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Kohichiroh Yasui,
Etsuko Hashimoto,
Yasuji Komorizono,
Kazuhiko Koike,
Shigeki Arii,
Yasuharu Imai,
Toshihide Shima,
Yoshihiro Kanbara,
Toshiji Saibara, Takahiro Mori,
Sumio Kawata,
Hirofumi Uto,
Shiro Takami,
Yoshio Sumida,
Toshinari Takamura,
Miwa Kawanaka,
Takeshi Okanoue
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ABSTRACT: Nonalcoholic steatohepatitis (NASH) can progress to hepatocellular carcinoma (HCC). We aimed to characterize the clinical features of NASH patients with HCC.
In a cross-sectional multicenter study in Japan, we examined 87 patients (median age, 72 years; 62% male) with histologically proven NASH who developed HCC. The clinical data were collected at the time HCC was diagnosed.
Obesity (body mass index ≥25 kg/m(2)), diabetes, dyslipidemia, and hypertension were present in 54 (62%), 51 (59%), 24 (28%), and 47 (55%) patients, respectively. In nontumor liver tissues, the degree of fibrosis was stage 1 in 10 patients (11%), stage 2 in 15 (17%), stage 3 in 18 (21%), and stage 4 (ie, liver cirrhosis) in 44 (51%). The prevalence of cirrhosis was significantly lower among male patients (21 of 54, 39%) compared with female patients (23 of 33, 70%) (P = .008).
Most patients with NASH who develop HCC are men; the patients have high rates of obesity, diabetes, and hypertension. Male patients appear to develop HCC at a less advanced stage of liver fibrosis than female patients.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 02/2011; 9(5):428-33; quiz e50. · 5.64 Impact Factor
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Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 05/2010; 107(5):703-11.
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ABSTRACT: Aim: We investigated the clinical and morphological features between acute and chronic autoimmune hepatitis (AIH) with or without acute exacerbation. Methods & Results: Serum total bilirubin on average was elevated to 12 mg/dL in acute AIH, alanine aminotransferase and aspartate aminotransferase peaked to more than 1000 U/L, and serum gamma-glutamyl transpeptidase was higher in the acute type compared with the chronic type without exacerbation. Serum immunoglobulin G was lowest in all other types of AIH. A liver biopsy showed interface or lobular hepatitis with lympho-plasmacytic infiltration, and rosette formations were frequently seen in acute AIH. There were morphological changes of central necrosis with plasmacytic infiltration and giant cell hepatitis. CK19-positive cholangiolar cells had proliferated in the periportal area with massive necrosis, and bile duct injuries were seen in acute AIH more frequently than in the chronic type. Conclusion: Laboratory data and liver histology in acute AIH differed from those of chronic AIH and were clarified for the diagnosis of acute AIH.
Hepatology Research 03/2008; 38(8):784-9. · 2.20 Impact Factor
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ABSTRACT: It is important to detect liver involvement in extranodal lesions in malignant hematologic disorders to make accurate diagnoses and estimate their clinical stage. We report seven cases of malignant lymphoma and a case of histiocytosis X. All patients expressed positive C-reactive protein and a high erythrocyte sedimentation rate, and a high serum value of alkaline phosphatase or lactic dehydrogenase was seen. Image analyses revealed enlarged livers without any space-occupying lesions. Peritoneoscopy with liver biopsy showed a diffuse presence of white maculae or peliosis hepatis on the liver surface among all the patients, and granulomas with or without malignant cells were observed histologically and congestion was seen in the lobules. Thus, peritoneoscopy with liver biopsy appears to be a useful tool not only to detect early liver involvement in malignant hematologic disorders but also to make their accurate diagnosis.
