Clinical course and management of acute and chronic viral hepatitis during pregnancy.

Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT.

HCV E1E2-MF59 vaccine in chronic hepatitis C patients treated with PEG-IFNα2a and Ribavirin: a randomized controlled trial.

Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 µg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte proliferation assay (LPA) for E1E2-specific-CD4 + T cells were performed at week 0-12-16-48. Viral kinetics were analysed up to week 16. The vaccine was safe, and a sustained virological response (SVR) was achieved in 4 P/R + V and 2 P/R patients. Higher SVR rates were observed in prior relapsers (P/R + V = 27.3%; P/R = 12.5%). Higher NOB titres and LPA indexes were found at week 12 and 16 in P/R + V as compared to P/R patients (P = 0.023 and 0.025, P = 0.019 and <0.001, respectively). Among the 22 patients with the strongest direct antiviral effects of IFN (ε ≥ 0.800), those treated with P/R + V (10) reached lower HCV-RNA levels (P = 0.026) at week 16. HCV E1E2MF59 vaccine in combination with Peg-IFNα2a + RBV was safe and elicited E1E2 neutralizing antibodies and specific CD4 + T cell proliferation. Upon early response to IFN, vaccinations were associated with an enhanced second phase viral load decline. These results prompt phase II trials in combination with new antiviral therapies.

In vivo liver expression of TLR2, TLR3 and TLR7 in chronic hepatitis C.

The role of innate immune response mediated by Toll-like receptors in HCV infection, is not yet well understood and there is a lack of data regarding liver tissue expression of these molecules in chronic hepatitis C (CHC). Our study is aimed to investigate ex vivo, liver expression of TLR2, TLR3 and TLR7, which are more involved in the immune-pathogenesis of CHC, and to explore possible correlations with features of disease. We obtained liver biopsies and collected peripheral blood mononuclear cells (PBMC) from 23 consecutive patients with CHC and from 6 patients of control, without liver disease, undergoing surgery for cholecystectomy. The levels of TLRs mRNA in the samples were determined using a real-time reverse transcription quantitative PCR (RT-qPCR). We found a significant high expression of TLR3 in the liver of CHC patients respect to controls (also higher than expression in the PBMC). Conversely no differences emerged in the TLR2 and TLR7 levels between cases and controls. Also we found a correlation of TLR2 and TLR7 levels with the grade of necro-inflammation in the liver. Furthermore TLR7 hepatic levels resulted related to a more advanced stage of liver fibrosis. Ours is the first study to provide data on tissue expression of TLRs during chronic hepatitis C and we believe that it could lead to a better understanding of the role of these molecules in the HCV-mediated liver damage.

Hepatitis C virus infection among drug addicts in Italy.

There is a lack of updated nationwide records regarding hepatitis C virus (HCV) infection among drug addicts in Italy. The prevalence and characteristics of HCV infection in a national sample of drug addicts in Italy were determined. Five hundred forty-three drug addicts (mean age 35.3 years, 85.1% males), selected from 25 Italian Centers for Substance Dependence were enrolled to be evaluated for anti-HCV, HCV-RNA, HCV genotype, HBV markers, anti-HDV, and anti-HIV during the period of April-November 2009. Anti-HCV prevalence was 63.9%. HCV-RNA was detected in 68.3% of patients positive for anti-HCV. Genotypes 1 and 3 prevailed (49.3% and 39.7%, respectively). However, 9.3% of the subjects had genotype 4, a rate over threefold higher than the one observed in 1996 among drug addicts in central Italy. Needle sharing was the strongest independent predictor of the likelihood to contract an HCV infection (OR 8.9; 95% CI: 5.0-16.0). Only 19.3% of subjects received antiviral treatment for HCV. The prevalence of HBsAg and HIV positivity was 2.8% and 3.1%, respectively. The pattern of HBV markers showed that nearly one-third of subjects had been vaccinated, while 42.3% were negative for any marker of HCV. The prevalence of HCV infection is high among drug addicts in Italy. The incidence of Genotype 4 is increasing and this may lead to the spreading of the disease to the general population in the near future. Efforts should be made to improve the rate of antiviral treatment for drug addicts with HCV infection and vaccination against hepatitis B.

Current practice of chronic hepatitis B treatment in Southern Italy.

