Hepatocellular carcinoma and survival in patients with primary biliary cirrhosis

Abstract

The incidence of hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) is not well known. The aims of this study are to determine HCC incidence and survival, and to identify risk factors associated with these outcomes in patients with PBC. We collected information on 396 patients with PBC at enrollment and followed-up from 6 to 271 months. They were all negative for hepatitis B and C virus markers. HCC was detected by scanning with ultrasonography, computed tomography, or both every 4 to 6 months. Life expectancy (LE) was approximated with the declining exponential approximation of LE. A total of 14 patients developed HCC. The cumulative appearance rate of HCC in patients with advanced-stage PBC (Scheuer's stage III or IV) was significantly higher than that for patients with early-stage (stage I or II) (12.3% and 7.7% by the tenth year, respectively. P ‫؍‬ .021). Proportional hazards analysis showed 3 factors are independently associated with the development of HCC: age at the time of diagnosis, male gender, and history of blood transfusion. Age, male gender, and advanced-stage PBC were associated with survival, but HCC development was not. The disease-specific annual mortality rate was estimated to be 0.008 for women and 0.028 for men with advanced-stage PBC. In conclusion, HCC develops in old patients with advanced-stage PBC, but HCC does not affect the patients' survival. P rimary biliary cirrhosis (PBC) is a chronic liver disease of unknown etiology presenting a variety of disease spectrum from asymptomatic disease state to full-blown cirrhosis. Patients with liver cirrhosis caused by chronic infection of hepatitis C virus (HCV) or hepatitis B virus (HBV) are at high risk of hepatocellular carcinoma (HCC); however, it is not known whether the HCC incidence is high in patients with PBC. Although there are 9 studies about HCC incidence in PBC, the results are not consistent. 1-9 Some studies 3,4 show that patients with PBC have no excess risk of developing HCC and others [5][6][7][8][9] show that the incidence of HCC is high in those patients. An Italian study indicated that HCC has a relatively high prevalence in PBC and HCV superinfection may play an important part in favoring HCC. 7 Even though without HBV or HCV infection, a study conducted in UK showed 5.9% of patients with PBC in precirrhotic or cirrhotic stage had developed HCC. 6 The authors of this large-scale cohort study concluded that men with advanced-stage PBC have a higher risk of developing HCC. A recent retrospective study in the Mayo Clinic also reported that patients with PBC 8 are at high risk of hepatobiliary malignancies but the authors did not mention risk factors for HCC development.The aims of the present study are to analyze the survival of patients with PBC, to quantify the incidence at which they develop HCC, and to identify HCC risk factors. In addition, we determined whether HCC affected the survival of patients with PBC. Therefore, we tested 2 hypotheses: (1) that the patients with advanced-stage PBC sur...

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 similarity resulted in a comparable prevalence and incidence of HCC carcinoma in Spain and Italy, which, on the other hand, are in the range reported in other studies performed in Western countries when analyzing lower numbers of patients and shorter periods of follow-up. 4,15 Thus, the prevalence of HCC in PBC is 3.35 cases per 100 patients, a figure that confirms earlier reported prevalences by the same groups. A higher prevalence has been observed when analyzing only patients with advanced disease.…”

“…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 incidence is lower than that calculated from other studies, a dissimilarity that can be explained, in part, by the longer follow-up in the current report (mean: 9.8 years; range 2.3 to 30 years) as compared with shorter periods in the other studies (from 3.3 to 7.3 years). 4,10,15,17 Advanced histological stage was the only factor associated with a high risk for developing HCC in PBC. This is in accordance with other studies that indicated that HCC only appears in patients with endstage disease and particularly when they have cirrhosis.…”

“…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.…”