Kan Toriyama

Possible new hepatitis B virus genotype, southeast Asia.

We conducted a phylogenetic analysis of 19 hepatitis B virus strains from Laos that belonged to 2 subgenotypes of a new genotype I. This emerging new genotype likely developed outside Southeast Asia and is now found in mixed infections and in recombinations with local strains in a geographically confined region.

High viral load is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis B virus infection

Background and Aims:  Hepatitis B virus (HBV) is considered a major risk factor for the progression to liver cirrhosis and hepatocellular carcinoma (HCC). The serum level of HBV‐DNA is correlated with progression of the disease. The aim of the present study was to determine the relationship between the level of HBV‐DNA and hepatocarcinogenesis in patients with chronic HBV infection.

Two cases of non-alcoholic steatohepatitis with development of hepatocellular carcinoma without cirrhosis

earlier loss of hepatitis C virus RNA in interferon therapy can predict a long-term response in chronic hepatitis C. J. Gastroenterol. Hepatol. 1997; 12 : 468–72. 4 Regimbeau JM, Colombat M, Mognol P et al. Obesity and diabetes as a risk factor for hepatocellular carcinoma. Liver Transpl. 2004; 10 : S69–

Human Papillomavirus Infection in Oral Verrucous Carcinoma: Genotyping Analysis and Inverse Correlation with p53 Expression

Objective: Verrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma, occurring mostly in oral mucosa. To clarify the role of human papillomavirus (HPV) in VC tumorigenesis, we investigated localization and genotypes of HPV and p53 expression in oral VC. Methods: We studied paraffin-embedded specimens of 23 VCs and 10 control non-neoplastic lesions in oral mucosa. To investigate HPV infection, HPV genotypes and p53 expression, we respectively employed in situ hybridization (ISH), sequence analysis following short PCR fragment-PCR assay and immunohistochemistry. Results: Of the 23 VC specimens, 11 (48%) had HPV-DNA (detectable by PCR), and 6 (26%) had intranuclear HPV in the upper portion of the squamous epithelium (detectable by ISH). Nine of the 11 PCR-positive specimens showed multiple infections with low- and high-risk HPVs. No HPV-16 infection was detected. Although HPV-6 and HPV-18 were frequently detected by PCR, no HPV could be found in control specimens by ISH. p53 expression was inversely correlated with HPV infection. Conclusion: Thus, multiple infections with low- and high-risk HPVs and their rapid replication during hyperkeratinization may participate in the histogenesis of oral VC. Oral VC tumorigenesis may involve the inactivation of p53, which is associated with HPV infection.

High genetic diversity including potential new subtypes of hepatitis C virus genotype 6 in Lao People's Democratic Republic

Sera from 105 anti-HCV-positive first-time blood donors collected in 2004, 2005 and 2008 in different provinces in Laos were investigated by PCR. Forty-five samples were positive for HCV (42.86%); two belonged to subtype 1b (2/45, 4.4%) and all others to genotype 6 (43/45, 95.6%), including subtypes 6b, 6h, 6k, 6l, 6n and 6q. Three groups of sequences were not clearly attributable to any genotype 6 subtype, two of which may be regarded as candidates for new subtypes of genotype 6. Two samples were mixed infected with different subtypes or clusters of genotype 6 viruses.

Clinicopathologic Study of Hepatic Penicillium marneffei in Northern Thailand

CONTEXT Penicillium marneffei, an opportunistic fungus, is endemic in Southeast Asia, especially in human immunodeficiency virus-infected individuals living in northern Thailand. OBJECTIVE We present the results of a clinicopathologic study of hepatic penicilliosis among human immunodeficiency virus/acquired immunodeficiency syndrome patients. DESIGN A search of liver biopsies in one institution from 1998 to 1999 identified 30 cases of penicilliosis. RESULTS Histologically, hepatic lesions could be classified into 1 of 3 patterns: diffuse, granulomatous, and mixed. The diffuse pattern showed a diffuse infiltration of foamy macrophages that contained numerous P marneffei. The granulomatous pattern showed a formation of multiple granulomata with various degrees of inflammatory cell infiltration. The mixed pattern showed features intermediate between the diffuse and granulomatous patterns. Liver function tests of the 3 pathologic pattern groups were evaluated, but there were no statistically significant differences in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase levels among the various histologic groups. CONCLUSION To our knowledge, this is the largest series to date that documents the liver pathology that results from this pathogen. We hypothesize that the histologic patterns seen on biopsy reflect the level of the hosts immunity. Hence, in addition to a diagnosis of penicilliosis, a liver biopsy may also provide an assessment of the hosts immune status, whereas liver function tests do not.

