Efficacy of lamivudine in HBeAg-negative chronic hepatitis B

The necessity of the search for new drugs to treat chronic hepatitis B (CHB) is explained by the necessity to prevent hepatic cirrhosis (HC) and hepatocellular carcinoma. Treatment of HBeAg-negative CHB rests on the same principles as of HBeAg-positive one. Efficacy of nucleoside analogue lamivudin is well studied in HBeAg-positive CHB. The aim of this study was to evaluate lamivudine efficacy in therapy of HBeAg-negative CHB. Lamivudine (epivir--150 mg/day or zeffix--100 mg/day) was given for 1 year to 10 patients (5 males, 5 females, mean age 49.5 +/- 13.5). Their blood serum contained no HBeAg but contained HBeAb and HBVDNA. Chronic hepatitis was verified morphologically in 9 patients of whom 2 had HC and 2 developing HC. Moderate activity of the disease was in 4 patients, low--in 5. All the patients had a high ALT level (150 +/- 140 U/l, 60-528 U/l, high normal value 40 U/l). ALT and HBV DNA in the serum were examined by polymerase chain reaction in the course of treatment and for 6 months after its end. To the end of the treatment a complete response (absence of HBVDNA and normalization of ALT) was achieved in 8 (80%) patients. 5 (63%) of them 2-4 months after the end of the treatment had the exacerbation with appearance of HBVDNA in the serum and elevation of ALT level. A persistent response (6 months after lamivudin treatment) was in 3 (30%) patients, in 2 of them HBsAg was not detected. Lamivudin therapy is effective in HBeAg-negative CHB. In this study a high baseline level of ALT was the factor predisposing to a lasting response to treatment.     

Two-year lamivudine treatment for hepatitis B e antigen-negative chronic hepatitis B: a double-blind, placebo-controlled trial

OBJECTIVE: We conducted a multicentre, double-blind, placebo-controlled, randomized study to investigate the efficacy of 2-year lamivudine treatment in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS: One-hundred-and-thirty-nine treatment-naive patients with HBeAg-negative chronic hepatitis B were randomized to receive either lamivudine (100 mg daily) or placebo in a 2:1 ratio for 24 months and were followed for an additional 6 months. The primary endpoint was complete response, defined as hepatitis B virus (HBV) DNA < 10,000 copies/ml and normalization of alanine aminotransferase (ALT) levels at month 24. RESULTS: On intent-to-treat analysis at month 24, significantly more patients in the lamivudine group than in the placebo group had complete response (56% and 11%, respectively; P < 0.001) or negative HBV DNA (26% and 6%, respectively; P = 0.006). After adjustment of baseline HBV DNA and ALT, the odds ratio for complete response of the lamivudine group versus the placebo group was 10.8 (95% confidence interval: 3.8-30.2; P < 0.001). The median log HBV DNA reduction was 3.21 copies/ml for the lamivudine group compared with 0.47 copies/ml for the placebo group (P < 0.001). Genotypic resistance was detected in 23% and 31% of patients in the lamivudine group at months 12 and 24, respectively. Negative HBV DNA at month 6 was associated with high complete response (84%) and low drug resistance (1%) at month 24. At month 30, there was no difference between lamivudine and placebo groups in the rates of complete response (26% vs 19%, respectively; P = 0.38) or negative HBV DNA (10% vs 2%, respectively; P = 0.09). CONCLUSIONS: Two-year lamivudine treatment is effective in HBeAg-negative chronic hepatitis B. However, the response is not sustained after treatment cessation.     

