The spectrum of hepatic functional impairment in compensated chronic hepatitis C: results from the Hepatitis C Anti‐viral Long‐term Treatment against Cirrhosis Trial<sup>1</sup>

Everson, Gregory T.; Shiffman, Mitchell L.; Morgan, Timothy R.; Hoefs, John C.; Sterling, Richard K.; Wagner, David; Kulig, Clark C.; Curto, Teresa M.; Wright, Elizabeth C.

doi:10.1111/j.1365-2036.2008.03639.x

Cited by 29 publications

(34 citation statements)

References 24 publications

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“…In the HALT-C cohort we found that the dual cholate test outperformed standard lab tests, Ishak fibrosis score, and other QLFTs in prediction of outcomes 14,24,26 . Subsequently, we compared the performance of DSI against Ishak fibrosis score, platelet count, and MELD score first by examination of respective ROC curves.…”

Section: Clinical Applicationsmentioning

confidence: 85%

“…The dual cholate test outperformed a battery of metabolic tests in predicting cirrhosis 14,24,26 , and DSI>19 predicted cirrhosis and risk for future clinical outcomes 27,28 . D4-cholate concentration >1μM at 60 minutes after oral dosing, is equivalent to DSI >19 27,28 .…”

Section: Clinical Applicationsmentioning

confidence: 95%

“…Evolving pathophysiologic changes during these earlier stages of disease are not detected nor quantified! In contrast, the clearance of orally administered cholate (Portal HFR) declines by 50% or more from fibrosis stages F0 to F3 25,26 . Based on the known relationships shown in Equation 5, the normal portal pressure and decreased Portal HFR likely reflect an increase in intrahepatic resistance.…”

Section: Quantifying the Portal Circulationmentioning

confidence: 99%

“…Modeling these test outputs for prediction of clinical outcomes produced a disease severity index (DSI) (Equation 4).

DSI = A (SHUNT) - B (Ln (Portal HFR)) - C (Ln (Systemic HFR)) + D

The coefficients A, B,and C and constant D were modeled from data from a long term study of patients with both early stage HCV 25 and advanced fibrosis or compensated cirrhosis (Figure 3) 24,26 . DSI quantifies global hepatic function and physiology and provides a direct link of DSI score to clinical outcome.…”

Section: Dual Cholate Testmentioning

confidence: 99%

“…Detecting and treating the medium to large varices prior to their rupture and hemorrhage is desirable. In the HALT-C trial cholate shunt >35% or DSI>19 identified nearly all of the patients with medium- or large-sized varices 14,24,26 , and DSI was more predictive than fibrosis stage 27,28 (Youden Index, J, was 0.51 for DSI versus 0.38 for Ishak fibrosis score).…”

Section: Clinical Applicationsmentioning

confidence: 99%

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Noninvasive assessment of liver function

Helmke

Colmenero

Everson

2015

Current Opinion in Gastroenterology

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Purpose of review It is our opinion that there is an unmet need in Hepatology for a minimally- or noninvasive test of liver function and physiology. Quantitative liver function tests (QLFTs) define the severity and prognosis of liver disease by measuring the clearance of substrates whose uptake or metabolism is dependent upon liver perfusion or hepatocyte function. Substrates with high affinity hepatic transporters exhibit high “first-pass” hepatic extraction and their clearance measures hepatic perfusion. In contrast, substrates metabolized by the liver have low first-pass extraction and their clearance measures specific drug metabolizing pathways. Recent Findings We highlight one QLFT, the dual cholate test, and introduce the concept of a disease severity index (DSI) linked to clinical outcome that quantifies the simultaneous processes of hepatocyte uptake, clearance from the systemic circulation, clearance from the portal circulation, and portal-systemic shunting. Summary It is our opinion that dual cholate is a relevant test for defining disease severity, monitoring the natural course of disease progression, and quantifying the response to therapy.

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Section: Clinical Applicationsmentioning

confidence: 85%

Section: Clinical Applicationsmentioning

confidence: 95%

Section: Quantifying the Portal Circulationmentioning

confidence: 99%

“…Modeling these test outputs for prediction of clinical outcomes produced a disease severity index (DSI) (Equation 4).

DSI = A (SHUNT) - B (Ln (Portal HFR)) - C (Ln (Systemic HFR)) + D

Section: Dual Cholate Testmentioning

confidence: 99%

Section: Clinical Applicationsmentioning

confidence: 99%

See 3 more Smart Citations

Noninvasive assessment of liver function

Helmke

Colmenero

Everson

2015

Current Opinion in Gastroenterology

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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

Everson¹,

Shiffman²,

Hoefs³

et al. 2012

Hepatology

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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.

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Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

et al. 2019

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Sustained virologic response (SVR) after direct acting antiviral agents (DAAs) holds promise for reducing hepatocellular cancer (HCC). DAAs have recently been available long enough to estimate the long‐term risk. We conducted a retrospective cohort study of hepatitis C virus (HCV) patients who achieved SVR with DAAs from 129 Veterans Health Administration hospitals between January 1, 2015, and December 31, 2015, with follow‐up through September 30, 2018. We calculated the overall and quarterly HCC incidence rates. We examined the effect of demographic, clinical, and behavioral factors and the decline or increase of FIB‐4 and aspartate aminotransferase to platelet ratio index (APRI) on HCC risk. Among the 18,076 patients with SVR, 544 incident cases of HCC were diagnosed during the mean 2.9 years of follow‐up. The cumulative 1, 2, and 3‐year risks of HCC were 1.1%, 1.9% and 2.8%, respectively. Cirrhosis was strongly associated with HCC risk (adjusted hazard ratio = 4.13, 95% confidence interval = 3.34‐5.11). The quarterly incidence rate of HCC remained stable between 1.00 and 1.23/100 person‐years (PY) and 1.5 to 2.3/100 PY in patients with cirrhosis. The risk of HCC was the highest in patients who had persistently high FIB‐4/APRI and both with and without cirrhosis. HCC risk fell in patients with cirrhosis who experienced a decrease of FIB‐4/APRI scores yet remained higher than the accepted threshold for HCC surveillance. HCC risk was also higher in patients with alcohol use, older age, and infection with HCV genotype 3. Most patients treated at an early stage of liver fibrosis had a stable low risk. Conclusion: Patients successfully treated with DAAs and at risk of HCC did not regress after 3.6 years of follow‐up. HCC risk remained above the accepted thresholds for surveillance in patients with cirrhosis. These data have important implications for HCC surveillance in cured HCV patients.

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The spectrum of hepatic functional impairment in compensated chronic hepatitis C: results from the Hepatitis C Anti‐viral Long‐term Treatment against Cirrhosis Trial¹

Abstract: SUMMARY BackgroundThe spectrum of functional impairment in patients with compensated chronic hepatitis C is incompletely defined.

Cited by 29 publications

References 24 publications

Noninvasive assessment of liver function

Noninvasive assessment of liver function

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

Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

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The spectrum of hepatic functional impairment in compensated chronic hepatitis C: results from the Hepatitis C Anti‐viral Long‐term Treatment against Cirrhosis Trial1

Abstract: SUMMARY BackgroundThe spectrum of functional impairment in patients with compensated chronic hepatitis C is incompletely defined.

Cited by 29 publications

References 24 publications

Noninvasive assessment of liver function

Noninvasive assessment of liver function

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

Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

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Product

Resources

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The spectrum of hepatic functional impairment in compensated chronic hepatitis C: results from the Hepatitis C Anti‐viral Long‐term Treatment against Cirrhosis Trial¹