阿德福韦酯联合安络化纤丸抗肝纤维化疗效及组织学变化观察

通过阿德福韦酯联合安络化纤丸治疗慢性乙型肝炎及其引起的肝硬化，探寻治疗肝纤维化、缓解肝硬化、降低肝硬化发生率的有效方法。方法：76例慢性乙型肝炎或乙型肝炎肝硬化患者，服用阿德福韦酯及安络化纤丸，观察肝功能、病毒学指标、肝纤4项、肝脏B超及组织学的变化。对照组69例，仅予护肝治疗，无抗病毒及抗肝纤维化治疗。结果：治疗组患者经3个月治疗，肝功能大部分复常；6个月，HBVDNA阴转或处于低水平，肝纤4项大部分复常；12个月，部分患者HBeAg阴转，肝穿活检组织学改善；18个月肝硬化患者肝脏B超明显改善。同期对照组患者仍反复肝功能异常，肝纤维化指标大部分无改善。结论：阿德福韦酯联合安络化纤丸对肝纤维化具有明显的疗效。     

人工肝支持系统治疗重型乙型肝炎52例临床观察

重型肝炎是因各种原因引起的肝细胞广泛和大量坏死所致的严重肝功能障碍或肝衰竭,预后较差.2002年12月～2005年12月,我们应用人工肝支持系统（ALSS）治疗重型肝炎52例,取得满意效果.现报告如下.     

神农软肝丸治疗肝炎肝硬化的临床研究

目的:观察神农软肝丸治疗肝炎肝硬化的临床疗效及安全性。方法:选择肝炎肝硬化患者150例,随机分为两组,治疗组口服神农软肝丸,对照组采用一般常规疗法,疗程6个月。观察治疗后的症状体征、肝功能、血清病毒学指标、血清肝纤维化指标、门脉血流动力学指标和临床综合疗效。结果:治疗组和对照组总有效率分别达93.33%及82.67%,两组比较差异有显著性意义,治疗组明显高于对照组(P<0.05)。治疗组在减轻或消除症状体征、降低肝功能和血清肝纤维化指标、改善门脉血流动力学指标等方面明显优于对照组。未发生与研究药物相关的严重不良反应。结论:神农软肝丸治疗肝炎肝硬化疗效显著,安全性良好。     

软肝缩脾丸治疗慢性肝纤维化的临床与实验研究

在1995-06/1998-06期间,我们承担河南省科委对慢性乙型肝炎及肝纤维化(慢纤化)的临床攻关课题,研制出纯中药制剂"软肝缩脾丸",应用此药治疗慢纤化患者96例(观察组),与复肝康治疗慢纤化患者82例(对照组)比较,并进行了动物实验,现将其临床及实验结果报告如下:     

神农软肝丸对肝硬化防治作用的实验研究

目的:研究纯中药制剂神农软肝丸对肝硬化的防治作用.方法:采用复合致病因素造成大鼠肝硬化模型,观察神农软肝丸对肝硬化大鼠血清转氨酶、白蛋白、肝脏羟脯氨酸、肝脾指数及肝脏组织病理学的影响.结果:神农软肝丸对治疗组大鼠血清转氨酶活性有明显改善作用,使肝脏羟脯氨酸水平降低,对肝细胞坏死及肝纤维化有一定的抑制作用.结论:中药神农软肝丸对实验性大鼠肝硬化有防治作用.     

肝性脑病的早期诊断与治疗

肝性脑病(hepatic encephalopathy,HE)系为肝衰竭(hepatic failure,HF)或重型肝炎病变基础上并发精神异常或意识障碍的临床症候群.肝衰竭可分为四种类型:急性肝衰竭(acuta liver failure,ALF)、亚急性肝衰竭(subacuta liver failure,SALF)、慢加急性(亚急性)肝衰竭(acute-no-chronic liver failure,ACLF)和慢性肝衰竭(chronic liver failure,CLF)[1].急性肝衰竭、亚急性肝衰竭及慢加急性肝衰竭多属重型肝炎类型,而慢性肝衰竭常为肝硬化失代偿的终末期临床表现.肝性脑病常与腹水、门静脉高压症、凝血功能障碍及肾功能衰竭等症候群合并发生,肝性脑病为重型肝炎诊断重要依据之一,病死率极高.开展肝性脑病早期诊断与早期治疗研究是提高肝性脑病存活率和治愈率最有效措施.     