Journal of Clinical Gastroenterology 10/2002; 35(3):262-5. · 3.16 Impact Factor
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ABSTRACT: The present study aimed to establish a novel efficient nonviral strategy for suicide gene transfer in hepatocellular carcinoma (HCC) in vivo. We employed branched polyethylenimine (PEI) and combined it with Epstein-Barr virus (EBV)-based plasmid vectors. The HCC cells transfected with an EBV-based plasmid carrying the herpes simplex virus-1 thymidine kinase (HSV-1 Tk) gene (pSES.Tk) showed up to 30-fold higher susceptibilities to ganciclovir (GCV) than those transfected with a conventional plasmid vector carrying the HSV-1 Tk gene (pS.Tk). The therapeutic effect in vivo was tested by intratumoral injection of the plasmids into HuH-7 hepatomas transplanted into C.B-17 scid/scid mutant (SCID) mice and subsequent GCV administrations. Treatment with pSES.Tk, but not pS.Tk, markedly suppressed growth of hepatomas in vivo, resulting in a significantly prolonged survival period of the mice. These findings suggest that PEI-mediated gene transfer system can confer efficient expression of the suicide gene in HCC cells in vivo by using EBV-based plasmid vectors.
Biochemical and Biophysical Research Communications 03/2002; 291(1):48-54. · 2.48 Impact Factor
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ABSTRACT: We investigated the effect of transfection with connexin (Cx) 26 gene on the malignant potential of PLC/PRF/5 hepatoma cells, observing changes in their morphological features, alpha-fetoprotein (AFP) expression, cell proliferation and apoptosis in vitro, and their tumor growth in vivo. Fluorescence-activated cell sorting (FACS) analysis showed that 10.6% of PLC/PRF/5 hepatoma cells transfected with Cx26 cDNA expressed excessive Cx26, and the spread of lucifer yellow was wider in the colony of stable transfectants (PLC/Cx26) after its microinjection than in control. Nucleo-cytoplasmic (N/C) ratio was significantly lower in PLC/Cx26 (P < 0.0001). Cell proliferation assay showed significantly lower numbers in PLC/Cx26 on day 10 after seeding than in control (P = 0.0039), and AFP level /10(5) cells was significantly lower in medium of PLC/Cx26 (P = 0.0039). The number of proliferating cell nuclear antigen (PCNA)-positive cells was less in PLC/Cx26 in vitro than in control (P = 0.0039), and single-stranded DNA (ssDNA)-positive cells were more abundant in the colony of PLC/Cx26 (P = 0.029). Tumor volume in SCID mice was significantly smaller in the group of PLC/Cx26 than in the control (P < 0.01) throughout the observation period, and tumor weight of PLC/Cx26 was significantly lower (P = 0.0019) week 9 after inoculation. Transfection with Cx26 cDNA inhibited dedifferentiation, suppressed cell proliferation, and apoptosis was induced. Tumor growth of PLC/Cx26 was retarded. These findings suggest that transfection with Cx26 gene into human hepatoma cells reduces their malignant potential.
Carcinogenesis 03/2002; 23(2):351-8. · 5.70 Impact Factor
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ABSTRACT: We describe liver fibrosis caused by iron overload after a long history of blood transfusion in a patient with chronic renal
failure. Pertinent laboratory data were: serum (s)-Fe 148 μg/dl; unsaturated iron binding capacity (UIBC) 14 μg/dl; s-ferritin
9350 ng/ml; human leukocyte antigen (HLA) A2, A24, B39, B55, Cw1, Cw7. Computed tomography revealed a high density in the
liver, and laparoscopy revealed a brown liver. Liver histology showed bridging fibrosis from portal tracts. A heavy iron deposit
was seen in Kupffer cells as well as in hepatocytes surrounded by fibrosis around the portal tracts. Immunocytochemistry revealed
α-smooth muscle actin in many stellate cells distributed along the fibrotic area, and electron microscopy revealed infiltrating
myofibroblastic stellate cells coexisting with collagen fibers around degenerated hepatocytes containing iron deposits. The
findings are consistent with the notion that stellate cells play an important role in liver fibrogenesis in both genetic and
transfusional iron overload hemochromatosis.
Journal of Gastroenterology 08/1998; 33(5):751-754. · 4.16 Impact Factor
