Long-Term Mortality after Transfusion-Associated Non-A, Non-B Hepatitis

Seeff, Leonard B.; Buskell‐Bales, Zelma; Wright, Elizabeth C.; Durako, Stephen; Alter, Harvey J.; Iber, Frank L.; Hollinger, F. Blaine; Gitnick, Gary; Knodell, Robert G.; Perrillo, Robert P.

doi:10.1056/nejm199212313272703

Cited by 643 publications

(265 citation statements)

References 23 publications

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“…An estimated 20-30% of infected individuals will develop cirrhosis while others largely remain asymptomatic. [1][2][3][4][5][6] The contrasting outcomes of HCV infection have been attributed to viral genotypes and external modulators including alcohol consumption, 7-9 but immunoregulatory host factors are also likely to be involved.…”

Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor gene polymorphisms in patients with cirrhosis from chronic hepatitis C virus infection

et al. 2000

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Pro-inflammatory cytokines including tumour necrosis factor (TNF) mediate the pathogenesis of hepatitis C virus (HCV) infection. The distribution of TNF gene polymorphisms was examined among cirrhotic and non-cirrhotic patients infected with HCV. Thirty Caucasians with cirrhosis due to chronic HCV infection and 114 HCV-infected patients histopathologically free of cirrhosis were genotyped for genetic variants in TNF, lymphotoxin ␣ and TNF-receptor type I using PCR-based techniques. Variability in the progression of HCV-related cirrhosis was assessed in a multivariate model including genetic and non-genetic factors such as gender, estimated duration of infection, alcohol consumption, and viral genotype. Viral genotype and non-genetic host features were not independently related to the occurrence or rate of development of cirrhosis in the patient population. In contrast, the TNF promoter variants TNF2 (−238A) and TNF3 (−308A) conferred a 3.2-fold and 5.1-fold risk of cirrhosis respectively (P = 0.03 for both). Reciprocal effects were observed with several TNF alleles and haplotypes defined by the −238G/A and −308G/A dimorphic sequences. Polymorphisms in the TNF␣ promoter appear to be associated with variability in the histological severity of chronic hepatitis C infection. Genes and Immunity (2000) 1, 386-390.

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Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor gene polymorphisms in patients with cirrhosis from chronic hepatitis C virus infection

et al. 2000

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“…The factors that influence the rate of fibrotic progression in hepatitis C virus (HCV) include age at the time of HCV infection and at initial evaluation, male sex, HCV genotype, and alcohol consumption. [1][2][3][4][5][6][7][8] It is less clear as to whether any of these factors influence the onset of liver-related complications other than by their effects on the rate of fibrotic progression.The proportion of all patients with hepatitis C who develop life-threatening complications is also unclear. Many studies are confined to either the first 20 years of HCV infection when complications appear to be unusual, [8][9][10][11][12][13][14][15] or to the late stage of the disease when cirrhosis is present.…”

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confidence: 99%

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Which patients with hepatitis C develop liver complications?

Khan

Farrell

Byth³

et al. 2000

Hepatology

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To identify variables that are independent predictors of adverse outcomes in chronic hepatitis C, we analyzed a cohort of 455 patients followed for a median of 4.7 years. Associations were sought between demographic and behavioral factors, hepatitis C virus (HCV) genotype, liver histology and liver tests at entry, and development of liver complications, hepatocellular carcinoma (HCC), hepatic transplantation and liver-related death. Independent predictors were identified by multivariate analysis. The following were associated with a significantly higher rate of liver complications: age; birth in Asia, Europe, Mediterranean region, or Egypt; transmission by blood transfusion or sporadic cases; HCV genotypes 1b and 4 (compared with 1/1a); fibrosis stage 3 or 4 (cirrhosis); serum albumin; bilirubin; prothrombin time; and ␣-fetoprotein. However, the only independent predictors of liver-related complications were sporadic transmission (P F .001), advanced fibrosis (P ‫؍‬ .004), and low albumin (P F .001). The corresponding independent risk factors for HCC were male gender (P ‫؍‬ .07), sporadic transmission (P F .001), and albumin (P F .001); bilirubin (P ‫؍‬ .02) was an additional predictor of transplantation or liver-related death. It is concluded that only patients with advanced hepatic fibrosis or cirrhosis, are at risk of developing hepatic complications of chronic hepatitis C during 5-year follow-up. Among such patients, abnormalities in serum albumin, bilirubin, or prothrombin time indicate a high probability of complications. The rate of fibrotic progression in chronic hepatitis C is highly variable, 1 and the natural history of the disease usually extends over several decades. In some patients, it may culminate in the life-threatening liver complications of portal hypertension, hepatocellular carcinoma (HCC), and liver failure requiring hepatic transplantation or leading to liverrelated death. Such complications are rarely noted in the absence of cirrhosis. The factors that influence the rate of fibrotic progression in hepatitis C virus (HCV) include age at the time of HCV infection and at initial evaluation, male sex, HCV genotype, and alcohol consumption. [1][2][3][4][5][6][7][8] It is less clear as to whether any of these factors influence the onset of liver-related complications other than by their effects on the rate of fibrotic progression.The proportion of all patients with hepatitis C who develop life-threatening complications is also unclear. Many studies are confined to either the first 20 years of HCV infection when complications appear to be unusual, [8][9][10][11][12][13][14][15] or to the late stage of the disease when cirrhosis is present. [13][14][15][16] Thus some cohort studies have found low mortality rates at 17 to 20 years, particularly among younger individuals and among those who have a risk factor other than blood transfusion. 8,9,11,12,17 Others have indicated that approximately 18% of patients develop liver-related complications or HCC or succumb to liver-related death within 18 year...

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“…1 Chronic HCV infection often leads to serious consequences, including liver cirrhosis and hepatocellular carcinoma. 2,3 Furthermore, some HCV-infected individuals continue to display no symptoms or signs of liver damage for a long time. 4,5 The factors that determine the development of chronic HCV infection have not yet been clarified.…”

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confidence: 99%