Clinicopathological significance of oxidative cellular damage in non-alcoholic fatty liver diseases.

Oxidative stress may play an important role in the progression of simple steatosis to non-alcoholic steatohepatitis (NASH). Oxidative stress is generated through multiple sources, including oxidation of free fatty acids, cytochrome P4502E1, iron overload, and necro-inflammatory cytokines including tumor necrosis factor-alpha. Oxidative stress may trigger damage to cellular membranes and nuclear DNA, which results in lipid peroxidation and oxidative DNA damage, respectively.

A murine model of NKT cell-mediated liver injury induced by alpha-galactosylceramide/d-galactosamine.

Natural killer-T (NKT) cells are rich in the liver. However, their involvement in liver injury is not fully understood. We developed here a new murine model of NKT-cell-activation-associated liver injury, and investigated a role of tumor necrosis factor alpha (TNF-alpha) and Fas in pathogenesis.

A clinicopathological study of inflammatory pseudotumors of the liver with special reference to vessels.

Background/aims: Inflammatory pseudotumor of the liver is rare, and patients with inflammatory pseudotumor frequently undergo unnecessary surgical resection as a result of misdiagnosis of malignancy. In this study, we therefore investigated inflammatory pseudotumor clinicopathologically to clarify its characteristics.

Methodology: Twenty patients including 3 with inflammatory pseudotumor and 17 with various malignant liver tumors were studied.

A new chemotherapeutic regimen for advanced unresectable hepatocellular carcinoma.

Background/aims: The aim of this study was to evaluate the efficacy and toxicity of a novel chemotherapeutic regimen for advanced unresectable hepatocellular carcinoma.

Methodology: Seventeen patients with unresectable hepatocellular carcinoma were treated by arterial infusion once a week of low-dose cisplatin (12 mg/m2) and doxorubicin (6 mg/m2) via a subcutaneously implanted injection port and by daily oral administration of 300 mg/day of UFT comprising 5-fluorouracil prodrug tegafur (FT) and uracil (U) at a ratio of 1:4.

Results: The median number of chemotherapy courses was 13 (range, 5-33).

Immunohistochemical detection of Fas and apoptosis in type-1 autoimmune hepatitis.

Background/aims: Although Fas expression has been reported in liver with chronic viral hepatitis and primary biliary cirrhosis, little is known about Fas expression and apoptosis in type-1 autoimmune hepatitis. The aim of this study was to investigate whether the expression of Fas and apoptosis are found in liver with autoimmune hepatitis. The relationship between Fas expression and clinicopathological findings including the occurrence of apoptosis was also investigated.

Life-threatening severe immune thrombocytopenia during alpha-interferon therapy for chronic hepatitis C.

Although mild thrombocytopenia is a common adverse effect of interferon therapy, severe life-threatening thrombocytopenia is extremely rare. Here, we report a case of chronic hepatitis C patient that developed severe thrombocytopenia during alpha-interferon therapy, possibly due to an autoimmune mechanism. A 24-year-old female presented chronic hepatitis C in May, 1998.

Expression of progenitor cell markers in livers with fulminant massive necrosis.

Studies of stem cells in various organs have greatly progressed, and progenitor cells have been confirmed even in liver by recognition of cytokeratin 14 (CK14), c-kit, flt-3, and CD34. We, therefore, immunohistochemically examined the expression of these progenitor cell markers in patients with confluent or massive necrosis, in addition to CK19, albumin, vimentin, and Ki-67. Our subjects were six survivors and 14 deceased patients.

Expression of SPARC by activated hepatic stellate cells and its correlation with the stages of fibrogenesis in human chronic hepatitis.

Secreted protein, acidic and rich in cysteine (SPARC), which functions in tissue remodeling, has been reported to be expressed by myofibroblasts in liver cirrhosis and hepatocellular carcinoma. This study aimed to reveal its expression in chronic hepatitis. Immuno-light and electron microscopy demonstrated that SPARC was expressed by nerve fibers and hepatic stellate cells (HSCs) in the liver parenchyma and myofibroblasts in the fibrous septa.

In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases.

Background/aims: Although oxidative stress is an important candidate in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), the localization and pathological significance of oxidative stress-induced cellular damage in NAFLD remains unclear.

Methods: Hepatic expression of 4-hydroxy-2'-nonenal (HNE) and 8-hydroxydeoxyguanosine (8-OHdG), as reliable markers of lipid peroxidation and oxidative DNA damage, respectively, was immunohistochemically investigated in NAFLD and the results were compared with histological findings.

Results: While no HNE adducts were observed in control livers, they were frequently detected in NAFLD.

Fatty change in human hepatocellular carcinoma cell lines derived from patients with antibodies to hepatitis C virus.

Background/aims: Evidence suggesting a relationship between fatty change in normal or malignant hepatocytes and hepatitis C virus has gradually accumulated, but less is known about the relationship between cell proliferation and fatty change in human hepatocellular carcinoma.

Methodology: We studied the latter issue in two human hepatocellular carcinoma cell lines (OCUH-16 and Nuk-1) derived from hepatitis C virus-associated tumors. We examined the relationship between degree of fatty change assessed by oil-red-O staining and electron microscopy, actively proliferating cells counted using a monoclonal antibody to MIB-1 protein, and apoptotic cells counted using DNA nick-end labeling in the above two hepatocellular carcinoma cell lines with time lapse.

Expression of Fas and Bcl-2 proteins and induction of apoptosis in human hepatocellular carcinoma cell lines.

Because the induction of apoptosis in cancer cells is very important in clinical management, it is useful to examine the association with the Fas-Fas ligand pathway and Bcl-2 protein family in apoptosis. We morphologically examined the expression of Fas and Bcl-2 proteins and induction of apoptosis by anti-Fas in four human hepatocellular carcinoma cell lines, PLC/PRF/5, Huh-6, and Huh-7, as well as OCUH-16, which was originally established in our university. Fas protein was expressed in 96% of OCUH-16 cells in cytoplasm, 24% of PLC/PRF/5 cells, 20% of Huh-6 cells, and no Huh-7 cells.