Yuriko Koike

The significance of blood transfusion in non-A, non-B chronic liver disease in Japan.

We performed a follow‐up study on 70 patients with acute non‐A, non‐B (NANB) posttransfusion hepatitis and a retrospective study on 283 chronic hepatitis, 70 cirrhosis and 53 hepatocellular carcinoma patients of type NANB. In acute NANB posttransfusion hepatitis, as judged by the transaminase levels, the duration of the disease exceeded 6 months in 46/70 = 65.7% and 1 year in 32/70 = 45.7%. The histological diagnosis of the 32 cases persisting for more than 1 year was chronic active hepatitis in 5, chronic persistent hepatitis in 2 and unresolved hepatitis in 6. The frequency of previous transfusion in chronic hepatitis, cirrhosis and hepatocellular carcinoma of type NANB was 42.8, 37.1 and 15.1%, respectively, whereas the incidence of early posttransfusion hepatitis was 8.5, 8.6 and 7.5%, respectively. In chronic liver diseases with a history of jaundice and/or hepatitis, previous transfusions are more frequently associated with type NANB than with type B disease. The present study demonstrates that NANB posttransfusion hepatitis tends to develop to chronic liver disease when analyzed prospectively as well as retrospectively.

Studies on DNA content of hepatocytes in cirrhosis and hepatoma by means of microspectrophotometry and radioautography

SummaryIn order to clarify the underlying mechanism of malignant transformation from cirrhosis to hepatoma the cell kinetics of hepatocytes were studied in these two conditions. The content and synthesis of DNA in hepatocyte nuclei were investigated, by means of Feulgen-microspectrophotometry and tritiated thymidine radioautography, in cirrhotic and noncancerous parts of hepatoma with concomitant cirrhosis. The distribution of ploidy patterns was widely spread, from hypodiploid to hyperpolyploid, in the noncancerous parts of a cirrhotic liver containing hepatoma. In normal liver, each paired nuclear DNA content of a binucleate cell recorded almost the same amount, whereas in the noncancerous as well as in hepatoma cells much difference of DNA content was observed between the paired nuclei of the binucleate cells. The ploidy pattern of hepatocytes in patients with liver cirrhosis, who had developed hepatoma during follow-up periods of several months to several years, appeared to resemble that in noncancerous parts of hepatoma cases. On the other hand, the incorporation of tritiated thymidine into hepatocytes was found to be markedly increased in noncancerous parts as well as in cirrhotic liver developing hepatoma during follow-up periods. These results suggest the possibility that the hepatocytes in noncancerous parts of hepatoma have deranged cell-kinetics which might be a driving factor for the development of malignancy.

HBs-Ag, HBc-Ag and virus-like particles in liver tissue.

SummaryHepatitis B surface antigen (HBs-Ag) and hepatitis B core antigen (HBc-Ag) in hepatic tissue of3 cases with various liver diseases were investigated by immunofluorescent method. Virus-like particles were demonstrated by electron microscopy in the nuclei of these 3 cases. The localization of HBs-Ag was restricted in cytoplasma or on the surface of hepatocyte, while HBc-Ag was almost in the hepatocytic nuclei. However, there was unexplainable discrepancy between the distribution of HBs-Ag and that of HBc-Ag, as more the former in number and less the latter, of hepatocytes. The size of virus-like particles in nuclei was 22–27 nm in diameter. Most of them were hollow, but some of them were wholly electron dense. Their distribution was various from case to case. Discussion was made on the correlation between the presence of Hepatitis B virus and HBs-Ag or HBc-Ag.

Clinical significance of e-antigen/anti-e, with special reference to HBc-antigen in the liver.

