Atsuo Shioda

Serum concentrations of human hepatocyte growth factor is a useful indicator for predicting the occurrence of hepatocellular carcinomas in C-viral chronic liver diseases

Numerous reports have examined the relationship between hepatocyte growth factor (HGF) and either the facilitation or suppression of the occurrence of hepatocellular carcinoma (HCC).

Long-term outcome, with monitoring of platelet counts, in patients with chronic hepatitis C and liver cirrhosis after interferon therapy

Objective: Because the determination of the stage of fibrosis depends on rather subjective judgment, more objective parameters are needed. In this study, we followed the long-term outcome, with monitoring of platelet counts, in patients with chronic hepatitis C or liver cirrhosis (LC) who had undergone interferon (IFN) therapy. Methods: 596 patients who were diagnosed at our institute from 1987 to 1998 with chronic hepatitis C and LC were treated with IFNs. A further 58 patients were not treated (NT). The annual rate of changes in platelet counts were calculated and compared for IFN-treated and NT patients. Results: The relationship between the efficacy of IFN therapy and the incidence of hepatocellular carcinoma (HCC) showed that the patients who were virologic sustained responders (VSR) had a significantly lower incidence of HCC than the nonresponders (NR) and NT patients. The change in platelet counts was +4,350/µl/year in the VSR, +1,010/µl/year in the biochemical sustained responders (BSR), –4,540/µl/year in the NR and –6,180/µl/year in the NT patients, indicating a significant platelet increase in the VSR, a decrease of the same magnitude in the NR and NT patients, and no change in the BSR. The cumulative probability of developing HCC and liver failure was significantly higher in groups with decreased platelet counts than in groups with increased platelet counts among patients who had undergone IFN therapy. Multivariate analyses revealed that a decrease in platelet counts was the cardinal risk factor for development of HCC and liver failure in chronic hepatitis C or LC patients. Conclusion: Investigation of platelet counts was useful for determining the long-term outcome of patients who had undergone IFN therapy and for predicting the development of HCC.

Decreased risk of hepatocellular carcinoma in patients with chronic hepatitis C whose serum alanine aminotransferase levels became less than twice the upper limit of normal following interferon therapy

Abstract: Aim: The incidence of hepatocellular carcinoma (HCC) in C‐viral chronic hepatitis (CH) and liver cirrhosis (LC) patients after interferon (IFN) therapy was evaluated according to alanine aminotransferase (ALT) levels.

Analysis of background factors and evaluation of a population at high risk of hepatocellular carcinoma.

Objective: We investigated the background clinical factors of patients with hepatocellular carcinoma (HCC) diagnosed at our institute and, from these results, determined those factors important for evaluation of a population at high risk of HCC. Methods: This study comprised 250 patients diagnosed with HCC from 1990 through 1995 in the Nihon University Itabashi Hospital. Background clinical factors, such as the results of blood chemistry at the time of the first angiography, were examined. Results: Markers of viral hepatitis in the 250 cases were as follows: type B (B-HCC), 29 (11.6%), type C (C-HCC), 201 (80.4%); type B+C, 3 (1.2%), and non-B, non-C (NBNC-HCC), 17 (6.8%). Approximately 35% of B-HCC and NBNC-HCC cases, but only 6% of C-HCC cases, exhibited platelet counts (PLT) equal to or more than 200,000/ml. On the other hand, 56.5% of the C-HCC cases exhibited PLT less than 100,000/ml, in contrast to less than 30% of the B-HCC and NBNC-HCC cases. Irrespective of the etiology of HCC, male sex and a history of smoking were characteristic risk factors. The percentages of abnormal results in combinations of tests in the B-HCC, C-HCC and NBNC-HCC subsets were: 69, 97 and 70% in the aspartate aminotransferase (AST) + PLT group (group A); 83, 98 and 70% in the group A + alanine aminotransferase (ALT) group (group B), and 86, 98 and 100% in the group B + γ-glutamyl transpeptidase (γ-GTP) group (group C), respectively. When hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCV-Ab) were also taken into account, abnormal results were found in every case in all of the HCC groups. Conclusion: C-HCC was found predominantly in cases with liver cirrhosis, whereas B-HCC and NBNC-HCC were observed more frequently in cases without liver cirrhosis. Testing for HBsAg and HCV-Ab, in addition to AST, ALT, PLT and γ-GTP, is considered necessary when screening for HCC.

A Case of Cutaneous Metastases of Gastric Carcinoma Showing Peculiar Clinical Features

A 52‐year‐old male patient presented with multiple cutaneous nodules on the face, trunk, and upper extremities. Examination of a skin biopsy specimen disclosed numerous signet ring cells throughout the dermis. Histopathologic examination of the stomach, along with gastroscopy, revealed that the cutaneous metastases were of gastric origin.

SEN virus infection influences the pathological findings in liver but does not affect the incidence of hepatocellular carcinoma in patients with chronic hepatitis C and liver cirrhosis

Background/Aims: This investigation compared the histological findings in the livers of chronic hepatitis C patients who were or were not co‐infected with SEN virus (SEN‐V) to determine the histological and clinical characteristics of SEN‐V infection in Japan.

