Viral hepatitis in elderly haemodialysis patients: current prevention and management strategies

Viral hepatitis continues to be a relevant topic for haemodialysis centres, although the number of infected dialysis patients is declining in most countries. Chronic hepatitis B and C lead to detrimental complications such as liver cirrhosis and hepatocellular carcinoma. These complications can be avoided by successful antiviral treatment. In individuals with normal renal function, drug therapy of chronic hepatitis B is evolving quickly. Today there are several options but no agreed standard therapy. In the absence of renal failure, chronic hepatitis C should be treated with a combination of pegylated interferon-alpha and ribavirin. For both infections, there is no general indication to treat all patients; several criteria can be used to predict benefits and downsides.Chronic renal failure severely alters immune function, particularly activation of T lymphocytes and cytokine production by mononuclear cells. Aging further influences the immune system with deviation of T-lymphocyte differentiation. Both effects seem to act additively, leaving the elderly haemodialysis patient with extensive immune dysfunction. While these effects do not put the patient at risk of opportunistic infection, they do have a relevant effect on the clinical course of viral hepatitis.Haemodialysis patients infected with hepatitis B manifest a subclinical, often anicteric disease, and at least 60% of the infections become chronic. These patients usually do not fulfil the criteria for successful antiviral treatment, since they have normal or slightly elevated liver enzyme levels and few histological signs of liver inflammation. In addition, the prognosis in terms of cirrhosis and hepatocellular carcinoma might be more favourable than in individuals with normal renal function. The former standard treatment of chronic hepatitis B with interferon-alpha or its derivate pegylated interferon was badly tolerated in dialysis patients and associated with low efficacy. Indeed, prior to the advent of nucleoside analogues there was a clear recommendation not to treat chronic hepatitis B infection in all except a few dialysis patients. However, the newer treatment options appear to work well. In particular, there is growing evidence for the effectiveness and tolerability of lamivudine in dialysis patients, including the elderly. Use of adefovir and entecavir has also been reported in a few cases. At present, while we still do not recommend treatment, therapy with nucleoside analogues might be an option in selected patients, for example, those planning renal transplantation. The major effort against hepatitis B should be directed at vaccination and hygienic precautions to prevent the infection.Treatment of hepatitis C in patients undergoing haemodialysis is also limited by the poor tolerability of interferons. Ribavirin is contraindicated because of severe haemolytic anaemia, although a few studies have attempted to manage this with administration of high doses of erythropoetin. Those patients who complete the full course of interferon therapy may expect sustained viral responses comparable with healthy individuals, but in most trials, 30-50% of patients were forced to interrupt treatment because of adverse effects. There is no general indication to treat chronic hepatitis C in haemodialysis patients. Arguments in favour of treatment include elevated liver enzymes, histological signs of relevant liver inflammation, younger age, a virus genotype other than 1 and planned renal transplantation.     

重型肝炎患者血糖、甲胎蛋白和胆碱脂酶检测的临床意义

目的探讨血糖、甲胎蛋白和胆碱脂酶水平对重型肝炎的诊断以及预后判断价值。方法回顾性分析慢性乙型肝炎、肝硬化失代偿、慢性重型肝炎、亚急性重型肝炎患者之间,以及重型肝炎好转组与死亡组之间血糖、甲胎蛋白、胆碱脂酶的差异。结果亚急性重型肝炎、慢性重型肝炎患者血糖和胆碱脂酶水平明显低于慢性乙型肝炎及肝硬化患者（均P〈0．05）;而甲胎蛋白水平显著高于慢性乙型肝炎（P〈0．01）;重型肝炎好转组血糖、甲胎蛋白、胆碱脂酶水平明显高于死亡组（均P〈0．05）。结论血糖、甲胎蛋白、胆碱脂酶检测对肝脏疾病的进展程度及预后估计有重要判断价值。     

早期重症乙型肝炎和肝硬化凝血酶原活动度改变意义

目的 探讨早期重症乙型肝炎和肝硬化患者病情和凝血酶原活动度(PTA)改变之间的关系.方法 采用单纯随机抽样方法,对2010年1月至2010年12月本院肝病科部分住院重症乙型肝炎和肝硬化病人的PTA做了回顾性分析.结果 一般急性肝炎组的PTA(％)比早期重症乙型肝炎组、肝硬化组较高(P＜0.01):早期重症乙型肝炎组的P...     

