Prognosis of acute viral hepatitis in patients with alcoholic cirrhosis

We report 20 cases of alcoholic cirrhosis with superimposed episodes of acute viral hepatitis. Four had acute type B hepatitis and 16, presumed non A non B hepatitis. Before hepatitis, 17 patients had stopped drinking and only four had a complicated cirrhosis. Eighteen patients had received a blood transfusion within the 6 months before the occurrence of hepatitis (mean: 52 days). All patients developed jaundice, 7 encephalopathy, and 5 ascites. The ASAT/ALAT ratio was greater than 1 in 18 patients. Two patients died of hepatic failure. Follow-up was known in 17 of the 18 surviving patients: in all patients jaundice disappeared and transaminases returned to values less than 3 times the upper limits of normal. In our experience, the prognosis is good when viral hepatitis occurs in patients with non complicated alcoholic cirrhosis.     

Hepatitis C virus (HCV) specific immune responses in anti-HCV positive patients without hepatitis C viraemia

BACKGROUND/AIMS: Most patients infected with hepatitis C virus (HCV) develop chronic infection and persistent viraemia. The immune mechanisms responsible for resolution of viraemia remain poorly understood. HCV specific humoral and cellular immune responses in patients with and without viraemia were investigated. METHODS: In vitro T helper (TH) lymphocyte responses to structural and non-structural HCV proteins were determined by means of proliferative response and cytokine production in 35 anti-HCV positive/HCV RNA negative patients and in 31 patients with chronic HCV infection and persistent viraemia. Humoral responses were determined by measuring HCV specific antibody quantity and specificity. RESULTS: A TH response to two or more HCV proteins was present in 18 of 35 patients with serological viral clearance compared with just one of 31 viraemic patients (p = 0.00001). HCV specific interferon-gamma production was increased only in the former group. In contrast, the antibody levels were significantly lower and directed at fewer HCV antigens in patients with undetectable HCV RNA. CONCLUSIONS: Patients without viraemia after HCV infection frequently have strong TH lymphocyte responses of the TH1 type to multiple HCV antigens many years after the onset of infection, whereas antibody responses are less marked. These results suggest that control of HCV replication may depend on effective TH lymphocyte activation.     

Perioperative blood transfusion affects hepatitis C virus (HCV)-specific immune responses and outcome following liver transplantation in HCV-infected patients

Objectives:Perioperative factors can affect outcomes of liver transplantation (LT) in recipients with hepatitis C virus (HCV) infection. This study was conducted to investigate whether the immunomodulatory effects of packed red blood cells (PRBC) and platelets administered in the perioperative period might affect immune responses to HCV and thus outcomes in LT recipients.Methods:Data for a total of 257 HCV LT recipients were analysed. Data on clinical demographics including perioperative transfusion (during and within the first 24 h), serum cytokine concentration, HCV-specific interferon-γ (IFN-γ) and interleukin-17 (IL-17) producing cells, and outcomes including graft and patient survival were analysed.Results:Patient survival was higher in HCV LT recipients who did not receive transfusions (Group 1, n = 65) than in those who did (Group 2, n = 192). One-year patient survival was 95% in Group 1 and 88% in Group 2 (P = 0.02); 5-year survival was 77% in Group 1 and 66% in Group 2 (P = 0.05). Group 2 had an increased post-transplant viral load (P = 0.032) and increased incidence of advanced fibrosis at 1 year (P = 0.04). After LT, Group 2 showed increased IL-10, IL-17, IL-1β and IL-6, and decreased IFN-γ, and a significantly increased rate of IL-17 production against HCV antigen. Increasing donor age (P = 0.02), PRBC transfusion (P < 0.01) and platelets administration were associated with worse survival.Conclusions:Transfusion had a negative impact on LT recipients with HCV. The associated early increase in pro-HCV IL-17 and IL-6, with decreased IFN-γ, suggests that transfusion may be associated with the modulation of HCV-specific responses, increased fibrosis and poor transplant outcomes.     

乙醇与乙型肝炎病毒重叠的肝硬化预后的临床探讨

乙醇与肝炎病毒共同作用已经成为我国东北地区肝硬化患者的第三大原因[1].本研究对乙醇与肝炎病毒共存肝硬化患者的临床预后进行了初步探讨.     

