国产基因工程干扰素α1治疗慢性乙型肝炎的临床研究

２２５例慢性乙型肝炎分三组治疗，Ａ和Ｂ组７４例配对随机用干扰素α１及安慰剂双盲对照观察，Ｃ组１５１例为干扰素α１４０微克连用三个月，ＨＢｅＡｇ、ＨＢＶ－ＤＮＡ、ＨＢｅＡｇ和ＨＢＶ－ＤＮＡ双转阴率及抗ＨＢｅ转阳率分别为４０．５％、５７．１％、３９．３％及２９．７％，与对照组差异有非常显著性（Ｐ＜０．０１）。扩大治疗组结果与Ａ组相似，均明显优于对照组。治疗组随访半年和一年ＨＢｅＡｇ及ＨＢＶ－ＤＮＡ转阴率与治疗结束时相似，表明有较持久的效果。     

中草药复方合无环鸟苷治疗乙肝40例疗效观察

采用中草药复方合无环鸟苷治疗乙肝４０例，其中慢性迁延性肝炎６例，ＨＢＶ－ＤＮＡ转阴率７６．９％（２０／２０６）、ＨＢｓＡｇ转阴率３８．５％（１０／２６）、抗－ＨＢｓ转阳率３０．８％（８／２６）、ＨＢｅＡｇ转阴率８４．６％（２２／２６）、抗－ＨＢｃ转阳率７６．９％（２０／２６）、抗－ＨＢｃ转阴率２６．９％（７／２６）、肝功能恢复显效率１００％（２６／２６）；无症状ＨＢＶ携带者１４例，ＮＢＶ－ＤＮＡ转阴率６４．４％（９／１４）、ＨＢｓＡｇ转阴率２８．６％（４／１４）、抗－ＨＢｓ转阳率２８．６％（４／１４）、ＨＢｅＡｇ转阴率７１．４％（１０／１４）、抗－ＨＢｅ转阳率５７．１％（８／１４）、抗－ＨＢｃ转阴率２１．４％（４／１４）、肝功能恢复显效率１００％（１４／１４）。临床实践证明，治疗乙肝运用中西医结合，从病机着手，整体出发，筛选出高效或超高效中草药组方，以免疫调节为重点，注意多环调节和双向调整，保持机体的阴阳、气血平衡，可取得较好稳定的疗效。     

HFRS疫苗对慢性乙肝血清学标志的影响

用肾综合征出血热（ＨＦＲＳ）疫苗治疗慢性乙肝患者８４例，重点观察其对乙肝血清学村志（ＨＢＶＭ）的影响，治疗前患者血清ＨＢｓＡｇ、ＨＢｅＡｇ抗－ＨＢＣ阳性，治疗３、６、１２个月时其中ＨＢｅＡｇ阴转率分别为３４．５％、３８．１％、２８．６％，ＨＢＶ－ＤＮＡ分别为２９．０％、３３．３％、２２．７％。结果显示，ＨＦＲＳ疫苗治疗慢性乙肝有一定疗效，能抑制ＨＢＶ复制，对ＨＢＶＭ有明显阴转作用。     

重组干扰素α─2b治疗慢性乙型肝炎的临床随访研究

随访观察重组干扰素α－２ｂ３×１０６Ｕ，每周３次，皮下注射，疗程３个月，治疗４４例慢性乙型肝炎的疗效，以未用于扰素的４４例慢性乙型肝炎病人作为对照，两组病例病型、年龄、性别、病程及ＡＬＴ等方面皆有可比性。治疗前所有病例ＨＢｓＡｇ、ＨＢｅＡｇ、ＨＢＶ－ＤＮＡ均阳性。结果发现重组干扰素α－２ｂ治疗组在治疗完成时、随访治疗后６个月、１年、２年、３年的ＨＢｅＡｇ阴转率分别为５０．０％、５１，２％、５５．３％、４０．９％和４２．９％；抗ＨＢｅ阳转率分别为２５０％、３４．１％、４２．１％、３６．４％和４２．９％；ＨＢＶ－ＤＮＡ阴转率分别为４５．５％、５１．２％、４２．１％、４０．９％和４２．９％；均显著高于对照组（Ｐ＜０．０５或Ｐ＜０．０１）．慢性活动性肝炎，治疗前ＡＬＴ超过１００ＩＵ／Ｌ，病程短于３年，女性病人，治疗开始后有发热者的疗效较好。副反应主要有发热、肌肉关节痛。结果提示重组干扰素α－２ｂ是一种有效的抗乙型肝炎病毒药物。     

