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Biomedical subjects

M W Yu

Publications and source records attributed to M W Yu.

At least 37 records · Page 2Linked to original sources
PubMed1997

Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers.

The authors conducted a study to assess the importance of underlying liver cirrhosis in the development of hepatocellular carcinoma (HCC) and the multifactorial etiology of liver cirrhosis in chronic carriers of hepatitis B virus (HBV). Between November 1980 and May 1990, all male hepatitis B surface antigen (HBsAg) carriers who routinely attended a clinic for asymptomatic HBV carriers at the Liver Unit of Chang-Gung Memorial Hospital, Taiwan, were enrolled in the study (n = 1,506). The authors used this cohort to investigate prospectively for liver cirrhosis and HCC at 6-month intervals by means of ultrasonography and clinical assessment. There were 16 incident cases of HCC and 89 cases of liver cirrhosis (78 of whom were detected during follow-up) identified after an average follow-up of 7.1 years. Subclinical liver cirrhosis diagnosed by ultrasonography was significantly associated with the risk for HCC (multivariate-adjusted relative risk (RR) = 11.8, 95% confidence interval (CI) 3.9-35.8). By multivariate analysis, the significant risk factors found for liver cirrhosis in HBsAg carriers were age, hepatitis B e antigen (HBeAg) carrier status, chronic hepatitis manifested by sustained elevated serum aminotransferase levels for > or = 6 months, cigarette smoking, non-A blood types, and low educational levels. Habitual alcohol drinking was not independently related to liver cirrhosis. However, the risk of liver cirrhosis associated with smoking was more striking among drinkers than nondrinkers (> or = 20 cigarettes/day vs. nonsmokers: drinkers, RR = 9.3, 95% CI 1.1-78.8; nondrinkers, RR = 1.85, 95% CI 0.98-3.51), which suggests a possible modification effect of alcohol drinking on the liver cirrhosis risk of cigarette smoking. The authors observed synergistic effects on liver cirrhosis development for cigarette smoking with HBeAg carrier status and chronic hepatitis.

Adult↗
PubMed1997

A recombinant single chain antibody neutralizes coronavirus infectivity but only slightly delays lethal infection of mice.

The variable region genes of a murine anti-coronavirus monoclonal antibody (mAb) were joined by assembly polymerase chain reaction and expressed in Escherichia coli in a single chain variable fragment (scFv) configuration. After induction of expression, the expected 32-kDa protein was identified by Western immunoblotting with specific rabbit anti-idiotype antibodies. The scFv fragments were purified from soluble cytoplasmic preparations by affinity chromatography on nickel agarose, which was possible with an N-terminal but not with a C-terminal histidine tag. Purified scFv fragments retained the antigen-binding properties of the parental antibody, could inhibit its binding to viral antigens with apparently higher efficiency than monovalent antigen-binding (Fab) fragments, but neutralized viral infectivity with lower efficiency (about sevenfold at a molar level). To evaluate the usefulness of these smaller and less immunogenic molecules in the treatment of viral diseases, mice were treated with purified recombinant scFv fragments and challenged with a lethal viral dose. A small delay in mortality was observed for the scFv-treated animals. Therefore, even though the scFv could neutralize viral infectivity in vitro, the same quantity of fragments that partially protected mice in the form of Fab only slightly delayed virus-induced lethality when injected as scFv fragments, probably because of a much faster in vivo clearance: the biologic half-life was estimated to be about 6 min. Since a scFv derived from a highly neutralizing and protective mAb is only marginally effective in the passive protection of mice from lethal viral infection, the use of such reagents for viral immunotherapy will require strategies to overcome stability limitations.

Amino Acid Sequence↗
PubMed1997

Effect of aflatoxin metabolism and DNA adduct formation on hepatocellular carcinoma among chronic hepatitis B carriers in Taiwan.