聚乙二醇干扰素α-2a治疗慢性乙型肝炎临床分析

目的观察聚乙二醇干扰素（PEG-IFN）α-2a治疗慢性乙型肝炎患者抗病毒的疗效及影响抗病毒疗效的因素。方法将85例丙氨酸转氨酶（ALT）〉2×正常值上限（ULN）的慢性乙型肝炎患者分成乙型肝炎病毒e抗原（HBeAg）阳性组和HBeAg阴性组。给予PEG-IFNu-2a 180μg皮下注射,每周1次,疗程12个月,3个月无治疗应答者停药,观察治疗结束时及治疗结束后6、12、18、24个月时ALT水平,乙型肝炎病毒（HBV）DNA载量对治疗应答的影响。结果①HBeAg阳性组患者治疗结束时的完全应答率及停药后6、12、18、24个月的完全应答率与HBeAg阴性组患者相似,差异无统计学意义。②两组患者治疗前ALT〉5×ULN者治疗结束时的完全应答率与ALT〉（2～5）×ULN者比较,差异有统计学意义。③治疗前HBVDNA栽量水平（低、中、高3个组）,HBeAg阳性组和HBeAg阴性组患者治疗结束时的完全应答率,差异无统计学意义。结论PEG-IFNa-2a对HBeAg阳性和HBeAg阴性的慢性乙型肝炎患者均有较好的治疗应答,血清ALT〉5×ULN的患者,PEG-IFNa-2a治疗的疗效好。     

Long-term follow-up of lamivudine treatment in patients with severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B

BACKGROUND: The long-term efficacy of lamivudine treatment for patients suffering from severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is unknown. METHODS: Consecutive patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B were prospectively recruited from 1999 to 2004 and treated with lamivudine. All patients had alanine aminotransferase (ALT) and serum bilirubin levels 10x and 3x above the upper limit of normal, respectively. HBeAg-positive patients without severe acute exacerbation served as controls. RESULTS: Forty-five patients with severe acute exacerbation and 31 controls were treated with lamivudine for a median of 2.8 (range 1.0-7.1) years and 3.8 (range 3.5-8.4) years, respectively. Compared with controls, patients with severe acute exacerbation had higher HBeAg seroconversion rates (78% versus 52%; P=0.02) and lower risk of virological breakthrough. However, 33% of patients with severe acute exacerbation still developed lamivudine resistance and virological breakthrough by year 5. HBV DNA levels at week 4 and prolonged baseline prothrombin time were independent factors associated with virological breakthrough. All patients with week 4 HBV DNA <3 log10 copies/ml had maintained virological response. Among 15 patients who stopped lamivudine after sustained HBeAg seroconversion for > or =6 months, 11 (73%) had virological relapse at a median of 1.4 (0.2-3.9) years. ALT increased beyond 10x the upper limit of normal in six (38%) patients who stopped lamivudine and two (7%) patients on maintained lamivudine treatment (P=0.02). CONCLUSION: Among patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B treated with lamivudine, virological breakthrough and post-treatment relapse are common despite a high rate of HBeAg seroconversion. Severe hepatitis flare is also common particularly among patients developing virological relapse after discontinuation of lamivudine.     

Treatment of patients with chronic hepatitis B who have failed previous antiviral treatment with pegylated interferon alpha2a (40 kda; PEGASYS)

BACKGROUND: Although nucleot(s)ide analogues can effectively suppress hepatitis B virus (HBV) replication, many patients experience relapse of hepatitis after cessation of treatment. We aimed to investigate the efficacy of pegylated interferon alpha2a (PEG-IFN-alpha2a) in these difficult-to-treat patients. METHODS: Chronic hepatitis B patients who have received antiviral drugs for > or =12 months and stopped for > or =6 months were treated by 48-week PEG-IFN-alpha2a. Virological response was defined as HBV DNA <10,000 copies/ml and hepatitis B e antigen (HBeAg) seroconversion (for HBeAg-positive patients). RESULTS: A total of 40 patients, 29 HBeAg-positive and 11 HBeAg-negative, with median log10 HBV DNA 7.3 copies/ml and alanine aminotransferase 110 IU/ml were studied. The last antiviral treatment was given for 92 +/- 61 weeks and stopped for 176 +/- 88 weeks. At the end of treatment, 22 (12 HBeAg-positive and 10 HBeAg-negative; 55%) patients had virological response and 16 (7 HBeAg-positive and 9 HBeAg-negative; 40%) patients had undetectable HBV DNA (<100 copies/ml). At 24 weeks post-treatment, 14 (8 HBeAg-positive and 6 HBeAg-negative; 35%) patients had virological response and 9 (5 HBeAg-positive and 4 HBeAg-negative; 23%) patients had undetectable HBV DNA. Two (5%) patients had lost hepatitis B surface antigen. HBV DNA levels at week 24 best predicted sustained virological response (area under curve 0.76, 95% confidence interval 0.60-0.92, P=0.007). At HBV DNA cutoffs of 3 logs and 5 logs at week 24, the sensitivity/specificity for sustained virological response were 50%/85% and 86%/62%, respectively. CONCLUSIONS: PEG-IFN-alpha2a was effective in the treatment of chronic hepatitis B patients who have failed previous antiviral treatment.     

