Diagnostic challenges in patients with alcohol-related liver disease

Abstract

Alcohol is globally the leading risk factor for cirrhosis and is subsumed under the term alcohol-related liver disease (ALD). However, only ca. 10% of people with harmful alcohol consumption (>40 gram alcohol per day) develop cirrhosis, while 15% have normal liver histology. Unfortunately, laboratory parameters and ultrasound hold little value to neither rule-in nor rule out alcohol related liver fibrosis. While several indices with combinations of liver associated markers such as FIB4 seem to be promising, non-invasive test strategies are urgently needed with cut-off’s that can be applied to guide clinical decision making. The aims of this review article are to highlight novel developments for the diagnosis of ALD and to identify topics of controversy and potential future directions. In the last 15 years, elastography to measure liver stiffness (LS) has significantly improved our screening strategies for cirrhosis. LS values below 6 kPa are considered as normal and exclude ALD. LS of 8 and 12.5 kPa represent generally accepted cut-off values for F3 and F4 fibrosis. Especially, transient elastography (TE) has been assessed in numerous studies, but similar performance can be obtained with point shear wave elastography, 2 SD shear wave elastography or MR elastography. Important confounders of elevated LS such as inflammation should also be considered and alcohol withdrawal not only improves liver inflammation but also LS. Liver stiffness measurement has signficiantly improved early diagnosis and follow-up of fibrosis in patients with ALD and patients with diagnosed manifest but clinically compensated cirrhosis should undergo further clinical examinations to rule out complications of portal hypertension. In addition, surveillance for the occurrence of hepatocellular carcinoma is recommended in all cirrhotic patients.

New Diagnostic and Prognostic Models for the Development of Alcoholic Cirrhosis Based on Genetic Predisposition and Alcohol History

“…Indeed, whereas the AUC of FIB-4 was 0.737, it was 0.868 and 0.887 for Model 1 and Model 2, respectively. In non-specialized units where transient elastography is not available, blood tests recommended for diagnosing compensated alcoholic cirrhosis include, in addition to the platelet count and serum AST and ALT used to calculate FIB-4 and APRI, INR and bilirubin, albumin, and serum creatinine [ 10 ]. Our models save the costs of measuring INR and serum AST and albumin.…”

“…The clinical diagnosis of liver cirrhosis in heavy alcohol users is based on the presence or history of complications of this disease, liver imaging, and blood tests of liver function and platelet counts [ 6 ]. Several easy-to-perform and low-cost non-invasive bioassays have also been developed to rule out advanced fibrosis or the presence of cirrhosis in alcoholics even when compensated, including the Fibrosis-4 Index (FIB-4) and the AST to Platelet Ratio Index (APRI) [ 7 , 8 , 9 , 10 , 11 , 12 ].…”

Enhanced liver fibrosis score as a noninvasive biomarker in hepatitis C virus patients after direct-acting antiviral agents

“…In a study, up to 10% variability in the staging of the same specimen after repeated assessments by a single observer was reported ( Vuppalanchi et al, 2009 ). Not surprisingly, noninvasive tests (NTIs) have been identified and validated to indirectly estimate liver fibrosis ( Krag et al, 2022 ). NTIs to identify fibrosis stage allow performing serial follow-up of patients or, in the case of viral hepatitis, to assess therapy response ( Stasi and Milani, 2016 ; Wong, 2018 ).…”