Background: Chronic HCV infection causes liver inflammation, fibrosis, and cirrhosis resulting in significant liver dysfunction and mortality, but progression is slow and patients often have few symptoms. Effective antiviral therapies are becoming available, but are very expensive, and it is difficult to prioritize patients for treatment.
Methods: In the HALT-C trial, chronic HCV patients without any prior clinical outcomes (defined as a 2 point increase in Child-Turcotte-Pugh score, variceal hemorrhage, ascites, hepatic encephalopathy, or liver-related death) were biopsied and tested at baseline with a variety of experimental liver function tests, and followed prospectively for up to 8.3 years, mean ▒ SD of 4.9 ▒ 2.2 years. The clearance of an oral dose (40 mg) of tetra-deuterated cholic acid (d4-CA), determined from 14 blood draws, could quantify hepatic portal perfusion and was highly predictive of outcomes (Hepatology 2012; 55:1019-1029). Archived baseline blood samples (N = 220 patients; 52 had future outcomes) were reanalyzed by LCMS. This study investigated the utility of the d4-CA concentration (ÁM) in a single blood draw 60 minutes after the oral dose, the HepQuant-STAT liver function test.
Results: STAT varied from 0.37 ▒ 0.11 ÁM, in healthy controls (Figure Panel A) up to ~5 ÁM in some HCV patients, indicating impaired liver function. The ROC curve, for baseline STAT to identify patients who would have future outcomes, had a C-statistic of 0.80, and the optimum cutoff was 1.11 ÁM (Panel B dashed line) as determined by the maximum Youden index (J = 0.49). STAT was correlated with biopsy fibrosis, R2 = 0.23 (Panel C), but not fat or inflammation. However, in identifying patients who would have outcomes, STAT (75% sensitivity, 74% specificity, 47% PPV, 91% NPV) outperformed biopsy fibrosis (71% sensitivity, 66% specificity, 39% PPV, 88% NPV). Interestingly, 41% of cirrhotic patients were at low risk, and 22% of patients with noncirrhotic fibrosis were at high risk for outcomes (Panel C).
Conclusion: HepQuant-STAT, a simple liver function test, could stratify HCV patients' risk of clinical outcomes better than biopsy. HepQuant-STAT could help prioritize for antiviral treatment those HCV patients at higher risk of clinical outcomes.
S. Lauriski, None
G. T. Everson, HepQuant, LLC: Member , Research support