Natural history of hepatocellular carcinoma including fibrolamellar and hepato-cholangiocarcinoma variants

J Gastroenterol Hepatol. 2002 Apr;17(4):401-5. doi: 10.1046/j.1440-1746.2002.02734.x.


The natural history of hepatocellular carcinoma (HCC) varies greatly with the global region, because the carcinogenic factors are not the same among countries. Besides the clinicopathological factors such as tumor characteristics, sex, and age, background liver disease is a major determinant of prognosis. Hepatocellular carcinoma, mainly associated with chemical carcinogens such as aflatoxin, does not have severe background cirrhosis, and grows quickly, whereas HCC developing in association with a virus in a cirrhotic liver generally grows more slowly, and the severity of cirrhosis is the major prognostic factor. The median survival of untreated sub-Saharan African patients is less than 1 month from diagnosis, contrasted by an average survival of 4 months in virus-induced HCC associated with cirrhosis. Tumor characteristics, such as size, number, and growth speed, which vary considerably from case to case, affect the prognosis. Vascular (portal) invasion portends a poor prognosis, and alpha-fetoprotein levels also correlate with prognosis. Several distinct clinical types of HCC occur, namely diffuse-type HCC caused by rapid portal spread of cancer cells, febrile-type caused by poorly differentiated sarcomatoid cancer cells, and cholestatic HCC caused by intraductal invasion; all have a short survival. There are several histological variant forms: combined hepato-cholangiocarcinoma behaves like HCC, with a poorer prognosis because of more frequent lymph node metastases; fibromellar carcinoma, which is relatively common in young Caucasian adults, has a good prognosis if diagnosed early, permitting resection; and cholangiolocellular carcinoma, which derives from the canalicular epithelium, is indistinguishable from HCC, with a similar prognosis.

Publication types

  • Review

MeSH terms

  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / physiopathology*
  • Carcinoma, Hepatocellular / secondary
  • Cholangiocarcinoma / etiology
  • Cholangiocarcinoma / pathology*
  • Cholangiocarcinoma / physiopathology*
  • Cholangiocarcinoma / secondary
  • Genetic Variation
  • Humans
  • Liver Neoplasms / etiology
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / physiopathology*
  • Neoplasm Invasiveness
  • Prognosis