Non-invasive Liver Fibrosis Models and Prognosis in HCV
Background & Aims: Liver fibrosis is prognostic of outcomes among patients with chronic hepatitis C (CHC). We evaluated the accuracy of non-invasive markers and liver biopsy in predicting morbidity and mortality in CHC patients.
Methods: Compensated CHC patients were evaluated over a 10-year period. Non-invasive markers including Hepascore, FIB-4, APRI and liver biopsy results were retrospectively collated. Follow-up morbidity and mortality data were obtained from the Western Australian Data Linkage System. The prognostic significance of baseline non-invasive markers and biopsy were assessed using Kaplan–Meier analysis.
Results: A total of 406 subjects (64% male, mean age 48 ± 11 years) were followed up for 2385 person-years, during which there were 22 (5.4%) deaths including 14 (3.4%) who died from liver disease or required liver transplantation. Sixteen (3.9%) subjects developed liver decompensation. Hepascore and liver biopsy (P < 0.005) but not APRI or FIB-4 were predictive of overall and liver-related mortality as well as liver decompensation. A Hepascore>0.5 was associated with increased overall mortality [Hazard Ratio (95%CI) 6.7 (2.6–17), P < 0.001], liver-related mortality [32.8 (4.3–250), P = 0.001] and risk of future decompensation [11.8 (3.3–41), P < 0.001], whereas a Hepascore ≤0.5 was associated with a 99% probability of not dying from liver-related causes over 10 years. Hepascore had comparable accuracy with liver biopsy in predicting liver-related mortality with AUROC of 0.86 (95%CI 0.80–0.90) and 0.87 (0.79–0.96), respectively.
Conclusion: Hepascore is predictive of overall and liver-related mortality and morbidity in CHC patients with comparable accuracy to liver biopsy. Hepascore may be a useful prognostic marker in clinical practice.
Chronic Hepatitis C (CHC) afflicts more than 175 million people worldwide and it is responsible for approximately 350 000 deaths each year. CHC infection is generally asymptomatic and many individuals present very late with advanced liver disease. Even for patients presenting early, treatment has significant side-effects, is difficult to tolerate and may be unsuccessful. Thus, many individuals choose either not to be treated because of the risk of adverse events or fail to respond to treatment and have persistent infection for decades. Untreated CHC infection has considerable morbidity with the development of cirrhosis and hepatocellular carcinoma (HCC), the two major complications. Among patients with CHC, approximately 20% develop cirrhosis after 20 years of infection with a 4–5% annual rate of hepatic decompensation. The annual incidence of HCC in patients with CHC associated cirrhosis is between 1 and 4%. Despite this, the majority of subjects with untreated CHC infection do not die or develop complications related to their liver disease. Therefore, accurate prognostication of outcomes is vital to guide management decisions and for patient counselling. This is particularly important among elderly individuals and those who are at increased risk of adverse effects with anti-viral treatment.
CHC results in liver fibrosis which is currently the best predictor of liver-related morbidity and mortality. The rate of fibrosis progression in CHC varies between individuals and is not linear over time. The degree of fibrosis, as assessed by liver biopsy, provides information on the likelihood of disease progression. Although liver biopsy is the gold standard for accurately assessing the degree of fibrosis and inflammation, it is invasive, associated with sampling errors, may cause complications such as pain and bleeding and is expensive. Because of these drawbacks, it is not attractive to patients and is not suitable for serial monitoring. Recent studies have shown that serum-based fibrosis markers such as Hepascore, FIB-4 or aspartate aminotransferase-to-platelet ratio index (APRI) can be used as an alternative non-invasive way of assessing liver fibrosis and have been validated as an accurate predictor of liver fibrosis in patients with CHC.
In this cohort study of CHC patients, we investigated whether the non-invasive fibrosis markers (Hepascore, FIB-4 and APRI) could be used as a predictor of overall and liver-related mortality by comparison with liver biopsy. In addition, we assessed the predictive value of non-invasive markers for liver decompensation and the development of HCC.
