Hepatitis C virus infection is associated with the development of hepatocellular carcinoma.

Abstract

A possible causative role for the recently discovered hepatitis C virus (HCV) in the development of hepatocellular carcinoma (HCC) was investigated by assay of sera from HCC patients in Japan for antibodies to a recombinant HCV antigen and to hepatitis B virus (HBV) antigens. Among the 253 HCC patients examined, 156 (61.7%) had no serum markers of either a previous or a current HBV infection (group I), 46 (18.2%) were negative for HBV surface antigen but positive for anti-HBV surface and/or anti-HBV core antibody, indicating the occurrence of a previous, transient HBV infection (group II), and 51 (20.2%) were chronically infected HBV carriers as evidenced by positivity for HBV surface antigen (group Ill). The prevalence of HCV antibody in group I (68.6%) and II (58.7%) patients was significantly higher than for group m1 (3.9%) or in 148 additional patients with other (non-HCC) cancers (10.1%) (P < 0.01). Thus, there appears to be a strong association between HCV infection and the development of HCC, particularly in patients for which HBV infection cannot be implicated as a causative factor. The data also suggest an additional mode of transmission for HCV other than blood transfusion, since a history of blood transfusion was shown in only about 30% of the HCV antibodypositive HCC patients in groups I and 11. A high prevalence of HCV antibody was also shown among patients with HCC whose disease was originally thought to be due to very high ethanol consumption.The development of specific serological tests for infection by hepatitis A virus (HAV) and hepatitis B virus (HBV) has revealed that a large proportion of hepatitis cases are not caused by either ofthese agents (1-3). The resultant diagnosis of exclusion, non-A, non-B hepatitis (NANBH), now accounts for 95% of all posttransfusion hepatitis and over one-third of sporadic, acute hepatitis cases in Japan. Although symptoms in the acute phase of this disease are generally less severe than with HAV or HBV infection, NANBH is much more likely to develop into a persistent, chronic state. Over 50% of posttransfusion NANBH cases become chronically infected versus less than 10% in the case of HBV infections; typically, no chronicity results from infection by HAV. It is also clearly established that chronic NANBH can develop into hepatic cirrhosis (4-6). Accumulated serological, pathological, epidemiological, and clinical evidence suggests a significant association ofthe HBV carrier state with hepatocellular carcinoma (HCC) (7,8). In Japan, however, less than one-third ofHCC patients are also chronic HBV carriers, and the number of surgically treated HCC cases with no serological markers of prior or current HBV infection has increased steadily in Japan during the last 10 years (9). This suggests another causative factor(s). It has been hypothesized that NANBH virus(es) might be the missing causative agent in HCC development (10)(11)(12)(13)(14).The etiological agent(s) of NANBH has long been sought by many research groups (15,16), and recently a NANBH agent, ter...

Polypyrimidine-tract-binding Protein is a Component of the HCV RNA Replication Complex and Necessary for RNA Synthesis

“…Blood screening based on the cloned HCV genome and its gene products has reduced significantly the blood-borne HCV transmission [1][2][3]. However, detailed studies of HCV (for example, virus replication, pathogenicity, and natural history of HCV) have been greatly hampered by the lack of efficient in vitro culture systems of HCV infection.…”

A potential RNA drug target in the hepatitis C virus internal ribosomal entry site

“…Infection by hepatitis C virus (HCV), the main causative agent of posttransfusion hepatitis, frequently leads to liver cirrhosis and hepatocellular carcinoma (Saito et al+, 1990)+ An estimated 170 million people are infected by the virus, of whom 10-20% are expected to suffer these life-threatening complications (Cohen, 1999)+ The viral proteins are translated from a 9+5-kb single-stranded positive sense RNA, which is flanked by 59 and 39 untranslated regions (UTRs) (Houghton et al+, 1994)+ The 59 UTR represents the most conserved region of the genome (Bukh et al+, 1992)+ It forms the highly structured internal ribosome entry site (IRES) (nt 40-370), which directs translation in a cap-independent manner (Reynolds et al+, 1996), a mechanism first observed in picornaviruses (Jackson et al+, 1990)+…”

Past exposure to hepatitis B virus as a risk factor for hepatocellular carcinoma in patients with chronic liver disease

“…Evaluation of the risk factors for HCC in CLD patients is imperative. Identification of the individuals who are at higher risk of HCC would contribute to the early diagnosis of this disease and to effective implementation of strategies for chemoprevention.Numerous epidemiological and biological studies have indicated that a chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) plays an important role in hepatocarcinogenesis (Bruix et al, 1989;Saito et al, 1990;Kim et al, 1991). As for HBV, serum hepatitis B surface antigen (HBsAg) positivity, which indicates a chronic HBV carrier state, is a well-established risk factor for HCC (Beasley et al, 1981;Chen et al, 1991).…”