Assessment of liver histology in chronic alcoholics with and without hepatitis C virus infection

Patients with alcoholic liver disease have a high prevalence of hepatitis C virus (HCV) infection. The histological appearances of the liver in patients with alcoholic liver disease and HCV infection are well described. However, liver histology in individuals with dual pathology, both chronic alcohol abuse and HCV infection, is less well understood. The purpose of the present study was to examine this issue and to determine if there is any correlation between specific histological features and the serum biochemical abnormalities seen in these patients. Eighty-six chronic alcoholics, 65 with HCV infection and 21 uninfected subjects, were included in the study. All patients had history of heavy alcohol abuse (consuming 80 g or more of ethanol a day for at least 10 years). The following data were collected on each patient: demographic information (age, gender, race), the amount and duration of alcohol intake, biochemical results, and liver biopsy abnormalities including the histological activity index (HAI) score. HCV-infected alcoholics were younger (P = 0.05) and were more often African American than Caucasian (P < 0.01). Alcohol consumption was significantly greater in uninfected alcoholics compared to those with HCV infection (P < 0.05). Liver histology in subjects with HCV infection showed higher HAI scores for intralobular necrosis (P = 0.008) and periportal inflammation (P = 0.004). Features of chronic hepatitis and focal lymphoid aggregates were more frequent in HCV-infected alcoholics (P = 0.001 for each). By contrast, cirrhosis was present in a higher proportion of uninfected alcoholics compared to those with HCV infection (P = 0.05). Histological findings of hepatic fibrosis and total HAI score showed a significant correlation with serum albumin and platelet count in HCV-infected alcoholics. Chronic alcoholics with HCV infection have specific histological appearances that can usually help distinguish these patients from uninfected alcoholics. Correlation analysis indicates that of the various laboratory tests, serum albumin and platelet counts are the best predictors of the severity of liver damage at histology. In chronic alcoholics, the development of cirrhosis is related more to the amount of alcohol consumed than to the presence of HCV infection.     

Comparison of liver histopathology between chronic hepatitis C patients and chronic hepatitis B and C-coinfected patients

BACKGROUND: The aim of the present study was to compare the histological characteristics of livers between chronic hepatitis C (CHC) patients with and without hepatitis B virus (HBV) coinfection. METHODS: A total of 336 CHC patients (male/female: 204/132, mean age: 46.1 +/- 11.7 years) were enrolled in the study; 32 patients (9.8%) were positive for hepatitis B surface antigen (HBsAg). The histological characteristics of livers were described according to the Knodell and Scheuer scoring system. RESULTS: The proportion of non-intralobular necrosis (score 0) was significantly lower and the mean intralobular necrosis score was higher among CHC patients with HBV coinfection than those without coinfection (43.8% vs 64.5%; 0.84 +/- 1.05 vs 0.53 +/- 0.89). The epidemiological and virological parameters, and other histological scores (periportal necrosis, portal inflammation, total necroinflammation and fibrosis) were not significantly different between these two groups. CONCLUSION: Chronic hepatitis C patients with HBV coinfection tend to have more severe intralobular necrosis than those with isolated HCV infection.     

复方二氯醋酸二异丙胺治疗慢性病毒性肝炎合并酒精性肝损伤的临床疗效观察

观察应用复方二氯醋酸二异丙胺治疗慢性病毒性肝炎合并酒精性肝损伤的临床疗效。选择确诊慢性病毒性肝炎合并酒精性肝损伤58例,随机分成两组。A组（n=30）在常规保肝治疗基础上,加用复方二氯醋酸二异丙胺（0.4-0.8）克溶于生理盐水中静脉滴注,每日一次;B组（n=28）常规保肝治疗,两组均4周为一疗程。两种药物临床总有效率分别为86.7%、64.3%,血清胆红素下降A组较B组明显（P〈0.05）。复方二氯醋酸二异丙胺对改善慢性病毒性肝炎合并酒精性肝损伤症状和降低血清转氨酶有较好的疗效,伴有高胆红素血症患者应用复方二氯醋酸二异丙胺优于常规保肝治疗。     

Hepatitis C virus infection in patients with clinically diagnosed alcoholic liver diseases

