levels was examined. ALT and HBV DNA levels showed no correlation in HBeAg‐positive CHB and only a weak correlation in HBeAg‐negative patients. Furthermore, 35% of HBeAg‐negative patients with detectable HBV DNA had a normal ALT. Conversely 38% of HBeAg‐negative patients with no detectable HBV DNA had an elevated ALT. A persistently normal ALT over 24 months was seen in five of nine HBeAg‐negative patients with normal initial ALT and detectable HBV DNA. Conclusion: Appropriate evaluation of HBeAg‐negative CHB must include HBV DNA because the ALT is not a reliable guide to underlying viral replication.     

Therapeutic vaccination in chronic hepatitis B

AIMS: The aim was to test the efficacy of a pre-S2-containing vaccine (Genhevac-B) in chronic hepatitis B (CHB). Twenty-five naive patients (22 male, three female; median age 35; range: 6-69 years) with CHB were recruited. The inclusion criteria were: hepatitis B e antigen (HBeAg) positive or HBV-DNA detectable with liquid hybridization; alanine aminotransferase (ALT) is at least 1.5-fold the upper normal limit and histological evidence of chronic hepatitis. METHODS: In the first period, all patients received monthly injections of 20, 40 and 60 microg of the vaccine. One month after the last injection, patients who still had HBV-DNA were divided into two randomly assigned groups. While the patients in the first group and the patients who lost HBV-DNA in the first period continued to receive monthly injections of 20 microg vaccine for a further 6 months, the patients in the second group received 9 MU interferon alpha-2b (Roferon-A), three times per week using the same method as for the first group. Patients were followed up after 12 months without treatment. Response was defined as the loss of HBV-DNA and normalization of ALT. RESULTS: Six of the 25 patients lost HBV-DNA after 3 months. Nine of the remainder were randomly placed in the first group (vaccine-only) and 10 were placed in the second group (vaccine + interferon). End-of-treatment response was achieved, overall, 8/15 from the vaccine group and 6/10 from the combination. One patient from each group relapsed during the follow up. Overall, the sustained response (SR) rate was 46% (7/15) in the vaccine group, and 50% (5/10) in the combination group. Histological improvement was achieved in 6/7 SR with vaccine-only and all five with combination treatment, while 1/8 of failures of vaccine and 2/5 of failures of combination improved. CONCLUSIONS: It was concluded that Genhevac-B decreases serum HBV-DNA levels in the majority of patients with CHB and sustained clearance was achieved in some patients. Combination of interferon-alpha with Genhevac-B is effective for the vaccine failures and may increase sustained response compared to interferon-alpha alone. However, the mechanism of action is yet to be explained.     

Significant hepatic histopathology in chronic hepatitis B patients with serum ALT less than twice ULN and high HBV-DNA levels in Indonesia

OBJECTIVE: To study the prevalence of significant hepatic histopathology in chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) ≤ twice upper limit of normal (ULN) and its association with age, HBeAg status, hepatitis B virus (HBV)‐DNA level and viral genotype. METHODS: A prospective study was conducted over a 3‐year period in treatment‐naive CHB patients with ALT ≤ twice ULN. Patients with a history of acute flare hepatitis, use of alcohol and hepatotoxic drugs, hepatitis C, hepatitis D and human immunodeficiency virus (HIV) co‐infection were excluded from the study. Hepatic histopathology was assessed according to the METAVIR scoring system. RESULTS: A total of 145 patients were recruited, 81 (55.9%) of whom were male. The patients’ mean age was 41.50 ± 10.74 years (range 16–70 years). Significant hepatic inflammation was found in 59.3% of these patients, and significant hepatic fibrosis was found in 62.1%, the latter being associated with hepatitis B e antigen status, ALT levels and serum HBV‐DNA, but not with their age group or viral genotype. Significant hepatic fibrosis was found in 24 of 35 CHB patients (68.6%) who were previously considered in an immunotolerance phase. CONCLUSIONS The prevalence of significant hepatic histopathology in CHB patients with serum ALT levels ≤ twice ULN is high. Delayed antiviral treatment can be harmful.     

国产拉米夫定治疗慢性乙型肝炎少年患者的疗效与安全性研究

目的 探讨国产拉米夫定治疗慢性乙型肝炎(CHB)少年患者的疗效及安全性。方法 随机对105例l2～16岁的CHB病毒感染者予以口服国产拉米夫定片剂100mg／d，共52周，基线丙氨酸氨基转移酶(ALT)水平异常者为第1组，基线ALT水平正常者为第2组。评价治疗前后患者血清乙型肝炎病毒(HBV)DNA、HBV标志物、ALT变化，同时记录不良事件。结果 治疗52周时血清HBV DNA阴转率第1组为92．0％，第2组为76．1％;第1组在治疗12、24、52周时ALT复常率分别为59．0％、66．7％和76．0％；HBV DNA阴转伴ALT复常率分别为44．9％，64．1％与70．7％。治疗52周时，第1组乙型肝炎e抗原(HBeAg)血清转换率为23．9％，HBeAg血清转换并有I{BVDNA阴转率为22．5％，第2组均为14．2％，两组比较差异无显著性；在治疗期间发生的不良事件中，仅有6例次可能与拉米夫定有关，无严重不良事件发生。结论 有HBV活动复制的CHB少年患者，用国产拉米夫定治疗52周安全有效，能迅速抑制HBV复制，并使大多数患者ALT正常化，部分患者发生HBeAg阴转或血清转换且有随基线ALT水平升高而增加的趋势。     