BACKGROUND/AIMS: Aflatoxins (AFs) are established hepatic carcinogens in several animal species. This study was performed to establish whether aflatoxin exposure may affect the risk of developing hepatocellular carcinoma in chronic hepatitis B virus carriers. METHODS: Urinary AF metabolites were measured for 43 HCC cases and 86 matched controls nested in a cohort of 7342 men in Taiwan. Thirty hepatocellular carcinoma cases and 63 controls were also tested for AFB1-albumin adducts. RESULTS: There was a dose-response relationship between urinary AFM1 levels and risk of hepatocellular carcinoma in chronic hepatitis B virus carriers. Comparing the highest with the lowest tertile of urinary AFM1 levels, the multivariate-adjusted odds ratio (OR) was 6.0 (95% confidence interval (CI) = 1.2-29.0). The hepatocellular carcinoma risk associated with AFB1 exposure was more striking among the hepatitis B virus carriers with detectable AFB1-N7-guanine adducts in urine. Compared with chronic hepatitis B virus carriers who were negative for AFB1-albumin adducts and urinary AFB1-N7-guanine, no elevated risk was observed for those who were positive for either marker. But an extremely high risk of hepatocellular carcinoma among those having both markers was found (OR = 10.0, 95% CI = 1.6-60.9). The proportion of AFB1 converted to AFM1 decreased with the progress of liver disease, whereas the formation of AFP1 increased. The difference in patterns of AFB1 metabolite formation was an independent risk factor for hepatocellular carcinoma after adjustment for total AFB1 excretion. There was a synergistic interaction between glutathione S-transferase M1 genotype and AFB1 exposure in hepatocellular carcinoma risk. CONCLUSIONS: AFB1 intake and expression of enzymes involved in AFB1 activation/detoxification may play an important role in hepatitis B virus-related hepatocarcinogenesis.

Adult↗
PubMed1997

Plasma antioxidant vitamins, chronic hepatitis B virus infection and urinary aflatoxin B1-DNA adducts in healthy males.

Epidemiological evidence indicates that aflatoxin B1 (AFB1) intake is associated with an increased risk of hepatocellular carcinoma (HCC). The hepatocarcinogenesis is initiated by covalent binding of AFB1 to cellular DNA. To determine whether nutritional factors and hormonal status may influence the binding of AFB1 to hepatic DNA, a cross-sectional study was performed on a total of 42 male asymptomatic hepatitis B surface antigen (HBsAg) carriers and 43 male non-carriers in a cohort study on the multistage development of HCC in Taiwan. The major AFB1-DNA adduct in vivo, AFB1-N7-guanine, was measured by high-performance liquid chromatography in urine. Urinary AFB1-N7-guanine was detectable in 40% of the subjects. HBsAg carriers had a higher detection rate of urinary AFB1-DNA adducts than non-carriers and the difference was statistically significant after multivariate adjustment. After taking into account the total AFB1 urinary metabolite level, chronic HBsAg carrier status, and other potential confounders, plasma levels of cholesterol, alpha-tocopherol, and alpha- and beta-carotene were positively associated with the detection rate of the AFB1-DNA adducts in a dose-dependent manner, whereas plasma lycopene level was inversely related to the presence of the adducts in urine. The association of urinary AFB1-DNA adducts with the plasma levels of cholesterol, alpha-tocopherol, lycopene, and alpha- and beta-carotene was observed at both low and high exposure levels of AFB1. There was a synergistic interaction of plasma alpha-tocopherol with alpha- and beta-carotene on the adduct levels. No association with the adducts was found for plasma levels of retinol and testosterone. This study demonstrated different associations of antioxidant vitamins with AFB1-DNA adduct formation. The data consistent with our previous finding in cultured woodchuck hepatocytes that alpha-tocopherol and beta-carotene enhanced AFB1-DNA adduct formation suggest that prospective investigation of the relationship between plasma micronutrients and risk of AFB1-related HCC is warranted.

Adult↗
PubMed1997

Epidemiological characteristics and risk factors of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the major cancers in the world. There is a striking variation in HCC incidence rates between various countries, with a highest-to-lowest ratio of 112.5 for males and 54.7 for females. The high-risk populations are clustered in sub-Saharan Africa and eastern Asia. The male-to-female ratio for HCC ranges from < 1 to 6.4 and mostly from 2 to 4. There exist significant variations in the incidence of HCC among different ethnic groups living in the same area and among migrants of the same ethnic groups living in different areas. The age curves of HCC are significantly different in various countries, suggesting variability in exposure to risk factors. Chronic carriers of hepatitis B and C viruses (HBV and HCV, respectively) have an increased risk of HCC. The relative and attributable HCC risk of HBV and HCV carrier status varies in different countries. There exists a synergistic interaction on HCC between the two viruses. Aflatoxin exposure, cigarette smoking, heavy alcohol consumption, low vegetable intake, inorganic arsenic ingestion, radioactive thorium dioxide exposure, iron overload and the use of oral contraceptives and anabolic steroids have been documented as HCC risk factors. Recent molecular epidemiological studies have shown that low serum retinol levels as well as elevated serum levels of testosterone, neu oncoprotein and aflatoxin B1-albumin adduct are associated with an increased HCC risk. There is a synergistic interaction on HCC between chronic HBV infection and aflatoxin exposure. Familial aggregation of HCC exists and a major susceptibility gene of HCC has been hypothesized. Patients of some genetic diseases are at an increased risk of HCC. The genetic polymorphisms of cytochrome P450 2E1 and 2D6 and arylamine N-acetyltransferase 2 are associated with the development of HCC. A dose-response relationship between aflatoxin exposure and HCC has been observed among chronic HBV carriers who have null genotypes of glutathione S-transferase M1 or T1, but not among those who have non-null genotypes. Human hepatocarcinogenesis is a multistage process with the involvement of a multifactorial aetiology. Gene-environment interactions are involved in the development of HCC in humans.

