Prospective study on the risk of hepatocellular carcinoma among hepatitis C virus‐positive blood donors focusing on demographic factors, alanine aminotransferase level at donation and interaction with hepatitis B virus

Abstract

The risk for hepatocellular carcinoma (HCC) among asymptomatic hepatitis C virus (HCV) carriers is not well understood. A community-based prospective study was conducted for over 8 years by record linkage to the Osaka Cancer Registry. The subjects were 1,927 individuals who were positive for anti-HCV through screening for secondgeneration HCV antibody (passive hemagglutination assay: > Key words: hepatitis C virus; hepatocellular carcinoma; blood donor; alanine aminotransferase; hepatitis B virus; interaction; prospective studyApproximately 170 million persons worldwide have persistent infection with hepatitis C virus (HCV), 1 which is a risk factor for hepatocellular carcinoma (HCC). Some patients with persistent HCV infection advance through incrementally severe stages of chronic hepatitis to cirrhosis, occasionally culminating in HCC, although the majority of persons with persistent HCV infection remain asymptomatic. The incidence of HCV-associated HCC is increasing in several developed countries, including the United States, 2,3 Italy, 4 France 4 and Japan. 5 However, it is not well understood what proportion of asymptomatic HCV-positive persons will develop HCC during their lifetime.Many prospective studies have been conducted that assessed the risk of severe liver disease, including HCC, among individuals with chronic HCV infection. 6 -18 Some studies were conducted in tertiary-care treatment facilities, 6 -11 and the proportion of severe cases may have been overestimated due to referral bias. On the other hand, several follow-up studies reported that patients with chronic HCV infection have a very low risk of developing severe liver disease. [12][13][14][15][16][17] This result may have been obtained due to an insufficient length of follow-up to describe the full extent of adverse sequelae of HCV infection or because the subjects were too young to develop severe liver disease. In a cohort study of patients with non-A, non-B, transfusion-associated hepatitis over a period of almost 25 years, liver-related mortality was only 4.1%. 18 As this cohort had high all-cause mortality probably resulting from the condition that required the original transfusion, the liverrelated mortality reported in that study may have been underestimated. Studies performed in community-based settings have an advantage in clarifying the risk of HCC among asymptomatic HCV-positive persons, who comprise the majority of HCV-infected persons. However, several previous community-based prospective studies had a relatively small sample size. 19 -21 In another community-based prospective study, the subjects were persons who had been infected with HCV through injection drug use and who had high competing mortality. 22 Screening blood donors for the antibody to HCV (anti-HCV) in the early 1990s revealed that there was a large group of apparently healthy individuals who were positive for anti-HCV. We conducted a prospective study to determine the absolute risk of developing HCC among persons who were incidentally detected of having HCV at t...

The Impact of Type 2 Diabetes on the Development of Hepatocellular Carcinoma in Different Viral Hepatitis Statuses

“…In some countries, HBV rather than HCV infection created a higher risk of hepatocellular carcinoma (4). On the other hand, HCV rather than HBV infection created a higher risk of hepatocellular carcinoma in other countries (30,31). The present community-based cohort with simultaneously hyperendemic HBV and HCV infection provided a good opportunity to compare the risks of these two major etiologies for hepatocellular carcinoma; it showed that HCV infection had the higher hazards ratio for developing hepatocellular carcinoma.…”

Hepatitis C virus infection in the general population: A large community-based study in Mianyang, West China

“…However, there usually were no symptoms in HCV-infected individuals when ALT was slightly elevated. Once symptoms appear, most HCV infected persons have already developed HCC (38). Since abnormal ALT comprised a large proportion of individuals infected with HCV in the current study, it is important for these people to receive early antiviral treatment and regular follow-up to reduce the risk of developing HCC.…”

“…Because ALT was presumed to be a marker of hepatic inflammation, our finding demonstrated that HCV infection could lead to chronic necro-inflammatory hepatic damage. Moreover, some prospective studies showed that persistently abnormal serum ALT levels were strongly associated with high incidences of HCC in individuals positive for anti-HCV (37,38). However, there usually were no symptoms in HCV-infected individuals when ALT was slightly elevated.…”

Alanine aminotransferase level as a predictor of hepatitis C virus‐associated hepatocellular carcinoma incidence in a community‐based population in Japan

“…[2][3][4] Furthermore, with an increasing global incidence of 80% over the past 20-30 years, HCC has become the fifth most common cancer and ranks third with respect to cancer-related mortality. [5][6][7] In developed countries, including the United States and Japan, HCV infection has been identified as the main risk factor for HCC. [8][9][10] Although the exact pathogenesis of HCV-associated HCC is unknown, chronic inflammation related to the immune response to HCV infection, with a resultant increased proliferation of hepatocytes, likely promotes carcinogenesis in the liver.…”

“…Recently, Tanaka et al reported that an elevated serum alanine aminotransferase (ALT) level at blood donation was positively associated with subsequent HCC risk among HCVinfected donors in Japan. 7 ALT is an enzyme present in the liver, which is released into the blood stream with increasing liver tissue damage, and thus represents activated inflammatory necrosis of hepatocytes. Other studies in Japan have shown that sustained elevated ALT levels in HCV-infected liver disease patients lead to increased HCC risk and recurrence of HCC.…”