BACKGROUND: Treatment choice for chronic HBV infection is a continuously evolving issue, with a wide range of options. We aimed to evaluate the current practice of HBV therapies in the real world in Southern Italy. METHODS: A prospective study enrolling over a six month period (February-July 2010) all consecutive HBsAg positive subjects, never previously treated, referred to 16 liver units in two Southern Italy regions (Calabria and Sicily). RESULTS: Out of 247 subjects evaluated, 116 (46.9%) had HBV-DNA undetectable or lower than 2000 UI/ml. There were 108 (43.7%) inactive carriers, 103 (41.7%) chronic hepatitis, and 36 (14.6%) liver cirrhosis. Antiviral treatment was planned in 94 (38.0%) patients (26 cases with Interferon or Pegylated Interferon and 68 with nucleos(t)ides analogues). As many as 49.5% of subjects with chronic hepatitis did not receive antiviral treatment. DISCUSSION: The majority of chronic HBsAg carrier referring centres for evaluation were not considered suitable for antiviral treatment. Nucleos(t)ides analogues are the preferred first choice for therapy. A long-lasting period of observation may be needed to make appropriate therapeutic decisions in several cases.

Retrospective, observational, multicentre study on an Italian population affected by chronic hepatitis C who failed to clear HCV-RNA after the combined therapy (PEG-IFN and ribavirin): NADIR study.

There is a lack of information on the characteristics of patients with chronic hepatitis C virus infection (HCV) who fail to respond to antiviral treatment. We studied HCV-positive subjects with chronic liver diseases treated with pegylated-interferon (PEG-IFN) and ribavirin (RBV) who failed to clear HCV in routine clinical practice. A total of 2150 consecutive adult patients treated with PEG-IFN plus RBV therapy in 46 Italian centres between 1 July 2004, and 30 June 2005, were studied. Of the 2150 patients, 923 (42.9%) (M/F 585/335, mean age 54.8 years) failed to achieve a serum HCV-RNA clearance. Of these 923 patients, 429 (46.5%) were nonresponders, 298 (32.3%) relapsers, 168 (18.2%) drop-outs for noncompliance or adverse events and 28 (3.0%) were lost during follow-up. Overall, 642 (70.6%) patients received adequate therapy (defined as more than 80% of the drug doses for >80% of the time). Genotypes 1-4 were observed in 76.9% of cases; genotypes 2-3 in 21.2% and mixed in 1.9%, respectively. Multiple logistic regression analysis identified genotypes 1 and 4 as the sole independent predictors of the likelihood of nonresponse to therapy compared with relapse (OR: 4.38; 95% CI = 2.28-8.4). Age older than 65 years was the sole independent factor associated with no adherence to therapy (OR: 2.22; 95% CI = 1.36-3.62). Patients who fail to respond to treatment are a nonhomogeneous population with different features, and the sole factor that discriminates nonresponse from relapse is the distribution of genotypes 1-4. Co-morbidities are unable to determine the type of treatment failure and inadequate adherence to therapy mostly affects patients older than 65 years of age.

Clinical course and outcomes of drug-induced liver injury: nimesulide as the first implicated medication.

BACKGROUND AND AIMS: Drug-induced liver injury (DILI) is the most common cause of death from acute liver failure, and accounts for approximately 13% of cases of acute liver failure in the United States. The clinical presentation of DILI covers a wide spectrum, from asymptomatic liver test abnormalities to symptomatic acute liver disease, prolonged jaundice and disability, or overt acute or subacute liver failure. The aim of our study was to evaluate the number of DILI cases admitted to our Unit and to identify the drugs responsible. Thus, we reviewed all clinical records of patients with DILI admitted to our Unit from 1996 to 2006. PATIENTS AND METHODS: A database was constructed, reporting demographic, clinical features at onset, laboratory results, suspected drugs and follow-up. Liver damage was defined as hepatocellular, cholestatic or mixed, according to clinical and laboratory data. RESULTS: Forty-six patients were admitted with a diagnosis of DILI. Presentation was jaundice in 22 patients and hepatic failure in 3 (all attributed to nimesulide). Liver damage was of a cytolytic pattern in 19 cases (41%), cholestatic in 15 (33%) and mixed in 12 (26%). Jaundice was found to be higher in nimesulide-induced liver damage compared to other drugs (p=0.007). Three out of 14 patients with nimesulide-induced DILI developed encephalopathy and/or ascites. Time of recovery in the nimesulide group was significantly lower than DILI from other drugs (p<0.001). CONCLUSION: Non-steroidal anti-inflammatory drugs, psychotropic drugs and antimicrobials are the most common causes of DILI. Nimesulide-induced DILI is usually reversible upon discontinuation of the drug, but occasionally progresses to liver failure.