Impact of mild to moderate elevations of alanine aminotransferase on liver stiffness measurement in chronic hepatitis B patients during antiviral therapy

Aim: The accuracy of liver stiffness measurement (LSM) in the diagnosis of liver fibrosis is affected by elevated serum alanine aminotransferase (ALT) levels. The aim of this study was to assess the impact of mild to moderate elevations of ALT on LSM in patients with chronic hepatitis B (CHB) during antiviral therapy. Methods: A total of 58 CHB patients with their ALT levels falling into the range of ×2 to ×10 the upper limit of normal (ULN) were recruited. ALT and LSM values were periodically assessed at baseline and 12, 24 and 48 weeks. Results: The median ALT levels were 153.5 (76–544), 50.5 (11–475), 36.5 (9–265) and 30 (12–239) IU/L at baseline and 12, 24 and 48 weeks, respectively. The corresponding median value of LSM was 8.8 (3.2–47.3), 6.15 (3.2–31.2), 5.9 (3.1–29.1) and 5.5 (2.8–21.5) kpa. However, after the ALT levels were normalized by the treatment, the values of LSM did not vary significantly (6.1 [3.0–17.7] vs 5.25 [2.8–21.5] kpa, P = 0.381). Pretreatment fibrosis stages of liver biopsies corresponded with LSM after ALT normalization rather than baseline LSM (F0–1, 12/27 vs 23/25, P < 0.001). Conclusion: The LSM values decreased in parallel with the decline in ALT levels in CHB patients with mild to moderate elevation of ALT. LSM became more accurate when applied to document the liver fibrosis or cirrhosis in CHB patients after the elevated ALT level has been treated to normal level.     

Efficacy of ribavirin in patients with chronic hepatitis B

This study aimed to evaluate the efficacy and safety of a 6-month course of ribavirin (Rb) (1200 mg/day) in the treatment of chronic hepatitis B (CHB). Sixty patients with CHB were randomly assigned in a double-blind placebo (Pl) controlled study; 30 patients received oral Rb (1200 mg/day) and 30 received Pl for 24 weeks. Patients were hepatitis B surface antigen (HBsAg); hepatitis B envelope antigen (HBeAg); and hepatitis B virus (HBV)-DNA-positive, with alanine aminotransferase (ALT) levels 1.5 times higher than normal values. Clinical evaluations and laboratory tests were carried out at regular intervals; tests included total blood cell count, liver function tests, and HBV serum markers. Baseline and control liver biopsies were carried out. HBeAg seroconversion occurred in 50.0% of the patients in the Rb group (vs 6.6% in the Pl group; P = 0.00019); HBV DNA negativization occurred in 33.3% in the Rb group (vs 6.6% in the Pl group; P = 0.009); and improvement in the necroinflammatory index occurred in 53.3% in the Rb group (vs 23.3% in the Pl group; P = 0.02). The drug was well tolerated; the most important side effect in the Rb group was hemoglobin reduction, which was reversible once the treatment was stopped. Ribavirin was an effective treatment, demonstrated by decreased ALT levels, alleviation of histological damage, seroconversion of HBeAg, and HBV-DNA negativization; Rb may be an alternative agent in the treatment of CHB, without significant side effects. Received: June 1, 1999 / Accepted: October 22, 1999     

Four years of lamivudine treatment in Chinese patients with chronic hepatitis B

BACKGROUND AND AIMS: This study assessed the efficacy and safety of up to 4 years of lamivudine treatment and the clinical relevance of the emergence of YMDD-variant hepatitis B virus (HBV). METHODS: Fifty-eight Chinese adult patients with chronic hepatitis B (CHB) were randomized to lamivudine 100 mg/day for up to 5 years and were monitored for YMDD-variant HBV, hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg and detectable antibody to HBeAg) and serum alanine aminotransferase (ALT) concentrations. Four-year data are reported here. RESULTS: The rate of HBeAg seroconversion increased with extended therapy and also with higher baseline ALT concentrations. YMDD-variant HBV was detected in 67% (39/58) of patients at some point during treatment. After 4 years, a total of 47% (27/58) of patients achieved HBeAg seroconversion. Thirty-three per cent (13/39) of patients with YMDD-variant HBV achieved HBeAg seroconversion; this increased to 57% (8/14) in patients with moderately elevated (>2-5 x upper limit of normal) pre-treatment ALT concentrations. The proportion of patients that achieved normal serum ALT increased from 29% (17/58) at baseline to 69% (31/45) following 4 years of treatment. That included 68% (23/34) of patients with YMDD-variant HBV and 73% (8/11) of those without the variant. All patients receiving lamivudine had reduced serum concentrations of HBV-DNA compared with baseline, despite the emergence of YMDD-variant HBV in 39 patients. Lamivudine was generally well tolerated; there was little change in the number or type of drug-related adverse events in the fourth year of the study. CONCLUSIONS: Despite the emergence of YMDD-variant HBV, Chinese patients showed increased HBeAg seroconversion and improvement in ALT levels with an increased duration of treatment with lamivudine.