硫代磷酸反义寡核苷酸对乙型肝炎病毒抗原表达的体外抑制作用

目的 研究硫代磷酸反义寡核苷酸（Ｓ－ＡＳＯＮ）的抗乙型肝炎病毒（ＨＢＶ）作用。方法 作者以２．２．１５细胞作为研究对象，在ＨＢＶ基因Ｓ区和Ｃ区的翻译起始位点设计合成了２段１６聚Ｓ－ＡＳＯＮｓ，采用酶联免疫吸附试验检测了培养细胞上清中表面抗原（ＨＢｓＡｇ）和ｅ抗原（ＨＢｅＡｇ）的分泌情况。结果 当Ｓ－ＡＳＯＮ浓度为每天２μｍｏｌ／Ｌ时，对ＨＢｓＡｇ和ＨＢｅＡｇ的抑制率可分别达到８８％和７５％，而无关     

猪苓多糖联合乙肝疫苗治疗慢性乙型肝炎对血清HBV标志的影响

观察了猪苓多糖联合乙肝疫苗治疗慢性乙型肝炎对患者血清ＨＢＶ标志的影响。治疗结束后半年，治疗组ＨＢｓＡｇ、抗－ＨＢｃ，ＨＢｅＡｇ和ＰＨＳＡ－Ｒ的阴转率分别为６０％，０，２３．１％和１８．８％。抗－ＨＢｓ无１例阳转，无１例ＨＢＶ标志全部阴转者。对照组分别为３．９％，０，１９．３％和１６．３。亦无１例产生抗－ＨＢｓ。两组ＨＢＶ标志的转换率差异无显著性（Ｐ＞０．０５）。结果表明：猪苓多糖联合乙肝疫苗对清除和抑制ＨＢＶ无明显效果。     

多聚酶链式反应在慢性乙型肝炎血清学标志物检测中的应用

作者应用多聚酶链式反应检测９５例慢性乙型肝炎患者的血清标本，ＨＢｓＡｇ、ＨＢｅＡｇ、抗－ＨＢｃ阳性组，ＨＢｓＡｇ、抗－ＨＢｅ、抗－ＨＢｃ阳性组，ＨＢｓＡｇ、抗－ＨＢｃ阳性组，抗－ＨＢｓ阳性组，抗－ＨＢｅ，抗－ＨＢｃ阳性组其ＨＢＶＤＮＡ阳性率分别为９６．５５％（２８／２９例），７８．９５％（１５／１９例），４０％（８／２０），２０％（２／１０例），１０％（１／１０例），并提出乙型肝炎病毒复制和传染性     

重组干扰素α—2b治疗慢性乙型肝炎的临床随访研究

随访观察重组干扰素α－２ｂ３×１０＾６Ｕ，每周３次，皮下注射，疗程３个月，治疗４４例慢性乙型肝炎的疗效，以未用干扰素的４４例慢性乙型肝为病人作为对照组，两组病例病型，年龄，性别，病程及ＡＬＴ等方面皆有可比性，治疗前所有病例ＨＢｓＡｇ，ＨＢｅＡｇ，ＨＢＶ－ＤＮＡ均阳性，结果发现重组干扰素α－２ｂ治疗组在治疗完成时，随访治疗后６个月，１年，２年，３年的ＨＢｅＡｇ阴转率分别为５０．０％，５５．３％，４０     