Carcinoma, Hepatocellular↗
PubMed1996

L-myc, GST M1 genetic polymorphism and hepatocellular carcinoma risk among chronic hepatitis B carriers.

In order to assess associations between the genetic polymorphism of L-myc and glutathione S-transferase M1 (GST M1) and the risk of hepatocellular carcinoma (HCC), a total of 46 surgically treated HCC patients who were seropositive in hepatitis B surface antigen (HBsAg) and 88 HBs-Ag positive controls were recruited for this study. L-myc and GST M1 genetic polymorphism was examined using a polymerase chain reaction-based restriction fragment length polymorphism assay on DNA extracted from liver and peripheral blood samples. There was no significant difference in GST M1 genotypes between HCC patients and matched controls. A gene dosage trend of association with HCC risk was observed for L-myc genotype. The dose-response relationship remained statistically significant in the multiple logistic regression analysis.

Age Factors↗
PubMed1996

Genetic control of anti-idiotypic vaccination against coronavirus infection.

The idiotypic network can be experimentally altered to induce protective immune responses against microbial pathogens. Both internal image and noninternal image anti-idiotypic (anti-Id) antibodies have been shown to trigger antigen (Ag)-specific immune responses. Therefore, mechanisms of anti-Id vaccination appear to go beyond structural mimicry of Ag, but remain undefined. Using the neurotropic murine coronavirus animal model, we have previously shown that a polyclonal noninternal image anti-Id (Ab2) could vaccinate BALB/c mice. To characterize its mode of action, we have examined the immune modulating capability of this Ab2 in vivo in strains of mice with different H-2 haplotypes. Even though only internal image anti-Id are expected to induce non-genetically restricted immunity, this noninternal image Ab2 induced protective immunity in four of eight genetically different strains of mice susceptible to coronavirus infection. These were BALB/c (H-2d), DBA/2 (H-2d), DBA/1 (H-2q), and SWR (H-2q) mice. Protection was generally correlated with the induction of specific antiviral Ab (Ab3) that showed biological properties, such as virus neutralization in vitro, similar to the initial Ab1. To evaluate the genetic implication of the H-2 haplotypes in protection, congenic mice were also tested. Vaccination profiles suggest that cooperation between background gene(s) of the BALB/c mouse with H-2d and H-2q loci is necessary for an optimal protective immune response, although the main genetic element(s) regulating the antiviral response to Ab2 inoculation appeared to be located outside the major histocompatibility complex. These results are consistent with the ability of Ab2 to induce protective antiviral antibodies in genetically different animals by biological mimicry.

Animals↗
PubMed1996

Chronic hepatitis B carriers with null genotypes of glutathione S-transferase M1 and T1 polymorphisms who are exposed to aflatoxin are at increased risk of hepatocellular carcinoma.

This study was carried out to elucidate the effect of glutathione S-transferase (GST) Ml and Tl polymorphisms on the aflatoxin-related hepatocarcinogenesis among chronic carriers of hepatitis B surface antigen (HBsAg). A total of 32 newly diagnosed hepatocellular carcinoma (HCC) cases and 73 age-matched controls selected from a cohort of 4,841 chronic HBsAg carriers who had been followed for 5 years were studied. The level of aflatoxin B1 (AFB1)-albumin adducts in their serum samples collected at the recruitment was examined by competitive enzyme-linked immunosorbance assay, and genotypes of GST M1 and T1 were determined by PCR. There was a dose-response relationship between serum level of AFB1-albumin adducts and risk of HCC. The biological gradients between serum AFB1-albumin adducts level and HCC risk were observed among chronic HBsAg carriers who had null genotypes of GST M1 and/or T1 but not among those who had non-null genotypes. The multivariate-adjusted odds ratios of developing HCC for those who had low and high serum levels of AFB1-albumin adducts compared with those who had a undetectable adduct level as the referent (odds ratio = 1.0) were 4.1 and 12.4, respectively, for HBsAg carriers with null GST M1 genotype (P < .01, on the basis of the significance test for trend); 0.7 and 1.4 for those with non-null GST Ml genotype (P = .98); 1.8 and 10.2 for those with null GST T1 genotype (P < .05); and 1.3 and 0.8 for those with non-null GST T1 genotype (P = .93). The interaction between serum AFB1-albumin adduct level and polymorphisms of GST M1 and T1 was at marginal statistical significance levels (.05 < P < .10).

