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

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 degrees 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 less than 0.05) and a lesser score of alcoholic hepatitis (0.19 +/- 0.57 vs 0.74 +/- 0.74; p less than 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.     

Chronic hepatitis C virus infections in leukemia survivors: prevalence, viral load, and severity of liver disease.

The natural history of chronic hepatitis C (HCV) infections in long-term leukemia survivors has not been well characterized. We studied the prevalence of HCV infections, measured HCV RNA levels, and evaluated the severity of liver disease in patients with leukemia who achieved long-term remissions after intensive chemotherapy or bone marrow transplantation (BMT). HCV antibody tests were performed by the enzyme-linked immunosorbent assay (ELISA) and positive tests confirmed by the recombinant immunoblot assay (RIBA). HCV RNA levels were measured by the branched DNA (bDNA) assay. Seventy-five leukemia survivors with 25 or more blood donor exposures were identified. Nine (12%) were anti-HCV positive. All were infected before 1992 when second generation HCV screening tests were implemented. Mean HCV RNA levels were 10.3 x10(6) eq/mL versus 3.2 x 10(6) eq/mL (P =.056) in a control group of 20 anti-HCV positive immunocompetent individuals of comparable age who were infected twice as long (17.8 +/- 6.5 years v 9.0 +/- 4.4 years in leukemia survivors, P =.001). Liver biopsies were performed on six of the nine anti-HCV positive leukemia survivors. All showed at least moderate portal inflammation and half had evidence of bridging fibrosis. We conclude that viral loads in anti-HCV positive leukemia survivors are markedly higher than in immunocompetent controls. Our results suggest that long-term leukemia survivors with chronic HCV may have more rapidly progressive liver disease than has been previously recognized.     

Hepatitis C viremia and anti-HCV antibodies in alcoholics

We determined serum hepatitis C status using a RIBA2 kit and a sensitive PCR procedure in 62 chronic alcoholics, 36 of whom had anti-HCV antibodies (Ab) detectable in an ELISA1 assay. Anti-HCV antibodies were detected in 22 patients using RIBA2. HCV RNA was detected by means of PCR in 18 patients who were RIBA2 positive and in none who were RIBA2 negative. Liver biopsies, available for 12 HCV RNA-positive patients, revealed histological features of purely alcohol-related lesions in seven and mixed alcohol-viral lesions in five. These results indicate that HCV replication is maintained in most alcoholics who score positive for anti-HCV Ab in the RIBA2 test, and that HCV viremia can be associated with histological features typical of alcoholic liver disease.     

Epidemiology,serological markers,and hepatic disease of anti-HCV ELISA-2-positive blood donors

The epidemiology associated with hepatitis C virus (HCV) infection, serologic reactivity, and hepatic disease related to anti-HCV-positive donors of Granada were researched. From 1990 through 1993, medical and epidemiological information and anti-HCV and HCV RNA testing were evaluated in 46,741 blood donors. Serum samples were obtained for anti-HCV ELISA and RIBA and HCV RNA determination. A liver biopsy was conducted in all anti-HCV positives by confirmatory second-generation RIBA to analyze the hepatic lesion and the presence of HCV RNA. The anti-HCV prevalence was 1.12%. A total of 228 anti-HCV second-generation ELISA positive blood donors were analyzed. Intrafamiliar transmission rate was 1.7%. Transfusion and intravenous drug abuse (IVDA) antecedents were associated with a higher risk of seroconversion. A RIBA-positive result was related to high second- and third-generation ELISA ratios (90%), HCV RNA positivity (89%), and elevated alanine aminotransferase (ALT) levels (88%). Approximately 50% of donors with normal ALT levels had high ELISA ratios and second-generation RIBA and HCV RNA positive results. Of the second-generation RIBA indeterminate results, 42% and 82% of the c22 and 33% and 100% of the c100 reactivities were third-generation RIBA and HCV RNA positive, respectively. Liver biopsy was conducted in 85 donors, 74% of whom had a chronic hepatitis and 83% had detectable HCV RNA levels. Chronic hepatitis was diagnosed in 88% vs 43% of donors with elevated and normal alanine aminotransferase levels, respectively. ELISA and confirmatory HCV RNA determinations should be routinely employed in donor screening. A liver biopsy should be conducted in patients with elevated ALT levels and normal ALT levels when viremic.     

