青年人与老年人原发性肝癌的临床分析

为提高青年人和老年人原发性肝癌临床诊断和防治水平，作者比较５５例青年人与７８例老年人原发性肝癌的临床病理特征，结果显示：血清ＨＢｓＡｇ阳性者青年组高于老年组；合并肝硬化者老年组较高；两组肿瘤类型和临床ＴＮＭ分期等亦有差异。两组原发性肝癌患者在某些临床特征方面存在差异。     

Spectrum of hepatitis B virus infection in Ethiopia

A total of 304 Ethiopian patients with acute or chronic hepatitis B have been found to be positive for hepatitis B surface antigen (HBsAg) at the Virology Section of the Central Laboratory and Research Institute in Addis Ababa over the period 1981-1984. On the basis of the spectrum of hepatitis B virus (HBV) infection, the 304 patients could be divided into 5 groups. The first group includes the vast majority of the patients, i.e., up to 85% (260/304) and is characterized by rapid clearance of HBsAg and by rapid recovery from infection. In this group of patients, hepatitis B was a self-limiting infection. The second group comprises the 10% (30/304) of patients identified as asymptomatic chronic carriers of HBsAg; liver function tests on these patients were usually normal after two and a half months from the onset of infection, but HBsAg persisted in the patients for more than 6 months. The third group, which accounts for 5% (14/304) of patients includes those chronically infected by HBV and suffering from some form of malignant liver disease, mainly hepatocellular carcinoma (HCC). The specific markers detected in those patients with HCC were HBsAg and alpha-fetoprotein. Most of the patients in this group were comparatively old (55 years and above). The fourth group consists of a subgroup of patients of the first group with self-limiting hepatitis B, who were simultaneously infected by the delta agent, as shown by the detection of anti-delta antibody in 2.7% (3/111) of the patients. The fifth group is constituted by the young males between the ages of 21 and 30 years, accounting for 40% (122/304) of patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

The prevalence of anti-hepatitis C virus among Chinese patients with hepatocellular carcinoma.

To evaluate the role of hepatitis C virus (HCV) in Chinese patients with hepatocellular carcinoma (HCC), the antibodies to HCV (anti-HCV) were detected by enzyme immunoassay in 41 (12.6%) of the 326 patients with HCC. However, none of 35 patients with metastatic carcinoma of the liver had detectable anti-HCV. The prevalence of anti-HCV was significantly higher in patients with hepatitis B surface antigen (HBsAg)-negative HCC than those with HBsAg-positive HCC (37.3% versus 4.1%, P less than 0.0001). However, the prevalence of anti-HCV was much higher in patients with HCC with negative results for HBsAg and antibody to hepatitis B core antigen (54.5%). The mean age of patients with HCC with positive results for anti-HCV was significantly greater than that of patients with HBsAg-positive HCC (65.1 versus 55.5 years, P less than 0.0001). Alpha-fetoprotein levels greater than 20 ng/ml were found in 70.7% of patients with HCC with positive results for anti-HCV and in 73.3% of patients with HBsAg-positive HCC. Of the Chinese patients with HCC, 74.5% had HBsAg-positive results and 96.6% had positive results for antibody to hepatitis core antigen. These data indicate that, although HCV may play an etiologic role in HCC, hepatitis B virus is still the most important causal agent among most Chinese patients with HCC.     

Hepatitis B and C virus infection as risk factors for hepatocellular carcinoma in Chinese: A case-control study

To assess whether hepatitis B and C virus infection were risk factors for hepatocellular carcinoma (HCC), antibody to hepatitis C virus (anti-HCV), hepatitis B surface antigen and e antigen (HBsAg and HBeAg) were tested in 150 HCC patients. Another 150 case-control pairs matched individually by sex and age were also enrolled. Univariate analysis demonstrated that both the anti-HCV and the carrier status of HBsAg and HBeAg were significantly associated with HCC. Multi-variate analysis revealed that both anti-HCV and HBsAg were risk factors for HCC. The population-attributable risk was estimated as 14.2% for anti-HCV alone, 59.4% for HBsAg alone and 8.0% for both anti-HCV and HBsAg in Taiwan. In conclusion, both hepatitis B and C virus infection are independent risk factors for HCC in Chinese in southern Taiwan.     

