Toronto HCC risk index: A validated scoring system to predict 10-year risk of HCC in patients with cirrhosis.

BACKGROUND & AIMS: Current guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in all patients with cirrhosis, regardless of etiology. However, HCC incidence is not well established for many causes of cirrhosis. We aimed to assess the disease-specific incidence of HCC in a large cohort of patients with cirrhosis and to develop a scoring system to predict HCC risk. METHODS: A derivation cohort of patients with cirrhosis diagnosed by biopsy or non-invasive measures was identified through retrospective chart review. The disease-specific incidence of HCC was calculated according to etiology of cirrhosis. Factors associated with HCC were identified through multivariable Cox regression and used to develop a scoring system to predict HCC risk. The scoring system was evaluated in an external cohort for validation. RESULTS: Of 2,079 patients with cirrhosis and ≥6months follow-up, 226 (10.8%) developed HCC. The 10-year cumulative incidence of HCC varied by etiologic category from 22% in patients with viral hepatitis, to 16% in those with steatohepatitis and 5% in those with autoimmune liver disease (p<0.001). By multivariable Cox regression, age, sex, etiology and platelets were associated with HCC. Points were assigned in proportion to each hazard ratio to create the Toronto HCC Risk Index (THRI). The 10-year cumulative HCC incidence was 3%, 10% and 32% in the low-risk (<120points), medium-risk (120-240) and high-risk (>240) groups respectively, values that remained consistent after internal validation. External validation was performed on a cohort of patients with primary biliary cirrhosis, hepatitis B viral and hepatitis C viral cirrhosis (n=1,144), with similar predictive ability (Harrell's c statistic 0.77) in the validation and derivation cohorts. CONCLUSION: HCC incidence varies markedly by etiology of cirrhosis. The THRI, using readily available clinical and laboratory parameters, has good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis. LAY SUMMARY: HCC incidence varies markedly depending on the underlying cause of cirrhosis. Herein, using readily available clinical and laboratory parameters we describe a risk score, THRI, which has a good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis.

Management of HCV in cirrhosis-a rapidly evolving landscape.

Despite the rapid progress in treatment, chronic hepatitis C virus (HCV) infection remains a growing cause of liver-related mortality globally. Patients who have been infected for decades are now presenting with advanced liver disease with the complications of cirrhosis and liver cancer. Early attempts at treatment with peginterferon and ribavirin were limited by toxicity, long treatment duration, and limited efficacy. This was especially relevant for patients with cirrhosis, where exposure to peginterferon-based therapy was relatively ineffective and led to high rates of toxicity. However, the recent development of multiple novel direct-acting antivirals (DAAs) has revolutionized the treatment of HCV. The majority of patients can now be cured with short courses of extremely well-tolerated all-oral regimens. However, the real test of these regimens comes in patients with more advanced liver disease, both in terms of safety and efficacy. Patients with cirrhosis have the greatest need for therapy and have traditionally been the most difficult to cure. The new therapies are rapidly changing this paradigm. Accumulating data suggest that high cure rates are achievable in patients with compensated cirrhosis and may even be possible in patients with signs of liver failure. This review will focus on the treatment of HCV in patients with cirrhosis, with an emphasis on the challenges that remain and strategies to deal with this important population.

Acute hepatitis C: management in the rapidly evolving world of HCV.

The acute phase of hepatitis C (HCV) infection is typically defined as the initial 6 months following exposure to the virus; however, in some individuals, the acute phase of the infection can last much longer (Orland et al. Hepatology 33:321-27, 2001). Although some patients have symptoms of acute hepatitis, most infected individuals are entirely asymptomatic. As a result, many patients are unaware of the infection until it progresses to chronic infection, and may not develop symptoms until decades later with the onset of decompensated cirrhosis or hepatocellular carcinoma (HCC). A substantial proportion (20-40%) of infected patients clear the virus during the acute phase. Interferon-based treatment is also much more likely to be successful in the acute phase of infection but is relatively poorly tolerated. Therefore, recognition of acute HCV infection is critical to prioritize those patients who do not spontaneously clear the infection for immediate therapy. However, the promise of highly effective well-tolerated all-oral therapies in development may alter the management approach. This review will focus on the epidemiology, natural history, diagnosis, and treatment of acute HCV infection.