Molecular analysis of hepatitis B virus isolates in Mexico： Predominant circulation of hepatitis B virus genotype H

INTRODUCTIONHepatitis B virus(HBV)is an important cause of morbidity and mortality worldwide.It is estimated that2billion people are infected with HBV and350million individuals suffer from chronic HBV infection in the world[1,2].Chronic HBV infection may …     

Unveiling the biological role of sphingosine-1-phosphate receptor modulators in inflammatory bowel diseases

Inflammatory bowel disease(IBD) is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide. The increasing disease burden worldwide, lack of response to current biologic therapeutics, and treatment-related immunogenicity have led to major concerns regarding the clinical management of IBD patients and treatment efficacy. Understanding disease pathogenesis and disease-related molecular mechanisms is the most important goal in developing new and effec...     

Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma： A multicenter study of 412 patients

INTRODUCTION Hepatocellular carcinoma (HCC) is one of the most common neoplasms and its incidence is currently rising worldwide[1-3]. HCC usually occurs in cirrhotic livers and less than 30% of patients presenting with HCC are considered candidates for re…     

The “return” of hepatitis B

INTRODUCTION Hepatitis B virus (HBV) infection is a global health problem. This infection is especially endemic in Asia, South Pacific Region, sub-Saharan Africa and South America[1]. It is estimated that over 350 million people worldwide are chronically …     

Relationship between the severity of hepatitis C virus-related liver disease and the presence of Helicobacter species in the liver： A prospective study

INTRODUCTION Chronic hepatitis C virus (HCV) infection is a major public health problem with over 170 million people infected worldwide. It is the leading cause of chronic liver disease and the main indication for liver transplantation in the Western worl…     

Nucleoporin 88 expression in hepatitis B and C virus-related liver diseases

INTRODUCTIONHepatocellular carcinoma (HCC) ranks fifth of the most common cancers worldwide and its incidence is rising in the Western world[1]. Due to the high mortality associated with HCC it is the third leading cause of cancer death worldwide[1]. The …     

Food allergy in gastroenterologic diseases： Review of literature

INTRODUCTION Food allergy is recognized as a common worldwide prob- lem, and, like other atopic disorders, its incidence seems to increase. Moreover, food-related allergic disorders are the leading cause of anaphylactic reactions treated in the emer- genc…     

Reducing cholesterol to prevent coronary heart disease

Coronary heart disease (CHD) remains the number one killer of men and women in the United States of America despite major advances in interventional technologies for the treatment of coronary artery disease. CHD is rapidly becoming a major cause of morbidity and mortality in developing nations as well and is now recognized as the leading cause of death worldwide.……     

Health related quality of life after surgery for colonic diverticular disease

Diverticular disease(DD) of the colon is very common in developed countries and is ranked the fifth most important gastrointestinal disease worldwide.The management of acute diverticulitis without perforation and peritonitis is still debated.Health related quality of life(HRQL),subjectively perceived by patients,is becoming a major issue in the evaluation of any therapeutic intervention,mainly in patients with chronic disease.To date only a few published studies can be found on Medline examining HRQL in pat...     

α干扰素对慢性乙型肝炎e抗原阴性患者的疗效及影响因素

目的 了解α干扰素(1FN - α)对慢性乙型肝炎e抗原(HBeAg)阴性患者的疗效及影响因素。 方法 65例HBeAg阴性经肝穿刺活检证实的慢性乙型肝炎(CHB)患者,给予r1FN α 1b治疗,每次5 MU,每周3次。治疗结束后随访至少12个月。以188例HBeAg阳性CHB患者作对照。 结果 HBeAg阴性组治疗未时联合应答(CR)率为58.5％(38/65),与对照组差异无显著性;随访12个月时CR率为75.4％(49/65),高于对照组(X2=4.796,P<0.05)。治疗后12个月内复发率为15,8％(6/38),与对照组差异无显著性。终点疗程中位数为6个月,与对照组差异无显著性。多变量(?)分类Logistic回归分析结果显示,性别、年龄、肝组织炎症活动度、肝组织纤维化程度、丙氨酸氨基转移酶、天冬氨酸氨基转移酶 HBV DNA水平、抗-HBe诸因素中仅肝组织炎症活动度为疗效影响因素。 结论 1FN α对HBeAg阴性CHB患者近期疗效和持续效就与HBcAg阳性都相仿;肝组织炎症活动度高者疗效较佳。     