Serum BLyS/BAFF predicts the outcome of acute hepatitis C virus infection.

B-lymphocyte stimulator/B activating factor (BLyS/BAFF) is a tumour necrosis factor-family cytokine that plays a key role in generating and maintaining the mature B-cell pool. BLyS/BAFF expression by macrophages is stimulated by interferon-gamma and interleukin-10, and its serum levels are increased in chronic hepatitis C (CHC). The aim of this study was to assess serum levels of BLyS/BAFF in patients with acute hepatitis C (AHC) and correlate them with disease outcome. We studied 28 patients with AHC (14 males, mean age 59.3 +/- 15 years), followed for at least 7 months since onset, comparing them with 86 CHC patients and 25 healthy blood donors (HBD). BLyS/BAFF levels were assessed at baseline (within 4 weeks of onset) and during follow-up. BLyS/BAFF median levels were significantly higher in AHC (1485 pg/mL) than in CHC (1058 pg/mL) and in HBD (980 pg/mL) (P < 0.001). BLyS/BAFF levels were higher in AHC patients evolving to chronicity (1980 pg/mL) than in those with a self-limited course (1200 pg/mL), (P = 0.02). By logistic regression analysis, higher BLyS/BAFF levels were independently associated with persistence of HCV infection (OR 29.7; 95% CI: 1.73-508.20). High serum levels of BLyS/BAFF at onset of AHC can predict its evolution to chronic infection.

Prospective, randomized, crossover comparison of sublingual apomorphine (3 mg) with oral sildenafil (50 mg) for male erectile dysfunction.

PURPOSE: We established the efficacy and safety of sublingual apomorphine compared with oral sildenafil in comparable groups of patients with erectile dysfunction (ED). MATERIALS AND METHODS: This prospective, randomized, crossover study included 77 heterosexual men with ED of various etiologies and severities. A total of 62 men were randomized but only 34 were evaluable for efficacy and tolerability. The study started with a run-in period of 2 to 4 weeks. The first 4 weeks of treatment were followed by a washout period of 4 weeks, after which patients changed to the alternate treatment for an additional 4-week period. The sequence of the 2 treatments was established by a randomization list in blocks in closed packets. The primary efficacy end point was the percent of attempts resulting in erection firm enough for intercourse. Additional variables were the percent of attempts resulting in intercourse and improvement in ED, as evaluated by the erectile function domain score of the International Index of Erectile Function questionnaire. RESULTS: Sildenafil was significantly more effective than apomorphine in regard to the percent of attempts resulting in erection firm enough for intercourse (85% vs 44%, p <0.0001) and actually resulting in intercourse (81% vs 43%, p <0.0001) as well as erectile function evaluated by the erectile function domain score of the International Index of Erectile Function (p <0.001). The incidence of adverse events was not significantly different for the 2 drugs. Although the number of patients was small, this study had strong statistical power due to the striking difference in results. CONCLUSIONS: Sildenafil was significantly more effective than apomorphine for ED. No statistical difference in adverse events was noted.

Therapy expectations and physical comorbidity affect quality of life in chronic hepatitis C virus infection.

UNLABELLED: Hepatitis C virus (HCV) infection is associated with a significant reduction of health related quality of life (QOL), the causes and mechanisms of which are still unknown. To explore whether treatment history could affect QOL, we examined patients with detectable HCV viraemia who had a different therapeutic background. Two hundred sixty-four consecutive subjects with chronic HCV infection and detectable viraemia were enrolled. Of these, 163 were untreated patients, 43 were relapsers, 58 were nonresponders (NR) to nonpegylated interferon (IFN) therapy. To assess QOL, three self-report instruments were employed: the Short Form-36 (SF-36), the Chronic Liver Disease Questionnaire (CLDQ-I) and the World Health Organization Quality of Life assessment (WHOQOL-BREF). Clinical and demographic data were collected, and the QOL scores of HCV-positive patients were compared with those of an Italian normative sample and healthy controls. Further antiviral treatment was offered to untreated and relapsed patients but not to NR. All patient groups displayed lower QOL scores compared with the normative sample and controls. NR displayed lower QOL scores in several areas compared with untreated patients and relapsers. In multivariate regression analyses, being NR and having a physical comorbidity were significantly associated with poorer QOL. CONCLUSIONS: Treatment history and expectations and physical comorbidity may affect QOL in HCV-positive patients. Untreated and relapsed patients have comparable levels of QOL and higher scores than NR.

