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

Abstract

Hepatocellular carcinoma (HCC), the commonest among liver cancers, is one of the leading causes of mortality among malignancies worldwide. Several reports demonstrate autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) to confer increased risk of hepatobiliary malignancies, albeit at lower frequencies compared to other liver diseases. Several parameters have been recognized as risk factors for HCC development in AIH and PBC, including demographics such as older age and male sex, clinical features, the most decisive being cirrhosis and other co-existing factors, such as alcohol consumption. Moreover, biochemical activity and treatment response have been increasingly recognized as prognostic factors for HCC development in AIH and PBC. As available treatment modalities are effective only when HCC diagnosis is established early, surveillance has been proven essential for HCC prognosis. Considering that the risk for HCC is not uniform between and within disease groups, refinement of screening strategies according to prevailing demographic, clinical, and molecular risk factors is mandated in AILDs patients, as personalized HCC risk prediction will offer significant advantage in patients at high and/or medium risk. Furthermore, future investigations should draw attention to whether modification of immunosuppression could benefit AIH patients after HCC diagnosis.

APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis

“…Of note is that signs of portal hypertension can develop even before the establishment of cirrhosis, which is presinusoidal in nature [ 66 ]. The risk of hepatocellular carcinoma (HCC) in PBC patients also increased, especially in men or those who have already developed cirrhosis [ 67 – 69 ].…”

“…In addition, an international cohort study showed that biochemical non-response at one year of UDCA treatment (Paris-II not fulfilled) significantly increased the future risk of HCC [ 172 ]. Other risk factors associated with HCC in PBC including older age, any signs of portal hypertension, thrombocytopenia, past HBV infection, diabetes, obesity and alcohol consumption, as summurized by two recent reviews [ 67 , 69 ].…”

Hepatocellular carcinoma in viral and autoimmune liver diseases: Role of CD4+ CD25+ Foxp3+ regulatory T cells in the immune microenvironment

“…HCC arises almost exclusively in the setting of chronic liver inflammation and, unlike the elevated risk associated with chronic viral (HBV and HCV) infections, it has been reported that the tumor is less common in liver cirrhosis caused by autoimmune liver diseases[ 12 - 15 ]. However, it is known that, regardless of etiology, cirrhosis per se represents a precancerous condition leading to an increased risk of HCC[ 15 , 16 ].…”

Familiarity Breeds Strategy: In Silico Untangling of the Molecular Complexity on Course of Autoimmune Liver Disease-to-Hepatocellular Carcinoma Transition Predicts Novel Transcriptional Signatures

“…While PBC and PSC primarily involve biliary inflammation, autoimmune manifestations of AIH involve inflammation of the hepatic epithelium, characterized by hypergammaglobulinemia, circulating autoantibodies such as anti-nuclear antibody (ANA), anti-smooth muscle antibody (SMA) and high IgG titers [4]. The etiology of these AILDs remains unknown, but evidence suggests an amalgamation of genetic susceptibility and environmental risks [5], culminating in a loss of immune tolerance leading to the destruction of hepatocytes, which often end up into malignant conditions such as hepatocellular carcinoma (HCC) [6][7][8][9]. Common treatment modalities against AILDs involve immunosuppressant corticosteroid therapies, either as monotherapy or as combination therapy when co-administered with azathioprine [10].…”

“…Although the defined mechanism is still unclear, accumulating evidences suggest the AILDs to be key factors participating in HCC development [6][7][8][9]. Briefly, end-stage AILDs often lead to HCC, most likely due to the prolonged, robust hepato-inflammation.…”