Predicting the Development of Liver Cirrhosis by Simple Modelling in Patients With Chronic Hepatitis C

S. Lens; F. Torres; M. Puigvehi; Z. Mariño; M.-C. Londoño; S. M. Martinez; I. García-Juárez; Á. García-Criado; R. Gilabert; C. Bru; R. Solà; J. M. Sanchez-Tapias; J. A. Carrión; X. Forns


Aliment Pharmacol Ther. 2016;43(3):364-374. 

In This Article

Abstract and Introduction


Background Data are scarce on the natural history of chronic hepatitis C (CHC) in patients with mild hepatitis C who did not respond to anti-viral therapy.

Aim To predict the risk of progression to cirrhosis, identifying patients with the more urgent need for therapy with effective anti-virals.

Methods A cohort of 1289 noncirrhotic CHC patients treated with interferon-based therapy between 1990 and 2004 in two referral hospitals were followed up for a median of 12 years.

Results Overall, SVR was achieved in 46.6% of patients. Data from a randomly split sample (n = 832) was used to estimate a model to predict outcomes. Among nonresponders (n = 444), cirrhosis developed in 123 (28%) patients. In this group, the 3, 5 and 10-year cumulative probabilities of cirrhosis were 4%, 7% and 22%, respectively, compared to <1% in the SVR-group (P < 0.05). Baseline factors independently associated with progression to cirrhosis in nonresponders were: fibrosis ≥F2, age >40 years, AST >100 IU/L, GGT >40 IU/L. Three logistic regression models that combined these simple variables were highly accurate in predicting the individual risk of developing cirrhosis with areas under the receiving operating characteristic curves (AUC) at 5, 7 and 10 years of ~0.80. The reproducibility of the models in the validation cohort (n = 457, nonresponders = 244), was consistently high.

Conclusions Modelling based on simple laboratory and clinical data can accurately identify the individual risk of progression to cirrhosis in nonresponder patients with chronic hepatitis C, becoming a very helpful tool to prioritise the start of oral anti-viral therapy in clinical practice.


Treatment of chronic hepatitis C (CHC) using a combination of pegylated interferon and ribavirin (PR) results in a sustained virologic response (SVR) in ~50% of treated patients.[1] New direct anti-viral therapies (DAAs) have been approved in the U.S and Europe and have become the new standard of care for CHC therapy.[2] Besides increased efficacy, one of the main advantages of these drugs is their excellent safety profile and the possibility of achieving SVR in an all-oral interferon-free combination.[3–7] Nevertheless, the wide use of such drugs implies a high economical burden so the Health Care Systems of many countries will not afford treating all HCV-infected patients. In this setting, a careful selection of patients is essential, at least during the next few years.

The main goal of viral clearance in patients with chronic hepatitis C is to avoid progression to liver cirrhosis and its complications. Although the progression rate of liver fibrosis in patients with CHC is highly variable, cirrhosis develops in approximately 15–20% of patients over time.[8] A community-based study in Germany in patients with known data of HCV infection provided evidence of disease progression 35 years after infection, with the highest proportion of patients with clinical signs of cirrhosis in the non-SVR group (15%).[9]

A recent study established a risk score to assess long-term mortality among patients with advanced fibrosis;[10] however, due to the slow progression of CHC, large cohorts and long follow-up periods are necessary to reach solid conclusions in patients with mild fibrosis.

The main aim of this study is to identify which factors are related to disease progression in patients with chronic hepatitis C who did not respond to anti-viral therapy and are potential candidates for oral anti-viral treatment. A common question in patients, particularly in those with mild disease who may not fulfil criteria for drug reimbursement, is if receiving anti-viral therapy can be delayed and, more importantly, for how long.