Short-term lamivudine for the treatment of chronic hepatitis B

Short-term lamivudine and its withdrawal were evaluated as regards an immunomodulatory therapy of chronic hepatitis B. Lamivudine was given for 3 or 6 months to 23 patients with chronic hepatitis B who were infected with hepatitis B virus (HBV) genotype C, including 15 with hepatitis B e antigen (HBeAg) and 8 without it. It decreased serum levels of alanine aminotransferase (ALT) and HBV DNA in HBeAg-positive patients. Flare-ups of ALT and HBV DNA after treatment were observed in most patients, and 4 of the 12 (33%) patients with 6-month lamivudine treatment remained in remission 6 months after withdrawal of the therapy. In HBeAg-negative patients, however, flare-ups of ALT and HBV DNA were mild. Normalization of ALT and a decrease in serum HBV DNA were accomplished in 6 of the 9 (75%) patients. Breakthroughs or serious side effects were not observed in any patients. Short-term lamivudine is safe and may offer a therapeutic option to patients with chronic hepatitis B.     

Long-term lamivudine monotherapy in renal-transplant recipients with hepatitis-B-related cirrhosis

BACKGROUND: Chronic hepatitis B virus (HBV) infection is an important cause of morbidity and mortality in renal-transplant recipients. The aim of the study was to assess the efficacy and safety of long-term lamivudine monotherapy in renal-transplant recipients with HBV-related cirrhosis. METHODS: Seventeen such patients [median age: 45 years; 7 with hepatitis B e antigen (HBeAg)] received daily oral doses of 75-150 mg lamivudine for a median of 48 (range 11-81) months. All patients had baseline serum levels of HBV DNA of over 6 log10 copies per ml and of alanine transaminase (ALT) of over 1.5 times the upper normal limit (UNL). Clinical lamivudine resistance was defined as a rebound of serum HBV DNA above 5.3 log10 copies per ml and of serum ALT of over 1.5 times the UNL in patients who initially responded with HBV DNA levels of less than 5.3 log10 copies per ml and normal ALT values. Controls were 14 renal-transplant patients (median age 44 years; 3 with HBeAg) with HBV-related cirrhosis, naive to any anti-HBV therapy, followed for 58 months (4-135). RESULTS: Thirteen (77%) treated patients had a persistent response throughout the study period, including three (18%) who developed genotypic resistance, compared with none of the untreated controls (77% versus 0%, P < 0.0001). Four (23%) developed clinical resistance. Two of three patients with initially decompensated cirrhosis had a durable response and clinical improvement compared with the transient responder, whose liver function worsened following lamivudine resistance. Two responders developed chronic rejection requiring chronic haemodialysis. Overall, one treated patient developed liver-related complications, compared with eight untreated controls (6% versus 57%, P < 0.01). CONCLUSIONS: Most renal-transplant patients treated with lamivudine achieved a rapid and durable suppression of HBV, which substantially lowered the risk of liver decompensation and death.     