Adult↗
PubMed1996

Effects of multiple risk factors for hepatocellular carcinoma on formation of aflatoxin B1-DNA adducts.

Covalent binding of aflatoxin B1 (AFB1) with hepatic DNA may be a critical step in hepatocarcinogenesis. The extent of the AFB1 binding to DNA may depend on various endogenous factors and concurrent exposure to other environmental agents. This study was performed to determine whether any individual characteristics correlated with the formation of AFB1-DNA adducts. The major AFB1-DNA adduct, AFB1-N7-guanine, was measured using a high performance liquid chromatographic assay in urine samples from 43 asymptomatic hepatitis B virus surface antigen carriers and 43 noncarriers randomly selected from a cohort study in Taiwan. The total aflatoxin metabolite level was associated with the detection rate of urinary AFB1-N7-guanine adducts in a dose-dependent manner. The AFB1-DNA adduct excreted in the urine was detectable in 60% of individuals who smoked cigarettes but abstained from alcohol, 64% of individuals who had a habit of drinking alcohol but not smoking cigarettes, and only 29% of those who neither smoked nor drank alcohol. The association between urinary AFB1-DNA adduct level and habits of smoking cigarettes and drinking alcohol remained statistically significant when adjustment was made for potential confounders. There was a significant increase with age for the detection rate of urinary AFB1-N7-guanine adducts. Age and habits of cigarette smoking and alcohol drinking were also found to be associated with a higher percentage of AFB1-N7-guanine in total AFB1 metabolite excretion, indicating an increased activation of AFB1. No significant association with the AFB1-DNA adduct level was observed for hepatitis B virus surface antigen carrier status, educational level, and ethnicity. These data suggest a potential role of age, cigarette smoking, and alcohol drinking in AFB1-induced hepatocarcinogenesis.

Aflatoxin B1↗
PubMed1995

Vegetable consumption, serum retinol level, and risk of hepatocellular carcinoma.

A cohort of 8436 men in Taiwan was recruited with personal interview and blood sample collection between 1984 and 1986. During the 5-year follow-up period, 50 incident cases of hepatocellular carcinoma (HCC) were identified. Retinol levels were measured for 35 HCC patients whose serum samples were available and 140 matched controls randomly selected from cohort members without HCC. Lower vegetable intake was significantly associated with an increased risk of HCC after adjustment for other HCC risk factors (P = 0.006). The effect of low vegetable intake on HCC risk was limited to hepatitis B virus chronic carriers and cigarette smokers. As compared with subjects who had a weekly vegetable consumption frequency of six or more meals, the multivariate-adjusted relative risk of HCC for subjects who had a frequency of less than six meals was 4.7 (95% confidence interval, 2.0-11.1; P = 0.0004) among chronic hepatitis B virus carriers and 3.8 (95% confidence interval, 1.7-8.5; P = 0.001) among cigarette smokers. There was an inverse dose-response relationship between the prediagnostic serum retinol level and the development of HCC (trend test, P = 0.003). The odds ratio of HCC for men with a retinol level in the lowest tertile was 9.0 (95% confidence interval, 2.1-39.1) compared with those with a level in the highest tertile. The relation remained after multivariate adjustment for cigarette smoking, habitual alcohol drinking, and either the seropositivity of hepatitis B virus surface antigen and/or anti-hepatitis C virus antibody or the past history of liver diseases through conditional logistic regression analysis. The association was more striking for men 55 years or younger and for those who smoked 10 or more cigarettes/day. There was a significant synergistic effect of hepatitis B virus surface antigen carrier status and low serum retinol level on the development of HCC. These data suggest a potential role of retinol in the chemoprevention of HCC.