Prevalence of hepatitis C virus markers in Sri Lankan patients with alcoholic cirrhosis

Abstract A high prevalence of antibodies against hepatitis C virus (HCV) has been reported in patients with alcoholic cirrhosis. There are, however, doubts regarding the specificity of the first generation anti-HCV antibody assays used. We prospectively investigated HCV status in 47 Sri Lankan patients with alcoholic cirrhosis. A first generation assay (Ortho HCV enzyme-linked immunosorbent assay [ELISA]) and two second generation tests (Abbott HCV enzyme immunoassay and United Biomedical Incorporated HCV enzyme immunoassay) were used. Positive results were confirmed by the second generation recombinant immunoblot assay (RIBA 2). Of the 47 patients (46 males, mean age 41.7 years), 17 (36.2%) had previously had one or more blood or plasma transfusions. Seven (14.9%) of the samples were positive for anti-HCV antibodies using the Ortho-HCV ELISA, but only one (2.1%) sample was positive when tested with the second generation assays. The positive result was confirmed by RIBA 2. The prevalence of HCV in the patients was low despite many of them being exposed to blood or blood products. Hepatitis C virus, therefore, may not be an important pathogenic factor in alcoholic cirrhosis in Sri Lanka.     

Hepatitis C virus RNA in southern African blacks with hepatocellular carcinoma.

We used a sensitive and specific cDNA polymerase chain reaction assay to detect hepatitis C virus (HCV) RNA in serum samples from 128 unselected southern African Blacks with hepatocellular carcinoma (HCC) and found HCV RNA in 26 (20.3%) of these patients. Antibodies to HCV (anti-HCV) were detected in 59 patients (46.1%) with a first-generation ELISA test, and only 19 of these patients were HCV RNA-positive. Anti-HCV was detected in 25 patients (19.5%) with a second-generation ELISA test, and 17 of these patients were HCV RNA-positive. Among the second-generation ELISA- and HCV RNA-positive patients, 14 were anti-HCV positive, 2 were indeterminate, and 1 was anti-HCV negative in a second-generation recombinant immunoblot assay, whereas all patients who were second-generation ELISA positive, but HCV RNA negative, were anti-HCV negative in this immunoblot assay. A total of 5 patients were negative in both ELISA tests but were HCV RNA positive. Seventy-one patients (55.5%) had evidence of a current HBV infection, 50 (39.1%) had evidence of a previous infection, and 7 (5.5%) had no evidence of a current or previous HBV infection. The prevalence of current HBV infection was significantly lower in patients who were positive for HCV RNA than in those who were negative (P = 0.001). This difference was not dependent on sex, age, or geographical location of the patients. The mean age of HCC patients positive for HCV RNA (52.3 years) was significantly higher (P < 0.001) than that of negative patients (40.3 years), and the difference was not dependent on HBV status or geographical location. Patients positive for HCV RNA were more likely to be urban than were negative patients. Thus, a significant number of southern African Blacks with HCC had a current HCV infection but not a current HBV infection, further suggesting that infection with HCV plays a role, albeit minor, in the development of HCC in this population.     

Intrafamilial transmission of hepatitis C virus in Japan

To study the intrafamilial transmission of hepatitis C virus (HCV), 36 family members of 16 patients with anti-HCV (anti-C100-3)-positive chronic liver disease were screened for anti-HCV by an enzymelinked immunosorbent assay (ELISA). Clusters of anti-HCV -positive individuals were observed in 2 of 16 families (12.5%). Four of 35 family members (11.4%) with no history of blood transfusion were positive for anti-HCV. Two of 17 offspring (11.8%) of anti-HCV-positive females were positive for anti-HCV, while 1 of 5 spouses (20.0%) was positive for anti-HCV. These data suggest that intrafamilial transmission is one of the possible routes of infection for HCV.     

Intrafamilial transmission of hepatitis C virus in Japan.