活血养血中药为主逆转肝纤维化的组织学观察——附20例治疗前后肝穿活检结果分析

以养血活血中药为主,结合辨证论治治疗乙型肝炎20例,通过二次肝穿活检对其肝纤维化或肝硬化的组织学逆转进行了观察。其中,11例Ⅱ度肝纤维化患者治疗后有10例纤维组织减少至Ⅰ度,有效率为90.9％,碎屑样坏死和桥状坏死也明显减轻;9例肝炎后肝硬变患者中,8例假小叶消失,有效率为88.9％,但碎屑样坏死及桥形坏死的改变不明显。而且患者肝功能也得到同步改善。提示应用中药逆转肝纤维化具有广阔的前景。     

人工肝联合肝移植治疗重型肝炎的初步研究

目的 观察并评价混合人工肝支持系统联合肝移植在救治重型病毒性肝炎（重型肝炎）中的作用与疗效。方法 采用自行研制的体外混合人工肝支持系统对8例中晚期重型肝炎患者进行人工肝过渡支持治疗,3－14d后行原位肝移植术。结果 8例重型肝炎患者经混合人工肝支持,肝衰竭得到有效控制,均成功等到肝移植。肝移植后4例存活,存活率为50％,另4例因肺部感染、肝肾综合征等死亡。结论 人工肝支持系统与肝移植联合可作为中晚期重型肝炎肝衰竭患者治疗的有效手段。     

肝功能衰竭39例患者的离体肝组织病理特点

目的了解肝功能衰竭患者的肝组织病理特点,并将病理诊断与临床诊断的结果相比较.方法选择排除肝癌的乙型肝炎病毒感染者39例,将其施行肝移植术后留下的离体肝组织行多部位切取组织标本,进行苏木精-伊红染色及网纤染色,分析其病理特点,并将病理诊断与临床诊断进行比较.结果1.39例离体肝组织标本,整个肝脏病变的范围和程度呈现相对均匀分布的特点,但是在同一取材的微观肝组织中,其病变特点可呈现不均一性.2.临床诊断为＂乙肝肝硬化（活动期）＂的4例肝组织病理特点均符合＂活动性肝硬化＂,而35例临床诊断为＂慢性乙型重型肝炎＂的肝组织病理符合＂活动性肝硬化＂者有18例、符合＂慢性重型肝炎＂病理诊断者仅有17例.结论临床诊断为慢性重型肝炎患者在病理学上分为坏死后肝硬化和肝脏大块坏死或亚大块坏死两种类型.     

护理干预对人工肝支持系统治疗重型肝炎患者康复的影响

重型肝炎,在短期内肝细胞大量坏死,出现严重的代谢紊乱和毒性物质聚积,毒性物质反过来影响肝细胞再生和功能恢复,形成恶性循环.重型肝炎的病情进展迅速,容易出现肝性昏迷、出血、感染、肝肾综合征等严重并发症,病死率达80%[1-2].人工肝支持系统(ALSS)是治疗重型肝炎、肝衰竭的一种极为重要的方法.以ALSS治疗重型肝炎,能有效地去除各种代谢产物、内毒素及各种有害细胞因子和炎症递质,补充蛋白质、调理素及凝血因子等多种生物活性物质,并改善机体内环境,为肝细胞再生和肝功能恢复创造有利条件[3].但由于很多患者及家属对人工肝治疗的误解,常认为人工肝就是肝移植,给患者和家属造成很大的心理压力,患者常表现为心情沉重、焦虑、恐惧,同时较高的治疗费用造成沉重的经济负担,因此,为避免患者在治疗中出现紧张、恐惧等不良情绪及减少术后并发症[4],对我院2009年1月-2009年8月60例重型肝病患者进行ALSS治疗,并进行护理干预,取得良好效果.现报道如下.     

人工肝支持系统治疗重型肝炎的疗效评价

目的 探讨应用人工肝支持系统（ＡＬＳＳ）治疗重型肝炎肝衰竭合并肝性脑病,研究其机制及评价疗效。方法 设治疗组和对照组,治疗组５１例重型肝炎（重肝）患者,急性、亚急性重肝１７例,慢性重肝３０例,酒精性重肝２例,钩体病黄疸型重肝１例,肝豆状核病肝衰竭１例。在综合护肝治疗基础上同时给予ＡＬＳＳ治疗。对照组３９例重肝患者,急性、亚急性重肝８例、急性重肝３１例,仅给予基础上同时给予ＡＬＳＳ治疗。对照组３９例     