Acute type B viral hepatitis due to accidental transfusion of blood containing HBs Ag in a patient with liver cirrhosis

Patients with liver cirrhosis have the opportunity of receiving blood transfusions rather frequently. Accidental transfusion of blood containing HBs Ag occurred in such a case. Recently, we encountered a case of hepatocellular carcinoma based on posthepatitic cirrhosis in which an emergency blood transfusion because of massive hematemesis from a gastric ulcer was followed by acute B type viral hepatitis. The remainder of the transfused blood was preserved an we tested it serologically when the symptoms of acute viral hepatitis were manifested. We are able to detect hepatitis B surface antigen in the serum. In this patient, the preceding liver cirrhosis did not influence on the clinical course of acute B type viral hepatitis and conversely, the acute B type viral hepatitis did not have any influence on the subsequent clinical course of the liver cirrhosis.     

Treatment of chronic hepatitis B: from research to clinical practice via the consensus conferences

The aim of antiviral therapy of chronic hepatitis B is to control Hepatitis B Virus (HBV) replication and to cure liver disease avoiding the progression of chronic hepatitis to cirrhosis and the end stage complications of cirrhosis. HBeAg/anti-HBe seroconversion is the hallmark of response in hepatitis B "e" antigen (HBeAg) positive patients. In the patients with antibody against HBeAg (anti-HBe positive) the combination of HBV DNA and anti-HBc IgM tests provides adequate diagnostic accuracy. Patients with biochemical and/or histological disease activity are eligible to therapy. The drug choice is based on age, disease severity, risk of complications, side effects and compliance, particularly in anti-HBe positive patients where prolonged treatment is needed. Interferon (5-6 MU daily or 9-10 MU thrice weekly for 4-6 months) is the first line therapy for HBeAg positive patients and (5-6 MU thrice weekly for 12-24 months) for anti-HBe positive patients. When IFN is contraindicated or ineffective, Lamivudine (100 mg) or Adefovir Dipivoxil (10 mg) are given as long as 4-6 months after HBeAg/anti-HBe seroconversion or for long-term treatments in HBeAg positive non-responders and anti-HBe positive patients. Patients with more advanced forms of cirrhosis and portal hypertension are to be treated within liver transplantation programs. Fifteen to 30% of treated patients achieve sustained response and more than 60% of them experience long-term disease remission during therapy. In perspectives, currently available molecular and immunologic tools and modelling of viral dynamics will help to address the therapy issue with more complex, efficacious and individually tailored treatment schedules.     

慢性重型病毒性肝炎病理观察

目的 观察慢性重型病毒性肝炎病程中肝组织学的变化。方法 202例慢性重型病毒性肝炎患在不同病期进行肝穿刺作肝脏病理检查。结果 早、中期肝组织学主要表现为在慢性肝炎和小结节性肝硬变基础上出现大块或亚大块坏死;恢复期肝脏以大小结节混合型肝硬变为主,少数为重度慢性肝炎的病理表现;晚期和死亡肝组织结构严重破坏,肝细胞数量明显减少。结论 慢性重型病毒肝炎不同病期的组织学各有一定特点。病程中多次肝穿刺对该病病理诊断及预后判断有一定意义。     

重型乙型肝炎血清铁蛋白水平分析

目的探讨重型乙型肝淼患者血清铁虿自（SF）水平与肝脏损害程度的关系,以及sF水平变化在判断预后等方面的临床意义。方法应用放射免疫法（mA）检测62例重型乙型肝炎患者sF,并与急、慢性乙型肝炎患者乙型肝炎肝硬化患者健康人sF水平进行对比研究。结果重型乙型肝炎患者sF显著高于急、慢性乙型肝炎乙型肝炎肝硬化患者及健康人sF。重型乙型肝炎患者sF水平与T—Bil、PT、TBA呈显著正相关,与A1b、ALT、AST、CHE呈显著负相关。重型乙型肝炎死亡患者sF水平显著高于存活者;存活者,随着病情逐渐好转,sF逐渐下降;死亡者随着病情逐渐恶化,sF逐渐升高。结论重型乙型肝炎患者sF水平与肝损害程度呈平行关系,肝细胞损害程度越严重,sF升高越明显;动态测定sF水平有助于判断重型乙型肝炎患者肝脏损害程度和预后。     