Summarye-antigen and anti-e were assayed in sera of asymptomatic HBs-Ag carriers and of patients with liver diseases. Thirteen out of 34 (38.2%) asymptomatic carriers were positive for e-antigen, which was in sharp contrast to the reports from USA and Europe. e-antigen was detected to a greater extent in patients with chronic active hepatitis, reversely anti-e in patients with chronic persistent hepatitis. However, e-antigen was found rarely in patients with cirrhosis and never in 23 cases with hepatoma positive for HBs-Ag.HBc-Ag in the liver was detected in 4 out of 8 e-antigen positive asymptomatic carriers and in 4 out of 5 patients with chronic liver diseases with e-antigen respectively, and moreover in 3 out of 14 anti-e positive cases, so that the presence of anti-e did not necessarily mean the negativity of HBc-Ag in the liver. Anti-HBc titer, however, was lower in anti-e positive sera than in e-antigen positive ones. This may implicate the decreased replication of HBV in cases with anti-e.These results emphasize that the investigation of e-antigen/anti-e is mandatory for the evaluation of the prognosis of asymptomatic carriers and of patients with chronic hepatitis.

Past history of hepatocellular carcinoma is an independent risk factor of treatment failure in patients with chronic hepatitis C virus infection receiving direct-acting antivirals

Direct‐acting antiviral (DAA) treatment can achieve a high sustained virological response (SVR) rate in patients with hepatitis C virus (HCV) infection regardless of a history of hepatocellular carcinoma (HCC [+]). We examined 838 patients (370 men, median age: 69 years) who were treated with DAAs for comparisons of clinical findings between 79 HCC (+) (9.4%) and 759 HCC (−) (90.6%) patients and associations with treatment outcome. Male frequency was significantly higher in the HCC (+) group (60.8% vs 42.4%, P = 0.006). There were significant differences between the HCC (+) and HCC (−) groups for platelet count (115 vs 152 ×109/L, P < 0.001), baseline alpha fetoprotein (AFP) (9.9 vs 4.5 ng/mL, P < 0.001) and the established fibrosis markers of FIB‐4 index (4.7 vs 3.0, P < 0.001), AST‐to‐platelet ratio index (APRI) (1.1 vs 0.7, P = 0.009), M2BPGi (3.80 vs 1.78 COI, P < 0.001) and autotaxin (1.91 vs 1.50 mg/L, P < 0.001). The overall SVR rate was 94.7% and significantly lower in the HCC (+) group (87.3 vs 95.5%, P = 0.001). Multivariate analysis revealed that a history of HCC was independently associated with DAA treatment failure (odds ratio: 3.56, 95% confidence interval: 1.32‐9.57, P = 0.01). In conclusion, patients with chronic HCV infection and prior HCC tended to exhibit more advanced disease progression at DAA commencement. HCC (+) status at the initiation of DAAs was significantly associated with adverse therapeutic outcomes. DAA treatment for HCV should therefore be started as early as possible, especially before complicating HCC.

Pathogenesis of giant hypertrophic gastritis

From 1966 to 1970 we had 192 cases of gastric benign lesion, which are gastrectomized after the pathological evaluation using the endoscopic biopsy. In 188 cases (97.9 per cent), the pathological diagnosis of the biopsied materials was correct. In 4 cases (2.1 per cent), however, the pathological findings of that were overread incorrectly (False Positive). These four cases are all the depressed lesion and consist of three cases of benign gastric ulcers and one case.s of React ive Lymphoreticular Flyperplasia (RLH) . In the former, the errors were due to the atypical but benign regenerated epi thel ium and in the lat ter (RLH) , due to the Lympho id tissue which was miss diagnosed as the poorly differentiated carc inoma containing the signet r ing cell. They had t0 be rebiopsied, for they were all diagnosed as the benign lesion on the gastrocamera, and two cases of these were not the conclusively mal ignant on the pathological diagnosis of the biopsied materials. The correct pathological j udgemen t of the atypical regenerated epi thel ium is one of the most important but difficult subject and the fur ther evaluation should be necded. The decision of signet ring cell carc inoma on the biopsied materials requires the mucus staining me thod in addition to the usual I-hE. staining specimen in some eases. Besides, the contaminat ion of the biopsied materials should be cared for sufficiently.