Older Age and Disease Duration Are Highly Associated with Hepatocellular Carcinoma in Patients with Autoimmune Hepatitis

Abstract

Background: Hepatocellular carcinoma (HCC) is rare in patients with autoimmune hepatitis (AIH). However, the overall burden of AIH cirrhosis in causing HCC and patients' risk factors are not well understood. Aims: To characterize the proportion of HCC linked to AIH at a large academic health center, and to identify variables associated with HCC in patients with AIH in a case-control study design. Methods: Over a 14.5-year period, medical records of all patients with HCC were reviewed. Cases are AIH patients identified from the cohort and controls are patients with AIH without HCC. Three controls were randomly chosen from the Genetic Repository of Autoimmune Liver Disease and Coexisting Exposures database for each eligible case. Results: Out of 1,250 eligible patients, 20 were linked to AIH (1.6%). Their median age was 64 years, 40% men, and 100% Caucasian. 10% of AIH patients did not have evidence of cirrhosis at HCC diagnosis. The proportion of HCCs due to AIH decreased during the time intervals of the study. Compared to controls, cases were more likely men (40.0% vs. 18%, P=0.049), with longer AIH duration (median 16 years vs. 5 years, P=0.004). Prolonged AIH duration (OR 1.68, p=0.006) and older age (OR 1.15, p=0.049) were risk factors for HCC. Conclusions: AIH is a rare cause (1.6%) for HCC in Midwestern United States with a decreasing trend over 14.5 years. 10% of AIH-HCC patients occurs without cirrhosis. Patients with prolonged duration of the disease and older age are at high risk to develop HCC.

Current Trends and Characteristics of Hepatocellular Carcinoma in Patients with Autoimmune Liver Diseases

“…Even though AIH has been linked to the development of HCC, the lower risk (<3%) of HCC in these patients compared to those with other hepatopathies has also been confirmed by several other studies ( Table 1 ) [ 47 , 49 , 50 , 55 , 62 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ].…”

“…Data on the evolving trend related to the incidence of HCC in AIH patients are inconsistent, as attested by a population-based study from Denmark demonstrating doubling of HCC incidence during the study period [ 47 ], while the incidence was reported to decline in a retrospective study from the US [ 67 ]. This considerable variation in HCC incidence among AIH patients is highlighted in a meta-analysis of 25 studies that demonstrated moderate heterogeneity.…”

“…Hence, the incidence of HCC is reportedly rising in patients being cirrhotic for more than five years [ 75 , 80 ]. The implication of cirrhosis as a risk factor for HCC has been highlighted in numerous other studies so far related to patients both from the West and the East [ 6 , 65 , 67 , 70 , 72 , 74 , 76 ].…”

“…Among other factors, older age has been another feature that has been associated with the development of HCC in AIH patients [ 67 , 76 , 77 ]. Several reports have specified male sex to be a risk factor for HCC, though this is not a unifying finding in all studies [ 47 , 49 , 62 , 70 , 77 ].…”

The Asian Pacific Association for the Study of the Liver clinical practice guidance: the diagnosis and management of patients with autoimmune hepatitis

“…Repeated relapse and elevated ALT also contribute to development of HCC [ 206 , 360 , 362 ]. Other risk factors may include old age, disease duration [ 366 ], male gender, immunosuppressive treatment for > 3 years [ 362 ]. Taken together, regular HCC surveillance is justified and should be scheduled in patients with AIH, especially in cirrhotic patients.…”