Serum somatomedin peptides measured by somatomedin A radioreceptor assay in chronic liver disease.

The levels of serum somatomedin peptides were determined with a somatomedin A radioreceptor assay utilizing human placental membranes. Low levels were found in 25 patients with liver cirrhosis and 28 patients with chronic hepatitis with the mean of 0.47 +/- 0.05 and 0.60 +/- 0.04 U/ml, respectively. There was a positive correlation between somatomedin A on one hand and serum albumin, cholinesterase, total cholesterol and thrombotest on the other. There was a negative correlation between somatomedin A and the indocyanine green retention test. These findings confirm earlier results obtained with bioassay.

Clinicopathological features of hepatocellular carcinoma--comparison of hepatitis B seropositive and seronegative patients.

Clinicopathological features were studied in 113 non-alcoholic patients with histology-proven hepatocellular carcinoma, of whom 35 were positive for hepatis B virus surface antigen (HBsAg), 23 were negative for all seromarkers for hepatitis B virus, and 55 were negative for HBsAg, but positive for anti-HBs and/or anti-core antibody (anti-HBc) with low titers. It was found that the age of the patient at the time of diagnosis was significantly lower in HBsAg cases than in the other two groups. Serum alpha-fetoprotein levels were often normal or below 100 ng/ml in the seronegative cases, and its measurement less frequently served as a diagnostic clue. Otherwise, clinically there was no difference between the three groups except for more frequent liver disease within the second degree of kinship in the HBsAg patients. Histopathological study of the livers showed that there were more expanding type hepatocellular carcinomas in the seronegative cases as compared with the HBsAg positive cases. There was no autoimmune chronic liver disease in these patients. These observations and data seem to indicate that there are certain differences between HBsAg positive and seronegative hepatocellular carcinomas. Since most patients had progressive liver disease, it is likely that many of these seronegative cases had chronic non-A, non-B viral disease, which is very common in Japan. It may be inferred further that non-A, non-B hepatitis virus is less carcinogenic as compared with hepatitis B virus.

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 viruses in southern Taiwan--mass survey of 2985 inhabitants.

A survey of 2985 apparently healthy Taiwanese in southern Taiwan revealed a high prevalence (18.2%) of hepatitis B surface antigen (HBsAg). It was significantly higher in males (22.3%) than in females (13.6%), but no correlation with family origin, socioeconomic status or residence was established. About one-third of the breeding female HBsAg carriers were HBeAg-positive, and these may be an important source in the spread of HBV. Subtyping of HBsAg in 63 subjects showed adw to be dominant in this area, and 8 subjects with suspicious results had overlapping heterotypic HBV's (7 adwr and 1 adyw) in addition to 2 subjects in which coexistence of HBsAg and anti-HBs was recognized. The association between HBsAg positivity and serum transaminase elevation was significant, especially in the older groups who had a higher abnormal rate. Hepatitis A virus infection was serious too, with nearly 100% of people above 20 years of age being anti-HA antibody positive.

Hepatocellular carcinoma arising in noncirrhotic and highly cirrhotic livers: a comparative study of histopathology and frequency of hepatitis B markers.

Hepatocellular carcinoma (HCC) associated with cirrhosis and HCC developing in a noncirrhotic liver may have differing pathogeneses. To study this possibility, 425 autopsied cases of HCC were investigated. Of these, 45 livers were not cirrhotic, 50 were highly cirrhotic (liver weight less than 99 g), and the remaining 331 were cirrhotic but not so highly. The average age was significantly older in the highly cirrhotic group, suggesting a longer premalignant period of chronic liver disease. The liver weight in the noncirrhotic group was about 3.5 times that in the highly cirrhotic group. Hepatitis B surface antigen was positive in serum in only 9.3% and in liver tissue in 10% in the noncirrhotic cases, the positivity rate being much lower compared with other groups (P less than 0.005--0.01), yet antibody to HB core was positive in 90%. The antibody titers were low, however, indicating that these noncirrhotic patients had in the past had HB virus (HBV) infection with no residual chronic B hepatitis. Analysis of the grades of anaplasia of cancer tissue demonstrated an inverse correlation between the degree of fibrosis and grade of anaplasia, i.e., the more advanced the fibrosis, the less anaplastic the cancer. These data suggest that HCC arising in highly cirrhotic liver and in noncirrhotic livers have different pathogenetic backgrounds, and that HBV infection, even though transient, has a certain role in hepatocarcinogenesis. The generally held conjecture that HCC in a noncirrhotic liver is caused by nonviral carcinogens and HCC arising on the ground of cirrhosis is due to HBV seems untenable in such a simple concept.

Clinicopathologic features of encapsulated hepatocellular carcinoma: a study of 26 cases.

The clinicopathologic features of 26 cases of hepatocellular carcinoma (HCC) surrounded by a grossly distinct capsule-like fibrous tissue were studied. The frequency of this type was 10.3% among autopsy cases of HCC. The mean age of the patients was 64.1 years, which was significantly older compared with that of 143 cases of nonencapsulated HCC. Hepatitis-B surface antigen in serum was positive in 18.7% of the cases studied, the positivity rate being lower than that of HCC in general. Histologically, the tumor was relatively well differentiated and the capsule was the product of slow expanding growth. Intravenous tumor invasion was less frequent compared with other types of HCC. Clinically, celiac angiography proves to be a most useful diagnostic method; a thick capsule may be demonstrated as a thin radiolucent rim around the mass. The clinical course from the early stage is protracted and, if detected early, this type of HCC may be removed surgically.