The Prevalence of antibody to hepatitis C virus (HCV) was studied in 207 patients with chronic liver disease of unknown etiology, in relation to clinical, epidemiological and histological features. Serum antibody to C-100 epitope of HCV was detected by ELISA in 82.6% of patients, with a significant difference compared with a group of patients with primary biliary cirrhosis (10%). The presence of anti-HCV antibody in serum did not correlate with age, sex, histological diagnosis, and activity and duration of the disease, nor with serum anti-HBc, used as a marker of exposure to hepatitis B virus infection. These results strongly support the view that most cases that were previously defined as cryptogenic forms of chronic liver disease are in fact related to HCV infection. There was a correlation between serum anti-HCV antibody and history of risk for parenteral exposure or of acute hepatitis. This correlation was particularly evident for transmission by parenteral route, suggesting that HCV infection may be transmitted often by this route (36.8% among anti-HCV antibody-positive patients and 11.1% among anti-HCV-negative patients). Liver disease in patients without risk factors for parenteral transmission and with lower prevalence of anti-HCV antibody may be caused by other as yet unidentified non-A, non-B (non-C) agents or may be of nonviral origin.

Our aim was to evaluate the role of N‐acetyltransferase (NAT2) and glutathione S‐transferase M1 and T1 (GSTM1 and GSTT1) polymorphisms in hepatocellular carcinoma (HCC) according to cigarette smoking, taking into account hepatitis B (HBV) and C (HCV) viral infection as well as alcohol consumption. A hospital‐based case‐control study was conducted in 2 areas of north Italy. Cases (n = 200) were patients hospitalized for HCC, and controls (n = 400) were patients admitted for reasons other than liver disease, neoplasms and tobacco‐ and alcohol‐related diseases. Genotypes were determined using PCR and the PCR/restriction fragment length polymorphism–based method. The putative risk genotypes NAT2 slow acetylator, GSTM1 null and GSTT1 null were not associated with HCC (OR = 1.3, 95% CI 0.8–2.0; OR = 1.0, 95% CI 0.6–1.5; OR = 0.8, 95% CI 0.4–1.4, respectively). Although not statistically significant, an increase in HCC risk was observed among light smokers (1–20 pack‐years) carrying GSTT1 null (OR = 1.7, 95% CI 0.6–4.7) and NAT2 slow acetylator (OR = 1.3, 95% CI 0.6–3.0) genotypes. In conclusion, there was no evidence for a gene–environment interaction in HCC risk for GSTM1, GSTT1 and NAT2 genotypes. © 2005 Wiley‐Liss, Inc.

Aim: To evaluate the prevalence of hepatitis B virus (HBV) infection among pregnant women, and the risk of mother-infant transmission of HBV infection, in children receiving full active and passive immunoprophylaxis at birth. Methods: A total of 24000 women, followed at the same Institution, 2002–2003, underwent screening for the presence of HBV surface antigen (HBsAg) during the last trimester of pregnancy. Newborns to HBV carrier women entered a follow-up programme, which included evaluation of surface antigen and markers of HBV at three and twelve months of age. Results: Newborns to mothers coming from developing countries were 4700 (20%).Women found positive for HBsAg were respectively 48 out of 19300 Italian pregnant women (0.24%; range: 0.1–0.4%) and 68 of 4700 immigrant women (1.44%; range: 1.1–1.8%). None of the children born to Italian mothers was found to be positive for HBsAg, while 2 (2.9%) infants born to immigrant women were positive for HBsAg at 3 months of life and developed acute hepatitis B. Sera of both children were tested for DNA, by polymerase chain reaction, with nested primers adjacent to the antigenic determinant a of the HBV S gene. The two children were found positive for HBV DNA and, after sequencing of amplified fragment, infected respectively by genotype D (wild type) the infant born to Egyptian mother and by genotype B (wild type) the child born to Chinese mother. Mother-child pairs resulted infected by the same genotype Conclusion: A close follow-up of children born to HBV carrier women is required, even if full active and passive immunoprophylaxis is performed, in order to monitor rate of vertical transmission of HBV infection and genotype involved.