Long-term lamivudine treatment is associated with a good maintained response in severe acute exacerbation of chronic HBeAg-negative hepatitis B

Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B is difficult to treat and there is little long-term data for lamivudine treatment of severe acute exacerbation. We report a prospective, consecutive cohort of severe acute exacerbation of HBeAg-negative chronic hepatitis B patients treated by lamivudine between 1999 and 2004. All patients had respectively increased alanine aminotransferase and serum bilirubin to at least 10 and 2 times the upper limit of laboratory normal. Thirty-two patients were treated with lamivudine for 130 +/- 58 (range 48-217) weeks. Five patients had evidence of virological breakthrough (HBV DNA >10,000 copies/ml) during lamivudine treatment. The cumulative probability of maintained response without any virological breakthrough was 94% (95% confidence interval [CI], 86-100%) at year 1, 94% (95% CI, 82-100%) at year 2 and 71% (95% CI, 41-100%) at year 3. At the last follow-up visit, 31 (97%) lamivudine patients had HBV DNA <10,000 copies/ml. The prevalence of lamivudine resistance mutation was 1 in 32 patients (3%; 95% CI, 0-9%) at year 1, 1 in 17 patients (6%; 95% CI, 0-17%) at year 2, 1 in 9 patients (11%, 95% CI, 0-32%) at year 3 and 1 in 4 patients (25%; 95% CI, 0-67%) at year 4 of lamivudine treatment. In conclusion, extended lamivudine treatment is associated with a high maintained virological response and a low rate of drug resistance in severe acute exacerbation of HBeAg-negative chronic hepatitis B.     

Adefovir dipivoxil for treatment of breakthrough hepatitis caused by lamivudine-resistant mutants of hepatitis B virus

OBJECTIVE: Adefovir dipivoxil (ADV) is a nucleoside analogue that inhibits wild-type hepatitis B virus (HBV) and lamivudine-resistant HBV mutants in vitro and in vivo. The aim of this study was to evaluate the efficacy of ADV against lamivudine-resistant mutants and of adefovir and interferon (IFN) add-on to lamivudine for patients with severe acute exacerbation of hepatitis caused by lamivudine-resistant mutants. METHODS: Fourteen patients with breakthrough hepatitis were treated with ADV. Four of the 14 patients also received IFN as combined treatment for severe acute exacerbation of hepatitis. RESULTS: At week 24, serum HBV DNA levels had significantly decreased by a median of over 4.8 log copies/ml in the ADV group and over 5.9 log copies/ml in the ADV + IFN group compared to baseline. The median decrease in alanine aminotransferase (ALT) levels from baseline to week 24 was -1.05 times the upper limit of normal (ULN) in the ADV group [significant at week 24 compared with baseline (p = 0.012)] and -22.3 times the ULN in the ADV + IFN group. CONCLUSIONS: Administration of ADV add-on to lamivudine for patients with breakthrough hepatitis reduced HBV DNA and ALT levels. ADV and IFN add-on to lamivudine could prevent a fatal course in patients with severe acute exacerbation of hepatitis.     

HBV DNA不同载量的CHB患者的HBeAg和ALT水平比较

目的 探讨乙型肝炎病毒(HBV)DNA不同载量的慢性乙型肝炎(CHB)患者乙肝病毒e抗原(HBeAg)与丙氨酸氨基转移酶(ALT)的关系,为临床治疗提供依据.方法 分别比较214例ALT正常的CHB患者中HBeAg(+)、HBeAg( -)患者与200名HBsAg( -)、ALT正常的健康对照者ALT水平的差异.将AL...     

Hepatitis B virus genotype-associated variability in antiviral response to adefovir dipivoxil therapy in Chinese Han population

It is well known that different genotypes of hepatitis B virus (HBV) have a different sensitivity to interferon-alpha or lamivudine (nucleoside analogue) antiviral therapy. However, for adefovir dipivoxil (ADV, a nucleotide analogue), the antiviral response of the different genotypes remains to be clarified. In order to evaluate the response of HBV genotypes to ADV therapy and to identify factors that might affect initial virological response, we performed a retrospective analysis on patients with chronic hepatitis B (CHB) in Chinese Han population. The study included 183 patients, who had been tested positive for hepatitis B e antigen (HBeAg) and had been treated with ADV (10 mg/day) for 48 weeks. The numbers of patients infected with HBV genotype B and genotype C were 98 and 75 cases, respectively, and the remaining 10 patients were mixture infection of genotypes B plus C or genotypes B plus D. The mean HBV-DNA reduction and HBV-DNA seroclearance of genotypes B and C at 48 weeks were 3.6 log(10) and 3.1 log(10) copies/ml (p < 0.05) and 41.8% and 34.6% (p < 0.05), respectively. There were no statistically significant differences between genotypes B and C in terms of HBeAg loss, anti-HBe seroconversion and normalization of serum alanine aminotransferase (ALT). Multivariate analysis showed that young age, low pretreatment HBV-DNA and/or elevated ALT level might be independent predictive factors associated with initial virological response. Thus, in Han CHB patients who are HBeAg-positive, HBV genotype B shows a better virological response to ADV therapy than does genotype C.     