甲,乙,丙型肝炎病毒重叠感染

４９３名健康献血员和１９２例ＨＢＶ感染者，用ＥＬＩＳＡ法检测抗－ＨＡＶ－ＩｇＭ和抗一ＨＣＶ，发现献血员之ＨＣＶ感染率为１．６２％。ＨＢＶ感染者的ＨＡＶ、ＨＢＶ二重感染率为１６．７％，ＨＢＶ、ＨＣＶ二重感染率为３．１３％，ＨＡＶ、ＨＢＶ、ＨＣＶ三重感染率为０．５２％。重叠感染者，３２例ＨＡＶ和ＨＢＶ二重感染者，ＨＢｅＡｇ２８例转阴，与１５３例单纯ＨＢＶ感染者５７例转阴比较，有显著性差异（ｐ〈０．０５     

华蟾素治疗慢性HBV携带者及慢性乙型肝炎的疗效观察

为了观察华蟾素治疗慢性ＨＢＶ携带者及慢性乙型肝为使乙肝病毒复制指标转阴的作用。我们选择ＨＢＶ携带者及慢性乙型肝炎６０例。治疗组用华蟾素４ｍｌ肌注,日一次,连用３个月,对照组不同华蟾素治疗,结果治疗组ＨＢｓＡｇ阳性者３０例中转阴１例,对照组无转阴者。ＨＢｅＡｇ阳性１６例中转阴８例,占（５０％）与对照组比Ｐ〈０．０２５,Ｐｒｅ－Ｓ２阳性者２３例中转阴１１例占（４７．８２％）与对照组比Ｐ〈０．０２５。结     

Ultrasound-Guided Liver Biopsy for Parenchymal Liver Disease (An Economic Analysis)

The use of ultrasound (US) to assist in liverbiopsy for nonfocal liver disease has been shown tosignificantly decrease the incidence of minorcomplications (defined as pain requiring treatment,hypotension, or bleeding). In this study, decision analysiswas used to estimate the average additional net chargefor US guidance. The risks for minor and majorcomplications were extracted from the literature. The incidence of minor complications such as painand bleeding not requiring hospitalization has beenreported as 49% for blind liver biopsy and 39% forUS-guided liver biopsy. Major complications requiring hospital admission occur in 4% of blind liverbiopsies and 2% of US-guided liver biopsies. A decisiontree was used to calculate the total charges of liverbiopsy and its associated complications. The charge for treating an episode of minor complicationswas estimated at $605. The charge related to an episodeof major complications was estimated at $1533. The totalcharge for an ultrasoundguided liver biopsy (except the added charge for the use ofultrasound) was $1770, or $102 less than the same chargefor blind liver biopsy. The addition of ultrasound inperforming liver biopsies for diffuse parenchymal liver disease is cost-saving if the additional chargeof US is less than $102.     

Long-term follow-up of 60 patients with chronic hepatitis B. I. Seroconversion in the hepatitis B e-system, frequency of delta infection and histological outcome

Sixty patients with liver biopsy documented chronic hepatitis B attending Roslagstull Hospital for Infectious Diseases, Stockholm, Sweden, were followed during a mean period of 53 months (range 7-133 months) in order to evaluate the frequency of delta infection and HBeAg seroconversion as well as the histological outcome as assessed by liver biopsy. Spontaneous HBeAg clearance and development of anti-HBe occurred among 17 of 36 initially HBeAg positive patients (47%), corresponding to an annual seroconversion rate of 11%. Biochemical improvement was noted in 7/17 patients (41%) after seroconversion as against in 2/19 patients (10.5%) with HBeAg persistence. Superinfection with the delta agent was seen to be associated with severe liver injury among drug addicts and immigrants with chronic hepatitis B. In the absence of a delta infection, progressive liver disease seemed to be associated with persistence of HBeAg. Although none of the homosexual men studied were delta superinfected, 71% developed chronic active hepatitis (CAH) with or without cirrhosis (CI).     

Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels

BACKGROUND: Natural history studies of hepatitis B virus infection have shown relapse of hepatitis in 5% to 15% of patients and progression to cirrhosis in 2% to 6% annually. Follow-up of patients beginning at the early phase of infection might provide data with less referral bias than in previous studies. METHODS: Test of liver biochemistry, assessment of virological markers, and ultrasound examinations were performed at regular intervals during the course of hepatitis B e antigen (HBeAg) to antibody (anti-HBe) seroconversion in 240 HBeAg carriers with normal alanine aminotransferase levels at baseline. Factors predictive of cirrhosis were identified by multivariate analysis. RESULTS: We enrolled 130 men and 110 women. The mean (+/- SD) age at entry was 27.6 +/- 6.2 years. During the HBeAg-positive phase, 29% of patients had alanine aminotransferase levels > or =200 U/L, 3% had bilirubin levels > or =2.0 mg/dL, and 5% had two or more episodes of alanine aminotransferase levels > or =200 U/L. The mean age at anti-HBe seroconversion was 31.3 +/- 7.0 years, with remission of hepatitis in all patients. However, hepatitis recurred in 36 patients (15%), with an annual rate of 2.2%. Thirteen patients (5%) progressed to cirrhosis. The annual incidence of cirrhosis was 0.5%, and the cumulative probability of cirrhosis after 17 years was 12.6%. Age at anti-HBe seroconversion and relapse of hepatitis were independent risk factors for cirrhosis. CONCLUSION: The clinical severity of chronic hepatitis B was milder in this cohort than in previous studies. Delayed HBeAg seroconversion and relapse of hepatitis were associated with increased risk of cirrhosis.     

Development of Cirrhosis after Chronic Type B Hepatitis: A Clinicopathologic and Follow-up Study of 46 HBeAg-Positive Asymptomatic Patients

The rate of HBeAg clearance and the outcome were analyzed in 46 patients with asymptomatic chronic hepatitis B virus (HBV) infection whose condition was followed for 1-4 yr (mean 2.4). Mean age was 32.5 yr (range 10-68), and 28 (61%) were males. All had chronic hepatitis, on biopsy, and were positive for HBcAg on hepatocytes. Alcoholics, homosexuals, drug abusers, immunocompromised patients, and those with advanced liver disease were excluded. During the follow-up, 25 patients (54%) cleared HBeAg and became seronegative for HBV-DNAp. The estimated annual rate of seroconversion was 26%. One patient cleared HBsAg. After seroconversion, 18 patients had no evidence of ongoing liver disease, proved by biopsy in eight and by clinical follow-up in 10 that refused biopsy. A second liver biopsy was available in 15 patients, and HBcAg was negative in all; histology was normal in eight, unchanged in one, and compatible with cirrhosis in six. All six had clinical and/or biochemical evidence of advanced liver disease. These were significantly older at the start of the study, and had chronic active hepatitis with bridging necrosis on initial biopsy. Early identification of patients with silent chronic HBV infection and high levels of viral replication for antiviral therapy could prevent transmission of the infection and stop progression to liver cirrhosis and hepatocellular carcinoma.     

Clinical course of inflammatory bowel disease and impact on liver disease outcomes in patients with autoimmune sclerosing cholangitis