Management of alcoholic hepatitis

About 5,000 people die each year from chronic liver disease in England and Wales alone. In many patients, the liver injury is due to chronic excessive alcohol consumption and manifests as alcoholic hepatitis (an acute inflammation of the liver), cirrhosis, or alcoholic hepatitis superimposed on a background of cirrhosis. Mild alcoholic hepatitis may be asymptomatic and reversible, but where the hepatitis is more severe, up to 65% of those affected die from it. The incidence of alcoholic hepatitis in the UK seems set to increase with the rise in heavy drinking, particularly among women. Here we review how patients with alcoholic hepatitis should be managed.     

江苏地区HBV病毒基因分型及其临床意义

目的 探讨江苏地区HBV基因分型特点及临床意义.方法 对175例乙型肝炎(乙肝)患者血清进行基因分型.结果 江苏地区乙肝患者基因型以B型和 C型为主,分别为29.7%和65.1%.急性肝炎(AH),慢性肝炎(CH),活动性肝硬化(LC),重症肝炎(SH)和原发性肝癌(PHC)组的基因型构成比差别有统计学意义(P＜0.05).C型中LC所占的百分比显著高于B型(P＜0.01),而在CH组中B型所占的百分比显著高于 C型.基因C型患者HBeAg阳性率显著高于B型患者.结论 江苏地区HBV基因型以C型和B型为主,HBV基因B型常见于轻型肝病,C型和肝脏病情加重有一定关系.     

Lamivudine monotherapy in HBeAg-negative chronic hepatitis B: prediction of response-breakthrough and long-term clinical outcome

BACKGROUND: Factors that predict response and breakthrough phenomenon to lamivudine monotherapy in patients with HBeAg-negative chronic hepatitis B have not been well defined. AIM: To determine pre-treatment and on treatment variables that predict initial response and breakthrough in patients with HBeAg-negative chronic hepatitis B receiving long-term lamivudine. METHODS: Seventy-nine patients, with chronic HBeAg-negative hepatitis B, who received lamivudine for a median of 31 months were included in the study. RESULTS: Initial virologic and biochemical response was observed in 73 (92%) and 70 (89%) patients, respectively, while 34 (47%) and 15 (21%) patients developed virological and biochemical breakthrough, respectively. High levels of necroinflammation in liver biopsy were associated with a higher probability of initial virological and biochemical response. Patients with pre-treatment serum hepatitis B virus DNA concentrations of more than 10(6) copies/mL were three times more likely to develop virologic breakthrough. Two patients died, one with baseline cirrhosis because of liver failure during biochemical breakthrough while the second death was liver and treatment unrelated. CONCLUSIONS: In HBeAg-negative chronic hepatitis B, initial response to lamivudine therapy is associated with necroinflammation, while baseline serum hepatitis B virus DNA exceeding 10(6) copies/mL is a strong predictor for breakthrough because of drug-resistant mutations. Severe complications are uncommon and are associated with biochemical breakthrough and pre-existing cirrhosis.     

Metabolic syndrome is associated with severe fibrosis in chronic viral hepatitis and non-alcoholic steatohepatitis