Hepatitis B virus serological markers in Africans with liver cirrhosis and hepatocellular carcinoma

Serum samples were collected at the time of hospitalization from 221 black Africans suffering from cirrhosis and 453 suffering from hepatocellular carcinoma (HCC). These patients came from Senegal, Burundi and Mali, and 6655 adults from different population groups in these countries were used as controls. Hepatitis B virus (HBV) serum markers, including hepatitis B surface antigen (HBsAg), anti-HBs, antibody to hepatitis B core antigen (anti-HBc), HBeAg and anti-HBe, were determined by radioimmunoassay, while alpha-fetoprotein and complexes between HBsAg and IgM were detected by ELISA tests. HBsAg was detected in 11.8-17.6% of controls as opposed to 63.3% of patients suffering from cirrhosis and 62.7% of patients suffering from HCC. There was less evidence for HBV replication in cirrhosis and HCC in older patients. A significant increase in the frequency of HBsAg/IgM complexes was found in passing from the HBsAg chronic carrier state (13.9%) to cirrhosis (29.9%) and finally to HCC (33.7%).     

A prospective study on the development of hepatocellular carcinoma from liver cirrhosis with persistent hepatitis B virus infection

We made a prospective study on the development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis with hepatitis B virus infection from April, 1973 to December, 1977. Seven out of 30 patients (23%) with hepatitis B surface antigen (HBsAg)-positive cirrhosis developed HCC. On the other hand, only 5.9% of the patients with HBsAg-negative liver cirrhosis developed HCC. These patients were classified into three groups according to their anti-HB core (anti-HBc) titers. When the anti-HBc titer, expressed as a dilution of serum, was 2(10) or more (Group I), 20-24% of the liver cirrhosis patients developed HCC either with or without a detectable amount of HBs Ag present in the sera. When the anti-HBc titer was 2(9) or less (Group II), only 0-5.7% developed HCC. There was no significant difference between this and the anti-HBc and HBsAg-negative group (Group III), which was 4.4%. In five individual cases from group I, HBsAg was detected in serum, and in biopsies of liver cells, before HCC could be detected by angiography and/or rising levels of alphafetoprotein (AFP). In all of these cases, the anti-HBc titer was higher than 2(10) throughout the observation period, even before the development of HCC. These findings indicate that active virus proliferation in chronic hepatitis B virus infection precedes the development of HCC as indicated by a higher anti-HBc titer. Therefore we have prepared these studies to show the pathogenic role of hepatitis B virus in the development of hepatocellular carcinoma.     

Hepatitis B related childhood hepatocellular carcinoma. Childhood hepatic malignancies

The case of hepatocellular carcinoma (HCC) with foci of hepatoblastoma in a 7-year-old boy, the son of a hepatitis B surface antigen (HBsAg) carrier mother, is described. Twelve other malignant liver tumors in children were tumors in children were also reviewed for HBsAg and hepatitis B core antigen (HBcAg). Both were negative in all (nine) hepatoblastomas. One of three HCC demonstrated positivity for HBsAg. These cases illustrate the importance of hepatitis B virus infection in early childhood and stress the need for careful screening in pregnant women, irrespective of ethnic backgrounds.     

Hepatitis-B surface antigen and hepatocellular carcinoma in Taiwan. With special reference to types and localization of HBsAg in the tumor cells

