慢性病毒性肝炎的多重感染

了解慢性病毒性肝炎多重感染,有助于临床诊断及治疗。采用ELISA和连续监测法对43例慢性病毒性肝炎多重感染及76例乙型肝炎单纯感染患者血清进行HBVM以及肝功能指标检测。慢性病毒性肝炎多重感染的检出率为2.1%,与其他病毒性肝炎相比,差异有显著性(x2=5.0,P<0.05),说明慢性病毒性肝炎患者多重感染者较多。多重感染与单纯感染相比,患者年龄高(t=3.119,P<0.01),住院时间长(t=3.780,P<0.01),临床症状和肝功能损害重,疗效差(x2=12.98,P<0.01),说明慢性病毒性肝炎多重感染会加重病情。     

复方甘草酸单胺应用于慢性乙型肝炎患者抗结核治疗中的临床观察

目的观察复方甘草酸单胺（美能）在慢性乙型肝炎患者抗结核治疗中的临床疗效与不良反应。方法将60例活动性肺结核并存慢性乙型肝炎患者随机分为治疗组与对照组各30例，两组均投予有效抗结核治疗，治疗组加用美能；对照组不给予任何保肝药。结果治疗8周时，治疗组肝功能损害发生率为13．3％，对照组为40．0％，两者比较有显著差异（P〈0．05）。结论美能在活动性肺结核并存慢性乙型肝炎患者抗结核治疗过程中能有效防治抗结核药物引起的肝功能损害。     

短程化疗中乙肝病毒标志物阳性对肝功能影响及处理

目的探讨抗结核治疗中乙肝病毒感染对肝功能的影响及其对策。方法回顾性分析818例肺结核病人及其中150例药物性肝损害的相关临床资料。结果160例乙型肝炎病毒标志物（HBVM）阳性结核病人中有77例（48．1％）出现肝功能损害。HBVM阴性患者658例中出现肝损害73例（11．1％）,HBVM阳性与阴性的肝损害发生率差异极显著（P〈0．01）。结论抗结核治疗中HBVM阳性患者发生肝损比率明显增加,损害程度也明显增高,在抗结核治疗前检查HBVM及肝功能十分必要,之后密切监测肝功能的变化。     

雌激素受体基因α多态性与乙型肝炎病毒感染慢性化的相关性研究

目的 了解雌激素受体α基因XbaI和PvuII多态性与乙型肝炎病毒感染慢性化的关系,从基因水平上探讨慢性乙型肝炎的发病机制。方法 采用聚合酶链反应-限制性片段长度多态性法检测93例乙型肝炎病毒感染恢复期患者和169例慢性乙型肝炎患者雌激素α受体基因PvuII和XbaI多态性。结果 慢性乙型肝炎患者雌激素受体基因PvuII多态性的C／T基因型和c等位基因频率（52．7％,44．1％）明显高于乙型肝炎病毒感染恢复期患者（37．6％,29．6％）;TT基因型和T等位基因频率（29．5％,55．9％）明显低于后者（47．3％,70．4％）,差异有统计学意义（P〈0．05）;CT＋CC基因型乙型肝炎病毒感染慢性化的风险是TT基因型的2．54倍（OR=2．539,CI：1．50～4．29）。雌激素受体基因XbaI多态性分布在慢性乙型肝炎患者和乙型肝炎病毒感染恢复期患者间比较,差异均无统计学意义（P〉0．05）。结论 雌激素受体基因PvuII C/T基因型和C等位基因可能是乙型肝炎病毒感染慢性化的遗传易感基因。     

降酶口服液对慢性乙型肝炎的治疗作用

目的：观察降酶口服液对慢性乙型肝炎的治疗作用，并探究其作用机制。方法：慢性乙型肝炎264例，随机分为两组，治疗组（184例）和对照组（80例）患者分别给予降酶口服液和护肝胶囊治疗2个月，观察治疗前后两组患者的肝功能（ALT、AST、TBil、PT、A／G）及肝脏病理组织学改变。结果：临床总有效率治疗组为89．1％，对照组为78．8％，两组比较差异有显著性意义（P〈0．05）。治疗后治疗组患者肝功能明显改善，19例患者行肝活检证实肝脏炎症活动度明显减轻，肝纤维化也有一定程度改善。结论：降酶口服液对慢性乙型肝炎有较好的临床疗效。     