To study the intrafamilial transmission of hepatitis C virus (HCV), 36 family members of 16 patients with anti-HCV (anti-C100-3)-positive chronic liver disease were screened for anti-HCV by an enzyme-linked immunosorbent assay (ELISA). Clusters of anti-HCV-positive individuals were observed in 2 of 16 families (12.5%). Four of 35 family members (11.4%) with no history of blood transfusion were positive for anti-HCV. Two of 17 offspring (11.8%) of anti-HCV-positive females were positive for anti-HCV, while 1 of 5 spouses (20.0%) was positive for anti-HCV. These data suggest that intrafamilial transmission is one of the possible routes of infection for HCV.     

Outcome of acute symptomatic non-A,non-B hepatitis: a 13-year follow-up study of hepatitis C virus markers

ABSTRACT— Thirty-nine of 61 prospectively followed patients who had had acute non-A, non-B hepatitis in 1978 were clinically reexamined in 1991 and tested for antibodies to hepatitis C virus (anti-HCV) with a second generation ELISA and RIBA and for HCV RNA by PCR. Acute hepatitis C was diagnosed in stored sera from 1978 in 24 patients, who were found still to be anti-HCV positive in 1991, and 16 of them were also HCV RNA positive. The majority of anti-HCV positive patients with or without HCV RNA had elevated serum ALT levels 13 years after onset of their acute hepatitis C. After 13 years follow-up, 1.6% of the patients had died of end-stage liver disease, 8% of anti-HCV positive patients had histologically confirmed liver cirrhosis, 79% of anti-HCV positive patients were judged to have chronic infection, whereas 21% seemed to have recovered. To conclude, we found that a majority of our patients with acute symptomatic hepatitis C continued to be viraemic 13 years after onset of hepatitis C, and that all continued to be anti-HCV positive by second-generation ELISA.     

Serum hepatitis C virus sequences in posttransfusion non-A, non-B hepatitis.

We investigated 17 patients (12 males and 5 females, ages 2 to 57 years old) with posttransfusion non-A, non-B hepatitis to determine relationships between clinical courses and hepatitis C virus (HCV) markers. The patients were grouped according to time course of abnormal serum alanine aminotransferase (ALT) levels into three categories (chronic biochemical disease, biochemically resolved chronic disease, and acute disease). Latest serum samples (1.3 to 10.8 years after blood transfusion) were used to detect antibodies against C100-3 antigen (anti-HCV) by enzyme-linked immunosorbent assay and HCV sequences by polymerase chain reaction (PCR) assay. Of the 17 patients, 13 patients (76.5%) were anti-HCV positive and 8 patients (47.1%), including one anti-HCV negative case, were positive for HCV RNA. In total, 14 patients (82.4%) were positive for either HCV markers. With respect to clinical course, HCV RNA was detected in six of eight patients (75%) with chronic biochemical disease, and in two of five patients (40%) with biochemically resolved chronic disease. HCV RNA was not detectable in convalescent sera from four patients with acute disease. These results show that there is a relationship between clinical status and HCV viremia, but that normal liver function tests do not always represent the clearance of the virus. Viremia in two patients with normal ALT level suggests that hepatitis is not only caused by viral cytopathic effects, but also by immunologic reactions against virus-infected cells. Thus, PCR is useful in determining the persistence of HCV infection as well as to diagnose anti-HCV negative HCV infection.     

Anti-hepatitis C virus core IgM antibodies correlate with hepatitis C recurrence and its severity in liver transplant patients

BACKGROUND: The significance of immunoglobulin (Ig) M antibody to hepatitis C virus (HCV) core antigen was studied in 60 patients with HCV infection after orthotopic liver transplantation (OLT) diagnosed by polymerase chain reaction. METHODS: Patients were followed up for a mean of 28 months after transplantation. Sera collected three months before transplantation, and one and 12 months after transplantation were analysed for anti-HCV core IgM (HCV-IgM EIA 2.0 assay). After OLT protocol biopsies, procedures were performed routinely every six months. Semiquantitative histopathological assessment of allograft hepatitis was performed using Knodell's score. The results were correlated with clinical features, liver histology findings, and virological features, such as genotype and viraemic levels assessed by a branched DNA assay. RESULTS: One year after liver transplantation, 29/60 (48%) patients had chronic hepatitis on graft biopsy. The presence of anti-HCV core IgM one month (p=0.004) and 12 months (p=0.003) after OLT was positively correlated with recurrence of chronic hepatitis. The positive predictive value of anti-HCV core IgM detected one month after transplantation was 0.88. A significant relationship was observed between severity of graft disease and presence of anti-HCV core IgM 12 months after transplantation. The mean Knodell score was 8.9 in anti-HCV core IgM positive patients compared with 3.6 in those who were anti-HCV core IgM negative (p=0.001). The presence of IgM anti-HCV did not correlate with serum HCV RNA level or HCV genotype. CONCLUSION: We confirm that the presence of anti-HCV core IgM after OLT is a marker of HCV induced graft damage. The recurrence and severity of HCV hepatitis in patients undergoing OLT for HCV cirrhosis is related to the presence of anti-HCV core IgM after liver transplantation. These findings have diagnostic relevance and confirm that measurement of IgM anti-HCV core may help to better monitor the treatment of HCV recurrence after transplantation.     