Abstract and Introduction
Abstract
Background & Aims: Liver fibrosis is prognostic of outcomes among patients with chronic hepatitis C (CHC). We evaluated the accuracy of non-invasive markers and liver biopsy in predicting morbidity and mortality in CHC patients.
Methods: Compensated CHC patients were evaluated over a 10-year period. Non-invasive markers including Hepascore, FIB-4, APRI and liver biopsy results were retrospectively collated. Follow-up morbidity and mortality data were obtained from the Western Australian Data Linkage System. The prognostic significance of baseline non-invasive markers and biopsy were assessed using Kaplan–Meier analysis.
Results: A total of 406 subjects (64% male, mean age 48 ± 11 years) were followed up for 2385 person-years, during which there were 22 (5.4%) deaths including 14 (3.4%) who died from liver disease or required liver transplantation. Sixteen (3.9%) subjects developed liver decompensation. Hepascore and liver biopsy (P < 0.005) but not APRI or FIB-4 were predictive of overall and liver-related mortality as well as liver decompensation. A Hepascore>0.5 was associated with increased overall mortality [Hazard Ratio (95%CI) 6.7 (2.6–17), P < 0.001], liver-related mortality [32.8 (4.3–250), P = 0.001] and risk of future decompensation [11.8 (3.3–41), P < 0.001], whereas a Hepascore ≤0.5 was associated with a 99% probability of not dying from liver-related causes over 10 years. Hepascore had comparable accuracy with liver biopsy in predicting liver-related mortality with AUROC of 0.86 (95%CI 0.80–0.90) and 0.87 (0.79–0.96), respectively.
Conclusion: Hepascore is predictive of overall and liver-related mortality and morbidity in CHC patients with comparable accuracy to liver biopsy. Hepascore may be a useful prognostic marker in clinical practice.
Introduction
Chronic Hepatitis C (CHC) afflicts more than 175 million people worldwide and it is responsible for approximately 350 000 deaths each year. CHC infection is generally asymptomatic and many individuals present very late with advanced liver disease. Even for patients presenting early, treatment has significant side-effects, is difficult to tolerate and may be unsuccessful. Thus, many individuals choose either not to be treated because of the risk of adverse events or fail to respond to treatment and have persistent infection for decades. Untreated CHC infection has considerable morbidity with the development of cirrhosis and hepatocellular carcinoma (HCC), the two major complications. Among patients with CHC, approximately 20% develop cirrhosis after 20 years of infection with a 4–5% annual rate of hepatic decompensation. The annual incidence of HCC in patients with CHC associated cirrhosis is between 1 and 4%. Despite this, the majority of subjects with untreated CHC infection do not die or develop complications related to their liver disease. Therefore, accurate prognostication of outcomes is vital to guide management decisions and for patient counselling. This is particularly important among elderly individuals and those who are at increased risk of adverse effects with anti-viral treatment.
CHC results in liver fibrosis which is currently the best predictor of liver-related morbidity and mortality. The rate of fibrosis progression in CHC varies between individuals and is not linear over time. The degree of fibrosis, as assessed by liver biopsy, provides information on the likelihood of disease progression. Although liver biopsy is the gold standard for accurately assessing the degree of fibrosis and inflammation, it is invasive, associated with sampling errors, may cause complications such as pain and bleeding and is expensive. Because of these drawbacks, it is not attractive to patients and is not suitable for serial monitoring. Recent studies have shown that serum-based fibrosis markers such as Hepascore, FIB-4 or aspartate aminotransferase-to-platelet ratio index (APRI) can be used as an alternative non-invasive way of assessing liver fibrosis and have been validated as an accurate predictor of liver fibrosis in patients with CHC.
In this cohort study of CHC patients, we investigated whether the non-invasive fibrosis markers (Hepascore, FIB-4 and APRI) could be used as a predictor of overall and liver-related mortality by comparison with liver biopsy. In addition, we assessed the predictive value of non-invasive markers for liver decompensation and the development of HCC.
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