Surveillance for hepatocellular carcinoma in patients with primary biliary cirrhosis

Abstract

Hepatocellular carcinoma (HCC) occurs with increased frequency in patients with primary biliary cirrhosis (PBC). Effectiveness of surveillance recommendations for HCC is controversial, and data are lacking in patients with PBC. In this study, we attempt to (1) establish the importance of surveillance for HCC in patients with PBC; (2) identify a target population of patients with PBC for HCC surveillance; and (3) propose surveillance recommendations for patients with PBC. We retrospectively identified 36 patients seen at the Mayo Clinic between 1976 and 2007 with a diagnosis of both PBC and HCC. Five patients (14%) were diagnosed incidentally, 17 patients comprised our surveillant population, and 14 patients were diagnosed outside a surveillance program. Patients in the surveillant population were more likely to undergo therapy (88% versus 43%; P ‫؍‬ 0.01) and had improved survival (P ‫؍‬ 0.002) compared with the nonsurveillant population. All cases of HCC except one were predicted to be at significant risk for HCC based on age, sex, evidence of portal hypertension, and history of blood transfusion using a previous predictive model. Conclusion: We established the importance of surveillance for HCC in patients with PBC. We demonstrated adequate performance of a predictive model and propose it should be refined and used to identify patients with PBC who should be screened for development of HCC. Further studies are needed so that optimal HCC surveillance recommendations in this population can be determined and included in the practice guidelines for PBC. H epatocellular carcinoma (HCC) is the most common primary malignancy of the liver, 1 and its incidence in the United States is rising. 2 Approximately 70% to 90% of all detected HCC cases occur within an established background of chronic liver disease and cirrhosis of all etiologies. 2,3 HCC is one of the main causes of death in patients with liver cirrhosis. 4 Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that affects predominantly middle-aged women. 5 The natural history of PBC usually consists of slow disease progression, which can result in liver cirrhosis, liver failure, and eventually require liver transplantation. 6 HCC occurs with increased frequency in patients with PBC, particularly in patients with advanced histological disease. [7][8][9][10][11][12][13][14][15][16][17][18][19][20] The exact frequency is unknown but is estimated to be between 0.7% and 16%. 19,21 Even though the effectiveness as well as cost-effectiveness of screening strategies remain controversial, the development of HCC in patients with cirrhosis argues for the opportunity to apply surveillance tests to detect liver cancer at an early and thus potentially curable stage. 22 Although HCC surveillance is widely recommended for patients with cirrhosis, the current practice guidelines for PBC by the AASLD do not include specific recommendations for HCC surveillance. 23 The AASLD practice guidelines for the management of HCC recognize stage 4 PBC 24,25 as a high-ris...

Incidence, risk factors, and survival of hepatocellular carcinoma in primary biliary cirrhosis: Comparative analysis from two centers

“…6 This seems reasonable taking into account the low number of patients with PBC exposed to tobacco smoking and moderate alcohol intake. However, our data on the markers of previous viral infection does not support earlier reports indicating that blood transfusion 14,15 and anti-HCV 6 are potential risk factors for HCC in patients with PBC. The lack of influence of these markers of viral infection in the development of HCC in PBC is further reinforced by the fact that no association between the presence of HBsAg and anti-HCV antibodies was observed independently in Spain and in Italy.…”

“…This is in conflict with the data reported in other studies, which suggest that older age equal or greater than 70 is one of the variables entering into the model for HCC development in PBC. [14][15][16] In this study only 6 of the 24 patients with HCC (25%) were 70 years or older, thus questioning that age is a critical feature for developing HCC. Probably what is more relevant is the duration of the disease and the progression toward cirrhosis.…”

“…This is in accordance with other studies that indicated that HCC only appears in patients with endstage disease and particularly when they have cirrhosis. 4,6,[10][11][12][13][14] All the patients indeed had cirrhosis when the liver cancer was diagnosed, as demonstrated by different procedures in addition to histological assessment. Moreover, 90% of the patients had features of portal hypertension such as ascites, variceal upper gastrointestinal bleeding, or hepatic encephalopathy, thus indicating the fact that HCC develops in patients with advanced disease.…”

“…3,[6][7][8][9][10][11][12][13][14] Actually, the first case reports of primary liver cancer in PBC were published in 1979. 7 In this and other early reports, cancer development in PBC was considered very unusual and mainly observed in males, so it was concluded that gender was a risk factor for HCC in this disease.…”

“…5,6 Case reports and other studies have shown an increased risk to develop HCC in patients with an advanced histological stage at the diagnosis of PBC. [6][7][8][9][10][11][12][13][14] Advanced age, male sex, 4,5,[14][15][16] history of blood transfusion, 14,15 smoking habit, HBV and HCV (hepatitis B and C virus) infection 6 have also been associated with increased probability for HCC development in patients with PBC. [15][16][17] The limited information and the contrasting results may be explained by the low prevalence of PBC as compared with other chronic liver diseases, and by some geographical and environmental differences as well.…”