Thrombocytopenia associated with liver cirrhosis and hepatitis C viral infection: role of thrombopoietin

BACKGROUND/AIMS: Thrombocytopenia in chronic liver diseases has traditionally been considered a consequence of platelet pooling and destruction in spleen. We tried to evaluate the influence of thrombopoietin, the physiological regulator of thrombopoiesis, on the origin of this thrombocytopenia. METHODOLOGY: We determined serum thrombopoietin levels by ELISA in thrombocytopenic patients with liver cirrhosis (n = 32) and with chronic hepatitis C viral infection (n = 23). A group of 43 healthy subjects was used as a control. RESULTS: Liver cirrhosis patients presented slightly, but not significantly, lower serum thrombopoietin levels (104 +/- 56 pg/mL) than controls (121 +/- 58 pg/mL) or patients infected with chronic hepatitis C virus (125 +/- 40 pg/mL). No correlations were found between serum thrombopoietin concentrations and liver tests or hematological parameters. CONCLUSIONS: We conclude that low thrombopoietin production may play a role, along with hypersplenism, in the development of thrombocytopenia in patients with liver cirrhosis. Normal thrombopoietin levels exclude a defect in thrombopoietin production as a possible etiology for the thrombocytopenia in patients with chronic hepatitis C viral infection. However, a direct viral megakaryocyte infection or an immune mechanism could explain this thrombocytopenia, according to the thrombopoietin levels detected.     

慢性丙型肝炎病毒感染者外周血淋巴细胞增殖反应

目的　观察慢性丙型肝炎患者外周血淋巴细胞对丙型肝炎病毒（ＨＣＶ） 抗原刺激的增殖反应．方法　外周血单个核细胞（ＰＢＭＣ） 与ＨＣＶ 抗原ｃ２２ 、ｃ３３ 、ｃ１００ － ３ 、ＮＳ５ 和植物血凝素（ＰＨＡ） 分别共同孵育,加入胸腺嘧啶核苷（３ ＨＴｄＲ） ,然后收集细胞于液闪仪测定每分钟脉冲数（ｃｐｍ） ．结果　根据对不同ＨＣＶ 抗原的淋巴细胞增殖反应发现,以ｃ２２免疫原性最强,ｃ１００ － ３ 次之：淋巴细胞激活与ＨＣＶ 基因型关系不大;健康对照和慢性乙型肝炎患者对各ＨＣＶ 抗原未能显示有效的淋巴细胞增殖反应;与健康对照比较,慢性丙型肝炎和乙型肝炎患者对ＰＨＡ 刺激的淋巴细胞增殖反应降低．结论　ＨＣＶ 抗原ｃ２２ 免疫原性最强,丙型肝炎患者对ＨＣＶ 抗原的淋巴细胞增殖反应系特异性;慢性丙型肝炎和乙型肝炎患者存在抑制的细胞免疫应答．     

Effect of hepatitis C virus infection and abstinence from alcohol on survival in patients with alcoholic cirrhosis

GOALS: We assessed the effect of HCV infection and abstinence from alcohol on survival in a cohort of patients with alcoholic cirrhosis. BACKGROUND: Hepatitis C virus (HCV) infection may be an important cofactor for liver disease in chronic alcoholics. STUDY: The study population consisted of 213 patients with the diagnosis of alcoholic cirrhosis, 72 of these patients were infected by HCV. Complete alcohol abstinence after diagnosis of alcoholic cirrhosis was recorded in 86 patients. The reference group consisted of 89 patients with anti-HCV positivity who had never consumed alcohol. Survival was analyzed by the Kaplan and Meier method and predictors of survival by the Cox's multiple regression model. RESULTS: HCV infection was not a determinant factor for survival in alcoholic cirrhosis. Age and Child-Pugh grade at the time of diagnosis of cirrhosis and persistence of alcohol consumption after diagnosis were independent predictors of poor outcome. The cumulative survival curve in abstinent alcoholics was significantly different from that of alcoholics who maintained the same pattern of alcohol consumption (log-rank = 4.30, p = 0.0381). Moreover, the cumulative survival in patients with anti-HCV-positive cirrhosis who stopped drinking after diagnosis was similar to that in patients with HCV-positive cirrhosis who had never consumed alcohol (log-rank 0.26, p = 0.61). CONCLUSIONS: Cumulative survival in alcoholic cirrhosis does not seem to be influenced by the presence or absence of markers of HCV infection. Once liver cirrhosis has been diagnosed in the alcoholic patient, complete alcohol abstinence should be strongly recommended.     

