Tommaso Stroffolini

UNLABELLED: The effect of achieving a sustained virological response (SVR) following interferon-alpha (IFNalpha) treatment on the clinical outcomes of patients with HCV-related cirrhosis is unknown. In an attempt to assess the risk of liver-related complications, HCC and liver-related mortality in patients with cirrhosis according to the response to IFNalpha treatment, a retrospective database was developed including all consecutive patients with HCV-related, histologically proven cirrhosis treated with IFNalpha monotherapy between January 1992 and December 1997. SVR was an undetectable serum HCV-RNA by PCR 24 weeks after IFNalpha discontinuation. HCC was assessed by ultrasound every 6 months. Independent predictors of all outcomes were assessed by Cox regression analysis. Of 920 patients, 124 (13.5%) were classified as achieving a SVR. During a mean follow-up of 96.1 months (range: 6-167) the incidence rates per 100 person-years of liver-related complications, HCC and liver-related death were 0, 0.66, and 0.19 among SVR and 1.88, 2.10, and 1.44 among non-SVR (P<0.001 by log-rank test). Multivariate analyses found that non-SVR was associated with a higher risk of liver-related complications (hazard ratio, HR, not applicable), HCC (HR 2.59; 95% CI 1.13-5.97) and liver-related mortality (HR 6.97; 95% CI 1.71-28.42) as compared to SVR. CONCLUSION: Thus, in patients with HCV-related, histologically proven cirrhosis, achievement of a SVR after IFNalpha therapy was associated with a reduction of liver-related mortality lowering both the risk of complications and HCC development. Irrespective of SVR achievement, all patients should continue surveillance because the risk of occurrence of HCC was not entirely avoided.

Hepatitis delta virus (HDV) was responsible for a high proportion of cases of acute and chronic liver disease in Southern Europe during the 1970s. Some data suggest that by the 1990s HDV circulation had substantially declined. We have assessed the prevalence of HDV infection and its clinical impact in 834 Italian hepatitis B surface antigen (HBsAg) carriers in 1997. Anti-HDV antibodies were sought in all consecutive chronic HBsAg carriers observed in 14 referral liver units throughout Italy. Risk factors for anti-HDV positivity were evaluated. Anti-HDV antibodies were found in 69 of 834 (8.3%) HBsAg-positive patients. Cohabitation with an anti-HDV-positive subject, intravenous drug addiction, residence in the South of the country, and the presence of cirrhosis were independently associated with the presence of anti-HDV antibodies. The overall prevalence of anti-HDV antibodies was lower than those observed in 2 multicenter surveys performed in 1987 and 1992 (23% and 14%, respectively). By 1997, the percentage of anti-HDV-positive subjects had sharply decreased in the 30 to 50 years age group, whereas it was almost unchanged in subjects over 50 years of age. The highest prevalence of anti-HDV antibodies (11.7%) was found in patients with cirrhosis. This prevalence was as high as 40% in the 1987 study. The circulation of HDV sharply decreased in Italy, by 1.5% per year, from 1987 to 1997. This decrease resulted mainly from the reduction in chronic HDV infections in the young, for whom high morbidity and mortality rates were recorded in the past. The results anticipate the almost complete control of HDV infection in the near future.

We studied 648 hepatitis B surface antigen (HBsAg)- and/or anti-hepatitis C virus (HCV)-positive patients to evaluate the virologic and clinical characteristics of multiple hepatitis viral infection. We defined as Case B-C an HBsAg/anti-HCV positive patient and as Case b-C an anti-HCV/anti-HBc-positive, HBsAg/anti-HBs-negative patient. For each Case B-C we scheduled as Control-B an HBsAg positive and anti-HCV negative patient and as Control-C an HBsAg/anti-HBs/anti-hepatitis B core antigen (HBc)-negative and anti-HCV-positive patient. Control group C was used as the control also for Case group b-C. Serum HBV DNA by molecular hybridization was found more frequently in Control group B (54% of 161 patients) than in Case group B-C (35.7% of 84, P <.01). The prevalence of HBV wild type was similar in Case group B-C (14. 3%) and in Control group B (17.4%), whereas the e-minus strain was less frequent in Case group B-C (10.7% vs. 33%; P <.01). HBV DNA by polymerase chain reaction (PCR) was detected in 40.8% of 71 patients in Case group b-C. HCV RNA was detected more frequently in Control group C (90.7% of 130 patients) than in Case group B-C (65.2% of 69, P <.0001). Moderate or severe chronic hepatitis or cirrhosis were more frequent in Case group B-C (62.9% of 65 patients) than in Control group B (46.7% of 90, P <.05) or C (40.8% of 98, P <.005), and in Case group b-C (71.1% of 76) than in Control group C. Thus, in multiple hepatitis we observed a reciprocal inhibition of the viral genomes and a more severe liver disease. In Case group b-C, serum HBV DNA was frequent and the clinical presentation was severe.

BACKGROUND: The epidemiology of acute hepatitis C has changed during the past decade in Western countries. Acute HCV infection has a high rate of chronicity, but it is unclear when patients with acute infection should be treated. METHODS: To evaluate current sources of hepatitis C virus (HCV) transmission in Italy and to assess the rate of and factors associated with chronic infection, we enrolled 214 consecutive patients with newly acquired hepatitis C during 1999-2004. The patients were from 12 health care centers throughout the country, and they were followed up for a mean (+/- SD) period of 14+/-15.8 months. Biochemical liver tests were performed, and HCV RNA levels were monitored. RESULTS: A total of 146 patients (68%) had symptomatic disease. The most common risk factors for acquiring hepatitis C that were reported were intravenous drug use and medical procedures. The proportion of subjects with spontaneous resolution of infection was 36%. The average timespan from disease onset to HCV RNA clearance was 71 days (range, 27-173 days). In fact, 58 (80%) of 73 patients with self-limiting hepatitis experienced HCV RNA clearance within 3 months of disease onset. Multiple logistic regression analyses showed that none of the variables considered (including asymptomatic disease) were associated with increased risk of developing chronic hepatitis C. CONCLUSIONS: These findings underscore the importance of medical procedures as risk factors in the current spread of HCV infection in Italy. Because nearly all patients with acute, self-limiting hepatitis C--both symptomatic and asymptomatic--have spontaneous viral clearance within 3 months of disease onset, it seems reasonable to start treatment after this time period ends to avoid costly and useless treatment.