ALT大致正常的CHB患者肝组织炎症活动度相关因素分析

【目的】了解血清谷丙转氨酶（ALT）大致正常的慢性乙型肝炎（CHB）肝组织炎症活动度（G）改变情况与各因素的关系。【方法】对本院826例血清ALT大致正常[ALT〈2倍正常值上限（ULN）]的CHB患者肝组织炎症活动度改变与ALT、HBeAg状态、年龄进行比较分析。【结果】ALT为1—2×ULN的肝组织炎症活动度G2及以上者显著高于ALT〈1×ULN者（P〈0．01）;HbeAg状态与肝组织炎症活动度无关（P〉0．05）;年龄与肝组织炎症活动度改变有密切关系,差异有显著性（P〈0．01）。【结论】ALT大致正常的CHB肝组织炎症活动度与ALT水平、年龄有关,与HBeAg状态无关,是否需要抗病毒治疗应根据肝脏活检组织学改变情况来决定。     

Sequential treatment with lamivudine and interferon-alpha monotherapies in hepatitis B e antigen-negative Chinese patients and its suppression of lamivudine-resistant mutations

OBJECTIVES: To assess the efficacy of sequential treatment with lamivudine and interferon-alpha monotherapies in Chinese patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS: One hundred and sixty-two patients with HBeAg-negative chronic hepatitis B were included in this study. Ninety-eight were treated with lamivudine alone (100 mg per day) for 48 weeks (group B). Sixty-four were treated with lamivudine alone (100 mg per day) for 20 weeks, then combined with interferon-alpha-2b (5 million units three times per week) for 4 weeks and then treated for another 24 weeks with interferon-alpha-2b alone (5 million units three times per week) (group A). All patients were followed for an additional 24 weeks. RESULTS: After 48 weeks of treatment, the percentage of patients with normalization of alanine aminotransferase (ALT) levels or hepatitis B virus (HBV) DNA levels below 1000 copies/mL was not significantly different between the lamivudine monotherapy group (55.10% and 55.10%, respectively) and the sequential treatment group (59.36% and 56.25%, respectively). The percentage of patients with normalized ALT levels was significantly higher in group A (53%) than in group B (36%) at week 72 (P<0.05). The percentage of patients with lamivudine-resistant mutations was significantly higher with lamivudine monotherapy (22.45%) than with sequential therapy (P<0.05). CONCLUSIONS: Sequential treatment of chronic hepatitis B with lamivudine and interferon-alpha monotherapies is as effective as lamivudine-alone treatment in Chinese patients. However, sequential treatment can significantly suppress the emergence of lamivudine-resistant mutations.     

Hepatitis B genotypes in chronic hepatitis B and lamivudine therapy

The influence of hepatitis B virus (HBV) genotypes on the natural history and the response to treatment of patients with chronic hepatitis B are of potential interest. Compared to the patients with HBV genotype C, those with genotype B were of a younger age and had a higher cumulative rate of hepatitis B e antigen (HBeAg) seroconversion during the initial 6 years of follow-up. The earlier HBeAg seroconversion in the patients with genotype B, however, did not provide them with a benefit in terms of a reduced risk of developing long-term complications. The response to lamivudine therapy was evaluated in 21 patients infected with HBV genotype B (all of subtype Ba) and 61 with genotype C. There were no differences in the virological response to lamivudine therapy, based on the reduction in median logarithmic HBV DNA titer as well as alanine aminotransferase (ALT) levels, normalization of ALT and the rate of HBeAg seroconversion between the patients with genotypes B and C. No differences were noted either, in the frequency of YMDD mutants at week 52 or the cumulative risk of HBV DNA breakthroughs with YMDD mutations during long-term lamivudine therapy (median 37.5 months). In conclusion, there is no influence of HBV genotypes on the development of long-term complications and lamivudine therapy in Hong Kong.     

