Incidence of liver disease (LD) associated with cystic fibrosis (CF) and its clinical characterization still is unsettled. We have assessed prospectively the incidence and risk factors of this complication, and its impact on the clinical course of CF. Between 1980 and 1990, we enrolled 177 CF patients without LD in a systematic clinical, laboratory, ultrasonography screening program of at least a 10-year duration. During a 14-year median follow-up (2,432 patient-years), 48 patients developed LD, with cirrhosis already present in 5. Incidence rate (number of cases per 100 patient-years) was 1.8% (95% confidence interval: 1.3-2.4), with sharp decline after the age of 10 years and higher risk in patients with a history of meconium ileus (incidence rate ratio, 5.5; 2.7-11), male sex (2.5; 1.3-4.9), or severe mutations (2.4; 1.2-4.8) at multivariate analysis. Incidence of cirrhosis was 4.5% (2.3-7.8) during a median period of 5 years from diagnosis of liver disease. Among the 17 cirrhotic patients, 13 developed portal hypertension, 4 developed esophageal varices, 1 developed liver decompensation requiring liver transplantation. Development of LD did not condition different mortality (death rate ratio, 0.4; 0.1-1.5) or higher incidence of other clinically relevant outcomes. In conclusion, LD is a relatively frequent and early complication of CF, whose detection should be focused at the first life decade in patients with history of meconium ileus, male sex, or severe genotype. Although LD does not condition a different clinical course of CF, in some patients it may progress rapidly and require liver transplantation.

approximately 3%. 3,4 Early detection of HCC in cirrhotic pa-A prospective study was performed to establish tients can usually be achieved by screening with noninvasive whether infection with specific hepatitis C virus (HCV) techniques, such as ultrasound (US) scan and serum a-fetogenotypes was associated with an increased risk of protein (AFP) concentration. 5,6 development of hepatocellular carcinoma (HCC) in cirOver the years, several lines of experimental evidence indirhosis. A cohort of 163 consecutive hepatitis C virus anticated that male sex, age, and alcohol consumption 4,7,8 were body (anti-HCV)-positive cirrhotic patients was proclosely associated with the development of HCC in cirrhotic spectively evaluated for the development of HCC at patients. The identification of additional variables associated 6-month intervals by ultrasound (US) scan and awith an increased risk of developing HCC would be particufetoprotein (AFP) concentration. HCV genotypes were larly important to optimize preventive medical programs in determined according to Okamoto. Risk factors associthis setting. Recent studies suggested a possible role for HCV ated with cancer development were analyzed by univarigenotype in chronic liver disease outcome and, specifically, ate and multivariate statistics. At enrollment, 101 pa-HCV type 1 was more frequently found in advanced liver tients (62%) were infected with type 1b, 48 (29.5%) were disease, such as cirrhosis and HCC, 9-11 and was associated infected with type 2a/c, 2 (1.2%) were infected with type with a more rapid deterioration of liver histology in chronic 3a, 1 (0.6%) was infected with type 1a, 3 (1.8%) had a hepatitis. 12 We have studied the distribution of HCV genomixed-type infection, and, in 8 patients (4.9%), genotype types in a cohort of patients with cirrhosis prospectively folcould not be assigned. After a 5-to 7-year follow-up (melowed for early detection of HCC, and we performed multivardian, 68 months), HCC developed in 22 of the patients, iate analysis to evaluate the independent risk for tumor 19 infected with type 1b and 3 with type 2a/c (P õ .005).development associated with specific HCV types and with Moreover, HCC developed more frequently in males (P other variables, including interferon treatment, which has õ .01), patients with excessive alcohol intake (P õ .01), been recently reported to reduce the cancer risk in HCVthose over 60 years of age (P õ .02), and in patients who induced cirrhosis. ated with the development of cirrhosis. 1 HCV infection alone was also calculated. Aliquots of sera collected at entry were stored accounts for over 25% of all cases of cirrhosis in Italy, 2 a at 030ЊC for further serological and molecular analysis. When hepacondition that is associated with an increased risk of hepato-titis C virus antibody (anti-HCV) serology became available, sera cellular carcinoma (HCC), with a yearly incidence rate of from 472 of 501 patients were tested by second-generation enzyme immunoassay (Ortho Diagnostic Systems, Raritan, NJ), and 240 sub...

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

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Reports from North America and Northern Europe have suggested that antimitochondrial antibody (AMA) negative primary biliary cirrhosis (PBC) is a distinct chronic cholestatic liver disease with high prevalence of serum non‐organ‐specific autoantibodies other than AMA. To evaluate if such a peculiar serum immunoreactivity is associated with clinically relevant characteristics, we reviewed our experience with 297 Italian patients who have had a clinical and histological diagnosis of PBC and were regularly followed‐up at our Center from June 1974 to June 1994. AMA‐negative and AMA‐positive patients were compared in terms of biochemical and clinical features, and clinical outcome of the disease. At presentation, 30 of 297 patients (10%) tested negative for AMA by indirect immunofluorescence. Six of them tested positive for antimitochondrial M2 antibodies (AMA‐M2) by immunoblotting analysis, therefore, diagnosis of AMA‐negative PBC was made in 24 patients (8%). At the initial visit, AMA‐negative and AMA‐positive patients were similar in terms of biochemical and clinical features. Antinuclear and anti‐smooth‐muscle antibodies (ANA and ASMA) were more frequently positive in the AMA‐negative patients (71% vs. 31%, and 37% vs. 9%; both P = .0002). Incidence of complications of cirrhosis and development of liver failure resulting in death or referral for liver transplantation did not differ significantly between the two populations. In conclusion, data from this historical cohort study suggest that the distinct serological features of AMA‐negative PBC are not associated with substantial differences in the clinical spectrum or course of the disease.