Background & AimsAutoimmune sclerosing cholangitis (ASC) is a childhood sclerosing cholangitis frequently associated with inflammatory bowel disease (IBD). We describe the IBD phenotype in ASC patients and associated liver disease outcomes.MethodsSingle center retrospective observational review of ASC patients, with a control population of pediatric IBD. Demographic and clinical parameters were obtained. Clinical endpoints were escalation of IBD therapy (biologic or colectomy) and transplant-free survival.ResultsIn 93 ASC patients (53.8% female) and median follow up of 172 months: 70% had IBD, 25.8% underwent liver transplant. Median age at liver transplant was 21.7 years, at 131 months from ASC diagnosis. There was no association between presence of IBD and transplant-free survival, whilst those requiring second-line immunomodulators for ASC had poorer long-term liver prognosis. During follow-up 22 (33.8%) ASC-IBD required biologic or colectomy. On multivariate analysis ASC was associated with a lower risk of escalation of IBD therapy (HR 0.14, 95% CI 0.05–0.42; P=.001), including biologic therapy (HR 0.21, 95% CI 0.08–0.55, P=.002), but not colectomy on univariate analysis (HR 1.54, 95% CI 0.43–5.44, P=.51).ConclusionsIBD is common in ASC and during longterm follow up a third of ASC-IBD required escalation of IBD therapy; however ASC-IBD was lower risk compared to IBD alone. IBD does not appear to impact on transplant-free survival in patients with ASC, however second-line immunomodulators for ASC are associated with poorer IBD and liver outcomes.     

Natural history of hepatitis B virus infection in children

Hepatitis B virus (HBV) infection during childhood can cause acute, fulminant or chronic hepatitis, liver cirrhosis, and liver cancer. Approximately 90% of the infants of hepatitis B e antigen (HBeAg) seropositive mothers become hepatitis B surface antigen (HBsAg) carriers. Children chronically infected are mostly asymptomatic. Although liver damage is usually mild during childhood, severe liver disease, including cirrhosis and hepatocellular carcinoma, may develop insidiously for 2–7 years. Spontaneous HBeAg seroconversion occurs gradually as the age of the child increases. Viral replication is reduced during this process, which is usually preceded by an elevation of aminotransferases. In a long‐term follow‐up study, the annual HBeAg seroconversion rate was 4–5% in children older than 3 years of age and less than 2% in children under 3 years. The annual seroconversion rate of HBsAg was very low (0.56%). Age at infection, maternal HBsAg and HBeAg status, host immune status, and possibly the HBV strain are the main factors determining the course of HBV infection in children.     

Chronic hepatitis B in children with or without malignancies:A 13-year follow-up

AIM:To evaluate the outcome of chronic hepatitis B(CHB)in children with or without malignancies.METHODS:Twenty four children(15 boys and 9 girls)with malignancies,followed up by the pediatric gastroenterology outpatient clinic for CHB between January 2000 and December 2013,were enrolled in the study(Group 1).Group 2 was formed with twenty five children(11 girls and14 boys)diagnosed with CHB without malignancies.The data from the patients’records were compared between the two groups.RESULTS:Hepatitis B e antigen(HBe Ag)/anti HBe seroconversion was observed in 3 patients(12.5%)in group 1 and 15 patients(60%)in group 2,with annual seroconversion rates of 1.61%and 16.6%,respectively,and the difference was significant(P0.01).One patient(6.6%)in Group 1 and 9 patients(53%)in Group 2 showed HBe Ag/anti HBe seroconversion after treatment and the difference between the two groups was significant(P0.06)Loss of hepatitis B surface antigen was observed in one patient in each of group1 and 2.No clinical,laboratory and imaging findings of liver disease were observed in any of the patients at the end of the study.CONCLUSION:HBe Ag/anti HBe seroconversion rate was lower in patients who had recovered from cancer.     

Long-term follow-up of children and adoles-cents with primary sclerosing cholangitis and autoimmune sclerosing cholangitis