基线HBeAg水平对HBeAg阳性慢性乙型肝炎阿德福韦酯治疗52周疗效的预测价值

目的评价HBeAg阳性慢性乙型肝炎患者的HBeAg基线水平对阿德福韦酯治疗1年疗效的预测价值。方法 98例HBeAg阳性、年龄18～60岁的慢性乙型肝炎患者进入研究。筛选时血浆HBV DNA定量≥1×106拷贝/ml,血清ALT水平1.5～10倍正常参考值上限,无其他原因引起的肝病。患者接受阿德福韦酯胶囊10mg/d治疗,共52周。定期随访,统一由专人检测HBV血清标志及HBV DNA。HBV血清标志物用Abbott试剂检测。HBeAg半定量采用样本值与截止值之比（s/co）表示,HBV DNA用实时荧光定量PCR方法检测,灵敏度为1×103拷贝/ml（3log10拷贝/ml）。结果阿德福韦酯治疗52周,HBV DNA水平较基线下降（3.63±1.26）log10拷贝/ml,HBV DNA检测不到率48.0%（47/98）,ALT复常率为83.7%（82/98）,HBeAg血清转换率为23.5%（23/98）。52周HBeAg血清转换组与无转换组患者的基线HBeAg水平分别为（251.9±117.3）s/co和（339.6±137.3）s/co（P=0.002）,基线HBeAg水平≤350s/co者分别占78.3%（18/23）和36%（27/75,P〈0.001）,而两组基线HBV DNA水平和ALT水平无统计学意义。基线HBeAg≤350s/co（n=45）组和〉350s/co（n=53）组比较,治疗12周两组HBV DNA检测不到率分别为35.6%和13.2%（P=0.009）,HBeAg阴转率为22.2%和0（P〈0.001）,ALT复常率为55.6%和17.0%（P〈0.001）;治疗52周HBV DNA检测不到率为64.4%和34.0%（P=0.003）,HBeAg血清转换率为42.2%和7.5%（P〈0.001）,ALT复常率为84.4%和83.0%。结论基线HBeAg水平对阿德福韦酯治疗HBeAg阳性慢性乙型肝炎患者的12周及52周疗效预测有一定的价值。基线HBeAg水平较低者能获得更好的早期病毒学应答和HBeAg血清转换率。     

替比夫定治疗慢性乙型病毒性肝炎的近期疗效分析——附57例报告

目的：评价替比夫定治疗慢性乙型病毒性肝炎的近期疗效。方法：57例慢性乙型病毒性肝炎患者分为HBeAg阴性组（12例）和HBeAg阳性组（45例）,均予替比夫定600mg／d治疗24周,于治疗0、4、8、12、16、24周时检查HBV DNA、ALT水平,于0、12及24周检查HBeAg及HBeAb.分析上述时间点两组患者HBV DNA阴转率、ALT复常率、HBVDNA下降速度,并分析影响病毒早期应答的因素。结果：HBeAg阴性组治疗4、8、12、16、24周时的HBV DNA阴转率分别为25％、42％、50％、67％及75％;24周时ALT复常率为83％。HBeAg阳性组治疗4、8、12、16、24周时的HBV DNA阴转率分别为0、7％、13％、27％及53％;24周时HBeAg血清学转换率及ALT复常率分别为27％及76％。两组HBV DNA水平均在前4周下降最明显,其后下降速度减慢,维持在较低水平。HBV DNA阴转者的基线HBV DNA水平明显低于未阴转者（P〈0．05）。结论：替比夫定可明显抑制HBV DNA的复制,并在早期（4—8周）将HBV DNA抑制到较低的水平,促进ALT恢复正常;基线HBV DNA水平是影响其24周病毒学应答的重要因素。     

