The within-individual reproducibility of the disease severity index from the HepQuant SHUNT test of liver function and physiology.

The HepQuant SHUNT test quantifies liver function and blood flow using systemic and portal clearances of cholate. The test can identify the risk of well-compensated patients to develop complications of cirrhosis. To confirm the reliability of a single HepQuant SHUNT test we defined its within-individual reproducibility. Healthy subjects (n = 16), 16 with nonalcoholic steatohepatitis (NASH), and 16 with chronic hepatitis C virus (HCV) underwent 3 HepQuant SHUNT tests on 3 separate days within 30 days. The test involves simultaneous administration of 20 mg 13C-cholate IV and 40 mg d4-cholate PO, and subsequent collection of 3 mL blood samples at 5, 20, 45, 60, and 90 minutes. Clearances are expressed as systemic and portal hepatic filtration rate. Portal-systemic shunting (SHUNT), a disease severity index (DSI), and an estimate of DSI (STAT) are calculated from the clearances. Reproducibility was determined by the intraclass correlation coefficient (ICC > 0.70) and Bland-Altman analysis. Equal numbers of NASH and HCV patients had either early (F0-F2) or advanced (F3/F4) stages of fibrosis. All F3/F4 subjects were clinically compensated. The intraclass correlation coefficient (ICC) for DSI was 0.94 (0.90-0.96 95% confidence interval) indicating excellent reproducibility. The other test parameters had ICCs ranging from 0.74 (SHUNT) to 0.90 (STAT). In Bland-Altman analysis, the mean of differences between measurements of DSI was 0.13 with standard deviation 2.12. The excellent reproducibility of the HepQuant SHUNT test, particularly DSI, supports the use this minimally invasive, blood-based test as a reliable test of liver function and physiology.

Functional elements associated with hepatic regeneration in living donors after right hepatic lobectomy.

We quantified the rates of hepatic regeneration and functional recovery for 6 months after right hepatic lobectomy in living donors for liver transplantation. Twelve donors were studied pre-donation (baseline); 8 were retested at a mean ± SD of 11±3 days after donation (T1), 10 were retested at a mean of 91±9 days after donation (T2), and 10 were retested at a mean of 185±17 days after donation (T3). Liver and spleen volumes were measured with computed tomography (CT) and single-photon emission computed tomography (SPECT). Hepatic metabolism was assessed with caffeine and erythromycin, and hepatic blood flow (HBF) was assessed with cholates, galactose, and the perfused hepatic mass (PHM) by SPECT. The regeneration rates (mL kg(-1) of body weight day(-1)) by CT were 0.60±0.22 mL from the baseline to T1, 0.05±0.02 mL from T1 to T2, and 0.01±0.01 from T2 to T3; by SPECT they were 0.54±0.20, 0.04±0.01, and 0.01±0.02, respectively. At T3, the liver volumes were 84%±7% of the baseline according to CT and 92%±13% of the baseline according to SPECT. Changes in the hepatic metabolism did not achieve statistical significance. At T1, the unadjusted clearance ratios with respect to the baseline were 0.75±0.07 for intravenous cholate (P<0.001), 0.88±0.15 for galactose (P=0.07), 0.84±0.08 for PHM (P=0.002), and 0.83±0.19 for the estimated HBF (P=0.06). At T1, these ratios adjusted per liter of liver were up to 50% greater than the baseline values, suggesting recruitment of HBF by the regenerating liver. Increased cholate shunt, increased spleen volume, and decreased platelet count, were consistent with an altered portal circulation. In conclusion, initial hepatic regeneration is rapid, accounts for nearly two-thirds of total regeneration, and is associated with increases in HBF and cholate uptake. Right lobe donation alters the portal circulation of living donors, but the long-term clinical consequences, if there are any, are unknown.

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.

UNLABELLED: Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C virus (HCV). 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 and 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(elim)), antipyrine (AP) clearance (Cl), MEGX concentration, methionine breath test (MBT), galactose elimination capacity (GEC), dual cholate (CA) clearances and shunt, perfused hepatic mass (PHM), and liver and spleen volumes (by single-photon emission computed tomography) were measured. Baseline QLFTs were significantly worse (P = 0.0017 to P < 0.0001) and spleen volumes were 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% confidence interval [CI]: 1.29-3.78) for GEC to 6.52 (95% CI: 3.63-11.71) for CA clearance after oral administration (Cl(oral)). 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 Cl(oral) 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 the noninvasive monitoring, counseling, and management of patients with chronic HCV.