分泌性重组人干扰素α-2a治疗慢性乙型肝炎患者疗效和安全性的研究

目的 观察国产分泌性干扰素治疗慢性乙型肝炎的疗效与安全性。方法 采用随机、开放、对照、多中心的研究方法，以国产普通干扰素作为对照药物，观察分泌性干扰素治疗慢性乙型肝炎6个月，停药随访6个月的疗效与安全性。结果 分泌性干扰素在治疗24周时，丙氨酸氨基转移酶(ALT)复常率为48．3％，优于对照组(35．7％)，但随访结束时两组差异无显著性。治疗后分泌性干扰素组的HBVDNA下降幅度优于对照组，但转阴率两组间差异无显著性。治疗结束时分泌性干扰素组与对照组的乙型肝炎e抗原(HBeAg)转阴率分别为26．5％和l9．4％，HBeAg血清转换率分别为13．5％和12．0％；随访结束时两组的HBeAg转阴率继续增加，分别为32．5％与27．2％，HBeAg血清转换率分别为19．0％和18．4％。两种干扰素的安全性良好。结论 分泌性干扰素治疗结束时在ALT复常率、HBVDNA下降幅度方面优于普通干扰素，随访结束时两组间差异无显著性。在HBeAg转阴率和HBeAg血清转换率方面两种干扰素差异无显著性。两种干扰素安全性良好。     

基线病毒载量对阿德福韦酯治疗HBeAg阳性慢性乙型肝炎疗效的影响

目的探讨不同基线病毒载量HBeAg阳性慢性乙型肝炎患者应用ADV抗病毒治疗的疗效。方法根据基线HBV DNA水平不同将72例HBeAg阳性慢性乙型肝炎患者分为低病毒载量组(A组)44例和高病毒载量组(B组)28例。A组HBV DNA<1×107拷贝/毫升,B组HBV DNA≥1×107拷贝/毫升,均应用ADV治疗,观察48周。结果在治疗12周、24周和48周时,A组HBV DNA水平分别为3.5±1.1lg拷贝/毫升、3.0±1.1lg拷贝/毫升和2.6±1.2lg拷贝/毫升,B组分别为3.8±1.3lg拷贝/毫升、3.6±1.3lg拷贝/毫升和3.1±1.4lg拷贝/毫升,其中仅在24周时两组差异有统计学意义(P<0.05);治疗12周时A组HBV DNA阴转率为18.2%、HBeAg阴转率为15.2%,HBeAg血清转换率为9.1%、ALT复常率为54.5%,B组分别为3.6%、10.7%、10.7%、32.1%,差异无统计学意义(P>0.05);24周A组HBV DNA阴转率为34.9%、HBeAg阴转率为27.9%,HBeAg血清转换率为11.6%、ALT复常率为86.0%,B组分别为14.3%、14.3%、10.7%、57.1%,仅ALT复常率差异有统计学意义(P<0.05);48周A组HBV DNA阴转率为52.3%、HBeAg阴转率为45.5%,HBeAg血清转换率为6.8%、ALT复常率为90.9%,B组则分别为25.9%、11.1%、7.4%、70.4%,除HBeAg血清转换率外,两组差异均有统计学意义(P<0.05);治疗48周A组发生病毒学突破1例,B组3例,差异无统计学意义(P>0.05)。结论基线病毒载量是影响ADV治疗CHB疗效的重要因素,并可作为疗效预测的重要参考依据。     

Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B

Current therapies for chronic hepatitis B (CHB) have a number of limitations, and better treatment options are needed. Peginterferon alpha-2a (40 kDa) is superior to conventional interferon alpha-2a in the treatment of chronic hepatitis C. This is the first report on peginterferon alpha-2a (40 kDa) in the treatment of CHB. In this phase II study, 194 patients with CHB not previously treated with conventional interferon-alpha were randomized to receive weekly subcutaneous doses of peginterferon alpha-2a (40 kDa) 90, 180 or 270 microg, or conventional interferon alpha-2a 4.5 MIU three times weekly. Twenty-four weeks of therapy were followed by 24 weeks of treatment-free follow-up. All subjects were assessed for loss of hepatitis B e antigen (HBeAg), presence of hepatitis B antibody (anti-HBe), suppression of hepatitis B virus (HBV) DNA, and normalization of serum alanine transaminase (ALT) after follow-up. At the end of follow-up, HBeAg was cleared in 37, 35 and 29% of patients receiving peginterferon alpha-2a (40 kDa) 90, 180 and 270 microg, respectively, compared with 25% of patients on conventional interferon alpha-2a. The combined response (HBeAg loss, HBV DNA suppression, and ALT normalization) of all peginterferon alpha-2a (40 kDa) doses combined was twice that achieved with conventional interferon alpha-2a (24%vs 12%; P = 0.036). All treatment groups were similar with respect to frequency and severity of adverse events. These results indicate that peginterferon alpha-2a (40 kDa) is superior in efficacy to conventional interferon alpha-2a in chronic hepatitis B based on clearance of HBeAg, suppression of HBV DNA, and normalization of ALT.     