BACKGROUND: Sclerosing cholangitis (SC) is a chronic cho-lestatic hepatobiliary disease with uncertain long-term prog-nosis in pediatric patients. This study aimed to evaluate long-term results in children with SC according to the types of SC.
METHODS: We retrospectively followed up 25 children with SC over a period of 4-17 years (median 12). The diagnosis of SC was based on biochemical, histological and cholangio-graphic ifndings. Patients fuliflling diagnostic criteria for probable or deifnite autoimmune hepatitis at the time of diag-nosis were deifned as having autoimmune sclerosing cholangi-tis (ASC); other patients were included in a group of primary sclerosing cholangitis (PSC). The incidence of the following complications was studied: obstructive cholangitis, portal hy-pertension, advanced liver disease and death associated with the primary disease.
RESULTS: Fourteen (56%) patients had PSC and 11 (44%) had ASC. Patients with ASC were signiifcantly younger at the time of diagnosis (12.3 vs 15.4 years,P=0.032) and had higher IgG levels (22.7 vs 17.2 g/L,P=0.003). The mentioned compli-cations occurred in 4 (16%) patients with SC, exclusively in the PSC group: one patient died from colorectal cancer, one patient underwent liver transplantation and two patients, in whom severe bile duct stenosis was present at diagnosis, were endoscopically treated for acute cholangitis. Furthermore, two other children with ASC and 2 children with PSC had elevated aminotransferase levels. The 10-year overall survival was 95.8% in all patients, 100% in patients without complicated liver disease, and 75.0% in patients with complications.
CONCLUSION: In children, ASC is a frequent type of SC, whose prognosis may be better than that in patients with PSC.     

拉米夫定治疗慢性乙型肝炎的临床观察及病理学研究

目的观察拉米夫定治疗慢性乙型肝炎患者的临床疗效、肝组织学改变及肝组织内乙型肝炎病毒(HBV)标志物的变化。方法随机选择70例慢性乙型肝炎患者予口服拉米夫定100mg／d，连用1年。观察HBVDNA、血清HBeAg／抗-HBe、肝功能以及血清肝纤维化指标的变化；对其中35例患者行治疗前后肝穿刺活检，行Knodell病理学评分，检测肝细胞内HBsAg、HBcAg、α平滑肌肌动蛋白(α-SMA)。结果治疗结束时，完全应答率为23．73％，部分应答率为69．49％，无应答率为6．78％。发生HBeAg血清学转换的患者治疗前血清ALT水平明显高于未发生血清HBeAg转换的患者。41．18％患者肝组织学活动指数得以改善，汇管区坏死、门静脉炎症及纤维化明显改善。血清HBeAg转换组肝组织内HBcAg、α-SMA的表达明显减少．HBsAg的表达无显著性改变。治疗期间不良反应轻，安全性良好。结论拉米夫定100mg／d可以迅速降低血清HBvDNA和ALT的水平，促进HBeAg血清转换，减轻肝脏炎症坏死活动度，延缓肝纤维化的进展。     

Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy

A study in Chinese patients with chronic hepatitis B showed that treatment with lamivudine for 1 year significantly improves liver histology and enhances hepatitis B e antigen (HBeAg) seroconversion compared with placebo. Fifty-eight patients from this 1-year study have received long-term treatment with lamivudine 100 mg; the outcome of 3 years of lamivudine is reported here. Before treatment, all patients had detectable HBeAg. HBeAg seroconversion (HBeAg-negative, anti-HBe-positive), hepatitis B virus (HBV)-DNA suppression, alanine transaminase (ALT) normalization, emergence of YMDD variant HBV, liver histology, and long-term safety were assessed. After 3 years of continuous treatment with lamivudine 100 mg daily, 40% (23 of 58) of patients achieved HBeAg seroconversion. In patients with baseline serum ALT >2 x upper limit of normal (ULN), the rate of HBeAg seroconversion was 65% (17 of 26). Median serum HBV-DNA concentrations were below the level of detection, and median ALT concentrations were within the normal range throughout 3 years of treatment. YMDD variant HBV emerged in 33 of 58 (57%) patients during the 3 years, of whom 9 (27%) achieved HBeAg seroconversion (6 after emergence of YMDD variant HBV). ALT levels and histologic scores after emergence of YMDD variant HBV did not show major deterioration. Lamivudine was well tolerated during 3 years of therapy. In conclusion, these data in Chinese patients with chronic hepatitis B show enhanced seroconversion rates with extended lamivudine treatment. Up to two thirds of patients with moderately elevated pretreatment ALT achieved HBeAg seroconversion after 3 years of therapy.