To examine the morbidity of compensated cirrhosis type B, a cohort of 349 Western European, white patients (86% men; mean age, 44 years) with biopsy-proven cirrhosis was followed up for a mean period of 73 months and was studied for occurrence of hepatocellular carcinoma (HCC) and decompensation. At entry into the study all patients were tested for hepatitis B e antigen (HBeAg; 34% of patients were HBeAg-positive) and antibody to hepatitis delta virus (anti-HDV; 20% of patients were anti-HDV-positive); 48% of 252 patients tested were hepatitis B virus (HBV)-DNA-positive. During follow-up HCC developed in 32 (9%) of the 349 patients and decompensation was observed in 88 (28%) of 317 tumor-free patients. Five years after diagnosis, the probability of HCC appearance was 6% and the probability of decompensation was 23%. After the first episode of decompensation the probability of survival was 35% at 5 years. Cox's regression analysis identified three variables that independently correlated with HCC: age, serum levels of platelets, and liver firmness on physical examination. HBV (HBeAg or HBV-DNA) and HDV (anti-HDV) markers at presentation had no prognostic value for the development of HCC. In conclusion, a high proportion of patients with HBsAg-positive compensated cirrhosis do not experience worsening of their condition for several years, but once decompensation occurs life expectancy is poor. European, white patients with compensated cirrhosis type B are at consistent risk for HCC. Prognostic factors for HCC reflect an advanced stage of cirrhosis and support the hypothesis that development of a tumor could be the likely consequence of long-standing hepatic disease.
Liver biopsy is required for staging hepatic fibrosis in patients with chronic hepatitis C, but it is an expensive procedure with occasional complications and poor patient acceptance. This cohort study was designed to assess the accuracy of a noninvasive method aimed to discriminate between patients with and without significant liver fibrosis (stages 2-4 versus 0-1). Clinically relevant variables were analyzed in a cohort of 476 consecutive untreated patients (estimation group, 351 patients; validation group, 125 patients) with chronic hepatitis C who underwent a liver biopsy. Multivariate analysis identified age, gamma glutamyl transpeptidase (GGT), cholesterol, platelet count, and prothrombin time as independent predictors of fibrosis. We constructed a model and a score system combining age, GGT, cholesterol, and platelet count that proved useful to identify patients without significant hepatic fibrosis. The area under the ROC curve was 0.86 for the estimation group and 0.81 for the validation group. Using the best cutoff score (less than 4.2), presence of significant fibrosis (F2 to F4) could be excluded with high accuracy (negative predictive value of 96%) in 125 (36%) of 351 patients. Similarly, it could be excluded with the same certainty in 49 (39%) of the 125 patients of the validation group. Only 2 patients with liver fibrosis stage 2 were incorrectly classified. In conclusion, a combination of easily accessible variables accurately predicts the absence of significant fibrosis and might render liver biopsy unnecessary in more than one third of patients with chronic hepatitis C. (HEPATOLOGY 2002;36:986-992.)
It is widely agreed that hepatitis B virus immunoglobulinSeveral reports have clearly shown that liver transplantation in patients with hepatitis B virus (HBV) infection-as defined by positivity for hepatitis B surface antigen (HBsAg)-is associated with a high rate of recurrence of HBV infection after transplantation, resulting in severe graft disease in most cases and in a significant decrease in both graft and patient survival. [1][2][3][4] It is widely accepted that the risk of HBV recurrence after liver transplantation is directly proportional to the level of viral replication before transplantation, with those recipients seropositive for HBeAg and HBV DNA by hybridization technique having the highest rate of recurrence after transplantation, irrespective of the type of liver disease. 2,4 Many prophylactic strategies have been proposed to prevent HBV infection of the graft, but only long-term passive immunoprophylaxis with HBV-specific immunoglobulin (HBIG) has obtained a significant reduction in the risk of HBV graft infection and in both graft and patient mortality after liver transplantation. [4][5][6][7] The presence of serum HBV DNA before transplantation is, however, a major predictor of lack of response to this prophylactic regimen.In light of these evidences, the European Concerted Action on Viral Hepatitis (EUROHEP) recommended in 1994 to refrain from transplanting chronic HBV carriers found to be positive for either hepatitis B e antigen (HBeAg) or HBV DNA by direct hybridization. Moreover, the rest of the recipients with HBV-related disease should receive HBIG immunoprophylaxis to maintain anti-HBs levels above 100 IU/L for at least 12 months after transplantation. 6 Currently, the beneficial effect of long-term HBIG administration has become widely accepted; still no consensus has been reached regarding the optimal duration of HBIG treatment. The rate of HBV graft infection recurrence 12 months after liver transplantation seems to be much decreased but it can still undoubtedly occur. 4,6,[8][9][10] Moreover the finding of HBV DNA in peripheral mononuclear blood beyond 12 months of effective HBIG prophylaxis argues in favor of a potentially indefinite risk of graft infection. 11-13 As a consequence, most liver transplant centers are currently administering HBIG on a life-long basis. Because HBIG use is highly expensive, an alternative strategy aiming at the discontinuation of HBIG prophylaxis during the second year of treatment would be an important cost-effective measure. We present here an assessment of the efficacy of a new prophylactic strategy consisting of the discontinuation of HBIG administration followed by active immunization with HBV vaccination in patients transplanted for HBVrelated liver diseases.
PATIENTS AND METHODSPatients. Between July 1990 and April 1996, 36 HBsAg-positive recipients were submitted to liver transplantation at the Hospital Abbreviations: HBV, hepatitis B virus; HBsAg, hepatitis B virus surface antigen; HBIG, hepatitis B virus immunoglobulin; HBeAg, hepatitis B vi...
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