The relationship between hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC), with or without cirrhosis, was assessed immunopathologically through the detection of tissue hepatitis B surface antigen (HBsAg) on paraffin sections of 284 biopsy and surgical specimens of HCC, which were performed from 1970 to 1979, by the indirect immunoperoxidase technique. In 190 cases with nontumorous liver tissue available for histologic and etiologic analyses, cirrhosis was identified in 69.8% (37 of 53) in needle biopsy, 67.4% (31/46) in wedge, and 30.8% (28/91) in the resection or lobectomy group. HBsAg was detected in the nontumorous liver parenchyma in 85.7% in the whole series, and 90.6% in the cirrhotic cases (96.8% in wedge and 100% in resection cases). The HBsAg positivity in the noncirrhotic cases of the resection group was 84.1% (53/63), whereas the 10 negative cases in this group were all noncirrhotic. This clearly demonstrates a strong association of HBsAg and HCC in both cirrhotic and noncirrhotic patients in Taiwan, particularly in the cirrhotic group, as evidenced by the high prevalence of HBsAg in wedge and resection series. On the other hand, the etiology in the HBsAg-negative and noncirrhotic group, which also had a less evident male predominance (male:female = 3.3:1 versus 6-19.5:1) and significantly less liver cell dysplasia than HBsAg-positive or cirrhotic groups, remains to be explained. In 223 cases where tumor tissue met the minimal requirement for analysis, HBsAg was demonstrated in 27 cases (12.1%) in the tumor cells (15% in the resection group). This investigation indicates an important etiologic role of HBV in hepatocellular carcinogenesis, and the development of HCC does not depend on the coexistence of cirrhosis in Taiwan.     

Maternal transmission of hepatitis B virus in childhood hepatocellular carcinoma

Fifty-one children, aged between 3 and 16 years, were diagnosed to have hepatocellular carcinoma (HCC) in the last 15 years. Serum hepatitis B surface antigen (HBsAg) was positive in all the latter 34 HCC children checked by radioimmunoassay, and was positive in five of the 17 earlier HCC children studied by double immunodiffusion method. Serum HBsAg was studied in 31 mothers of the latter 33 HCC children, including two pairs of affected siblings and was positive in 29 (94%). The positive rate was much higher than that (50%) of the mothers of control HBsAg carrier children (P less than 0.001). The serum HBsAg positive rate was also higher in the siblings of HCC children than that of the control group. On the contrary, the serum HBsAg positive rate was not different between the fathers of HCC children and that of the control group. Our observation demonstrated that transmission of hepatitis B virus from the mothers during the perinatal period or early childhood is the most important mode of hepatitis B virus infection in HCC children in Taiwan.     

High prevalence of hepatitis C virus infection in schistosomiasis japonica patients associated with hepatocellular carcinoma

Schistosomiasis japonica (SCJ) patients frequently develop hepatocellular carcinoma (HCC). This study investigated relationship between SCJ infection, hepatitis virus infection, and incidence of HCC, in 25 patients with chronic SCJ infection and HCC (SCJ with HCC group), 51 patients with chronic SCJ infection without HCC (SCJ group) and 65 HCC patients without SCJ (HCC group). Number of patients who were positive to HBsAg or hepatitis B virus DNA were 4 (16.0%) in the SCJ with HCC group, none (0%) in the SCJ group, and 5 (7.9%) in the HCC group; while number of patients who were positive to anti-hepatitis C virus antibody were 21 (87.5%) in the SCJ with HCC group, 3 (5.9%) in the SCJ group, and 58 (84.6%) in the HCC group. Biopsy was performed for all patients, and background histological features of each specimen were evaluated based on the histological activity index scoring system. Mean scores of inflammatory changes in both the portal area and parenchyma in the SCJ with HCC group were significantly higher than those in the SCJ group. Nodular formation which is common in post-viral hepatitis was frequently observed in the SCJ with HCC group, and histological changes in non-cancerous area of the SCJ with HCC group showed the characteristics of chronic viral hepatitis. We conclude that infection of hepatitis virus, particularly hepatitis C virus, affects synergistically on the hepatocarcinogenesis in patients having SCJ infection.     

Factors determining the development of hepatocellular carcinoma in hepatitis B surface antigen carriers. A comparison between families with clusters and solitary cases

This article documents five families with clusters of hepatocellular carcinoma (HCC), including one in which three successive generations were involved. All the 12 patients in these five families and 96.3% of the patients in 54 families with solitary cases of HCC seen during the same period were hepatitis B surface antigen (HBsAg)-positive. The prevalence of HBsAg in families with clusters and solitary cases of HCC was compared. The clustering of HCC in the five families reported could not be accounted for by a higher HBsAg carrier rate or an earlier age of onset of the hepatitis B virus infection. An attempt was made to identify the factors that determine the development of HCC in HBsAg carriers.     

Rate of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis.