Summary To determine the incidence of hepatitis C virus (HCV) infection in patients with alcoholic liver disease (AID), serum samples from 252 patients with AID were tested for anti-HCV and HCV RNA. Serial sera of these patients were collected and stored under optimal conditions to allow exact quantification of HCV RNA. Fifteen patients who visited our hospital during the same period of time with chronic HCV infections served as controls. In those with AID, anti-HCV and HCV RNA were positive in 55.5% and 41.2%, respectively. Patients with histologically diagnosed chronic hepatitis and hepatocellular carcinoma had much higher prevalence rates of HCV RNA (84% and 100%, respectively) compared to those with fatty liver (4.3%), hepatic fibrosis (10.1%) and alcoholic hepatitis (22.2%) ( P < 0.01). Although no difference in serum HCV RNA levels was observed between the patients with both AID and chronic HCV infection and those with chronic HCV infection alone, HCV RNA levels significantly (10-fold) dropped after abstinence in nearly half of the patients ( P < 0.01). These data indicate that HCV infection in patients with AID promotes progression of liver disease, and abstinence from alcohol is associated with a reduction in serum HCV RNA levels.     

HCV-marker-positive autoimmune-type chronic active hepatitis: a possible relation between HCV infection and liver autoreaction

This study focused on 32 patients who were diagnosed as having autoimmune hepatitis based upon clinical and histological factors. Fifteen of these patients were positive for HCV-RNA and for one of the HCV-related markers tested, including anti-C100, ELISA II, and RIBA 2 (Group 2). The remaining 17 patients were negative for all HCV-related markers (Group 1). Clinical factors in the two groups, including the frequency of autoantibodies, serum levels of aminotransferase and gammaglobulin, HLA phenotypes, and the response to corticosteroid treatments, were compared. The titer of serum anti-nuclear antibodies and the level of serum aminotransferase at initial diagnosis were significantly higher in Group 1 than in Group 2. Furthermore, the genetic background of the two groups, as indicated by HLA phenotypes, differed. All cases in Group 1 were HLA-DR4-positive, whereas only 60% of those in Group 2 cases had HLA-DR4. Also, all cases in Group 1 but only 66.7% of the cases in Group 2 showed good clinical responses to corticosteroid treatment. Finally, no cases of HCV-related-marker-positive autoimmune hepatitis (Group 2) had antibodies for LKM, suggesting that these cases were clinically different from type II autoimmune hepatitis. These data indicated that immunosuppressive treatment might be the preferred initial treatment in patients who either satisfy the criteria for AIH or who are sero-positive for an HCV-marker.     

Serum HCV RNA levels correlate with histological liver damage and concur with steatosis in progression of chronic hepatitis C

The role of HCV RNA levels and host factors in the severity of liver injury was studied. Enrolled were 298 consecutive liver biopsy-proven chronic hepatitis (CH) C patients (179 men; median age: 52 years, range 19–68; CH, 198; cirrhosis, 100) and 18 chronic hepatitis C with normal ALT. HCV genotypes were: 1a, 4.3%; 1b, 53%; 2a/c, 28%; 3a, 7%; 4, 1.3%, and mixed 6.4%. Serum HCV RNA levels were similar for all genotypes (median: 2.8 × 10⁶ eq/ml; range <0.2–69). In patients with chronic hepatitis without cirrhosis, the serum HCV RNA levels reflected the grade of liver necroinflammatory activity (R = 0.45; P < 0.001) and the stage of fibrosis (R = 0.51; P < 0.001), regardless of age, gender, HCV genotype, hepatic steatosis, and hepatic iron overload. Patients with high serum HCV RNA levels (3 × 10⁶ eq/ml) had higher ALT values (P < 0.002) than those with lower HCV RNA levels. Patients with normal ALT showed low HCV RNA levels (median: 0.82 × 10⁶ eq/ml) and histological features of minimal or mild chronic hepatitis. Cirrhotic patients showed significantly lower levels of viremia than those with chronic hepatitis with a similar HAI. The data of a subgroup of 62 patients with an established time of infection showed that for a similar duration of disease, patients with serum HCV RNA levels 3 × 10⁶ eq/ml had a significantly higher fibrosis score than those with lower levels. HAI and fibrosis score were significantly higher in patients with HCV RNA levels 3 × 10⁶ eq/ml and grade 3–4 steatosis than those with lower HCV RNA levels and steatosis grades. The data indicate that the liver damage is correlated with the HCV RNA levels and that a high viral load acts together with steatosis in accelerating the progression of liver injury.     