Genotype Analysis, Using PCR with Type-Specific Primers, of Hepatitis B Virus Isolates from Patients Coinfected with Hepatitis Delta Virus Genotype II from Miyako Island, Japan

Objectives: The aims of this study were to determine the hepatitis B virus (HBV) genotypes in hepatitis delta virus (HDV) RNA-positive patients and to characterize the HBV nucleotide sequences that may be found on a distant island of Japan. Methods: This study included three patients with chronic hepatitis who were positive for hepatitis B surface antigen (enzyme-linked immunosorbent assay; ELISA), HDV antibody (ELISA) and HDV RNA by polymerase chain reaction (PCR). The HBV genotype was determined by nested PCR using type-specific primers. The first-round PCR products from two patients were sequenced, followed by an investigation of nucleotide homology. Results: Viruses from all three patients in this study were classified as HBV genotype B. Comparison with HBV isolates from geographically neighboring regions revealed that the two HBV isolates had 97.9–98.6% identity at the nucleotide level to a Chinese isolate, 98.3–98.6% identity to the Okinawa isolate and 98.6–98.8% identity to a Japanese isolate of genotype B. On phylogenetic analysis, the HBV isolates from the two patients were classified as HBV genotype B. The HBV isolates of cases 1 and 3 clustered in the same group as isolates from the Chinese mainland and Japanese mainland, which are geographically near Miyako Island. Conclusion: The HBV isolates coinfected with HDV found on Miyako Island were of genotype B. The PCR method based on genotype-specific primers was useful in determining HBV genotypes.

TT Virus Infection Does Not Affect the Clinical Profiles of Patients with Hepatitis B and C in Yanbian City, China

China is an area of high endemicity for viral hepatitis, and the molecular epidemiological investigation of TT virus (TTV) infection is of interest. In the present study, we investigated the epidemiology, clinical significance and molecular characteristics of TTV infection in patients with chronic hepatitis B and C in Yanbian City, China. Serum samples obtained from 74 patients with hepatitis B and hepatitis C who visited Yanbian Hospital, located in northeast China, were analyzed in this study. The study group included 22 cases of chronic hepatitis B (B-CH), 17 cases of liver cirrhosis B (B-LC), 7 cases of hepatocellular carcinoma (B-HCC), 16 cases of chronic hepatitis C (C-CH), 11 cases of liver cirrhosis C (C-LC) and 1 case of hepatocellular carcinoma (C-HCC). Detection of TTV DNA was performed as described by Nishizawa et al. The second-round PCR products from 7 subjects were sequenced, followed by investigation of nucleotide homology and phylogenetic analysis. TTV DNA was present in 18.2, 5.9, 28.6, 6.3, 9.1 and 0% of the patients with B-CH, B-LC, B-HCC, C-CH, C-LC and C-HCC, respectively. The highest prevalence of TTV infection was seen in the groups aged 40–50 and over 60 years. There was no significant correlation between the presence of TTV DNA and the clinical parameters in patients with hepatitis B and C. The various isolates showed 97.9–100% with isolates reported previously from Japan and 98.4–100% with isolates reported previously from China. Nucleotide sequence analysis revealed that the Yanbian isolates could be classified in the same group as the Japan and China isolates. We concluded that chronic coinfection with TTV did not affect the serological features of chronic hepatitis B and C in China, as found in Tokyo, Japan.

The clinical significance of serum KL-6 levels in patients with type C liver diseases

We determine whether the serum KL-6/MUC1 (KL-6) levels in patients with type C liver disease can be used to assay inflammatory activity and the stage of fibrosis of patients, as well as to screen high-risk groups for the development of hepatocellular carcinoma (HCC). Study subjects included 130 patients with type C chronic hepatitis (CH), 15 patients diagnosed with type C acute hepatitis (AH) and 17 healthy control subjects. Frozen serum samples were obtained from each subject to determine the KL-6 levels using an enzyme-linked immunosorbent assay (EIA) method. The mean KL-6 levels in patients were as follows: 150.1 U/ml for healthy controls, 203.7 U/ml for AH patients, 225.7 U/ml for F0 stage, 207.4 U/ml for F1 stage, 235.8 U/ml for F2 stage, 193.3 U/ml for F3 stage, and 276.2 U/ml for F4 stage in CH patients. The mean serum KL-6 level in patients with F4 stage was significantly higher than that in healthy controls. No relationship was observed between the serum KL-6 levels and liver histology. However, the degree of irregular regeneration (IR) of hepatocytes and the levels of KL-6 were significantly correlated according to the progression of F stages. The cumulative incidence of HCC in the high KL-6 level group (>/=300 U/ml) was significantly greater than that in the low level group. Our results suggest that the determination of serum KL-6 levels may be useful in screening high-risk groups for the development of HCC.

An adult patient with acute hepatitis type B which was protracted and complicated by polyarteritis nodosa: a case report

Polyarteritis nodosa (PAN), an extra-hepatic complication of hepatitis type B, is usually treated with a combination of immunosuppressive and antiviral drugs. Less commonly, interferon (IFN) has been used alone. A 57-year-old man was admitted to our hospital with epididymitis and acute hepatitis with genotype A, hepatitis B virus (HBV). He became a carrier with complicating PAN. The administration of interferon alpha2b (IFNalpha2b) at a dose of 6 MU/day for 4 weeks alleviated abdominal and neuronal symptoms related to PAN, although HBV replication was not eliminated. This is the first case of PAN with HBV of genotype A and which was treated with IFN alone. This case indicates the possibility that IFN is efficacious for extra-hepatic complications of hepatitis type B and suggests that differences in genotype may be associated with variation in the likelihood of progression to persistent infection and the incidence of extra-hepatic complications in Japan.