BACKGROUND: Cirrhosis of viral etiology due to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is a risk factor for hepatocellular carcinoma (HCC). The current study evaluated the rate of incidence of HCC in patients with compensated cirrhosis of viral etiology. METHODS: Two hundred fifty-nine cirrhotic patients (66 hepatitis B surface antigen [HBsAg] positive, 166 HCV positive, and 27 HBsAg/HCV positive) were longitudinally examined every 6 months by serum alpha-fetoprotein test and liver ultrasonography. The rates of incidence of HCC were calculated by the person-years method. The Kaplan-Meier method was used to estimate the cumulative probability of HCC development. Differences in survival time were evaluated by a log rank test. Independent predictors of HCC development were estimated by Cox proportional hazard regression analysis. RESULTS: During a mean follow-up of 64.5 months, HCC developed in 51 (19.7%) patients: in 34 of 166 HCV positive subjects (20.5%) (mean follow-up, 66.3 months), in 6 of 66 of those HBsAg positive (9.1%) (mean follow-up, 55.06 months), and in 11 of 27 of those with dual HBsAg/HCV infection (40.7%) (mean follow-up, 76.4 months). The rate of incidence of HCC per 100 person-years of follow-up was 3.7 in HCV positive subjects, 2.0 in those HBsAg positive, and 6.4 in those with dual infection. Cumulative HCC appearance rates in HBsAg positive, HCV positive, and HBsAg/HCV positive subgroups were 10%, 21%, and 23% at 5 years, 16%, 28%, and 45% at 10 years, and 16%, 40%, and 55% at 13 years, respectively. Multivariate analysis indicated that age >50 years (hazard risk [HR], 4.5; 95% confidence interval [CI] = 2.1-9.4), male gender (HR, 2.8; 95% CI = 1.1-5.3), and HBsAg/HCV coinfection (HR, 2.3; 95% CI = 1.1-4.6) were independent predictors of HCC development. CONCLUSIONS: These findings confirm that male gender and more advanced age (>50 years) are risk factors for HCC in patients with cirrhosis. Furthermore, the data indicate that subjects with dual HBsAg/HCV infection are at highest risk for HCC. Surveillance programs for early detection of HCC should focus especially on these patients.     

A meta-analysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China

We investigated whether concurrent infection by hepatitis B virus (HBV) and hepatitis C virus (HCV) in China, a hyperepidemic area for these infections, was associated with a higher risk of causing hepatocellular carcinoma (HCC) than each infection alone in a meta-analysis in China, 32 case-control studies involving 3201 cases and 4005 controls, identified from a computer-based literature search from 1966 to 2004. The pooled odds ratio and 95% confidence interval (CI) for HBsAg positivity was 14.1 (95% CI: 10.6-18.8); for anti-HCV/HCV RNA positivity was 4.6 (95% CI: 3.6-5.9); for HBsAg positivity and anti-HCV/HCV RNA negativity were 15.6 (95% CI: 11.5-21.3); for HBsAg negativity and anti-HCV/HCV RNA positivity were 8.1 (95% CI: 5.0-13.0); and positivity for both HBsAg and anti-HCV/HCV RNA was 35.7 (95% CI: 26.2-48.5). We conclude that HBV and HCV infections are important independent risk factors for HCC in China, and that dual infection by HBV and HCV is associated with a higher risk of causing HCC than each infection alone, suggesting a synergism between HBV and HCV.     

Age, gender, and local geographic variations of viral etiology of hepatocellular carcinoma in a hyperendemic area for hepatitis B virus infection.