Background The prevalence of metabolic syndrome and its possible impact on the severity of liver histological lesions have not been studied prospectively in chronic liver diseases. Aim To investigate the prevalence of metabolic syndrome in patients with chronic viral hepatitis or non‐alcoholic steatohepatitis, and to determine its associations with histological severity. Methods We prospectively included 317 patients (hepatitis B e antigen‐negative chronic hepatitis B: 95, chronic hepatitis C: 176, non‐alcoholic steatohepatitis: 46) with liver biopsy. Metabolic syndrome was defined using the Adult Treatment Panel III criteria. Histological lesions were evaluated according to Ishak’s or Brunt’s classification. Results Metabolic syndrome was present in 10.4% of patients being significantly more prevalent in non‐alcoholic steatohepatitis than in chronic viral hepatitis (41.3% vs. 5.1%, P < 0.001). In chronic viral hepatitis, cirrhosis (stages 5–6) was independently associated with increasing age, higher aspartate aminotransferase and gamma‐glutamyl‐transpeptidase levels, severe necroinflammation and metabolic syndrome (P = 0.016). In non‐alcoholic steatohepatitis, severe fibrosis (stages 3–4) was independently associated with severe necroinflammation and metabolic syndrome (P = 0.033). Presence of metabolic syndrome was not associated with presence or severity of steatosis both in chronic viral hepatitis and in non‐alcoholic steatohepatitis. Conclusion Metabolic syndrome is more prevalent in non‐alcoholic steatohepatitis than in chronic viral hepatitis; it is associated independently with more severe fibrosis but not with the severity of steatosis, both in chronic viral hepatitis and in non‐alcoholic steatohepatitis.     

Disease progression in Chinese chronic hepatitis C patients with persistently normal alanine aminotransaminase levels

BACKGROUND: Although chronic hepatitis C virus-infected patients with persistently normal alanine aminotransaminase levels usually have mild liver disease, disease progression can still occur. However, it is uncertain which group of patients is at risk of disease progression. AIM: To examine the severity of liver disease on liver biopsy in Chinese patients with persistently normal alanine aminotransaminase levels, and their disease progression over time. METHODS: Eighty-two patients with persistently normal alanine aminotransaminase levels were followed up longitudinally. The median time of follow-up was 8.1 years. Forty-seven of the 82 patients (57.3%) had a second liver biopsy. RESULTS: At the time of analysis, six of the 82 patients (7.3%) developed decompensated liver cirrhosis. Patients with an initial fibrosis stage F2 or F3 [6/23 (26.1%) vs. 0/59 (0%), P < 0.0001] or inflammatory grade A2 or A3 [5/40 (12.5%) vs. 1/42 (2.4%), P = 0.04] were more likely to develop decompensated liver cirrhosis. On multivariate analysis, initial fibrosis stage F2 or F3 was independently associated with progression to decompensated liver cirrhosis (relative risk 2.3, 95% confidence interval 0.03-2.5, P = 0.02). CONCLUSION: Chinese chronic hepatitis C virus patients with persistently normal alanine aminotransaminase levels with moderate to severe fibrosis at initial evaluation are more likely to develop decompensated liver cirrhosis.     

Hepatitis C, B, D, and A: contrasting features and liver function abnormalities in heroin addicts

Over 90% of intravenous heroin addicts (IVHAs) carry the hepatitis C virus (HCV). The other hepatitis viruses, A, B, D, and G are relatively unimportant in IVHAs compared to HCV although active hepatitis B may demonstrate a chronic, degenerative course identical to that of HCV. The clinical course of HCV and active hepatitis B may span three or more decades. It is helpful to classify patients as in the active, cirrhosis, or liver failure stages. Only in the active, early stage are the liver enzymes, ALT and AST, likely to be elevated. It is this stage that will most likely respond to antiviral therapy. HCV has so many extra-hepatic manifestations including immune suppression, collagen diseases, and possibly lymphoma and leukemia that the disease is best termed HCV syndrome rather than simple hepatitis.     

Liver disease in drug addicts: clinical course-toxicological and clinical pharmacological aspects.

Drug addicts admitted to the hospital had acute hepatitis in 44%, chronic hepatitis in 34%, toxic liver injury in 16%. About 50% of the patients with acute hepatitis were HAA positive. Patients with intravenous drug abuse acquired acute hepatitis after a mean period of 1.8 years. Acute hepatitis in drug addicts shows a prolonged course in the majority of the cases. Biochemically increases in serum bilirubin and transaminase levels are less pronounced as compared to non-addicted persons. 30-35% of the patients develop chronic hepatitis. Speed abuse promotes the tendency to cholestasis in acute episodes of liver disease. A toxic effect of the drug preparations upon the liver cells is assumed. Chronic hepatitis in drug addicts mainly develops from earlier acute hepatitis with prolonged course. In our material, the percentage of chronic hepatitis at present is 47.5%. Besides toxic effects, also repeated infections have to be discussed with regard the etiology and pathogenesis of the disease.     

