Editor’s note: In May, the American Gastroenterological Association presented an evidence-based review addressing HCC risk in patients with NAFLD and provided Best Practice Advice statements to address key issues in clinical management. Here is a  key portion of those new guidelines.

The association between NAFLD cirrhosis and HCC is well-established, and most experts believe that screening should be recommended in this setting. The decision to enter a patient into a screening program for HCC is determined by the level of risk for HCC, while also taking into account the patient’s age, overall health, functional status, and willingness and ability to comply with screening assessment and, if found, to have an HCC, whether this individual would be an appropriate candidate for treatment. Understanding the aforementioned caveats, HCC screening should be offered for patients with cirrhosis of varying etiologies when the risk of HCC is approximately ≥1.5% per year, as has been noted with NAFLD cirrhosis. It is now well-established from several observational cohort and case–control studies that cirrhosis due to NAFLD is associated with an increased risk of HCC, and emerging data suggests that the incidence of NAFLD-related HCC is rising in the United States, thereby, necessitating the importance of screening for HCC in this patient population.

Both NAFLD cirrhosis and HCC share common risk factors, including obesity, metabolic syndrome, and diabetes.

This becomes particularly relevant as approximately 80% of patients with NAFLD cirrhosis have co-existing diabetes or obesity.

The risk of incident HCC in NAFLD cirrhosis is estimated in the literature to range between 1% and 3% per year.

Ascha et al conducted a retrospective study including 195 patients with NASH cirrhosis who were followed for a median duration of 3.2 years, and 25 of them developed incident HCC at a cumulative incidence rate of 2.6% per year.

On multivariable analyses, older age and consumption of alcohol were the only independent predictors of incident HCC in NAFLD cirrhosis. In a Japanese study including 69 patients with NASH cirrhosis who were followed for a median duration of 5 years, 11 developed HCC at an annual incidence rate of 2.3%.

 A recent large retrospective cohort study from the national Veterans Affairs system in the United States estimated HCC risk in 296,707 NAFLD patients and 296,707 matched controls without known liver disease and found the risk of HCC to be several fold higher than controls. Among patients with NAFLD, those with cirrhosis had the highest overall annual incidence of HCC (1.06% annual risk), but it ranged from 0.2% in women to 2.4% in older Hispanics with cirrhosis. Most estimates of HCC in subgroups of age, sex, and race were close to or exceeded 1% per year and, therefore, although these differences are possibly informative to disease pathophysiology, we do not recommend using (age, sex, and ethnicity-specific) them yet in the clinical decision making of whether to screen or not for HCC in NAFLD-related cirrhosis.

In general, the incidence rate of HCC in NAFLD cirrhosis is estimated to be >1.5% per year and, therefore, screening for HCC in this group is justifiable, based on cost-effectiveness considerations. Therefore, we recommend that best practice guidance is to consider and offer HCC screening to all patients with NAFLD cirrhosis. At this point, we believe that HCC screening benefit is restricted to patients with compensated cirrhosis or those with decompensated cirrhosis listed for liver transplantation.

Source: Loomba R, Lim JK, Patton H, El-Serag HB. AGA Clinical Practice Update on Screening and Surveillance for Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: Expert Review. Gastroenterology. 2020;158(6):1822-1830. doi:10.1053/j.gastro.2019.12.053