Flow cytometric DNA analysis of vascular soft tissue tumors, including African endemic-type Kaposi's sarcoma

Vascular tumors of the soft tissue display a wide spectrum of histologic features and biologic behavior. Flow cytometric DNA analysis was performed on 40 vascular tumors, including nine African endemic-type Kaposis sarcomas, nine angiosarcomas, seven hemangiopericytomas, six glomus tumors, and nine capillary hemangiomas. Six of the nine angiosarcoma cases (67%) and one of the seven hemangiopericytomas cases (14%) were aneuploid. All benign vascular tumors and Kaposis sarcomas were diploid. Clinically, five of the six angiosarcoma patients with aneuploidy died within 2 to 28 months, while the remaining patient, who had the smallest tumor (2 x 1 cm), survived more than 4 years after the initial diagnosis was made. All three angiosarcoma patients with diploidy died within 10 to 14 months. One hemangiopericytoma patient with aneuploidy died within 1 month. No cases of benign tumor recurred. These results suggest that most vascular tumors, which generally follow a benign clinical course, were diploid and that the majority of those with a poor outcome were aneuploid. However, flow cytometrically assessed DNA ploidy has no prognostic value in angiosarcomas or hemangiopericytomas.

Synaptophysin immunoreactivity in adrenocortical adenomas: a correlation between synaptophysin and CYP17A1 expression

DESIGN AND METHODS The adrenal cortex is not considered to be an intrinsic part of the diffuse neuroendocrine system, but adrenocortical neoplasms possess neuroendocrine properties. In this study, we examined synaptophysin (SYP) and neural cell adhesion molecule (NCAM) expression in adrenocortical adenomas in relation to adrenal function. RESULTS Immunohistochemical analysis showed that 50.7 and 98.6% of the cortical adenomas showed SYP and NCAM immunoreactivities respectively. There was no apparent difference in NCAM immunoreactivity among the adenomas. However, the immunostaining for SYP was significantly stronger in cortisol-producing adenomas (CPA) than in aldosterone-producing adenomas (APA), nonfunctioning adenomas (NFA), showing no clinical or endocrinological abnormality, or adenomas associated with preclinical Cushings syndrome (preCS). Western blotting and real-time PCR demonstrated that the expression level of SYP protein and mRNA was significantly higher in CPA than in APA or NFA. Additionally, the SYP mRNA level showed a positive correlation with CYP17A1 mRNA. In addition to the plasma membrane, mitochondria, and smooth endoplasmic reticulum, SYP immunoreactivity was detected in the Golgi area, which is known to be involved in the regulation of mitochondrial cholesterol and the transport of steroid intermediates. It was unexpected that the ratio of positive cells for SYP in preCS was less than that in APA and NFA. However, further examination is required, because the number of preCS cases we investigated was very small. CONCLUSIONS We propose that SYP expression in adrenocortical cells may be involved in some aspect of adrenal function such as transport or secretion of glucocorticoids.

Significance of Hepatic Insulin Clearance in Patients with Chronic Hepatitis C and Non-alcoholic Fatty Liver Disease

Objective Hyperinsulinemia plays an important role in the pathophysiological processes of chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). However, there are few reports on hepatic insulin clearance in patients with these diseases. Methods A total of 74 CHC patients and 37 NAFLD patients were enrolled in this study. We evaluated their hepatic insulin clearance, insulin sensitivity and β-cell function with an oral glucose tolerance test. Results Hepatic insulin clearance in the patients with CHC was significantly correlated with platelets (r=0.271, p=0.020) and liver fibrosis (r=-0.234, p=0.045) and was significantly affected by both steatosis (mild: 0.157±0.078, severe: 0.114±0.053, p=0.024) and fibrosis (mild: 0.167±0.0857, severe: 0.125±0.052, p=0.010). There were no significant differences in (homeostasis model assessment) HOMA-β among steatosis and fibrosis stages. In the NAFLD patients, those with severe fibrosis had significantly reduced hepatic insulin clearance (mild: 0.135±0.045, severe: 0.098±0.031, p=0.013) and significantly increased HOMA-β (mild: 115.6±67.1, severe: 172.8±65.7, p=0.018) compared with the patients with mild fibrosis. Conclusion Liver fibrosis development is associated with hepatic insulin clearance in both the CHC and NAFLD patients.

A clinico-pathological study of 163 untreated cases of chronic hepatitis C.

We performed a clinico-pathological study of 163 untreated cases of chronic hepatitis C. Eighty five percent of the patients were clinically asymptomatic and their physical examinations showed unremarkable or minimal changes at the time of the liver biopsy. Liver function tests tended to present slight abnormalities, involving mild elevations of the activity of the aminotransferases and gamma-glutamil transferase levels. In spite of these mild abnormalities, advanced chronic liver disease was histologically detected in eighty nine percent of the patients, mainly showing chronic active hepatitis. The most characteristic histological finding was an interlobular bile duct damage, which correlated with the presence of lymphoid aggregates in the portal tracts and with the development of fibrosis.