Antiviral therapy for chronic hepatitis B: a review

Chronic hepatitis B virus (HBV) infection is a well-recognized risk factor for the development of hepatocellular carcinoma (HCC), which is becoming a more prevalent clinical problem, especially in HBV-endemic areas. It is estimated that 1.25 million people in the United States and more than 300 million people worldwide are chronically infected with HBV. Despite the introduction of universal vaccination against hepatitis B in over 100 countries, persistent HBV infection is still a serious problem worldwide, causing an estimated annual death rate of one million. It may take several decades until the effect of vaccination will be translated into reduced transmission and morbidity. Meanwhile, patients with persistent HBV infection require better antiviral therapeutic modalities than are currently available. It is well accepted that antiviral therapy for chronic hepatitis B is effective to improve prognosis of patients with HBV by preventing development of hepatitis state and HCC. The therapeutic endpoints for hepatitis B treatment are: 1) sustained suppression of HBV replication, as indicated by HBsAg and HBeAg loss, 2) decrease of serum HBV DNA of an undetectable level by a non-PCR method, 3) remission of disease, as shown by normalization of ALT, 4) improvement in liver histology, and 5) reduction of the acute exacerbation, cirrhosis, and HCC. In the present, the antiviral treatment of hepatitis B consists of either interferon alpha or oral lamivudine alone or in combination with existing therapy. Each major antiviral drug of interferon alpha and lamivudine has pros and cons, and effect of combination therapy of both drugs is also still limited. More powerful and safe new antiviral therapies are required to achieve final goal of these therapeutic endpoints. Management of chronic hepatitis B requires significant knowledge of approved pharmacotherapeutic agents and their limitations. Therapeutic options for managing hepatitis infection after liver transplantation (LT) are also evolving.     

血清前白蛋白测定在肝脏疾病中的意义

目的:探讨血清前白蛋白(PA)测定在不同肝病中的变化以及肝病时前白蛋白与其肝功能之间的关系。方法:应用免疫比浊法,在日立7150全自动生化分析仪对342例各种肝病进行PA测定及常规肝功能检测。结果:与正常人比较除轻度慢性乙肝(慢乙轻度)差异无显著性(P>0.05),其余肝病患者血清PA均明显低于正常对照组(P<0.01或P<0.005);各肝病间比较,肝硬化代偿期与肝癌及急性肝炎间差异无显著性(P>0.05),重度慢性乙肝(慢乙重度)与肝硬化失代偿期间差异有显著性(P<0.05),其余各肝病间差异均有非常显著性(P<0.01)。结论:血清PA不仅是肝细胞早期受损的敏感指标之一,也是鉴别不同肝病及肝病的不同阶段的有效指标。持别是联合ALT等其它常规肝功能结果,对急、慢性肝炎、肝硬化、肝癌不同阶段的诊断、疗效观察和预后判断有较大意义     

Platelet activation in patients with chronic hepatitis C

OBJECTIVE: To elucidate the mechanisms of thrombocytopenia in chronic hepatitis C (CHC), we investigated platelet activation in patients with chronic viral liver diseases. METHODS: Platelet activation was evaluated with flow cytometry in twenty-five patients with chronic viral hepatitis and 11 patients with liver cirrhosis of viral etiology. Liver biopsies were carried out in all patients. RESULTS: The platelet counts decreased significantly in patients with CHC and in patients with liver cirrhosis compared to controls, but not in patients with chronic hepatitis B (CHB). Patients with CHC had a significantly higher percentage of platelets positive for activation-dependent monoclonal antibodies (MoAbs), and also had a higher percentage of platelet microparticles (PMP), a marker of platelet activation, than patients with CHB. There was a significant correlation between the percentage of PMP and the levels of liver fibrosis markers, such as serum hyaluronate and N-terminal propeptide of type III procollagen (P-III-P), in CHC, suggesting the relationship between platelet activation and liver fibrosis. Platelet activation was markedly enhanced in CHC patients with high histological scores of liver fibrosis. CONCLUSION: Patients with CHC have increased platelet activation, which may contribute to the occurrence of thrombocytopenia in CHC. Liver fibrosis may play a role in activation of platelets in CHC.     

