High Prevalence of Liver Fibrosis Among European Adults With Unknown Liver Disease: A Population-Based Study.

BACKGROUND & AIMS: Liver fibrosis is the main determinant of long-term outcome in chronic liver diseases. Little is known about the prevalence of liver fibrosis in the general population. The aim of the study was to investigate the prevalence of liver fibrosis in the general adult population with unknown liver disease. METHODS: This was a population-based, cross-sectional study performed in the Barcelona metropolitan area. Subjects aged 18 to 75 years old were identified randomly from citizens included in the primary health care registry. Of 4866 subjects invited, 3076 participated (63.2%). Liver fibrosis was estimated by measuring liver stiffness (LS) with transient elastography (TE). Liver histology was assessed in 92 subjects with increased LS. RESULTS: Prevalence estimates of increased LS (≥6.8, ≥8.0, and ≥9.0 kPa) were 9.0%, 5.8%, and 3.6%, respectively. The etiology of liver disease was mainly nonalcoholic fatty liver disease (NAFLD), followed by alcohol risk consumption (consumption of ≥21 standard drinking units/wk in men and ≥14 standard drinking units/wk in women). Factors independently associated with increased LS were male sex, abdominal obesity, type 2 diabetes, serum glucose, high-density lipoprotein, and triglyceride levels. Subjects without risk factors for NAFLD or without alcohol risk consumption had a very low prevalence of increased LS. The best cut-off value of LS for significant liver fibrosis (F2-F4) was 9.2 kPa, with high sensitivity and specificity. TE was more accurate than alanine aminotransferase, NAFLD fibrosis score, or Fibrosis 4. An algorithm for screening for liver fibrosis using TE in the community setting is proposed. CONCLUSIONS: These findings show a high prevalence of silent liver disease with advanced fibrosis mainly related to NAFLD in adult European subjects without known liver disease. An LS value less than 9.2 kPa predicts the absence of significant liver fibrosis with high accuracy and could be used for screening purposes.

Efficacy and Safety of Ombitasvir, Paritaprevir, and Ritonavir in an Open-Label Study of Patients With Genotype 1b Chronic Hepatitis C Virus Infection With and Without Cirrhosis.

BACKGROUND & AIMS: Interferon-free treatment options are rapidly evolving for patients with chronic hepatitis C virus (HCV) genotype 1b (GT1b) infection with cirrhosis and for nonresponders to prior pegylated interferon and ribavirin therapy. We performed a phase 2b, open-label trial of the combination of ombitasvir (a NS5A replication complex inhibitor), paritaprevir, and ritonavir (an NS3/4A protease inhibitor)-an interferon- and ribavirin-free regimen-in difficult-to-treat patients, including prior null responders and patients with cirrhosis. METHODS: In an international study, 82 patients without cirrhosis (42 treatment-naive and 40 prior null responders) and 99 with cirrhosis (47 treatment-naive and 52 treatment-experienced with prior relapse or a null or partial response) with chronic HCV GT1b infection received ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily for 12 weeks (without cirrhosis) or 24 weeks (with cirrhosis). The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). RESULTS: In treatment-naive and null responder patients without cirrhosis, rates of SVR12 were 95.2% and 90.0%, respectively. In treatment-naive and treatment-experienced patients with cirrhosis, rates of SVR12 were 97.9% and 96.2%, respectively. No clinically meaningful differences in rates of SVR12 were observed between patients with or without cirrhosis. Virologic relapse occurred in 3 null responders without cirrhosis and 1 with cirrhosis; virologic breakthrough occurred in 1 null responder without cirrhosis. Common adverse events included headache, asthenia, pruritus, and diarrhea. One patient discontinued taking the drugs because of treatment-related adverse events. CONCLUSIONS: An interferon- and ribavirin-free regimen of ombitasvir, paritaprevir, and ritonavir, achieved high rates of SVR12 in patients with HCV GT1b infection with and without cirrhosis. This regimen was well tolerated and was associated with low rates of treatment discontinuation. ClinicalTrials.gov no: NCT01685203.

Serum concentrations of insulin-like growth factor-I (igf-I) as a marker of liver fibrosis in patients with chronic hepatitis C.

Liver biopsy was until recently the only way of evaluating liver fibrosis. Noninvasive tests for hepatic fibrosis, without potential risks, are desired by clinicians as well as patients. Insulin-like growth factor-I (IGF-I) synthesis is disturbed in liver fibrosis and reflects the severity of the clinical stage. We assessed serum IGF-I levels in patients with chronic hepatitis C (CHC) to correlate with liver fibrosis and antiviral therapy. Forty patients with CHC and persistently abnormal alanine aminotransferase values were enrolled and treated with peginterferon alpha-2a 180 microg per week plus ribavirin for 24 (n=20) or 48 (n=20) weeks. All patients underwent liver biopsy before treatment (METAVIR fibrosis stage F0, n=13; F1-F2, n=14; F3, n=7; F4, n=6). Serum IGF-I was measured at baseline, at the end of treatment period, and 24 weeks after finishing treatment. Mean IGF-I values were significantly lower in patients with advanced fibrosis (F4, 65.9+/-17.9 ng/mL) than in the others (F0, 145.2+/-47.1; F1-F2, 150.3+/-89.6; and F3, 121.4+/-35.2 ng/mL; P < .05). Serum IGF-I levels increased during combined therapy, being this increment markedly higher in patients with sustained virologic response. In conclusion, IGF-I synthesis is disturbed in CHC and reflects the severity of the liver fibrosis. Combined therapy improves serum IGF-I levels. IGF-I could represent a good, noninvasive marker of liver fibrosis.