Long-term treatment of chronic hepatitis C with ursodeoxycholic acid: influence of HCV genotypes and severity of liver disease

Abstract: Aims/Background: Current therapy for chronic hepatitis C virus (HCV) infection is based on the administration of interferon alpha (IFN) alone or in combination with other anti-viral agents. However, such therapy is effective in only a minority of selected patients. Long-term ursodeoxycholic acid (UDCA) treatment has been reported to improve liver function and structure especially in cholestatic disorders. We investigated the effect of long-term UDCA treatment on liver function in respect to the severity of chronic liver disease and HCV genotypes. Methods: Forty-five patients with non-cholestatic laparoscopy-biopsy proven HCV-associated chronic hepatitis (n=16) or cirrhosis (n=29) who had not responded to, or were unsuitable for IFN, were randomly assigned to receive UDCA (600 mg/day; n=23) or no therapy (n=22) for 12 months. At entry, all patients were evaluated by means of conventional and quantitative liver function tests (LFTs), including galactose elimination capacity and antipyrine clearance, HCV antibodies, HCV-RNA and HCV genotypes. LFTs were measured at 6 and at 12 months, whereas HCV-RNA was determined again after treatment. Results: Baseline characteristics were comparable in the two study groups. Long-term UDCA therapy was well tolerated. Based on the analysis of variance, there was a significant decrease in serum transaminase, LDH and GGT levels in UDCA treated patients. By contrast, the activities of these enzymes increased in untreated patients, with AST levels reaching statistical significance only. Statistical analysis also showed that the improvement in biochemical markers was more pronounced in UDCA treated patients with liver cirrhosis than in those with chronic hepatitis but was similar in patients with HCV genotype lb and non-1b. However, HCV-RNA was positive in all patients after treatment. Quantitative LFTs remained, on average, stable over the 12 months of the trial in all groups. Conclusions: Long-term UDCA treatment is well tolerated in patients with HCV-associated chronic liver disease. The effect appears to be greater in cirrhotics than in patients with chronic hepatitis but is independent of HCV genotypes. Thus, long-term UDCA treatment, despite the absence of an anti-viral effect, seems beneficial in reducing disease activity in patients with chronic hepatitis or cirrhosis who are unsuitable for IFN therapy.     

酒精性肝病合并肝炎病毒感染的临床特点分析

目的 探讨酒精性肝病合并肝炎病毒感染的临床特点,评价酒精性肝病与肝炎病毒感染的关系.方法 选择我院2004年1月至2011年5月收治经确诊的271例酒精性肝病患者,对其临床资料及实验室结果进行回顾性分析.结果 271例酒精性肝病中118例(43.5％)肝炎病毒标志物阳性,其中乙型肝炎病毒标志物阳性的101例(37.3％),丙型肝炎病毒标志物阳性的2例(0.7％),戊型肝炎病毒标志物阳性的14例(5.2％),甲型肝炎病毒标志物阳性的1例(0.3％),无肝炎病毒感染的153例(56.5％).肝炎病毒感染阳性组上消化道出血、肝性脑病百分率比较差异有统计学意义(P＜0.05).两组血清肝功能均有不同程度的异常,且阳性组ALT、AST、TBil、GGT明显高于阴性组,差异有统计学意义(P＜0.05).结论 酒精与肝炎病毒对肝脏损伤有协同作用,酒精性肝病合并肝炎病毒感染加重肝脏的损伤.     

Synergism of chronic alcoholism and hepatitis B infection in liver disease

One hundred and fifty-seven patients with alcoholic liver disease were studied. Hepatitis B surface antigen (HBsAg) was positive in 20.4% of the patients. Those who were positive for the HBsAg presented at an earlier age, had a lower albumin level, a higher globulin level, a more prolonged prothrombin time, were more likely to have features of cirrhosis in the liver biopsy, and were probably more likely to suffer from hepatic encephalopathy in the follow-up compared with those negative for HBsAg. The mortality of subjects was low both on admission and during follow-up. It is concluded that chronic alcoholism and hepatitis B virus infection act synergistically in producing more severe liver damage and causing cirrhosis at a younger age compared with chronic alcoholism alone. One possible reason for the low mortality of the patients might have been their relatively good nutritional status.     