肝移植术后丙肝复发抗病毒治疗患者持续病毒应答影响因素分析

目的分析肝移植术后丙肝复发抗病毒治疗患者产生持续病毒应答(SVR)的影响因素。方法回顾性分析2003～2009年39例肝移植术后丙肝复发并进行抗病毒(聚二乙醇干扰素和利巴韦林)治疗的患者的临床资料。结果本组中21例因不良反应停药,18例完成全疗程规范治疗,疗程25～105周;有4例(22.22%)获得SVR,其平均治疗周期是57周。统计分析显示,非ⅠB型基因(P=0.023)、治疗前丙肝病毒载量<10~6 copies/ml(P=0.044)以及早期病毒应答(EVR)(P=0.019)与SVR的获得有关。结论非ⅠB基因型、低水平HCV RNA和EVR是肝移植后丙肝复发抗病毒治疗产生SVR的影响因素。     

Acute viral hepatitis superimposed on alcoholic liver cirrhosis: clinical and histopathologic features

Of 20 patients with alcoholic liver cirrhosis and a superimposed episode of acute viral hepatitis, 12 developed hepatic encephalopathy or ascites or both. Four died of hepatic failure. Seventeen patients had received blood transfusions within 6 months before the acute hepatitic episode. Two patients were HBsAg-positive; the other 18 were presumptively diagnosed as having non-A, non-B hepatitis. However, hepatitis A virus infection was excluded in only three of the 18 patients. Histologic examination performed in 13 cases disclosed necrotizing inflammatory activity, which is commonly observed in acute viral hepatitis. The distinctive histologic feature was a meager regenerating activity. We conclude that patients with alcoholic cirrhosis complicated by acute viral hepatitis frequently develop hepatic failure and have a high fatality rate (20% in our series).     

Optimizing hepatitis C therapy in HIV/hepatitis C virus (HCV) coinfected patients: Analysis of HCV viral kinetics on treatment

INTRODUCTION:

Hepatitis C virus (HCV) infection is potentially curable, but the sustained virological response (SVR) has been shown to be lower in patients coinfected HIV. A single-centre experience treating individuals with HCV and HIV coinfection is reported.

METHODS:

Twenty-one patients who received standard doses of pegylated interferon with weight-based dosing of ribavirin (mean 14.3 mg/kg) were retrospectively reviewed. Qualitative HCV polymerase chain reaction (PCR) was performed prospectively every four weeks if the patient remained HCV PCR positive. All patients with HCV genotype 1 were treated for 48 weeks. Patients with genotype 2 or 3 were treated for 24 weeks and 32 weeks to 36 weeks if their HCV RNA level was undetectable after four weeks (RVR4) or eight weeks (RVR8) of therapy, respectively. If RVR8 was not achieved, the treatment was continued for 48 weeks.

RESULTS:

There were no dropouts or dose reductions within the first 12 weeks of treatment. SVR status was available for 20 patients and adequate serum for viral kinetics analyses was available for 17 patients. Eighty per cent of the patients achieved SVR (50% genotype 1; 100% genotypes 2 and 3). The week 8 viral load remained elevated for all genotype 1 nonresponders.

DISCUSSION:

High effectiveness rates were seen, particularly in patients with HCV genotype 2 and 3 who were treated for shorter durations. HCV viral loads after eight weeks of therapy helped distinguish patients with HCV genotype 1 who would respond to therapy.     

The extrahepatic manifestations in hepatitis C virus (HCV) infection

The hepatitis C virus (HCV) infection could affect not only the liver, but also other tissues, organs and systems. The number of the reported in the literature extrahepatic lesions by HCV incessantly increases. A reliable association between the infections by HCV and the mixed cryoglobulinaemias, membrano-proliferative glomerulonephritis and porphyria cutanea tarda is confirmed. The participation of HCV in the pathogenesis of some diseases of the thyroid gland, the lymphocytic sialadenitis, lichen planus, diabetes mellitus, thrombocytopenia, antiphospholipid syndrome, etc., is assumed. The extrahepatic lesions by HCV are probably connected with the participation of the immune system, but they may be as well due to the replicating virus in the affected tissues, organs and systems. The pathogenetic mechanisms of the extrahepatic and autoimmune manifestations of the infection with HCV are not elucidated, which poses difficult therapeutic problems regarding the choice of interferon and/or corticosteroid hormones.     