HCV infection is a risk factor for gallstone disease in liver cirrhosis: an Italian epidemiological survey.

We assessed the prevalence of gallbladder disease (i.e. gallstones plus cholecystectomy) among patients with liver disease and its association with the severity and aetiology of hepatic injury. Subjects, referred to 79 Italian hospitals, were enrolled in a 6-month period. The independent effect of the severity and aetiology of liver disease on gallstone disease prevalence was assessed by multiple logistic regression analysis. Overall, 4867 subjects tested anti-hepatitis C virus (HCV) positive alone, 839 were hepatitis B virus surface antigen (HBsAg) alone, and 652 had an excessive alcohol intake. The prevalence of gallstone disease was 23.3% in anti-HCV-positive patients, 12.4% in HBsAg positive and 24.2% in subjects reporting excessive alcohol intake, respectively. Gallstone disease prevalence increased by age in each aetiological category. The proportion of patients with gallstone disease who had a cholecystectomy was the highest in HCV+ subjects. After adjusting for the confounding effect of age and body mass index, compared with patients with less severe liver disease, subjects with HCV-related cirrhosis, but not those with alcohol-related cirrhosis, were more likely to have gallstone disease. Subjects with HCV-related cirrhosis (OR 2.13, 95% CI: 1.38-3.26) were more likely to have gallstone disease when compared with those with HBV-related cirrhosis. HCV infection is a risk factor for gallstone disease. In Italy, the high prevalence of HCV infection among cirrhotic patients has important implications, as cholecystectomy in these subjects is associated with high risk of morbidity and mortality.

The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C.

AIMS: To assess whether host metabolic factors influence the degree of hepatic steatosis and fibrosis in patients infected with hepatitis C virus, and to evaluate the impact of anti-viral therapy on insulin resistance and serum levels of adipocytokines. METHODS: Clinical and biochemical features, anthropometrical characteristics, and levels of fasting insulin, leptin, adiponectin and resistin were measured in 'naïve' patients with chronic hepatitis C, before, during and after therapy with Peg-Interferon-alpha 2a plus Ribavirin. RESULTS: Forty-eight patients were included (M/F 28/20; mean age 50.0 +/- 12.6 years; 62.5% genotype-1). Body mass index was 26.4 +/- 4.0 kg/m(2), and visceral obesity was present in 24 patients. At multivariate analysis (RR; 95% CI), steatosis was associated to older age (1.08; 1-1.18), necroinflammatory activity (17.67; 1.6-194.46), and raised insulin levels (1.39; 1.1-1.77). Fibrosis was related to necroinflammatory activity (25.73; 2.54-261.11), and steatosis (6.47; 1.09-38.29). Sustained viral response was achieved by 62.5% of patients and was associated with younger age (0.92; 0.85-0.99), genotype non-1 (10.61; 1.52-73.76) and absence of visceral obesity (13.78; 2.36-80.29). At the end of follow-up, insulin and the homeostasis model assessment for insulin resistance were reduced and adiponectin increased when compared with baseline, all unrelated to the outcome of treatment. CONCLUSIONS: Visceral obesity correlates with the degree of steatosis and fibrosis, and it negatively affects treatment response. Significant changes of insulin resistance and adipocytokines occur under treatment, irrespective of virological outcome.

Characteristics of HCV positive subjects referring to hospitals in Italy: a multicentre prevalence study on 6,999 cases.