Incidence of hepatitis B virus infection in alcoholic liver disease,HBsAg negative chronic active liver disease and primary liver cell cancer in Britain

ABSTRACT— A study has been undertaken to determine the incidence of serum markers of hepatitis B virus (HBV) infection in British caucasian patients with biopsy-proven alcoholic liver disease (n = 56), HBsAg negative chronic active liver disease (CALD) (n = 47) and primary liver cell cancer (PLCC) (n = 27), compared to a hospital control population without liver disease (n = 112). No increased incidence of any serum marker of HBV infection was found in alcoholic liver disease or in ‘lupoid’ CALD (antinuclear factor positive 1:40 and/or smooth muscle antibody positive > 1:40). In contrast, the incidence of antibody to HB surface and core antigens was significantly increased (p<0.05) in patients with cryptogenic CALD. The incidence of hepatitis B surface antigen and antibodies to HB core and ‘e’ antigens was significantly increased (p<0.005) in PLCC.     

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).     

A novel immunocompetent rat model of HCV infection and hepatitis

BACKGROUND & AIMS: Hepatitis C virus (HCV) infects millions of people worldwide. Therapy is limited, and treatment does not produce a sustained response in the majority of patients. Development of new agents has been hampered by the lack of a convenient animal model. The aim of this study was to determine whether an immunocompetent rat, tolerized and transplanted with a human hepatoma cell line (Huh 7 cells), could be used to sustain an HCV infection. METHODS: Fetal rats were tolerized in utero with 10(5) Huh 7 cells. One day after birth, rats were transplanted with 5 x 10(6) Huh 7 cells and, a week later, inoculated with HCV, genotype 1. RESULTS: In tolerized, transplanted, and HCV-infected rats, Huh 7 cells were found in the liver, and HCV viral replication was detected by the presence of negative strand HCV RNA. HCV levels in serum were measured at 11,000 copies/mL at week 4, peaked at 22,500 copies/mL by week 12. In tolerized, transplanted, inoculated rats, but not controls, serum alanine aminotransferase (ALT) values increased to 60 IU/L by week 4 and reached a peak of approximately 120 IU/L by week 13. Histology showed foci of mononuclear infiltrates in portal and central regions. CONCLUSIONS: HCV-inoculated immunocompetent rats tolerized and transplanted with Huh 7 cells support HCV gene expression, viral replication, and develop biochemical and histologic evidence of hepatitis.     

Hepatitis C virus (HCV) genotypes and chronic liver disease in Pakistan

Hepatitis C virus (HCV) is classified into different types depending on nucleotide sequence variability. Detailed information on the distribution of various HCV genotypes in some geographical areas is available but little is known about Pakistan. In this study, a 5’ non-coding region (NCR)-based restriction fragment length polymorphism (RFLP) genotyping assay was used to investigate the genotype distribution in a large series of HCV-infected patients in Karachi, Pakistan. Serum samples from 74 hepatitis B surface antigen (HBsAg)-negative patients with a clinical diagnosis of chronic liver disease (60 patients) and hepatocellular carcinoma (HCC) (14 patients) were assayed for anti-HCV antibody by second generation enzyme immunoassay and 48 were confirmed anti-HCV-positive (33 males, 15 females). Other causes of chronic liver disease (e.g. haemochromatosis, Wilson's disease and immunemediated injury) were ruled out. Liver biopsy was done in 27/48 anti-HCV-positive patients and in all HCC patients. Genotypes were determined for 45/48 anti-HCV-positive study patients; 39/45 (87%) were type 3; four (9%) were type 1; one was type 2; and one was type 5. Past blood transfusion was the main identifiable risk factor found in 10 patients, all type 3. Seven of the 14 HCC patients were anti-HCV positive, (six were type 3). Most patients with hepatitis C presented with established cirrhosis and complications of portal hypertension and liver failure. In conclusion: (i) genotype 3 is the most common isolate in HCV-associated chronic liver disease in Pakistan; (ii) a significant proportion of HBsAg-negative cirrhotics are non-B, non-C in aetiology; and (iii) half of the patients with HCC have serological evidence of HCV infection.     