拉米夫定的疗程及早期应答与疗效的关系

目的探讨拉米夫定治疗慢性乙型肝炎的方法与疗效的关系。方法收集179例接受拉米夫定治疗的乙型肝炎e抗原（HBeAg）阳性的慢性乙型肝炎患者的资料，分析早期应答、病毒变异、疗程等与疗效的关系。结果随着治疗时间延长，丙氨酸氨基转移酶（ALT）、HBVDNA、HBeAg和HBeAg／抗-HBe各项指标逐渐改善；1年疗程的HBVDNA阴转率（57．0％）、HBeAg阴转率（39．7％）及HBeAg／抗-HBe转换率（16．8％）均明显高于治疗3个月时的水平（X2值分别为28．489、33．238、12．690，P〈0．01）。治疗12周时血清HBVDNA水平越低，到治疗52周及随访6个月末时HBVDNA转阴率及HBeAg／抗-HBe血清学转换率越高。疗程为1年、1．5年时，出现HBeAg／抗-HBe转换者HBVDNA反弹率均为40．0％，远低于无转换者（88．2％、85．0％，x^2值分别为12．424、10．237，P〈0．01）。结论拉米夫定治疗是安全有效的，疗程以1．5年为佳。早期应答者疗效较好，如不能在治疗的前3个月内达到DNA应答、1年内出现血清学转换，预示疗效欠佳。     

Hepatitis B virus DNA prediction rules for hepatitis B e antigen-negative chronic hepatitis B

After hepatitis B e antigen (HBeAg) seroconversion, hepatitis B may become inactive or progress to HBeAg-negative hepatitis with persistent or intermittent alanine aminotransferase (ALT) elevation. The aim of this study was to prospectively identify factors predictive of the clinical course in HBeAg-negative chronic hepatitis B (CHB). Patients were stratified by ALT and HBeAg status and followed every 3 months for up to 5 years. Kaplan-Meier and Cox regression analysis using the change from normal ALT to elevated ALT as endpoints were performed to determine factors associated with ALT elevation/normalization. Seventy-four HBeAg-negative and 32 HBeAg-positive patients were prospectively evaluated. For HBeAg-negative patients, hepatitis B virus (HBV) DNA was predictive of future ALT. Only 1 patient with normal ALT and an HBV DNA value lower than 10,000 copies/mL developed an elevated ALT within the subsequent year, whereas 67% with an HBV DNA value greater than 100,000 copies/mL had a rise in ALT above normal within 1 year. Patients with a previous history of ALT elevation and longer follow-up at all levels of HBV DNA were more likely to experience ALT elevations. For HBeAg-negative patients with elevated ALT and all HBeAg-positive patients, HBV DNA did not predict future ALT. Other viral and host factors were not predictive of future ALT. CONCLUSION: HBeAg-negative CHB has a fluctuating course. HBV DNA values lower than 10,000 copies/mL predict persistently normal ALT for at least 1 year. Patients with HBV DNA values between 10,000 and 100,000 copies/mL can safely be followed at 6 monthly intervals, whereas HBV DNA values greater than 100,000 copies/mL are highly predictive of future ALT elevation and should prompt regular follow-up.     

拉米夫定联合胸腺肽治疗慢性乙型肝炎的疗效观察

目的 评价拉米夫定联合胸腺肽治疗慢性乙型肝炎(CHB)的近、远期疗效和安全性，探讨两者联合治疗的协同作用。方法 将207例HBV DNA及HBeAg阳性的CHB患者随机分为甲乙两组，甲组采用拉米夫定和胸腺肽联合治疗，乙组单用拉米夫定治疗。胸腺肽15mg口服，每日1次，疗程6个月。两组拉米夫定治疗均为100mg，每日1次，口服，其中甲组92例(92／124)、乙组70例(70／83)用药超过12个月。两组在治疗6个月、12个月时分别进行疗效评价，治疗结束后继续随访12个月。结果 治疗6个月时，甲乙两组ALT复常率分别为87．1％和74．7％，甲组显著高于乙组(P＜0．05)，但两组HBV DNA阴转率、HBeAg阴转率及HBeAg／抗—HBe血清转换率均无显著性差异(P＞0．05)。治疗12个月时，甲乙两组ALT复常率和HBV DNA阴转率无显著性差异(P＞0．05)，甲组HBeAg阴转率及HBeAg／抗-HBe血清转换率均显著高于乙组(P＜0．05)。随访结束时，甲组从量复常率、HBV DNA阴转率、HBeAg阴转率及HBeAg／抗—HBe血清转换率均显著高于乙组(P＜0．05)。结论 拉米夫定与胸腺肽联合治疗CHB，疗效明显优于单用拉米夫定，是CHB患者安全有效的治疗方法。     

Clevudine-induced viral response, associated with continued reduction of HBsAg titer, was durable after the withdrawal of therapy

Background

This study was conducted to evaluate the durability of clevudine-induced viral response after the withdrawal of treatment.