肿瘤坏死因子及层粘连蛋白与肝病的关系

目的检测肿瘤坏死因子-α(TNF-α)及层粘连蛋白(LN)在不同阶段肝病患者血清中的水平,以观察二者之间是否具有相关性。方法血清标本均来自住院患者和健康体检者。将观察对象分为4组:对照组(A组)20例、急性肝炎组(B组)15例、慢性肝炎组(C组)80例、肝炎肝硬化组(D组)85例。采用放射免疫分析法检测患者血清TNF-α和LN。结果(1)肝病患者血清TNF-α含量均较对照组增高,差异有统计学意义(P<0.05)。急性肝炎、慢性肝炎、肝炎肝硬化患者的血清TNF-α含量逐渐增高(P<0.05)。慢性重度肝炎组血清TNF-α显著高于正常对照组,也明显高于慢性轻度肝炎组(P<0.01)。血清TNF-α含量从ChildA→B→C级逐渐升高,差异有统计学意义(P<0.05)。(2)急性肝炎组患者血清LN含量较对照组较有增高趋势,但无统计学意义(P>0.05)。慢性重度肝炎组血清LN含量明显高于正常对照组、急性肝炎组和慢性轻度肝炎组(P<0.05)。肝硬化组LN升高幅度较大,与慢性肝炎组相比差异有统计学意义(P<0.01)。ChildA→B→C级LN含量逐渐增高,且C级显著高于A级,差异有统计学意义(P<0.01)。(3)TNF-α与LN二者显著相关(P<0.01)。结论在肝细胞损伤及其纤维化发展进程中,随着病情进展,TNF-α及LN含量逐渐增高,二者之间呈正相关关系。     

Genetic heterogeneity of hepatitis viruses and its clinical significance

The genetic heterogeneity of hepatitis B virus (HBV) (8 genotypes A-H) has been applied for tracing the route of HBV transmission and the geographical migration of HBV carriers but it also appeared to have clinical implications. The secondary structure of e encapsidation signal could explain why the precore mutant virus prevails in Mediterranean countries, where genotype D is most prevalent, while the wild type virus is frequent in Western countries, where genotype A is most prevalent. There is increasing evidence that patients infected with genotype C have more severe outcome of chronic liver disease than those infected with genotype B. Genotype B was associated with fulminant hepatitis and more severe episodes of acute exacerbation of chronic HBV infection. Patients infected with genotype B appeared to seroconvert earlier than those infected with genotype C. The hepatitis delta virus (HDV) has 3 genotypes (I, II, III) which are associated with different disease patterns. Genotype III is the most distantly related HDV genotype and is associated with the most severe outcome while genotype II with relatively mild liver disease. The most geographically widespread genotype is I and is associated with a broad spectrum of chronic liver disease. The hepatitis C virus (HCV) displays high genetic heterogeneity with six genotypes (1-6), multiple subtypes and quasispecies. This viral diversity has epidemiological and clinical implications and has been associated with the severity of liver disease, prognosis, response to treatment and failure to generate an effective protective vaccine. HCV genotype 1 is the predominant genotype in Western countries and has been associated with a low response rate to interferon-alpha (IFN-alpha) or to the combination of ribavirin and IFN-alpha. Consequently the duration of treatment has been tailored according to HCV genotype.     

国产阿德福韦酯治疗乙型肝炎肝硬化的安全性与疗效观察

目的：观察国产阿德福韦酯（亿来芬）治疗代偿期乙型肝炎肝硬化的安全性与临床效果。方法：70例乙型肝炎肝硬化失代偿期患者随机分成两组,分别给予国产与合资企业产阿德福韦酯治疗72周,观察生化学指标、HBV DNA阴转、HBeAg阴转、抗-HBe阳转以及组织学指标炎症活动度（G）分级和纤维化程度（S）分期的差异。结果：两组患者生化指标均有明显改善,两组HBeAg血清转换率分别为26.09%和27.27%,HBV DNA阴转率两组分别为42.86%和45.71%,两组G分级和S分期均有明显改善,以上各项指标两组比较均无统计学意义（P〉0.05）。结论：国产和合资企业产阿德福韦酯治疗乙型肝炎肝硬化有相同的安全性和疗效。