Adult↗
PubMed1995

Cytochrome P450 2E1 and glutathione S-transferase M1 polymorphisms and susceptibility to hepatocellular carcinoma.

BACKGROUND & AIMS: Genetic polymorphisms in enzymes involved in carcinogen metabolism have been found to influence susceptibility to cancer. The aim of this study was to examine whether cytochrome P450 2E1 (CYP2E1) and/or glutathione S-transferase M1 (GSTM1) genetic polymorphisms were related to susceptibility to hepatocellular carcinoma (HCC). METHODS: Genotyping of CYP2E1 and GSTM1 was performed using the polymerase chain reaction on peripheral white blood cell DNA from 30 patients with HCC and 150 controls nested in a cohort study. RESULTS: The c1/c1 genotype of CYP2E1, detected by PstI or RsaI digestion, was found in 83.3% of patients with HCC and in 63.3% of controls (P = 0.034). Homozygosity for the c1/c1 genotype significantly increased the risk of developing HCC in cigarette smokers (P = 0.001) but posed no increased risk in those who never smoked. The HCC risk associated with cumulative exposure to cigarette smoke was also more striking in individuals who carried the c1/c1 genotype. Habitual alcohol drinking modified the HCC risk of cigarette smoking among those with the c1/c1 genotype. No association with the risk of HCC was observed for the DraI polymorphism of CYP2E1 or for the GSTM1-null genotype. CONCLUSIONS: Polymorphisms of CYP2E1 may play an important role in cigarette smoking-related hepatocarcinogenesis.

Adult↗
PubMed1995

Hepatitis C virus RNA in factor VIII concentrates.

BACKGROUND: Hepatitis C virus (HCV) RNA was measured in commercial factor VIII concentrates, that is, antihemophilic factor (human) (AHF), to allow the retrospective evaluation of the effect of various virus-inactivation procedures. The impact on AHF of recent anti-HCV screening of plasma was also investigated. STUDY DESIGN AND METHODS: A total of 183 lots of AHF made by six United States-licensed manufacturers from anti-HCV-unscreened (1976-1991) or screened (1992-1993) plasma were examined. Detection and quantitation of HCV RNA were achieved by reverse transcription and nested polymerase chain reaction at limiting dilution. Anti-HCV in AHF was also measured. RESULTS: Earlier AHF lots subjected to non-virus-inactivated treatment (36 lots), dry heat (11 lots), or heating in n-heptane (4 lots) had relatively high levels of HCV RNA. Most (76%) wet-heated lots prepared before 1992 contained HCV RNA. No HCV RNA was detected in lots purified by immunoaffinity and subsequently heated or solvent/detergent (S/D)-treated. However, trace levels of HCV RNA were detected in S/D-treated lots made by one of four manufacturers before 1992. Since the start of anti-HCV plasma screening in 1992, 38 lots prepared by six manufacturers were negative for HCV RNA. Prevalence of anti-HCV was also associated with earlier concentrates and with S/D-treated lots from that single manufacturer. CONCLUSION: Anti-HCV screening of plasma by manufacturers in conjunction with current virus-inactivation procedures, wet-heating or S/D treatment (either process with or without affinity purification), appears to reduce HCV RNA to undetectable levels in AHF.

Base Sequence↗
PubMed1994

Correlations of chronic hepatitis B virus infection and cigarette smoking with elevated expression of neu oncoprotein in the development of hepatocellular carcinoma.

To investigate the potential role of neu oncogene expression in hepatocarcinogenesis, a nested case-control study was conducted within a cohort of 9691 male adults in Taiwan. Blood samples of study subjects were collected during 1984-1986 and frozen at -30 degrees C until subsequent analysis. The neu oncoprotein level in the stored serum was measured by an enzyme-linked immunosorbent assay for 27 cases of newly developed hepatocellular carcinoma (HCC), 12 liver cirrhosis cases, and 40 healthy controls. The mean level of neu oncoprotein was significantly higher in HCC and liver cirrhosis cases than in controls. The risk of HCC increased significantly with increasing serum level of neu oncoprotein (trend test, P = 0.02). The proportion of subjects having an elevated serum level of neu oncoprotein, defined as a level greater than the mean level of all controls, was significantly higher among asymptomatic HBsAg carriers than noncarriers (P = 0.05), showing a multivariate-adjusted odds ratio of 4.0. Among HCC cases, a strong association was observed between cigarette smoking and elevated prediagnostic serum level of neu oncoprotein. The association remained highly significant (P = 0.017) even when adjustment was made for potential confounders. The multivariate-adjusted odds ratio of having an elevated serum level of neu oncoprotein, defined as a level greater than the mean plus 1 SD of control levels, for HCC cases who smoked more than 10 cigarettes a day was as high as 386.5 compared with the cases who smoked less than 10 cigarettes a day or nonsmoking cases. The results suggest that both HBsAg carrier status and cigarette smoking are related to the increased expression of neu oncogene, and cigarette smoking seems to play a significant role in the latter stages of hepatocarcinogenesis. There was no association between alcohol drinking and serum neu oncoprotein level.