Methods

Patients who showed a complete response [alanine aminotransferase (ALT) normalization and hepatitis B virus (HBV) DNA <4,700?copies/mL for hepatitis B envelope antigen (HBeAg)-negative patients; ALT normalization, HBV DNA <4,700?copies/mL, and HBeAg seroconversion for HBeAg-positive patients] in the previous clevudine phase III trials were followed for an additional 96?weeks without any treatment for hepatitis B.

Results

Of the 63 patients in the study cohort, 73% and 35% of the patients had HBV DNA <141,500 and <4,700?copies/mL, respectively, and 75% of the patients had normal ALT at the end of follow-up. HBeAg seroconversion was maintained in 81% of the patients and hepatitis B surface antigen (HBsAg) loss occurred in 3 patients. Continued HBsAg titer decrease (?0.5?log?IU/mL) was observed in the sustained viral responders, suggesting the reduction of covalently closed circular DNA in hepatocytes.

Conclusions

The clevudine-induced viral response was durable in the majority of patients for 2?years after the withdrawal of treatment.     

拉米夫定与α干扰素联合治疗慢性乙型肝炎

目的 观察拉米夫定(LAM)联合干扰素α1b(IFNα1b)治疗慢性乙型肝炎的近期疗效和安全性。方法 HBV DNA和HBeAg均阳性的90例慢性乙型肝炎患者，按1：1：1的比例进入三个不同的治疗组。联合治疗组：用IFNα1b 5MU，隔日肌肉注射，及口服LAM 100mg／d，共6个月，随后单用口服LAM 100mg／d6个月；LAM组：口服LAM 100mg／d共12月：IFN组：IFN α1b 5MU，隔日肌肉注射，共6个月。结果 治疗结束时，HBV DNA转阴率，联合治疗组为90．0％，LAM组为80％，IFN组为46．7％。丙氨酸氨基转移酶(ALT)复常率，联合治疗组为90．0％，LAM组为80．0％，IFN组为53．3％。HBeAg／抗HBe血清转换率，联合治疗组为46．7％，LAM组为13．3％，IFN组为33．3％。联合治疗组患者治疗结束时无一例检测到YMDD变异。结论 联合治疗组对HBV DNA抑制作用及ALT复常率高于单用干扰素组，与单用拉米夫定组接近。HBeAg／抗HBe血清转换率高于拉米夫定组，与单用干扰素组相近。初步显示联合治疗组发生YMDD变异较少。     

Retreatment of chronic hepatitis B e antigen-positive patients with recombinant interferon alfa-2a. The European Concerted Action on Viral Hepatitis (EUROHEP).

Fifty-seven patients with chronic hepatitis B, hepatitis B virus (HBV) e antigen (HBeAg) and HBV DNA positivity, and aminotransferase elevation despite a previous course of any type of adequate interferon alfa (IFN-alpha) therapy were included in a multicenter prospective randomized controlled trial. The objective of the study was to compare a second course of IFN-alpha therapy (9 million units [MU] of IFN-alpha-2a, Roferon-A, thrice weekly for 6 months) versus no therapy in terms of loss of HBV DNA and HBeAg. At the end of the study, a sustained clearance of HBV DNA and HBeAg was observed in 9 of the 27 (33.3%) patients who had received retreatment with IFN-alpha compared with 3/30 (10%) patients who spontaneously cleared these markers in the untreated control group (chi2 = 4.66, P =.031; odds ratio: 4.5, 95%; confidence interval: 1.1-18.9). None of the responders lost HBsAg. Patients retreated with IFN-alpha were more likely to have biochemical remission in association with HBV clearance (5/27, 18.5%) compared with untreated patients (1/30, 3. 3%; Fisher's exact test P =.09 ). Histological improvement in the liver necroinflammatory activity was observed among sustained responders to IFN-alpha retreatment, consisting of regression of the portal and periportal inflammation and of the piecemeal necrosis; there was no change in the degree of liver fibrosis. Side effects were similar to those previously reported during IFN-alpha treatment; these were mild and reversible on IFN-alpha discontinuation. None of the baseline features were associated with response by Cox's regression analysis. In summary, viremic patients with chronic HBeAg-positive hepatitis may experience disease remission following retreatment with IFN-alpha. Thus, retreatment with IFN-alpha may be considered a therapeutic option.