戊型肝炎与慢性乙型肝炎重叠戊型肝炎病毒感染的临床特征比较

目的分析比较戊型肝炎与慢性乙型肝炎重叠戊型肝炎病毒感染患者的临床特征,并初步探索戊型肝炎慢性化问题。方法对66例戊型肝炎与37例慢性乙型肝炎重叠戊型肝炎病毒感染患者的临床资料进行回顾性分析比较及统计。结果慢性乙型肝炎重叠戊型肝炎病毒感染患者较戊型肝炎患者丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)升高水平及发生率无显著差异,而在白蛋白(A)、白蛋白/球蛋白(A/G)及凝血酶原活动度(PTA)降低与肝纤维化系列各项指标增高方面更突出,消化道症状更重。结论慢性乙型肝炎重叠戊型肝炎病毒感染后肝功能损害更严重,凝血酶原时间长,慢性肝病特征常见,但单纯戊型肝炎患者慢性化问题也值得重视。     

乙型,丁型病毒性肝炎重叠感染的临床分析

本文试图通过乙、丁型病毒性肝炎重叠感染的临床肝功能损害情况和肝纤维化程度,与单纯乙型病毒性肝炎进行比较,以了解丁型肝炎病毒对肝病的影响。（一）材料和方法１．观察对象：①观察组：病例系我院１９９７年３月至１９９８年３月住院的乙、丁型病毒性肝炎重叠感染患者,共９４例。男７６例（８０．８５％）,女１８例（１９．１５％）,年龄２０～７７岁,平均４６岁。诊断分型根据１９９５年第五届全国传染病寄生虫病学术会议修订标准,其中慢性肝炎４４例（４６．８１％）,活动性肝硬化４１例（４３．６２％）,慢性重型肝炎９例（…     

肝宝对脂肪性肝炎和慢性乙型肝炎合并脂肪性肝炎的治疗作用

目的：观察肝宝对脂肪性肝炎和慢性乙型肝炎合并脂肪肝炎的临床疗效。方法：观察56例脂肪性肝炎和53例慢性乙型肝炎（慢乙肝）合并脂肪性肝炎患者主要临床症状，体征，肝功能与血脂水平，及肝胆B超影像等出现的异常率；同时评价肝宝的临床疗效。结果：（1）肝宝对脂生肝炎和病原学小三阳（25例）与大三阳（28例）的慢乙肝合并脂肪性肝炎患者的乏力、纳差、肝区痛有明显改善作用；（2）肝宝对3组患者肿大之肝、脾均有不同程度的复常作用；（3）肝宝能显著降低所有患者的ALT，AST，TCh(总胆固醇），和TG（甘油三酯）水平，有效率以脂肪性肝炎为高，（4）有82．14％－98．21％的患者脂肪浸润消失或减退，及37．93－48．15％的虱胆囊壁由毛糙恢复到稍毛糙或光滑，结论：肝宝对脂肪性肝炎和慢性乙型肝炎合并脂肪性肝炎患者症状体征，肝功能，血脂及B超检测结果的改善均有较好的疗效。     

病毒性肝炎与糖尿病关系的临床研究

目的探讨病毒性肝炎与糖尿病发病的关系。方法对84例慢性乙型肝炎与83例慢性丙型肝炎患者,76例同期住院患者（对照组）进行病例分析研究,明确其是否合并糖尿病。结果慢性乙型肝炎患者糖尿病并发率为5．9％,慢性丙型肝炎患者糖尿病并发率为13．3％,对照组患者糖尿病并发率为7．9％,慢性丙型肝炎组糖尿病的并发率明显高于慢性乙型肝炎组和对照组患者（P〈0．05）,慢性乙型肝炎组和对照组患者糖尿病并发率差异无统计学意义（P〉0．05）。慢性肝炎合并糖尿病男女比例为2．2：1。三组中合并糖尿病与未合并糖尿病的患者均为中老年人,在年龄、体质量指数、空腹血糖方面差异无统计学意义。合并糖尿病的慢性乙型肝炎和慢性丙型肝炎患者血清丙氨酸氨基转移酶、门冬氨酸氨基转移酶及总胆红素水平高于未合并糖尿病者（P〈0．05）。结论慢性丙型肝炎病毒感染易合并糖尿病,丙型肝炎病毒感染可能是糖尿病的发病因素之一。     

慢性乙型肝炎重叠HCV,HDV感染80例分析

近几年来，由于免疫学和分子生物学技术的进展，病毒性肝炎病原学诊断逐步得以明确，临床上诊断肝炎病毒混合感染和重叠感染的报道增加．为探讨本地区慢性乙型肝炎重叠丙型肝炎病毒（ＨＣＶ）、丁型肝炎病毒（ＨＤＶ）感染的情况及其临床特点，笔者对我院１９９５０１／１９９８１２所收治的１４５１例各型肝炎中的２４６例慢性肝炎患者的血清标志物检测结果进行分析，其中对８０例慢性乙型肝炎重叠ＨＣＶ，ＨＤＶ感染的患者进行系统的临床观察，并与单纯慢性乙型肝炎８０例进行对比，现将结果报道如下．１　材料和方法１．１　材料　本…     