In 2001, 6,999 anti-HCV positive subjects referred to 79 Italian hospital in a 6 months enrollment period were evaluated. Of them, 5,632 (80.5%) tested anti-HCV positive alone, 1,163 (16.6%) reported also an excessive alcohol intake, and 204 (2.9%) were also HBsAg positive. Normal biochemistry was observed in 7.8% of cases, chronic hepatitis in 67.9% of cases, liver cirrhosis in 18.9% of cases, and hepatocellular carcinoma in 3.6% cases. HCV positive subjects with excessive alcohol intake were statistically significantly younger, of male sex, and having more severe liver disease than those without excessive alcohol intake. Adjusting for the confounding effect of age and sex by multiple logistic regression analysis, HCV positive chronic hepatitis cases drinking more than four alcoholic drinks daily were 2.2-fold (CI 95% = 1.3-4.0) more likely to progress to liver cirrhosis than teetotallers. These findings indicate that nearly a quarter of HCV positive subjects referred to hospitals in Italy have a severe liver disease causing a remarkable impact on the national health system. Excessive alcohol intake in HCV chronic hepatitis cases increases the risk of progression to liver cirrhosis.

Iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis and the quality of life: a new therapeutic protocol.

OBJECTIVES: To evaluate the clinical efficacy and the effects on the quality of life of iloprost, a prostacyclin analogue, used according to a new protocol in patients with Raynaud's phenomenon secondary to systemic sclerosis. METHODS: In this randomized study, we treated 30 patients with iloprost, given by intravenous infusion, at progressively increasing doses (from 0.5 to 2 ng/kg/min) over a period of 6 h each day for 10 days in two consecutive weeks, with repeated cycles at regular intervals of 3 months for 18 months. The results were compared with those obtained in 30 other patients who received the same drug but with different dosing schemes. RESULTS: The total average daily duration of the attacks, the average duration of a single attack and the average daily frequency of the attacks were reduced significantly in all treatment groups, but the comparison between the groups demonstrated significant differences between patients treated with the new protocol and the others at later times (12 and 18 months). The effects on the quality of life in the group treated with the new protocol, evaluated with the Short Form-36, demonstrated a marked improvement regarding both the scale relating to the physical aspect of the illness and, especially, the scale relating to the mental aspect. CONCLUSIONS: In patients with systemic sclerosis, cyclic intravenous iloprost infusion is efficacious in the treatment of Raynaud's phenomenon. The protocol that we used, compared with others, not only has favourable clinical effects but also leads to a marked improvement in the quality of life.

Exposure to HAV infection in patients with chronic liver disease in Italy, a multicentre study.

We carried out a multicentre study on 2830 patients with chronic liver disease from 79 liver units (25 in northern, 24 in central and 30 in southern Italy) to evaluate naturally acquired immunity against hepatitis A virus (HAV) in relation to age, sex, geographical area of origin and entity of liver disease, and to define the strategy for specific vaccination. Antibody to HAV (anti-HAV) was detected in 1514 (53.5%) of the 2830 patients tested; the prevalence was 50.4% in males and 59.1% in females. Both in central and southern Italy the prevalence of anti-HAV positive subjects increased with increasing age from 43.3 and 44.7%, respectively, in the 0-30-year-old subjects to 80.1 and 68.3%, respectively, in those aged over 60 years. The overall prevalence was much lower in northern Italy, as were the variations from one age group to another, from 28.4% in the 0-30-year-old subjects to 38% in those aged over 60 years. 40.6% of patients with cirrhosis lacked naturally acquired protection against HAV; this percentage was higher in northern (60.5%) than in central (34.9%, P < 0.0001) and southern Italy (27.6%, P < 0.0001). The high prevalence of patients in Italy with chronic hepatitis or cirrhosis who lack naturally acquired immunity to HAV warrants the implementation of vaccination programmes against hepatitis A in such patients.

Acute polymyositis during treatment of acute hepatitis C with pegylated interferon alpha-2b.

Hepatitis C virus is not cleared after primary infection in 50-85% of subjects exposed to hepatitis C virus. Anti-viral treatment during the early phase of infection significantly enhances the likelihood of a sustained clearance of hepatitis C virus. Although, a variety of autoimmune-related side effects have been observed during interferon therapy for chronic hepatitis, immuno-mediated adverse reactions have not been reported during treatment of acute hepatitis C. We describe the case of a patient who developed acute hepatitis C virus infection and, while receiving pegylated interferon alpha-2b monotherapy, developed a severe polymyositis. This case illustrates the potential risk of autoimmunity by interferon, also for acute hepatitis, and underlines the importance of a prompt diagnosis and a rapid discontinuation of interferon treatment for an improvement of clinical outcomes.

Prospective, randomized, crossover comparison of sublingual apomorphine (3 mg) with oral sildenafil (50 mg) for male erectile dysfunction.