Adult↗
PubMed1994

Influence of vitamins A, C, and E and beta-carotene on aflatoxin B1 binding to DNA in woodchuck hepatocytes.

BACKGROUND: There is extensive epidemiologic evidence suggesting a protective role for micronutrients in cancer incidence. This evidence comes from studies of fruit and vegetable intake and serum levels of specific micronutrients. There also is limited in vitro evidence demonstrating that micronutrients can influence the first step in carcinogenesis, binding of chemical carcinogens to DNA. These in vitro studies allow the determination of specific effects of individual micronutrients. The influence of micronutrients on DNA binding of aflatoxin B1 (AFB1), a potent hepatocarcinogen, in mammalian cells is unknown. Woodchuck hepatocytes were used as a model to investigate the effects of vitamin A (all-trans retinol), C (ascorbic acid), ascorbyl palmitate (a synthetic lipophilic derivative of ascorbic acid), vitamin E (alpha-tocopherol), and beta-carotene on AFB1-DNA binding. METHODS: Woodchuck hepatocytes were treated with 4 doses (0.080, 0.40, 2.0, and 10 microM) of [3H]AFB1 or with different combinations of AFB1 and the vitamins for 6 hours, and adduct levels determined. Western blot analysis of protein extracts of treated cells was used to determine the effects of vitamin A and beta-carotene on glutathione-S- transferase M1 levels. RESULTS: Vitamin A inhibited formation of AFB1-DNA adducts in a dose-dependent manner throughout a concentration range of 34-122 microM by 40-80%. Vitamin C (0.080-10 mM) was much less effective than vitamin A as an inhibitor of AFB1-DNA binding. Treatment with 6.0-48.3 microM ascorbyl palmitate reduced adduct levels at lower AFB1 concentrations but had no significant effect at higher AFB1 concentrations. beta-Carotene and vitamin E enhanced covalent binding of AFB1 to DNA. Enhancement with beta-carotene was observed when both tetrahydrofuran or liposomes were used as the administration vehicle. Western blot analysis indicated that neither the vitamin A nor beta-carotene treatment affected glutathione-S-transferase M1 protein levels. CONCLUSIONS: These results demonstrate that micronutrients play a complex role in the process of chemical carcinogenesis. Although protective effects were seen with several antioxidant vitamins, increased DNA adduct formation was observed with beta-carotene and vitamin E. This antioxidant activity may be unrelated to the inhibition of DNA adduct formation. Additional studies are needed to understand the mechanism of enhanced adduct formation.

Aflatoxin B1↗
PubMed1994

A nested case-control study on association between hepatitis C virus antibodies and primary liver cancer in a cohort of 9,775 men in Taiwan.

Most studies on the association between antibodies against hepatitis C virus (anti-HCV) and primary liver cancer (PLC) were limited to case-series, or cross-sectional case-control studies leaving a controversy on causal temporality. A nested case-control study on 38 newly-developed PLC patients and 152 matched controls selected from a cohort of 9,775 men in Taiwan recruited from September, 1984, to February, 1986, was carried out to examine the relation between HCV infection and PLC. Case-control pairs were matched on age (+/- 1 year), residence, and the date at recruitment. Serum samples collected from study subjects at the initial recruitment were examined for anti-HCV by enzyme immunoassay and hepatitis B surface antigen (HBsAg) by reverse passive hemagglutination assay combined with radioimmunoassay. History of cigarette smoking, alcohol consumption, vegetable consumption, vegetarian habit, and chronic liver diseases were also obtained through standardized interviews according to a structured questionnaire at the recruitment. After adjusting for HBsAg status and other risk factors, the anti-HCV was significantly associated with the development of PLC showing a multivariate-adjusted relative risk of 88.24. The results suggest that HCV infection may play an important role in the etiology of human PLC in Taiwan.

Adult↗