Careful interviewing of alcoholics who wish to undergo alcohol withdrawal programmes reveals that some are past intravenous drug abusers. As these two potentially hepatotoxic types of substance abuse could cause liver disease or influence its clinical course, we studied biological, histological and virological features in 26 alcoholics with a past history of intravenous (i.v.) drug abuse, compared with paired controls (alcoholics without i.v. drug abuse). There were no differences with regard to routine liver test results. In contrast, the former drug abusers had a significantly higher prevalence of serum markers of hepatitis C (76.9%) and hepatitis B viruses (76.9%) than the other patients (16.7 and 12.5%, respectively). Eight patients, all of whom were HBs Ag negative, were positive for serum HBV-DNA; three were former drug abusers and five were not, giving an overall prevalence of HBV markers in the two groups of 80.8 and 25%, respectively. Two former drug abusers had anti-HIV antibodies and one had anti-hepatitis delta virus antibodies. Ten of the 17 former drug abusers who underwent liver biopsy had histological signs of viral infection. These data underline the need for careful interviews of alcoholic patients, together with serological tests for viral infections and histological analysis of the liver, as some will have liver-damaging viral diseases and may be candidates for anti-viral (i.e. interferon) treatment.
This Phase 3 study evaluated telaprevir (T) in combination with pegylated-IFN alfa-2a (P) and ribavirin (R) in well-characterised G1 prior-PR treatment failure patients including prior PR non-responders (null and partial) and relapsers.
Method
REALIZE was a randomised, international, multicentre, double-blind, placebo-controlled trial evaluating efficacy, safety and tolerability of T (750 mg q8 h) plus P (180μg/w) and R (1000–1200 mg/d) compared with PR alone. The treatment arms (randomised 2:2:1, stratified by viral load and prior response) were: 12-weeks T/PR, followed by 36-weeks PR (T12PR48); 4-weeks PR followed by 12 weeks T/PR (T delayed start, DS), then 32-weeks PR (T12(DS)/PR48); 48-weeks PR (Pbo/PR48). The primary objective was efficacy of the T/PR arms in non-responders and relapsers. Secondary objectives included evaluation of T DS and efficacy in prior-null and -partial responders. HCV RNA was quantified using COBAS TaqManÆ v2.0 assay (LLOQ=25 IU/ml).
Results
833 patients were screened, and 662 treated. 70% of patients were male, 93% Caucasian, 26% had cirrhosis, and 89% had baseline HCV RNA ≥800 000 IU/ml. AEs reported more frequently in T arms were rash, pruritus, diarrhoea, anorectal disorders and anaemia. 13% of T/PR patients had premature discontinuation (D/C) of T due to AEs: rash (4%) and anaemia (3%) were the most common AEs leading to T D/C.
Conclusion
T/PR SVR was significantly superior to PR in all prior-treatment failure populations including null- and partial-responders. A telaprevir delayed start did not have a significant impact on SVR rates. Safety profile of T/PR was consistent with that observed in treatment naive subjects.
We prospectively determined the value of liver biopsy for microbiological diagnosis of infection in patients infected with the human immunodeficiency virus (HIV) who had unexplained fever and whose serum levels of alkaline phosphatase or gamma-glutamyl transferase were at least 1.5 times the upper limit of normal. From December 1989 to December 1991, 108 HIV-infected patients were referred to the Liver Unit at Hôpital Laënnec (Paris) with liver abnormalities related to viral hepatitis (generally chronic), AIDS-related sclerosing cholangitis, or nonspecific lesions (detected on histologic examination). Twenty-four patients had unexplained fever and increased levels of alkaline phosphatase or gamma-glutamyl transferase, and none had evidence of hepatobiliary disease. All 24 patients had undergone routine microbiological tests to determine the cause of their chronic fever. The results of all microbiological tests were negative. We performed liver biopsies for these 24 patients and examined the specimens by means of standard direct microbiological techniques; in addition, the specimens were cultured, the specimens were analyzed by standard histopathologic methods, and specific histologic studies for fungi, mycobacteria, and viruses were performed. A microbiological diagnosis was made in 13 (54%) of the 24 cases within 12 hours to 3 days of the liver biopsy. In conclusion, liver biopsy is a powerful diagnostic tool for rapid diagnosis of infection in HIV-infected patients who have unexplained fever and abnormal liver function test results.