Background/Aims: The role of coffee in the development of hepatocellular carcinoma (HCC) is debated. The aim of this study was to investigate the role of coffee in HCC, taking the main risk factors into account.Methods: A hospital-based case-control study was conducted in an area of northern Italy. We recruited 250 HCC cases and 500 controls hospitalized for any reasons other than neoplasms, and liver and alcohol-related diseases. Subjects were interviewed on their lifetime history of coffee consumption using a standardized questionnaire.Results: Coffee consumption in the decade before the interview was associated with a decreasing risk of HCC with a clear dose-effect relation. With respect to non-drinking subjects, the odds ratios (ORs) were: 0.8, (95% CI 0.4-1.3) for 1-2 cups/day, 0.4 (95% CI 0.2-0.8) for 3-4 cups/day and 0.3 (95% CI 0.1-0.7) for 5 or more cups/day. The ORs for HCC decreased for drinking >2, compared to 0-2 cups/day of coffee, for an alcohol intake >80 g/day (OR from 5.7 to 3.3), for presence of hepatitis B virus infection (OR from 16.4 to 7.3) or hepatitis C virus infection (OR from 38.2 to 9.0).Conclusions: Coffee drinking was inversely associated with HCC regardless of its aetiology. (C) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Retreatment of chronic hepatitis C patients nonresponders to interferon (IFN) alone with the standard dose of IFN [3 million units (MU) thrice weekly (TIW)] plus ribavirin for 24 weeks has yielded low sustained virological response (SVR), averaging 8%. The aim of the present, open-labelled, randomized study was to evaluate the efficacy of IFN induction therapy followed by prolonged high dose of IFN plus ribavirin in nonresponders. One hundred and fifty-one patients were randomized to receive 5 MU daily of IFN alfa-2b (group 1, n = 73) or 5 MU TIW of IFN alfa 2b (group 2, n = 78) for 4 weeks followed by IFN (5 MU TIW) plus ribavirin (1000/1200 mg/daily) for 48 weeks in both groups. In an intention-to-treat analysis, the sustained virological response (SVR) at 24-week follow-up was 33 and 23% for group 1 and 2, respectively (P = 0.17). The overall SVR was 52 and 18% in patients with genotype 2/3 and 1/4, respectively. Among genotype 1/4 patients the SVR was 29 and 11% for age younger or older than 40 years. Compared with genotype 2/3 patients, the risk (95% confidence interval) of nonresponse to retreatment was 3.0-fold (1.17-8.0) in younger genotype 1/4 patients and 8.4-fold (3.0-23.29) in older genotype 1/4 patients. In conclusion these results suggest that retreatment with a reinforced regimen should be focused in nonresponder genotype 2/3 patients and younger genotype 1/4 patients, who are most likely to benefit. Induction therapy does not improve SVR.

Il 28/07/03 un donna di 36 anni è giunta all'Ospedale di Gemona del Friuli lamentando da circa 24 ore cefalea, vomito e dolore alle spalle.Circa 2 settimane prima la paziente aveva presentato per 3 giorni una sindrome simil-influenzale.La paziente riferiva un morso di zecca durante un week-end trascorso in montagna in Provincia di Udine (Moggio-Chiusaforte). All'atto del ricovero si rilevava: 39°C, rigidità nucale, paralisi degli arti superiori (prevalentemente braccio sx e spalle), ipostenia dell'arto inferiore sx.Gli esami eseguiti evidenziavano: GB 13.840 x 10 9 /L (PMN 83%), TC encefalo negativa, liquor: limpido, GB 343/mm 3 (300 PMN), glicorrachia 48 mg/dL, protidorrachia 900 mg/dL.Veniva instaurata una terapia antibiotica empirica.Trasferita presso la Neurologia dell'Ospedale di Udine, veniva effettuata la RMN del rachide cervicale che dimostrava una lesione infiammatoria del midollo, con esclusivo interessamento delle corna anteriori.Poiché le sierologie per agenti neurotropi eseguite su siero e liquor risultavano negative, veniva eseguita la ricerca per TBEV: liquor IgM 4.7 index (positivo > 1 index) e IgG 48 U/ml (positivo > 5 U/ml ), siero IgM 6.8 index e IgG 49 U/ml.Analoga positività si è avuta con i test HIT e NT (ISS), confermando la diagnosi di meningo-encefalo-mielite da TBEV.