Coinfection with hepatitis B and C or B, C and δ viruses results in severe chronic liver disease and responds poorly to terferon-a treatment

SUMMARY. Chronic coinfection with the hepatitis B (HBV) and hepatitis δ (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon-α2b (IFN-α) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied: 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN-α2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and δ coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone. Short-and long-term responses to doses of IFN-α that are used to treat HCV are infrequent, but further studies are required to determine whether higher-dose IFN-α may benefit patients with combined hepatitis virus infections.     

Hepatitis B virus/hepatitis C virus coinfection: epidemiology, clinical features, viral interactions and treatment

Because of the shared modes of transmission, hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection is not uncommon in highly endemic areas and among subjects with a high risk of parenteral infections. The worldwide prevalence of HBV/HCV coinfection is unknown and might be underestimated with the phenomenon of silent (occult) HBV infection. HCV superinfection in patients with chronic HBV infection was the most common clinical features of coinfection in Asia-Pacific countries. Further, most, but not all, clinical observations suggested that interference between the two viruses was more frequently characterized by an inhibition of HBV replication exerted by HCV. However, longitudinal follow-up studies have demonstrated that the virological patterns in coinfection cases are widely divergent and have dynamic profiles over time. As compared with monoinfected patients, HBV/HCV coinfected persons tend to have more severe liver injury, a higher probability of liver cirrhosis and hepatic decompensation, and a higher incidence of hepatocellular carcinoma. Detailed serological and virological evaluations are required for coinfected patients before initiation of antiviral therapy. Previous studies demonstrated that HBV/HCV coinfected patients responded poorly to interferon (IFN) monotherapy. Currently, for patients with dominant HCV infection and low level HBV viremia (<10(4) IU/mL), IFN or pegylated IFN plus ribavirin can achieve comparable sustained virus response as expected with HCV monoinfection. However, phenomenon of reciprocal viral interference can happen, and resultant "flare" of hepatitis activity may cause liver function deterioration. For coinfected patients with dually-active HBV/HCV, the optimal regimen for therapy remains unclear although adding oral nucleos(t)ide analogs to pegylated IFN and ribavirin seems a reasonable empiric option.     

The significance of antibody to hepatitis C virus in patients with chronic hepatitis B.

We assessed the prevalence and clinical significance of antibodies to hepatitis C virus among a cohort of 148 patients with chronic hepatitis B virus infection. Sixteen patients (11%) had anti-hepatitis C virus detectable by enzyme-linked immunoassay. The results from eight of these patients were positive by recombinant immunoblot assay. The results of recombinant immunoblot assay testing were not consistent; therefore the analysis of the patients' data was based on anti-hepatitis C virus enzyme-linked immunoassay results. Patients with chronic hepatitis B with anti-hepatitis C virus were more likely to be cirrhotic (44% vs. 21%) and to have decompensated liver disease (24% vs. 6%). Hepatitis B virus replication appeared to be suppressed in patients with both infections as measured by hepatitis B virus-associated DNA polymerase activity (mean = 2,055 vs. 2,555 cpm). Human immunodeficiency virus infection was more common in the anti-hepatitis C virus positive group (36% vs. 11%). Thus hepatitis C virus appears to suppress hepatitis B virus replication and to cause more severe liver disease in patients with chronic hepatitis B infection.     

Vaccination against hepatitis b in patients with chronic liver disease

The prevalence of chronic liver disease is increasing, while at the same time, many at-risk populations are witnessing a resurgence of hepatitis B virus (HBV) infection. Thus, more patients are likely to have multiple causes of liver disease, as risk factors often overlap. Such patients may develop either acute viral hepatitis superimposed on pre-existing chronic liver disease or chronic infection with two hepatitis viruses. Patients with chronic HBV and hepatitis C virus coinfection have more severe laboratory abnormalities, more hepatic fibrosis, and greater frequency of cirrhosis, in addition to more complications of cirrhosis and a higher incidence of hepatocellular carcinoma. Acute hepatitis B superimposed on chronic hepatitis C may result in fulminant hepatitis, although this outcome is not as well proven as the increased morbidity of chronic hepatitis B and C coinfection. Both acute and chronic coinfection with HBV can be prevented. Vaccines for hepatitis B are safe in patients with chronic liver disease of a variety of causes and are effective, particularly if used early. Early vaccination against hepatitis B, as well as hepatitis A, should be part of the routine management of chronic liver disease.     

