Risk of liver and other types of cancer in patients with cirrhosis: A nationwide cohort study in Denmark

Abstract

Cancer risk in patients with cirrhosis could be modified by factors such as changes in hormonal levels, impaired metabolism of carcinogens, or alteration of immunological status. We investigated the risk of liver and various forms of cancer in patients with cirrhosis in a follow-up study. We identified 11,605 1-year survivors of cirrhosis from the files of the Danish National Registry of Patients (NRP) from 1977 to 1989. Occurrence of cancer through 1993 was determined by linkage to the Danish Cancer Registry. For comparison, the expected number of cancer cases was estimated from national age-, sex-, and site-specific incidence rates. Overall, 1,447 cancers were diagnosed among the study subjects, as compared with 708.1 expected, to yield a standardized incidence ratio (SIR) of 2.0 (95% CI: 1.9 to 2.2). In all diagnostic subgroups of cirrhosis, the risk of primary liver cancer, mainly hepatocellular carcinoma, was markedly elevated, with 245 observed cases and an overall 36-fold elevated risk (59.9-fold elevated for hepatocellular carcinoma and 10-fold for cholangiocarcinoma). Substantial and persistent excesses during follow-up were seen for all types of cancer associated with tobacco and alcohol habits (cancer of the lung, larynx, buccal cavity, pharynx, pancreas, urinary bladder, and kidney), while moderate excesses were seen for cancers of the colon and breast. The latter, however, were not complemented by any decrease in the risk of prostate cancer (SIR: 1.0; 95% CI: 0.7 to 1.3). A slightly increased risk was seen for testis cancer, but disappeared after 10 years. We found evidence of an increased risk for liver and several extrahepatic cancers in patients with cirrhosis. Although part of this increase is likely attributable to alcohol and tobacco consumption, our study opens up the possibility that cirrhosis plays a role in the carcinogenesis of types of cancer other than liver cancer. (HEPATOLOGY 1998;28:921-925.)

Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma

“…Cirrhosis has been reported to be a risk factor for ICC. 2,3,7,8,12,14) In essential agreement, we found worsening of liver fibrosis status (via chronic hepatitis to cirrhosis) to be associated with development of ICC. By univariate analysis, an elevated serum concentration of total bilirubin, elevated activities of aspartate aminotransferase and alanine aminotransferase, a decreased serum concentration of albumin, and a decreased platelet count were significant risk factors for ICC.…”

“…10,11) Indeed, the prevalence of HCV infection among ICC patients differs considerably among areas. 8,12) Where HCV infection is prevalent, it is an important pathogenetic factor in ICC. Although a high prevalence of HBV infection in ICC patients has been reported by the Liver Cancer Study Group of Japan (4.0% to 14.5%), 13) we did not find HBV infection to be an ICC risk factor in this study.…”

Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence

“…Cohort studies performed in the USA and Northern Europe all showed an increased risk of developing cirrhosis or HCC due to alcohol drinking, although some of them found a doseeffect relationship (Klatsky and Armstrong, 1992;Becker et al, 2002) whereas others found a threshold effect of 50-75 g/day, after which the risk does not increase further (Sorensen et al, 1998;Kamper-Jorgensen et al, 2004). Various factors may have caused these contrasting results, mainly confounding by other factors, inaccuracy in estimating the level of intake during follow-up, and the low power of the studies.…”

“…In fact, population-based cohort studies in North Europe showed that the risk of HCC was about 10-fold higher among subjects with hospital discharge diagnosis of cirrhosis, with or without alcoholism, compared to those with diagnosis of alcoholism without cirrhosis, suggesting that cirrhosis is a necessary intermediate for the development of HCC among subjects with alcoholism (Adami et al, 1992;Sorensen et al, 1998;Kuper et al, 2001). A role of alcohol in the absence of cirrhosis as a 'pure' carcinogen seems of minor importance.…”

International Trends in Liver Cancer Incidence Rates

“…Although ICC only represents 10% to 25% of primary liver cancers in most parts of the world, it is the most frequent subtype of liver cancer diagnosed in Thailand due to the extremely high prevalence of chronic liver fluke infestation, the major risk factor for ICC (2). Cirrhosis is also an important risk factor for ICC (6).…”