Profiles of antinuclear antibodies in chronic active hepatitis,primary biliary cirrhosis and alcoholic liver disease

ABSTRACT— The profiles of specific antinuclear antibodies were determined in sera from 23 patients with the idiopathic type of chronic active hepatitis (CAH), 15 patients with primary biliary cirrhosis (PBC) and 25 patients with alcoholic liver disease (ALD). The indirect immunofluorescence test for antinuclear antibodies using cultured human embryonic fibroblasts as substrate was positive in 78% in CAH, in 73% in PBC and in 24% in ALD. Seventeen percent of CAH sera and 33% of PBC sera stained small speckles in interphase nuclei. This staining pattern probably represents a new subset of ANA as the centromeres (kinetochores) were not stained. Antibodies to native DNA by the Crithidia luciliae test were found in only one serum from a patient with CAH. In addition, 17 percent of the CAH sera reacted with the saline extract of rabbit thymus by double immunodiffusion. Antibodies to the Sm- or RNP-antigens were not found. SS-B antibodies could be demonstrated in 39% of the CAH sera by a sensitive immunoenzymatic technique. Patients with CAH also had significantly higher levels of antibodies against denatured, single-stranded DNA (ss-DNA) and a synthetic RNA molecule, poly(A) as compared to other groups. Patients with an atypical cholestatic CAH had an antinuclear-antibody profile resembling that of the other CAH patients, but different from that of PBC patients. Patients with alcoholic cirrhosis had significantly higher levels of ss-DNA- and poly(A)-antibodies than other patients with ALD. It is concluded that the determination of an antinuclear-antibody profile using the ELISA seems to be clinically useful in the classification of chronic liver diseases.     

慢性乙型肝炎与非酒精性脂肪性肝病患者内皮功能检测*

目的探讨慢性乙型肝炎（CHB）、非酒精性脂肪性肝病（NAFLD）和CHB合并NAFLD患者内皮功能和脂质代谢的差异。方法在CHB患者32例,NAFLD患者35例和CHB合并NAFLD患者44例,使用Endo-PAT 2000内皮功能检测仪测定外周动脉张力（PAT）,并计算血管反应性充血指数（RHI）;检测空腹血糖（FPG）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、甘油三脂（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白A（apoA）、载脂蛋白B（apoB）、脂蛋白a（LP-A）和游离脂肪酸（FFA）等血液生化指标。结果NAFLD患者RHI（1.95±0.44）显著高于CHB患者[（1.68±0.28）,P<0.05];NAFLD和CHB合并NAFLD患者体质指数【BMI分别为（24.77±3.13） kg/m²和（25.79±2.80） kg/m²]、TG [（1.52±0.70） mmol/L和（1.68±0.89） mmol/L]、TC[（4.32±0.1.32） mmol/L和（4.18±1.18） mmol/L]、LDL-C [（10.72±46.51） mmol/L和（2.71±0.96） mmol/L] apoB [（0.90±0.20）g/L和（0.85±0.28）g/L]均显著高于CHB患者[（22.63±3.14）kg/m²、（0.89±0.26） mmol/L （3.51±0.74） mmol/L（2.23±0.56） mmol/L （0.68±0.15）g/L,P<0.01]。结论CHB与NAFLD患者内皮功能和脂质代谢可能存在差异。     

High prevalence of antibody to hepatitis C virus in heavy drinkers with chronic liver diseases in Japan

To investigate the prevalence of antibody to hepatitis C virus (anti-HCV) in heavy drinkers with liver disease in Japan, we tested serum samples from 113 heavy drinkers with liver disease and 121 without liver disease. All were negative for HBsAg with no history of blood transfusion. These subjects had consumed more than 80 g of ethanol daily for 5 years or more. Findings for anti-HCV determined by recombinant immunoblot assay testing were positive in 14 (35.9%) of the 39 patients with liver cirrhosis, 14 (58.3%) of the 24 patients with hepatocellular carcinoma and in 8 (53.3%) of the 15 patients with chronic hepatitis. The anti-HCV positive rate in the drinkers with these liver diseases was significantly higher than in those with such disorders as fatty liver (0/10), hepatic fibrosis (0/22), and alcoholic hepatitis (0/3), as well as in the alcoholics without liver disease (5/121, 4.2%). Considering histologic findings in the anti-HCV positive cirrhotics, the occurrence of lymph follicle formation (71.4%), piecemeal necrosis (78.6%) and loose fibrosis (64.3%) were observed to a significantly higher extent than in cirrhotics who were negative for anti-HCV. These findings suggest that advanced chronic liver disease among heavy drinkers in Japan, especially of hepatocellular carcinoma, is closely associated with HCV infection. In the livers of heavy drinkers who were positive for anti-HCV, histologic findings indicated the possibility of viral infection.     

