LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries.

BACKGROUND: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. METHODS: This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. DISCUSSION: This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. TRIAL REGISTRATION: This study is registered on Clinicaltrials.gov ( NCT03789825 ).

Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases.

Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate -18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression.

A multidisciplinary support programme increases the efficiency of pegylated interferon alfa-2a and ribavirin in hepatitis C.

BACKGROUND & AIMS: Adherence to antiviral treatment is important to achieve sustained virological response (SVR) in chronic hepatitis C (CHC). We evaluated the efficiency of a multidisciplinary support programme (MSP), based on published HIV treatment experience, to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in CHC. METHODS: 447 patients receiving antiviral treatment were distributed into 3 groups: control group (2003-2004, n=147), MSP group (2005-2006, n=131), and MSP-validation group (2007-2009, n=169). The MSP group included two hepatologists, two nurses, one pharmacist, one psychologist, one administrative assistant, and one psychiatrist. Cost-effectiveness analysis was performed using a Markov model. RESULTS: Adherence and SVR rates were higher in the MSP (94.6% and 77.1%) and MSP-validation (91.7% and 74.6%) groups compared to controls (78.9% and 61.9%) (p<0.05 in all cases). SVR was higher in genotypes 1 or 4 followed by the MSP group vs. controls (67.7% vs. 48.9%, p=0.02) compared with genotypes 2 or 3 (87.7% vs. 81.4%, p=n.s.). The MSP was the main predictive factor of SVR in patients with genotype 1. The rate of adherence in patients with psychiatric disorders was higher in the MSP groups (n=95, 90.5%) compared to controls (n=28, 75.7%) (p=0.02). The cost per patient was € 13,319 in the MSP group and € 16,184 in the control group. The MSP group achieved more quality-adjusted life years (QALYs) (16.317 QALYs) than controls (15.814 QALYs) and was dominant in all genotypes. CONCLUSIONS: MSP improves patient compliance and increases the efficiency of antiviral treatment in CHC, being cost-effective.