Intrafamilial transmission of hepatitis C virus

Abstract The intrafamilial transmission pattern of hepatitis C virus (HCV) was examined in 118 family members of 61 index patients with type C chronic liver disease using anti-HCV antibodies and HCV RNA assay. The study subjects consisted of eight parents, 49 spouses, 50 children, eight siblings and three other relatives. The positivity rates of anti-C100, anti-JCC, second-generation anti-HCV and HCV RNA were 6.8, 12.7, 12.7 and 11.0%, respectively. Positivity in one or more anti-HCV antibody assay was detected in 3/24 (12.5%) father-child pairs, 3/17 (17.6%) mother-child pairs, 2/8 (25%) sibling pairs, 6/38 (15.8%) husband-wife pairs and 2/13 (15.4%) wife-husband pairs. In spouses, positivity for anti-HCV antibody or HCV RNA was observed after 40 years of age. None of 11 spouses married < 15 years was positive for any anti-HCV assay or HCV RNA. In spouses whose age was > 50 years and duration of marriage was > 25 years, anti-HCV or HCV RNA was frequently detected (32.0%). However, when seven pairs involving four spouses, one mother-daughter pair and two sibling pairs were subtyped, the same HCV subtypes were found in only four pairs (type II in three pairs and type III in one pair). Further, the agreement rate between anti-HCV and HCV RNA was > 90%. These results suggest that intrafamilial transmission of HCV, revealed by the subtyping method, is considered lower than the percentage of positivity for anti-HCV antibodies or HCV RNA in family members of patients with type C chronic liver disease. Thus, the intrafamilial transmission of HCV seems to be quite rare and much less common than that of HBV.     

Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission

Antibody to the recently identified hepatitis C virus (HCV) was investigated in sera of 50 leukemic children who had chronic liver disease (CLD), observed for 1 to 12.6 years after therapy withdrawal. All patients were tested for anti-HCV at regular intervals: Ortho- enzyme-linked immunosorbent assay (ELISA) test was performed in all cases. Reactive sera were also tested by recombinant immunoblotting assay to define the specificity of the results obtained by ELISA. Twelve cases (24%) were persistently positive (group A), 11 (22%) were transiently anti-HCV+ positive (group B), and 27 (54%) were negative. Mean SGPT peak during follow-up was significantly higher in group A (P = .014, A v B and P less than .00001, A v C). SGPT normalized off- therapy in 1 of 12 cases (group A), 10 of 11 (group B), and 19 of 27 (group C) (P = .0004, A v B and P = .012, A v C). Accordingly, liver histology, available in 37 patients, showed signs of chronic hepatitis in all patients in group A while most patients in group B and C had less severe liver lesions. These results indicate that HCV plays a significant role in the etiology of chronic hepatitis in leukemic patients and that persistent anti-HCV activity correlates with a more severe CLD, which could jeopardize the final prognosis of children cured of leukemia.     

Hepatitis C in patients undergoing liver transplantation.