Delta hepatitis in the Los Angeles area: a report of 126 cases

We describe the clinical course in 126 patients with delta hepatitis who have been evaluated in Los Angeles since 1967. In approximately two thirds of all patients, delta infection was associated with chronic hepatitis B. Most patients were members of two major risk groups: 65.9% were intravenous drug abusers, 11.9% were male homosexuals, and another 9.5% were both intravenous drug users and male homosexuals. The overall case fatality rate was 23%; fulminant hepatitis caused 17 of 29 (59%) deaths. Advanced liver disease occurred significantly more frequently in patients who had established chronic delta infections than in hepatitis B virus carriers with recent delta superinfections. Nonfatal infections with both hepatitis B virus and delta hepatitis virus resulted in clearance of both agents, whereas superinfection in carriers of chronic hepatitis B virus usually led to chronic delta hepatitis. Spontaneous loss of chronic delta infection was not observed. Delta hepatitis, a longstanding infection seen in patients in the Los Angeles area, has caused fulminant hepatitis and progressive liver disease in both intravenous drug users and male homosexuals.     

Hepatitis viruses (other than hepatitis B and C viruses) as causes of hepatocellular carcinoma: an update

Chronic hepatitis B and C virus infections are universally accepted as causes of hepatocellular carcinoma in humans. Hepatitis A and E viruses cause only acute self‐limiting infections of the liver. Of the remaining hepatitis viruses ‐ Delta hepatitis, hepatitis G (GB‐C), TT and SEN ‐ all have at some time been incriminated as causes of hepatocellular carcinoma. Delta hepatitis virus requires helper functions from hepatitis B virus to become invasive. Chronic Delta/hepatitis B viral co‐infection runs a more severe course than that resulting from chronic hepatitis B virus infection alone, with progression to cirrhosis being more likely and more rapid. A substantial majority of the early studies did not find an increased incidence of hepatocellular carcinoma in co‐infected individuals. But more recently, an increased incidence of the tumour has been recorded more often than no increase. Further studies are needed to draw a firm conclusion with regard to the hepatocarcinogenic effect of dual Delta/hepatitis B virus co‐infection. With one exception, no published study (of 13) has incriminated chronic infection with hepatitis G virus as a cause of hepatocellular carcinoma. The dissenting study, published in 1999, was the only one performed in the United States. Fewer studies of the hepatocarcinogenic effect of TT virus have been performed. Apart from one study, published in 1999, no convincing evidence is available that supports a causal role for TT virus in hepatocarcinogenesis. The exception was in Japanese patients with high hepatitis C viral loads but independent of chronic hepatitis C virus infection. No evidence has been produced to indicate that SEN virus causes hepatocellular carcinoma.     

Does co‐infection with multiple viruses adversely influence the course and outcome of sporadic acute viral hepatitis in children?

BACKGROUND: This study looked at the frequency of co-infection with multiple hepatotropic viruses and the effect of such infection on the course and outcome of acute sporadic viral hepatitis (AVH) and fulminant hepatic failure (FHF) in children. METHODS: Consecutive children up to 15 years of age presenting with AVH or FHF between January 1998 and July 2002 were evaluated prospectively. The following viral markers were assessed in all children: immunoglobulin M (IgM) anti-hepatitis A virus (HAV), IgM anti-hepatitis E virus (HEV), hepatitis B surface antigen (HBsAg), IgM anti-hepatitis B core (HBc), and anti-hepatitis C virus (HCV). RESULTS: A total of 149 children were included in the study, 122 with AVH and 27 with FHF. Co-infection with multiple viruses was detected in 30 (24.6%) AVH patients (A+E in 24, A+B in three, and E+B, A+C and A+E+B in one each) and seven (26%) FHF patients (A+E in five, and A+B and E+B in one each). The majority of single infections were due to HAV (AVH 70/92, FHF 14/20) followed by HEV (AVH 9/92, and FHF 5/20). HEV infection was associated with infection with another agent in 88% of patients with AVH (odds ratio 53, 95% confidence interval 15-186, P<0.0001). Frequency of anicteric state, prolonged cholestasis, relapsing hepatitis, ascites, hemolysis and mortality rates were similar in the single and multiple infection groups for both AVH and FHF patients. CONCLUSIONS: Co-infection with multiple viruses is observed in one-quarter of patients with sporadic AVH in childhood. Such infection does not produce a more severe disease. HEV positivity is a strong marker for multiple infections.     