PURPOSE: We established the efficacy and safety of sublingual apomorphine compared with oral sildenafil in comparable groups of patients with erectile dysfunction (ED). MATERIALS AND METHODS: This prospective, randomized, crossover study included 77 heterosexual men with ED of various etiologies and severities. A total of 62 men were randomized but only 34 were evaluable for efficacy and tolerability. The study started with a run-in period of 2 to 4 weeks. The first 4 weeks of treatment were followed by a washout period of 4 weeks, after which patients changed to the alternate treatment for an additional 4-week period. The sequence of the 2 treatments was established by a randomization list in blocks in closed packets. The primary efficacy end point was the percent of attempts resulting in erection firm enough for intercourse. Additional variables were the percent of attempts resulting in intercourse and improvement in ED, as evaluated by the erectile function domain score of the International Index of Erectile Function questionnaire. RESULTS: Sildenafil was significantly more effective than apomorphine in regard to the percent of attempts resulting in erection firm enough for intercourse (85% vs 44%, p <0.0001) and actually resulting in intercourse (81% vs 43%, p <0.0001) as well as erectile function evaluated by the erectile function domain score of the International Index of Erectile Function (p <0.001). The incidence of adverse events was not significantly different for the 2 drugs. Although the number of patients was small, this study had strong statistical power due to the striking difference in results. CONCLUSIONS: Sildenafil was significantly more effective than apomorphine for ED. No statistical difference in adverse events was noted.

Does an 'autoimmune' profile affect the clinical profile of chronic hepatitis C? An Italian multicentre survey.

Nonorgan-specific autoantibodies (NOSA) are common in patients with chronic hepatitis C virus infection. It is unclear whether serological markers of autoimmunity segregate in a cohort of cases with more severe liver damage. We assessed the relationship between NOSA and demographic, biochemical and histological features in 502 subjects with anti-HCV positive, HCV-RNA positive, HBsAg negative chronic hepatitis consecutively referred to four Italian liver units. Percutaneous liver biopsy was performed in all subjects. A single pathologist scored the biopsies using histology activity index classification. The overall prevalence of positivity for any NOSA was 36.9%. Antinuclear antibodies, anti-smooth muscle antibodies, and anti-liver/kidney microsomal antibodies were found in 15.7, 27.3 and 2.2% of cases. Multivariate analysis showed that gamma-globulin >2 g/dL was the only independent predictor of the likelihood of NOSA positivity (OR, 2.1; 95% CI, 1.3-3.4). No other clinical (age, gender, ALT, HCV genotype) or histological features (grading and staging score, bile ductular damage) were linked to NOSA. Antiviral therapy in 155 subjects with NOSA did not cause any adverse events related to autoimmunity during and after treatment. The presence of NOSA in patients with chronic HCV hepatitis is not related to specific demographic features and has no impact on the biochemical and histological profile of the liver disease at presentation and the response to antiviral treatment.

Characteristics of liver cirrhosis in Italy: results from a multicenter national study.

BACKGROUND: In 1992, the characteristics of liver cirrhosis in Italy were assessed in a cross-sectional study among 1829 cirrhosis patients attending 21 tertiary centres. AIM: To evaluate the characteristics of cirrhosis patients 9 years later. PATIENTS: A total of 2185 consecutive cirrhosis patients were enrolled over a 6-month period in 79 hospitals located throughout Italy, randomly selected by means of systematic cluster sampling. RESULTS: The main agent associated with cirrhosis was hepatitis C virus, which was found in 69.9% of the patients and was the only etiologic factor in 51.1% of the patients. Hepatitis B surface antigen was present in the serum of 13.0% of the cases (in 7.3%, it was the only etiologic factor). A history of alcohol abuse was found in 31.9% of the cases (12.4% without viral infection). Patients with hepatitis C virus-related cirrhosis were older (mean age of 64.4 years) and more likely to be female (male:female ratio of 0.7), compared to patients with other pathogenic factors. Virus-related cirrhosis was more likely to be observed in southern Italy, whereas alcohol-related cirrhosis was prevalent in the North. CONCLUSIONS: As found in the 1992 study, the results of the present study show that in Italy, liver cirrhosis is mainly associated with hepatitis C virus infection, reflecting the high prevalence of this infection in the general population.