Incidence of extrahepatic cancers among individuals with chronic hepatitis B or C virus infection: A nationwide cohort study

This study examined the association between chronic HBV or HCV infection and the risk of extrahepatic cancers. A total of 537 103 adults aged ≥20 years without history of cancer were identified from the Korean National Health Insurance Service‐National Sample Cohort between 2003 and 2013. The difference in cancer incidence was compared between those with and without chronic HBV or HCV infection. During 3 854 130 person‐years of follow‐up (median follow‐up: 8.0 years), 19 089 participants developed cancer. After adjusting for sex, body mass index, smoking, drinking, income percentile, residential area and comorbidities, hazard ratios (HRs) for incident extrahepatic cancer were significantly higher in participants with chronic HBV infection (HR: 1.27, 95% confidence interval [CI]: 1.20‐1.35), HCV infection (HR: 1.31, 95% CI: 1.16‐1.48) or HBV/HCV dual infection (HR: 1.41, 95% CI: 1.31‐1.72) compared to participants without HBV or HCV infection. In chronic HBV infection, the cancer risk was higher for haematologic malignancy [HR (95% CI) = 2.46 (1.92‐3.15)], gallbladder [1.55 (1.05‐2.29)], pancreas [1.52 (1.07‐2.15)], stomach [1.39 (1.22‐1.58)], lung [1.27 (1.04‐1.55)], colorectum [1.21 (1.03‐1.42)] and thyroid cancer [1.20 (1.05‐1.36)]. In chronic HCV infection, the cancer risk was higher for testis [10.34 (1.35‐79.78)], gallbladder [2.90 (1.62‐5.18)], prostate [2.51 (1.65‐3.82)] and thyroid cancer [1.46 (1.10‐1.93)]. In conclusion, chronic HBV or HCV infection was not only associated with an increased risk of liver cancer, but also associated with an increased risk of multiple extrahepatic cancers.     

重症酒精性肝炎与肝移植

饮酒相关性肝病包括酒精性脂肪肝（alcoholic steatosis,AS）、酒精性肝炎（alcoholic hepatitis,AH）和酒精性肝硬化（alcoholic liver cirrhosis,ALC）等一组疾病[1]。重症酒精性肝炎（severe alcoholic hepatitis, SAH）是AH的严重类型,可发生于无肝病史的人群（急性酒精中毒）,也可发生在AS或ALC患者。主要表现为发热、肝脏肿大伴触痛、血清胆红素和外周血白细胞显著升高,可伴有慢性肝损伤和门脉高压的表现。 SAH 患者Maddrey 判别函数（Maddrey discrimi-nant function,MDF）［MDF=4.6x（PT-正常对照）＋TBIL （mg/dl）］通常≥32分,极易并发感染和多器官功能衰竭[2]。即使积极治疗,SAH 患者近期病死率仍可高达35%至50%[3]。     

Pathogenesis of liver cirrhosis in alcoholic patients: histological evidence for hepatitis C virus responsibility

ABSTRACT— Hepatitis C virus (HCV) has been proposed to be a cofactor in the pathogenesis of cirrhosis in patients with chronic alcoholism. The demonstration of a different liver histological pattern in anti-HCV positive patients might provide additional evidence. We studied 164 patients with chronic alcoholism, and histologically proven cirrhosis. For all of them, serum samples were collected at the time of a liver biopsy and stored at –80°C. Testing for anti-HCV antibodies was done using the Ortho Diagnostic Systems Anti-HCV ELISA test. Only reproducible results were considered positive. A semi-quantitative assessment of seven histological parameters was made independently on liver biopsy samples. In the study group, 29 patients (18%) had anti-HCV antibodies. When compared with anti-HCV negative patients, both groups had similar ALT and AST seric activities. Anti-HCV positive patients had a greater score of mononuclear cells infiltrate (0.71±0.57 vs 0.41 ±0.52; p<0.05) and a lesser score of alcoholic hepatitis (0.19 ±0.57 vs 0.74 ±0.74; p<0.005). The scores for steatosis, perisinusoidal and perinodular fibrosis, and hepatocellular necrosis were similar in the two groups. In anti-HCV positive patients, with a clearly positive recombinant immunobinding assay (RIBA, Chiron-Ortho Diagnostic Systems), a greater score for hepatic necrosis and a lesser one for fibrosis were demonstrated. Among the seven patients with active cirrhosis, six were anti-HCV positive. Therefore, HCV is likely to play a role in the pathogenesis of liver damage in a few patients with alcoholic cirrhosis, especially, those with active cirrhosis.