Importance of age in chronic hepatitis C virus infection

This study was designed to investigate the value of liver biopsy in the management of patients with chronic hepatitis C virus infection and to identify risk factors for fibrosis. It was a prospective audit of clinical, biochemical, virological and radiological features for predicting liver fibrosis in 140 consecutive patients seropositive for antibody against hepatitis C virus. Seventy-five per cent of patients were asymptomatic and 69% had no clinical signs of chronic liver disease. Serum transaminase levels were normal in 44% of patients, less than twice normal in 35% and more than twice normal in 21%. Ultrasound scan was unremarkable in 85%. Sixty-nine per cent of patients were viraemic at the time of liver biopsy. Liver histology revealed that fibrosis was absent in only 10% of patients (stage 0) while cirrhosis was evident in 7% (stage 5). Liver fibrosis was detected in 90% of patients (stage 1, 11%; stage 2, 41%; stage 3, 21%; and stage 4, 10%). Univariate analysis showed that increasing age, clinical signs of chronic liver disease and abnormal ultrasound scan findings were associated with liver fibrosis ( P <0.05); however, multiple linear regression analysis of all the clinical features did not reveal a useful model (sensitivity 42% and specificity 23%) for predicting liver fibrosis. Hence, no combination of clinical, biochemical, virological or radiological data was reliable in discriminating the stage of liver fibrosis in patients with chronic hepatitis C virus infection. However, older patients, especially those with clinical signs of chronic liver disease and abnormal ultrasound scan findings, were more likely to have advanced fibrosis. We recommend liver biopsy as the single most important investigation in detecting liver fibrosis.     

Hepatitis B virus and hepatitis C virus co-infection: additive players in chronic liver disease?

Hepatitis B virus (HBV) and hepatitis C virus (HCV) share modes of transmission and their combined infection is a fairly frequent occurrence particularly in areas where the two viruses are endemic and among subjects with a high risk of parenteral infections. Moreover, the number of coinfected patients is likely higher than is usually thought. In fact, many studies have shown that HBV genomes may also be present in HBsAg-negative patients, particularly in those with HCV-related chronic hepatitis. This condition is commonly called "occult HBV infection". Much evidence suggests that coinfection by HBV and HCV may have considerable clinical relevance. In particular, this condition is generally believed to be a factor favouring the progression of liver fibrosis toward cirrhosis and the development of liver cancer, and in case of both overt and occult HBV infection. In spite of its potential clinical impact, however, there is few information about the possible interplay between the two viruses. Here, we concisely reviewed the available data on the virological and clinical features of the dual HBV/HCV infection prospecting the aspects that should be highlighted in the nearest future for improving the knowledge on this important field of the hepatology.     

Proliferating cell nuclear antigen assessed by a computer-assisted image analysis system in patients with chronic viral hepatitis and cirrhosis

BACKGROUND: Assessment of liver cell proliferation by immunodetection of proliferating cell nuclear antigen may predict regenerative potential and survival of liver and hepatocellular carcinoma risk in patients with chronic viral hepatitis. AIM: To evaluate proliferating cell nuclear antigen status and its clinical significance in a large cohort of patients with chronic viral hepatitis and different degree of liver damage by a computer assisted imaging analysis system. MATERIALS: Liver biopsies from 358 patients with chronic hepatitis (259 males, 49 years, 63% with hepatitis C infection, 27% with hepatitis B virus, 10% with multiple infections) were studied. METHODS: Proliferating cell nuclear antigen was localised by immunoperoxidase on microwave oven pre-treated formalin-fixed, paraffin embedded sections using PC10 monoclonal antibody. Proliferating cell nuclear antigen labelling index was calculated by an automated imaging system (Immagini e Computers, Milan, Italy). RESULTS: Mean proliferating cell nuclear antigen labelling index ranged from 0.1% for patients with minimal changes to 3.6% for those with cirrhosis and hepatocellular carcinoma. Overall, proliferating cell nuclear antigen labelling index was higher in males, in older patients, in multiple infections and in hepatitis C virus compared to hepatitis B virus related cases. By linear regression analysis, proliferating cell nuclear antigen labelling index correlated with older age, male gender; higher transaminase levels, hepatitis C virus, higher histological gradIng and staging: by multivariate analysis male gender, hepatitis C virus, higher grading and staging resulted as independent variables. Both hepatitis C virus or hepatitis B virus cirrhotics had similar liver cell proliferation rate but those with hepatitis B virus had higher prevalence of liver cell dysplasia with respect to those with hepatitis C virus. CONCLUSIONS: Proliferating cell nuclear antigen labelling index was a reliable assay for assessing liver cell proliferation rate in patients with chronic viral hepatitis and correlated with liver disease severity