HBeAg对轻度慢性乙型肝炎病情活动度的影响

目的探讨乙型肝炎病毒e抗原（HBeAg）对轻度慢性乙型肝炎（CHB）患者机体的免疫应答功能及病情活动度的影响。方法通过检测81例轻度CHB患者血液中主要肝功能指标、白细胞介素-18（IL-18）、β2-微球蛋白（β2-M）等指标测定并做统计学分析。结果在轻度CHB患者中，22例HBeAg阴性患者的丙氨酸氨基转移酶（ALT）、胆红素（TB）、β2-M均明显升高（P〈0．05），IL-18含量明显升高（P〈0．01）；ALT异常率63．6％，IL-18升高率86．4％，二者比较差异有明显统计学意义（P〈0．05）。与59例HBeAg阳性组比较，乙型肝炎病毒脱氧核糖核酸（HBV DNA）拷贝量、HBeAg定量（S／CO值）2项指标明显较低（P〈0．01），TB、IL-18水平明显较高（P〈0．05，P〈0．01）；两组间ALT、β2-M差异无统计学意义（P〉0．05）。HBeAg阳性组的HBeAg与IL-18水平呈明显负相关（r=-0．536、P〈0．01）。结论在轻度CHB患者中，HBeAg阴性者HBV DNA复制较HBeAg阳性者明显低，但肝炎更重，活动性更高。HBeAg对机体的免疫应答功能及肝炎活动度有明显的影响。     

拉米夫定联合阿德福韦酯治疗E抗原阴性的慢性乙型肝炎患者疗效分析

目的：观察拉米夫定联合阿德福韦酯治疗E抗原阴性的慢性乙型肝炎患者的疗效和安全性。方法：2006～2007年来我院就诊的慢性乙型肝炎患者,给予拉米夫定100mg/d,阿德福韦酯100mg/d,观察治疗前及治疗后12、24及48周谷丙转氨酶水平、HBV DNA水平、乙型肝炎病毒血清标志物的应答效果及肾功能变化。结果：治疗12周、24周和48周时,HBV DNA转阴率分别为17%、43%和87%,且各组间差异具有统计学意义（P〈0.05）;ALT复常率分别为13%,67%和100%,且各组间差异具有统计学意义（P〈0.05）;治疗48周时,所有患者均未发生表面抗原的消失;整个治疗过程中,患者的耐受性良好,未发生一例严重不良事件。结论：拉米夫定联合阿德福韦酯治疗E抗原阴性的慢性乙肝患者,可获得较好的临床疗效,该治疗策略为临床抗病毒治疗提供了新的选择。     

拉米夫定耐药慢性乙型肝炎患者HBVP区基因突变模式与临床特征

目的分析慢性乙型肝炎患者在拉米夫定（LAM）治疗过程中出现耐药后,HBVP区基因突变模式及临床特征。方法对2009年4月～2009年12月在石家庄市第五医院就诊的116例临床诊断为LAM耐药慢性乙型肝炎患者进行HBVP区基因序列测定。结果116例临床诊断为LAM耐药患者血清HBVDNA水平为（5．34±1．21）log10拷贝／mL,ALT为（135±89）U／L,60．7％（70／116）的患者出现ALT升高。116例患者均出现基因耐药突变,共有7种突变模式,94．8％（110／116）发生YMDD基序突变,其中单纯YMDD突变占22．4％（26／116）,YMDD联合rtLl80M突变占72．4％（84／116）,5．2％（6／116）发生单纯rtLl80M突变。rtM204V联合rtLl80M突变的发生率为87．5％（56／64）,rtM204I联合rtLl80M突变的发生率为69．4％（50／72）,差异有显著统计学意义（P=0．04）。LAM耐药时,4种突变类型即rtM204I、rtLl80M＋rtM204V、rtLl80M＋rtM2041和rtLl80M＋r[IⅥ204V／I患者血清HBeAg、HBVDNA、ALT水平之间差异无统计学意义,P值分别为0．63,O．72,0．82。结论YMDD基序突变是LAM耐药后HBVP区基因突变的主要模式,rtM204V多以联合rtLl80M突变的形式存在,LAM耐药后患者肝组织损伤程度以及病毒复制水平可能与HBVP区突变类型无关。