Influence of ethanol consumption on experimental viral hepatitis

BACKGROUND: One important contributor to pathologic effects on the liver associated with alcohol abuse is viral hepatitis, especially hepatitis C virus (HCV) infection. Alcohol consumption has been shown to be associated with more severe HCV infection and hepatitis. The mechanisms of the more severe viral infection of the liver are unclear, and studies have been hampered by the lack of an animal model of hepatotropic viral infections. METHODS: We have established a murine model system of viral hepatitis in which C57BL/6 mice are infected with murine cytomegalovirus, a herpesvirus that produces self-limiting hepatitis in immunocompetent mice. Mice were fed a liquid diet containing 36% ethanol-derived calories with a pair-feeding protocol. After infection with a sublethal dose of murine cytomegalovirus, the severity of liver infection was determined by measuring serum levels of alanine aminotransferase and by histological evaluation. Other parameters determined included the serum levels of cytokines, cytokine RNA in liver samples, and viral concentration in liver samples. RESULTS: Ethanol-fed mice showed more severe hepatitis in the later stages of the infection as compared with the hepatitis noted in control mice. The ethanol-fed mice did not control the virus replication in the liver, which was associated with a greater mononuclear cell inflammatory response, composed predominantly of cells with morphological characteristics of lymphocytes and macrophages. The early production of interferon gamma, as well as production throughout the infection, was significantly lower in the ethanol-fed mice. The early production of interleukin 12 was also less in ethanol-fed mice. CONCLUSIONS: The more severe hepatitis seen in the ethanol-fed mice is likely to be the result of an inability to control the growth of the virus, which is associated with a continued inflammatory response. The inability to control the virus in the liver may be related to the decreased production of interferon gamma and interleukin 12.     

Evaluation of viral replication in children with chronic hepatitis B with and without interferon treatment

BACKGROUND: In chronic infection with hepatitis virus B the fact that HBeAg becomes negative does not always mean suppression of viral replication. METHOD: HBV replication was assessed in 74 patients with chronic hepatitis or viral B cirrhosis, in whom diagnosis was made according to clinical, biological, and histological criteria. The patients were divided into two groups: group I (36 patients with interferon- therapy, 3 million U/m 2/ dose, 3 doses/week over a period of 4-6 months) and group II (control group of 38 patients who did not undergo interferon therapy). After a follow up period of 6 years in which patients underwent clinical, biochemical and serologic monitorization, HBV DNA was detected by the hybridization method on solid medium. RESULTS: During evolution the levels of transaminases became normal in both groups. The HBe Ag/Ab seroconversion rate at the end of the interferon therapy was 52.8% and the spontaneous HBe Ag/Ab seroconversion rate was 72.7% in group II after an average evolution of 6 years. HBs Ag/Ab seroconversion was not detected in any patient. Assessment of viral replication by HBV DNA testing at the end of the follow up period showed higher levels as compared to the HBeAg testing (69.4% vs. 25% in group I, 55.2% vs. 7.9% in group II). The absence of viral replication (HBV DNA negative) had similar rates in both groups (30.6% in group I vs. 44.8% in group II, p>0.9) and HBV DNA titers in the two groups were not significantly different at the end of the follow up period. In both groups, HBV DNA titers were significantly higher in patients with positive HBeAg. The concordance between the two viral markers was 100%. CONCLUSION: Because of the fluctuating evolution, long-term follow up and monitorization (including HBV DNA testing) of patients with chronic hepatitis B and of inactive HBsAg carriers are necessary.     

Exacerbation of chronic hepatitis D during interferon alpha administration

Acute and severe impairment of liver function with jaundice and ascites occurred in two out of seven patients with chronic hepatitis D during interferon alpha administration (10 MU three times a week). Both of them were young women with histological diagnoses of moderate to severe chronic hepatitis and cirrhosis with no signs of portal hypertension. Only a slow and partial recovery was observed after interferon withdrawal. Autoantibodies against basal cell layer tested positive in these two patients. In the remaining five patients with hepatitis D who did not experience liver impairment during interferon administration, basal cell layer antibodies were found only in one case. We conclude that severe decompensation of liver cirrhosis related to hepatitis D may occur during interferon administration. Positivity of basal cell layer antibodies may be associated with the risk of developing such an adverse event but our data are not sufficient to prove this association.     