BACKGROUND: There are etiologic variations of hepatocellular carcinoma (HCC) in different geographic areas. Taiwan is a hyperendemic area for hepatitis B virus (HBV) infection. Hepatitis C virus (HCV) infection also plays an important role in HCC development in Taiwan. Identification of local HCV-endemic areas is important to keep HCV from spreading. This study investigated the etiologic variations of HCC in different geographic areas of Taiwan. METHODS: The authors evaluated the hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV) status of 284 patients (232 male, 52 female) with HCC. They also evaluated the gender ratio and mean age of these patients. RESULTS: The mean age of HBsAg positive patients was significantly lower than the mean age of HBsAg negative patients (52.6 +/- 12.3 vs. 61.3 +/- 11.2 years) (P < 0.05). The male-to-female ratio was 4.5:1 for all HCC patients, 7:1 for HBsAg positive HCC patients, and 2.8:1 for anti-HCV positive HCC patients. In Chaiyi County in southern Taiwan, the prevalence of anti-HCV in male HCC patients was 52%, significantly greater than that of Taiwan as a whole (27.6%) (P = 0.07). However, the prevalence of anti-HCV in male HCC patients in Taipei County in northern Taiwan was 8.7%, significantly less than that of Taiwan as a whole (P = 0.043). Of a total of 65 Chiayi-based HCC patients, 55.4% were anti-HCV positive and 46.2% were HBsAg positive. In the Chiayi area, results of multiple logistic regression showed that the HCC patients who were age 60 years or older or who were living in the city area both had highly HCV-related disease. CONCLUSIONS: The mean age of patients with HBV-related HCC was significantly lower than that of patients with non-HBV-related HCC. The male-to-female ratio for patients with HBV-related HCC was significantly higher than that of patients with HCV-related HCC. The authors identified an area of Taiwan in which HCV-related HCC was prevalent.     

Integration of hepatitis B virus DNA in hepatocellular carcinoma

Integration of hepatitis B virus (HBV) DNA into genomic DNA was investigated in 34 livers bearing hepatocellular carcinoma (HCC) by Southern blot hybridization using 32P-labeled, cloned and purified HBV DNA as a probe. Rehybridization of nitrocellulose paper with a probe containing only the cloning vector was performed after dehybridization to avoid possible false-positive results. Integrated HBV DNA was detected in all 9 hepatitis B surface antigen (HBsAg)-seropositive cases and 3 out of 25 (12%) HBsAg seronegative cases. The hybridization patterns of viral DNA were the same among several cancer nodules in two HCC cases with multiple liver tumors, indicating unicentric hepatocarcinogenesis in these two cases. These results, obtained with avoidance of false-positive results, showed that only a minority of HBsAg-seronegative HCC cases in Japan had demonstrable HBV DNA in the tumors studied by the Southern blot hybridization technique.     

Hepatitis viruses, alcohol, and tobacco in the etiology of hepatocellular carcinoma in Italy.

Mortality rates of hepatocellular carcinoma (HCC) are high in Italy compared with other Western countries. To elucidate further the role of hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol drinking, and tobacco smoking in the etiology of HCC, we carried out a hospital-based case-control study in two areas of Italy: the province of Pordenone in the Northeast and the town of Naples in the South. A total of 229 HCC cases (median age, 66 years) and 431 controls (median age, 65 years) answered a questionnaire and provided blood samples between 1999 and 2002. Odds ratios (OR), percent attributable risks, and corresponding 95% confidence intervals were computed using unconditional multiple logistic regression. ORs for hepatitis B surface antigen (HBsAg) positive versus HBsAg negative and for anti-HCV antibody positive versus anti-HCV antibody negative were 20.2 and 15.6, respectively. Positivity for both markers was associated with an OR of 51.6. Sensitive molecular techniques applied to sera in a subset of HCC cases disclosed a very small number of occult hepatites. Maximal lifetime alcohol intake of > or =35 versus <7 drinks/wk was associated with an HBV/HCV adjusted OR of 5.9. Tobacco smoking was unrelated to HCC risk overall but seemed to enhance HCC risk among virus carriers. Overall, 61% of HCC were attributable to HCV, 13% to HBV, and 18% to heavy alcohol drinking. In conclusion, our study confirms the importance of HCV in HCC etiology in Italy where the widespread dissemination of the virus dates back four or five decades.     

HLA antigen in Chinese patients with hepatocellular carcinomas

One hundred and fourteen Chinese patients with hepatocellular carcinomas (HCC) were studied for alpha-fetoprotein (AFP), hepatitis B surface antigen (HBsAg), anti-HBsAg, and HLA markers. Younger patients with HCC (less than 60 yr old) were more significantly associated with elevated serum AFP (P less than 0.0001) and serum HBsAg (P less than 0.0001) than were older (greater than or equal to 60 yr old) patients. A strong correlation existed between serum AFP and HBsAg among the patients (P less than 0.0001). Of 27 AFP-negative patients, 15 (55.6%) had HLA-B15 compared to 53 of 238 (22.3%) healthy controls (corrected P less than 0.003, relative risk = 4.4). The frequency of HLA-B15 was even higher in the AFP-negative plus HBsAg-negative subgroup (61%). AFP-negative patients also had a significant lack of blood group A.     