Differences in cognitive function between patients with viral and alcoholic compensated liver cirrhosis

As alcohol induces change in frontal cortex primarily involved in cognition, cognitive function may be different between viral and alcoholic liver cirrhosis (LC). This study aimed to determine the differences of cognitive function between viral and alcoholic compensated LC. From October 2011 to March 2013, 80 patients (viral: 37; alcohol: 43) with compensated LC were prospectively enrolled. Neuropsychological functions including attention, language, visuospatial, verbal memory, visual memory, and frontal/executive function were evaluated between two groups and compared with age-matched normal group (n = 1000). Cumulative incidence rate of overt hepatic encephalopathy (HE) was calculated. In the comparison with normal group, both two groups showed decreased memory function, frontal/executive function, and Korea-Mini Mental Status Examination. In the analysis of two groups, memory function by Verbal Learning Test (recognition: 20.1 ± 3.6 and 17.8 ± 4.8, p = 0.022), visuospatial function by Ray-Complex Figure Copy Test (recognition: 19.0 ± 2.6 and 17.3 ± 4.0, p = 0.043), frontal/executive function by Controlled Oral Ward Association (semantic: 17.1 ± 6.9 and 12.7 ± 6.9, p = 0.004), and the Korea-Mini Mental Status Examination (27.5 ± 1.9 and 26.2 ± 3.1, p = 0.03) showed low scores in alcoholic compensated LC patients. The 1-, 2-, and 3-year cumulative incidence rates of overt HE were 23 %, 26 %, and 26 % and 33 %, 43 %, and 49 % in the viral and alcoholic compensated LC group, respectively (p = 0.033). Impaired memory and frontal lobe executive functions and early development of overt HE were more common in patients with alcoholic LC. For patients with alcoholic LC, more integrated tests for early detection of minimal HE and intensive treatment should be considered to prevent overt HE.     

A histopathological study of alcoholics with chronic HCV infection: comparison with chronic hepatitis C and alcoholic liver disease

Abstract: To clarify the relationship between hepatitis C virus infection and excessive alcohol intake, we carried out histological examination of the liver in 46 alcoholics with chronic hepatitis C virus infection and compared the findings in 55 patients with chronic hepatitis C, 38 with alcoholic liver disease, and 27 with chronic hepatitis B. The majority of alcoholics with chronic hepatitis C virus infection displayed virus-related histological changes very similar to those in chronic hepatitis C, including frequent lymphoid follicles (34.7%) or aggregates (93.3%) in the portal tracts, mild necroinflammatory change (76.1%) in the parenchyma, and lymphocytosis in sinusoids (82.7%). Liver cell dysplasia and irregular regenerative activity of hepatocytes were rarely observed. The effects of alcohol on the liver were found to be minimal in the majority. These findings could suggest that the hepatic injury in the majority of alcoholics with chronic hepatitis C virus infection in Japan is due to persistent hepatitis C virus infection rather than to alcoholic injury. In addition, our study disclosed that the perivenular fibrosis which is designated as a histological characteristic of alcoholic liver disease is frequently observed in chronic hepatitis C. These similarities suggest that a similar fibrogenesis is present in chronic hepatitis C and alcoholic liver disease.     

Clinical significance of hepatitis C virus (HCV) infection in liver transplant recipients

Hepatitis C virus (HCV) infection was studied in 60 liver transplant recipients. Antibodies to HCV were tested by both a second-generation ELISA test and a four-recombinant immunoblot assay (4-RIBA) just before the transplant and every three months thereafter. HCV RNA detection was performed by polymerase chain reaction (PCR) at least three times after the transplant in all the patients. Thirty-nine patients tested negative by ELISA before LT (group A), 14 patients tested positive by both serological tests (group B), and seven tested positive only by ELISA (group C). Posttransplant hepatitis was diagnosed in 11/14 in group B in comparison with 3/39 in group A (P<0.001) and 1/7 in group C (P<0.05). HCV RNA was detected in the sera of 14/14 patients in group B but in only 1/7 in group C and 6/39 in group A. Only 2/15 patients developed posttransplant hepatitis in the absence of HCV RNA detection. These data suggest that HCV is the major cause of hepatitis after LT. Patients HCV seropositive by RIBA test before the transplant formed a group of high-risk patients for developing viremia and hepatitis afterwards.Part of this work was presented at the XIVth International Congress of the Transplantation Society. Paris. August 1992.This work was supported by a grant from Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS 92/0357).     