Long-term histological prognosis and serum fibrosis markers in chronic hepatitis C patients treated with interferon

BACKGROUND: Interferon (IFN) therapy is effective in 20-40% of patients with chronic hepatitis C, but the relationship between histological changes and the response to interferon is still unclear. We investigated the long-term histological prognosis and the changes of serum fibrosis markers after interferon therapy relation to the response. METHODS AND RESULTS: One hundred and eighteen patients with chronic hepatitis C who received interferon therapy were divided into four groups based on the detection of viremia and the serum alanine aminotransferase (ALT) level after treatment. A histological examination was performed by using the histological activity index and the criteria of the METAVIR score. Serum fibrosis markers were used to measure the levels of hyaluronic acid and type IV collagen 7s. Responders, whose serum ALT levels became normal after treatment, demonstrated histological improvement. Histological improvement was more rapid in sustained virological responders with hepatitis C virus (HCV) RNA seronegativity than in biochemical responders with HCV-RNA seropositivity. Only sustained virological responders exhibited histological cure. In partial responders, whose serum ALT levels decreased to less than twice the upper of normal, and non-responders whose serum ALT levels were not reduced, liver fibrosis was unchanged or showed progression. Serum fibrosis markers increased with progression of the histological stage and varied depending on the response to interferon. CONCLUSION: Normalization of serum ALT levels after interferon therapy led to a histological improvement, and that with viral clearance achieved histological cure. Serum fibrosis markers were useful indicators for long-term according to the response of IFN therapy.     

Interferon-alpha and liver fibrosis in patients with chronic damage due to hepatitis C virus

The present review focuses on the published information published regarding the effects of interferon alpha therapy on liver fibrosis in patients with chronic liver damage secondary to hepatitis C infection. Data reviewed included results of the in vitro effects of interferon on hepatic cell line cultures with regards to indirect markers of fibrosis, activation of hepatic stellate cells and oxidative stress response. In the clinical arena, there is current clear evidence of a favorable histological outcome in patients with sustained viral response to interferon therapy. For this reason, the current review focuses more on the histological outcomes regarding liver fibrosis in patients who have not attained viral response to therapy (non-responders) or who already have biopsy defined cirrhosis. Data in these patients were analyzed according to the results of objective testing of fibrosis through the assessment of liver biopsy and its change during time, specially because the morbidity and mortality of this disease is directly related to the complications of liver cirrhosis and not necessarily to the persistence of the hepatitis C virus. Lastly, it is concluded that the process of liver fibrosis/cirrhosis is a dynamic one and that there is some evidence to support the usefulness of interferon alpha therapy as a means to halt or retard the progression of hepatic fibrosis. The result of current clinical trials in which interferon therapy is being used to modify the progression of fibrosis in non-responders or cirrhotic patients is eagerly awaited.     

Über das Verhalten des Serotonins im Blut,der Aktivität der Serummonoaminooxydase und der 5-Hydroxyindolessigsäure im Tagesharn bei Kranken mit Virushepatitis

The level of serotonin in blood, the activity of MAO in serum and the value of 5-HIAA in 24 hour urine were estimated in 76 patients with viral hepatitis divided according to clinical parameters into three groups (mild, mild to severe and severe clinical course). A statistically significant increase of serotonin level in blood compared with the healthy control group was found. Highest values were observed in patients with the severe form of viral hepatitis. Decreased values of 5-HIAA in 24 hour urine in the early course of the disease showed a tendency to increase in later examinations. The activity of MAO in serum was significantly lowered in all clinical forms of viral hepatitis.     

Effects of interferon therapy in "non responder" patients with chronic hepatitis C

We reviewed the impact of interferon treatment on viral load, transaminase serum activity and histological features in patients with chronic hepatitis C in whom treatment did not result in a sustained virus eradication. As patients with cirrhosis are often called non responders, we also reviewed the impact of interferon on these end points as well as on hepatocellular carcinoma incidence and survival. This overview provides evidence that interferon in patients who have not cleared hepatitis C virus (HCV) significantly reduces viral load, serum ALT activity, improves histological activity and blocks progression of fibrosis compared to the natural history of the disease. Thus, patients who still have a positive HCV PCR should no longer be called non responders to interferon. Although the number of randomized trials is limited, there is also cumulative data suggesting that interferon could reduce the incidence of hepatocellular carcinoma incidence and mortality.     

Absence of detectable serum interferon in acute and chronic viral hepatitis

Amounts of interferon were measured in sera from 59 patients with acute viral hepatitis and 49 patients with chronic hepatitis B and compared to those from patients with nonviral liver disease or influenza, and from healthy controls. In all patients with acute and chronic viral hepatitis, no serum interferon could be detected, confirming data from earlier studies of acute viral hepatitis in which no circulating interferon was found. Our results disprove the view that the amounts of serum interferon, detected at the time of the acute clinical illness, may be a determinant of outcome.