Additive effect modification of hepatitis B surface antigen and e antigen on the development of hepatocellular carcinoma.

To assess the role of hepatitis B e antigen (HBeAg) and its interaction with hepatitis B surface antigen (HBsAg) on the development of hepatocellular carcinoma (HCC), this case-control study included 361 age- and sex-matched pairs of patients with histologically proven HCC and healthy control subjects. HBsAg, HBeAg and antibody to HBeAg (anti-HBe) were detected by radioimmunoassay. Antibodies to hepatitis C virus (anti-HCV) were detected by second-generation enzyme immunoassay. The prevalences of HBeAg (20.2%), HBsAg (80.3%) and anti-HCV (29.5%) in cases were higher than in controls (1.9%, 20.7%, and 2.7% respectively; each P < 0.0001). Using patients negative for HBsAg, HBeAg and anti-HBe as a referent group, univariate analysis indicated that HBsAg alone or HBsAg and HBeAg were risk factors for HCC (P for trend < 0.0001). Calculation of incremental odds ratio indicated that there was additive interaction between HBsAg and HBeAg. Multivariate analysis indicated that HCC development was strongly associated with the presence of HBeAg (odds ratio, 8.1; 95% confidence interval, 2.4-27.1), HBsAg (odds ratio, 68.4; 95% confidence interval, 20.5-227.8) and anti-HCV (odds ratio, 59.3; 95% confidence interval, 13.6-258.4). In conclusion, HBsAg, HBeAg and anti-HCV are independent risk factors for HCC. There is additive and independent effect modification between HBsAg and HBeAg on the development of HCC.     

Most of the patients with cirrhosis in Japan die from hepatocellular carcinoma.

A total of 424 patients with cirrhosis were entered into a registry in Japan. One hundred and seven patients were hepatitis B virus (HBV) associated cirrhosis while 252 were hepatitis C virus (HCV) associated cirrhosis. Patients were followed for a period of 3.3+/-3. 3 years. Fifty-six (80%) of 70 deaths in HBV patients and 151 (90%) of 161 deaths in HCV patients were due to complications associated with hepatocellular carcinoma (HCC). The complication rate of HCC in HCV group was significantly higher than in HBV group. In conclusion, most of the patients with cirrhosis died from HCC.     

Case-Control Study of Hepatocellular Carcinoma among Koreans Living in Osaka, Japan

Mortality rates from liver cancer among Koreans living in Osaka are 2–3 times higher than those among Japanese. Our previous study revealed that chronic hepatitis B virus (HBV) infection and excessive alcohol drinking are two major risk factors for hepatocellular carcinoma (HCC) among Koreans in Osaka, although more than 70% of the HCC cases were negative for hepatitis B surface antigen (HBsAg). Using a recently developed immunoassay for detecting serum hepatitis C virus antibody (HCV-Ab), the role of HCV infection was evaluated in a case-control study. The case group consisted of 90 Korean patients who were admitted to Kyowa Hospital in Osaka, and were newly diagnosed as HCC during the period from January 1989 to December 1992. The control group consisted of 249 Korean patients admitted to Kyowa Hospital during the same period and matched in age groups to the HCC cases. Seventy-four and 16.7% of cases were positive for HCV-Ab and HBsAg, respectively. Besides, 41.1% of cases were heavy drinkers. Multiple logistic regression analysis revealed that the adjusted relative risk was 92.4 for HCV-Ab positive and 58.2 for HBsAg positive, as compared with both HCV-Ab and HBsAg negative. Elevated risk was also demonstrated for males with a history of heavy drinking. There was no significant association between the risk of HCC and a history of blood transfusion or cigarette smoking. It was concluded that chronic HCV infection plays a major role in the etiology of HCC among Koreans living in Osaka, in addition to HBV and heavy drinking.