Hepatocellular carcinoma in primary biliary cirrhosis and its impact on outcomes

In this study we have determined the incidence of hepatocellular carcinoma (HCC) development in primary biliary cirrhosis (PBC) and its effects on patient survival. Six hundred and sixty seven patients with liver histology compatible with or diagnostic of PBC were seen over a 20‐year period. Two hundred and seventy three patients who had stage III or IV disease on their last biopsy and who had been followed up for at least 1 year following that biopsy (total follow‐up with advanced disease 2,010 patient years) were identified (243 female, 30 male). Patients who developed HCC were identified and their confounding risk factors were excluded. Mayo risk scores were calculated for each clinic attendance and expected survival for each time point was compared with subsequent actual survival. Sixteen cases of HCC were seen in the patients with stage III or IV disease on last biopsy, providing an overall incidence of 5.9% in this group. Fourteen of these patients had died of HCC related causes, and 2 patients were alive at the census point. The incidence of HCC was significantly higher in males with stage III/IV disease than in females (20% vs. 4.1%, P < .005). Nine of one hundred and eight (8.3%) total female deaths in this group was attributable to HCC compared with 5 of 11 (45.5%, P < .05) male deaths. HCC was not seen in any of the 394 patients with stage I and II PBC followed‐up over the same time period. Throughout the disease course of all PBC patients with HCC, the Mayo prognostic model over‐predicted survival. Whereas it is a relatively rare complication of cirrhotic PBC in women, HCC is a relatively common cause of death in male PBC patients with cirrhosis. HCC typically develops several years after the onset of cirrhosis, and is poorly predicted by prognostic models. In view of these findings, consideration should be given to careful screening for HCC in male PBC patients with cirrhosis. The risk of HCC development may be an additional reason to consider earlier transplantation in these patients.

[1]  F. Klion,et al.  Prediction of survival of patients with primary biliary cirrhosis. Examination of the Mayo Clinic model on a group of patients with known endpoint. , 1992, Gastroenterology.

[2]  N. Nagasue,et al.  Active uptake of testosterone by androgen receptors of hepatocellular carcinoma in humans , 1986, Cancer.

[3]  J. Hoofnagle,et al.  NIH conference. Hepatocellular carcinoma. , 1988, Annals of internal medicine.

[4]  B. Portmann,et al.  RISK FACTORS IN DEVELOPMENT OF HEPATOCELLULAR CARCINOMA IN CIRRHOSIS: PROSPECTIVE STUDY OF 613 PATIENTS , 1985, The Lancet.

[5]  H. Popper,et al.  Relationship Between Hepatocellular Carcinoma and Cirrhosis , 1984, Seminars in liver disease.

[6]  F. Izzo,et al.  Identification and Screening of 416 Patients with Chronic Hepatitis at High Risk to Develop Hepatocellular Cancer , 1995, Annals of surgery.

[7]  C. de Bac,et al.  Pathogenic factors in cirrhosis with and without hepatocellular carcinoma: A multicenter italian study , 1994, Hepatology.

[8]  G. Hansson,et al.  Incidence of primary liver cancer and aetiological aspects: a study of a defined population from a low-endemicity area. , 1996, British Journal of Cancer.

[9]  M. Kaplan,et al.  Primary Biliary Cirrhosis , 1987, The New England journal of medicine.

[10]  M. Kaplan,et al.  Hepatocellular carcinoma in primary biliary cirrhosis. , 1997, The American journal of gastroenterology.

[11]  M. Mathur,et al.  Enhancement of aflatoxin B1-induced hepatocarcinogenesis in rats by partial hepatectomy , 1988, Virchows Archiv. B, Cell pathology including molecular pathology.

[12]  P. Grambsch,et al.  Efficacy of liver transplantation in patients with primary biliary cirrhosis. , 1989, The New England journal of medicine.

[13]  G. Gores,et al.  Selection and timing of liver transplantation in primary biliary cirrhosis and primary sclerosing cholangitis , 1992, Hepatology.

[14]  Tohru Inoue,et al.  Difference in the in vitro uptake of bromodeoxyuridine between liver cirrhosis with and without hepatocellular carcinoma , 1989, Cancer.

[15]  E. Dickson,et al.  Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. , 1994, Gastroenterology.

[16]  K. Ohnishi,et al.  Clinical features and prognosis of hepatocellular carcinoma with reference to serum alpha‐fetoprotein levels. Analysis of 606 patients , 1989, Cancer.

[17]  J. Neuberger,et al.  Hepatocellular carcinoma in primary biliary cirrhosis: detection by alpha-fetoprotein estimation. , 1984, Gastroenterology.

[18]  David E. J. Jones,et al.  Ursodeoxycholic acid therapy in primary biliary cirrhosis , 1995, Hepatology.

[19]  M. Bassendine.  1 Aetiological factors in hepatocellular cancer , 1987 .

[20]  O. James,et al.  Clinical features and prognosis of hepatocellular carcinoma in Britain in relation to age. , 1994, Age and ageing.

[21]  B. Balkau,et al.  Ursodiol for the long-term treatment of primary biliary cirrhosis. The UDCA-PBC Study Group. , 1994, The New England journal of medicine.

[22]  A. Floreani,et al.  Hepatocellular carcinoma in primary biliary cirrhosis. , 1994, Journal of hepatology.

[23]  P. Scheuer.  Primary biliary cirrhosis. , 1967, Proceedings of the Royal Society of Medicine.

[24]  K. Chayama,et al.  A multivariate analysis of risk factors for hepatocellular carcinogenesis: A prospective observation of 795 patients with viral and alcoholic cirrhosis , 1993, Hepatology.

[25]  D. Altman,et al.  Prognosis after liver transplantation for primary biliary cirrhosis. , 1989, Transplantation.

[26]  M. Melegari,et al.  Risk factors for hepatocellular carcinoma in italy. Male sex, hepatitis b virus, non‐a non‐B infection, and alcohol , 1988, Cancer.

[27]  H. Adami,et al.  Cancer risk in primary biliary cirrhosis: A population‐based study from Sweden , 1994, Hepatology.

[28]  O. James,et al.  The Geoepidemiology of Primary Biliary Cirrhosis , 1997, Seminars in liver disease.