OBJECTIVE: To determine the prevalence of antibodies to hepatitis C virus (anti-HCV) among patients undergoing liver transplantation and the relation between anti-HCV and post-transplant hepatitis. DESIGN: Retrospective cohort. PATIENTS: Serum samples from 128 patients who underwent liver transplantation. Sixty-six patients who had 6 months of follow-up and for whom both pretransplant and post-transplant serum samples were available were included in a study to asses the relation between anti-HCV and post-transplant hepatitis. MEASUREMENTS: Sera were tested for anti-HCV using an enzyme-linked immunosorbent assay (ELISA) and, if positive, two confirmatory tests were done. Patients had a biopsy every week until two specimens showed no abnormal findings. MAIN RESULTS: Only patients with chronic non-A, non-B hepatitis (15 of 30; 50%), alcoholic cirrhosis (7 of 19; 37%), and chronic hepatitis B infection (3 of 11; 27%) were anti-HCV positive. No patient with another form of chronic liver disease or with acute liver failure due to non-A, non-B hepatitis was anti-HCV positive. After transplantation, loss of anti-HCV was frequent and acquisition rare. Hepatitis developed in the graft in 17% of patients, but the incidence was similar among anti-HCV negative and anti-HCV-positive patients. CONCLUSIONS: Hepatitis C virus is a common cause of chronic liver disease in patients requiring liver transplantation, but anti-HCV is rarely found in patients with acute liver failure. Previous HCV infection, based on detection of anti-HCV, is not an independent risk factor for post-transplant hepatitis.     

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.     

Incidence of Post-Transfusion Hepatitis before and after Screening for Hepatitis C Virus Antibody

To evaluate the effectiveness of screening test for antibody to hepatitis C virus (anti-HCV), the incidence of acute post-transfusion HCV infection in patients who underwent cardiovascular surgery and received blood transfusion was studied. All patients were followed prospectively with serum biochemistry tests and viral hepatitis markers before and periodically for at least 6 months after cardiovascular surgery. None of them had history of liver disease and none tested positive for anti-HCV prior to blood transfusion. Before blood donors were screened for anti-HCV with a second-generation HCV diagnostic kit, 28 (12.4%) of 226 patients or 0.49% of 5,690 unit transfusion had seroconverted to anti-HCV during a 6-month follow-up. The incidence of post-transfusion hepatitis (PTH) C in 91 patients who had received 1–12 units transfusion was significantly lower than in 135 patients who had received more than 12 units transfusion (6.6 vs. 16.3%, p<0.05). However, none of the 87 transfused patients, since anti-HCV screening in July 1992, developed PTH C (p<0.05). The result demonstrates that screening for anti-HCV by a more sensitive second-generation HCV diagnostic assay may protect the patients studied from PTH C. It further provides a firm argument for the necessity of a nation-wide blood donor screening.     

经血液(非静脉吸毒者)和性途径传播的HIV感染者合并HBV和HCV感染的现状

目的 探讨我国经血液(非静脉吸毒者)和性途径传播的HIV感染者合并乙型肝炎和丙型肝炎的状况.方法 回顾性分析2005年1至9月在全国13个研究中心就诊的362例HIV/AIDS患者(静脉吸毒者除外),应用酶联免疫试剂盒分别测定其HBsAg、抗-HBs,HBeAg、抗-Hbe、抗-HBc和抗-HCV.采用t检验和X2检验分别对计量和计数结果进行统计学分析.结果 315例检测血HBV和HCV的患者中,HBsAg阳性14例,占4.4%;抗-HCV阳性158例,占50.2%,抗-HCV阴性157例,占49.8%;HIV、HBV、HCV共感染2例,占0.6%.抗-HCV阳性组中经血液和性传播的比例分别占92%和4%,以血液传播为主;抗-HCV阴性组中经血液和性传播的比例分别占11%和66%,以性传播为主.抗-HCV阳性组的HIV确诊时间、CD4+T淋巴细胞绝对计数、ALT和AST均高于抗-HCV阴性组.两组患者的HBV标志物表达也存在差异,其中抗-HCV阳性组中HBsAg阳性2例,占1.3%,抗-HCV阴性组中HBsAg阳性12例,占7.6%,两组比较差异有统计学意义(X2=7.542,P<0.01).10例HBsAg阳性者进行HBV DNA检测,其中4例阳性,抗-HCV均为阴性.57例抗-HCV阳性患者进行HCV RNA检测,阳性者占63.2%.结论 我国输血和性传播途径的HIV感染合并HBV或HCV感染,以合并HCV感染为主,并多见于经输血感染者.合并HCV感染可加重HIV患者的肝脏损伤,同时也可能存在干扰HBV复制的情况.