summary. Retreatment of relapser patients with chronic hepatitis C with the standard dose of interferon (IFN) of 3 million units (MU) thrice weekly (tiw) plus ribavirin for 24 weeks achieves a sustained response in 30 and 73% of patients with genotype 1 and 2 or 3, respectively. The aim of this study was to evaluate the efficacy and safety of IFN alpha-2b induction therapy, followed by prolonged treatment with a high dose of IFN alpha-2b plus ribavirin in relapser patients. A total of 119 patients were randomized to receive IFN alpha-2b 5 MU daily (Group A: 59 patients) or IFN alpha-2b 5 MU tiw (Group B: 60 patients) for 4 weeks followed by IFN (5 MU tiw) and ribavirin (1000-1200 mg/day) for 48 weeks in both groups. The primary end point was hepatitis C virus (HCV)-RNA clearance at week 24 after the end of treatment. A sustained virological response (SVR) was achieved in 68 and 60% of Group A and B patients, respectively (P = 0.37). Logistic regression analysis identified genotype 2 or 3 as the only independent factor associated with response, whereas induction regimen and baseline viraemia levels did not affect the response. The overall SVR was 53 and 72% in patients with genotype 1 or 4 and 2 or 3, respectively. In conclusion, induction IFN therapy does not enhance the SVR to a 48-week combination therapy. Our study suggests that relapsed patients with genotype 1 or 4 may achieve significant response rates of approximately 50%, if retreated with 5 MU tiw IFN plus ribavirin for 48 weeks.

OBJECTIVES: We investigated the relation between hepatocellular carcinoma (HCC) etiology and biological and clinical parameters indicative of severity of liver disease and/or tumor characteristics and patient survival.METHODS: We prospectively recruited 384 patients (82.3% male) with first diagnosis of HCC from 1995 to 1998 in Brescia, Italy. Etiology was assessed by interviewing patients regarding their history of alcohol intake and by testing sera for hepatitis B surface antigen and anti-hepatitis C virus (HCV) antibodies and HCV RNA.RESULTS: Heavy alcohol intake (>60 g of ethanol per day for at least I decade) was found in 33.1% of cases, hepatitis B virus (HBV) infection in 9.4%, HCV in 19.8%, hemochromatosis in 1.3%, alcohol and HBV in 12.0%, alcohol and HCV in 16.1% HBV and HCV in 3.1%, and no factor in 5.2%. Patients with HBV infection with or without heavy alcohol intake were significantly younger than the others (61.7 vs 64.7 yr, p < 0.001). The proportion of males was significantly higher in patients with heavy alcohol intake alone than in the other patient groups (93.7% vs 77.3%, p < 0.001). Among patients with HCV infection with or without heavy alcohol intake, fewer patients had maximum tumor diameter > 5 cm than the others (12% vs 29.1%, p < 0.001). Eighty patients (20.8%) were alive at the end of follow-up (median survival, 17.7 months), and no differences were observed in survival rates by HCC risk factor.CONCLUSIONS: Although some differences were observed in severity of liver disease or tumor characteristics according to etiology, patient survival was not influenced by HCC etiology.

We carried out a 1-year trial to evaluate the efficacy and tolerability of lamivudine, an oral nucleoside analogue, in a small group of children with vertically acquired chronic hepatitis B. Patients were assessed for serum alanine aminotransferase (ALT) and serum hepatitis B virus (HBV) DNA at baseline and every 4 weeks thereafter, and for hepatitis B s antigen, hepatitis B e antigen and their antibodies every 12 weeks. Analysis of HBV mutation was undertaken at entry and on the occasion of the last positive control of HBV DNA. Lamivudine suppressed serum HBV DNA to undetectable levels in all treated patients within 24 weeks. Serum ALT levels returned to normal values within 36 weeks. Therapy was well tolerated, and although nausea and vomiting were reported in one child, it was not necessary to stop treatment. A new observation was that, contrary to previous data, seroconversion appeared to occur earlier in children with lower ALT levels at baseline.