Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: Results from the hepatitis C antiviral long-term treatment against cirrhosis trial

Abstract

Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C. We measured disease severity by quantitative liver function tests (QLFTs) to determine cutoffs for QLFTs that identified patients who were at low and high risk for a clinical outcome. Two hundred twenty seven participants in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial underwent baseline QLFTs and were followed for a median of 5.5 years for clinical outcomes. QLFTs were repeated in 196 patients at month 24 and in 165 patients at month 48. Caffeine elimination rate (k), antipyrine (AP) clearance (Cl), MEGX concentration, methionine breath test (MBT), galactose elimination capacity (GEC), dual cholate (CA) clearances and shunt, and perfused hepatic mass (PHM) and liver and spleen volumes (SPECT) were measured. Baseline QLFTs were significantly worse (p=0.0017 to <0.0001) and spleen volumes larger (p<0.0001) in the 54 patients who subsequently experienced clinical outcomes. QLFT cutoffs that characterized patients as “low” and “high risk” for clinical outcome yielded hazard ratios ranging from 2.21 (95%CI 1.29–3.78) for GEC to 6.52 (95%CI 3.63–11.71) for CA Cloral. QLFTs independently predicted outcome in models with Ishak fibrosis score, platelet count, and standard laboratory tests. In serial studies, patients with “high risk” results for CA Cloral or PHM had a nearly 15-fold increase in risk for clinical outcome. Less than 5% of patients with “low risk” QLFTs experienced a clinical outcome. Conclusion QLFTs independently predict risk for future clinical outcomes. By improving risk assessment, QLFTs could enhance noninvasive monitoring, counseling, and management of patients with chronic hepatitis C.

Pathobiology of liver fibrosis: a translational success story

“…An alternative and/or complementary diagnostic strategy is the use of tests that assess underlying functional liver reserve, whether using breath tests 134 or substrate clearance methods, 135 to predict clinical outcomes. One goal of these efforts is to establish their correlation with hepatic venous pressure gradient, since this measure clearly correlates with outcomes.…”

Association of Platelet Count and Mean Platelet Volume with Overall Survival in Patients with Cirrhosis and Unresectable Hepatocellular Carcinoma

“…Furthermore, it was thought to be a risk factor for the development of HCC [25]. However, it is unclear if thrombocytopenia per se is a risk factor for HCC development or just a phenomenon of more advanced liver disease, associated with an increased HCC incidence.…”

“…In contrast, thrombocytopenia, which is a hallmark of advanced liver disease and portal hypertension, has been associated with HCC development in cirrhotic patients with hepatitis C infection [24,25]. However, it is unclear if thrombocytopenia per se favors HCC or is just a marker of more severe liver disease [24].…”

Very Low Viral Load (VLVL) Relapse Following Treatment of Naïve Patients with Chronic Hepatitis C

“…Less than 10% of cirrhotic patients have normal values (100-110) with a PHM range of 40-99 in the rest [23,28,29] and the degree of abnormality correlates with clinical outcomes [28,29]. In the prospective HALT-C trial, PHM correlated with clinical outcomes over 7 years (46% outcomes with PHM \94 vs. 5% with [94) outperforming any combination of liver tests and histology [30]. Additional studies from the HALT-C trial have shown that preserved liver function is a better determinant of treatment success than is histology [31][32][33] and would support the possibility that these patients have a greater capacity to respond to therapy compared with cirrhotic patients with poor hepatic function.…”