Comparison of outcomes between patients with alcoholic cirrhosis and those with hepatitis C virus-related cirrhosis

Background and Aim:  The natural history of alcoholic cirrhosis, especially in Asian countries, has not been completely understood thus far.
Methods:  We retrospectively compared the outcomes of compensated cirrhosis between Japanese alcoholic and hepatitis C virus (HCV)-infected patients.
Results:  A total of 227 patients (75 alcoholic and 152 HCV-infected patients) with compensated cirrhosis were enrolled. The median follow-up period was 4.9 years. The cumulative rates of hepatocellular carcinoma (HCC) development were significantly lower in the alcoholic patients than in the HCV-infected patients (6.8% vs 50.3% at 10 years, P  = 0.0003), while the cumulative rates of hepatic decompensation (37.4% vs 51.7% at 10 years) and survival (53.8% vs 47.4% at 10 years) did not significantly differ between the two groups (Kaplan-Meir analysis). The main causes of death were hepatic failure and non-hepatic diseases in the alcoholic patients and HCC and hepatic failure in the HCV-infected patients. Multivariate analyses using the Cox proportional hazard model revealed that the risk of HCC was lower in alcoholic cirrhosis than in HCV-related cirrhosis (hazard ratio (HR), 0.46), while the risk of hepatic decompensation and mortality was the same. Predictors of decreased survival were non-abstinence (HR, 2.53) in the alcoholic patients and low serum albumin level (1.58) in the HCV-infected patients.
Conclusions:  Survival of patients with alcoholic cirrhosis was similar to that of patients with HCV-related cirrhosis. The risk of HCC development was lower in alcoholic cirrhosis than in HCV-related cirrhosis. Abstinence from alcohol was important for improving the survival of patients with alcoholic cirrhosis.     

Protein C in patients with alcoholic cirrhosis and other liver diseases.

The coagulation inhibitor protein C was measured in 151 patients with various liver diseases. The protein C level was significantly decreased in patients with alcoholic cirrhosis (n = 73) compared to patients with steatosis (n = 24) (40 +/- 2%) vs. 88 +/- 4%, mean S.E., p less than 0.001). It was also decreased in cases of acute liver damage (n = 8) and in patients with non-alcoholic cirrhosis (n = 15) (35 +/- 7% and 36 +/- 4%, respectively). A significant correlation was found between protein C and Normotest, antithrombin, heparin cofactor II, (r = 0.83, r = 0.82, r = 0.81, respectively, p less than 0.001). There was also a significant correlation between protein C and serum concentrations of albumin (r = 0.61, p less than 0.001), but a negative association to bilirubin (r = -0.56). No significant association was found between protein C and aspartate aminotransferase, alaline aminotransferase, and gamma-glutamyltranspeptidase. In conclusion, protein C is low in advanced liver diseases and gives the same amount and type of information as Normotest, antithrombin and heparin cofactor II.     

Maintenance hemodialysis decreases serum hepatitis C virus (HCV) RNA levels in hemodialysis patients with chronic HCV infection

OBJECTIVE: Hepatitis C virus (HCV) infection is a major complication among hemodialysis patients the world over. To determine the natural course of HCV viremic levels in patients on maintenance hemodialysis, we prospectively quantified the HCV RNA levels in serial blood samples from hemodialysis patients and compared them with those in nonuremic subjects. METHODS: The population studied included 98 hemodialysis patients and 228 nonuremic subjects with chronic HCV infection. HCV RNA was detected by polymerase chain reaction (PCR) and the levels were determined by branched DNA probe assay. HCV RNA genotypes were determined by PCR using type-specific primers. RESULTS: HCV RNA levels were significantly lower in hemodialysis patients (median, 0.4x10(6) genome equivalent [Meq]/ml) than in nonuremic subjects (median, 3.0 Meq/ml) (p<0.05). HCV of genotype 1b was prevalent in the hemodialysis patients (81.6%) and nonuremic subjects (88.6%). HCV RNA levels in 20 hemodialysis patients with genotype 1b were significantly reduced after each hemodialysis procedure (p<0.05). The 3-yr prospective observation from 1995 to 1998 showed a significant decrease of HCV RNA levels in 47 hemodialysis patients with genotype 1b (median, 1.9-0.9 Meq/ml, p<0.05), whereas levels in 155 nonuremic subjects with genotype 1b did not decrease (median, 2.6-3.0 Meq/ml). There were no patients or nonuremic subjects with undetectable HCV RNA by a PCR assay during the observation period. CONCLUSIONS: These observations suggest that maintenance hemodialysis decreases the HCV RNA levels in hemodialysis patients with chronic HCV infection, but does not produce clearance of the viremia.