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Pituitary dysfunction including growth hormone (GH) deficiency may be associated with non-alcoholic fatty liver disease (NAFLD). Since the relationships among GH, IGF-1, IGFBP-3, and development of NAFLD without hypopituitarism are unclear, we examined the role of these hormones in the development of NAFLD based on clinical, laboratory and liver histology data. A total of 55 consecutive patients (20 males and 35 females) with NAFLD. Aspartate amino transferase (AST), AST/ALT, platelet count and IGF-1, levels were significantly associated with differences in fibrosis, since these variables differed between stage 0–1 and stage 2–3 NAFLD. In multivariate analysis, platelet count ( P = 0.0223, relative risk (RR), 5.899; 95% confidence interval (CI), 1.288–27.017), and IGF-1 ( P = 0.0363, RR, 4.568; 95% CI, 1.101–18.945) showed significant associations with stage 2–3 NAFLD. Additionally, hyaluronic acid levels had a negative relationship with IGF-1 and the IGF-1/IGFBP-3 ratio. There was no relationship of fibrosis with GH level, but decreased GH ( P = 0.0414, RR, 0.199; 95% CI, 0.042–0.989) was significantly associated with steatosis of stage 2–3. Low GH/IGF-1 and GH/IGFBP-3 ratios were found in advanced steatosis. GH, IGF-1 and IGFBP-3 are associated with hepatic fibrosis and steatosis in NAFLD. Low levels of IGF-1 might be associated with fibrosis while low level of GH with hepatic steatosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several clinical studies have suggested a possible link between chronic hepatitis caused by hepatitis C virus (HCV) and the development of diabetes mellitus. We investigated the association between liver fibrosis and glucose intolerance in HCV-infected patients by measuring insulin sensitivity and β-cell function. METHOD: A total of 83 chronic HCV-infected patients were recruited into this study. We evaluated insulin sensitivity and β-cell function of all patients in a fasting state (homeostasis model assessment of insulin resistance [HOMA-R] and homeostasis model assessment of β-cell function [HOMA-β]) and after an oral load of 75 g glucose (whole-body insulin sensitivity index [WBISI] and Δ-insulin/Δ-glucose 30). RESULTS: In a multivariate analysis, severe fibrosis was the only independent factor associated with insulin resistance. There were significant differences in both HOMA-R ( P= 0.0063) and WBISI ( P= 0.0159) between patients with mild fibrosis (N = 34) and those with severe fibrosis (N = 49). Although HOMA-β was increased significantly in the subjects with severe fibrosis compared with those with mild fibrosis ( P= 0.0169), Δ-insulin/Δ-glucose 30 showed no significant difference in stage of liver fibrosis, suggesting an uncertain association between liver fibrosis and β-cell function. CONCLUSION: Our findings suggest that the development of liver fibrosis is associated with insulin resistance in HCV-infected patients. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, induces apoptosis in a variety of cancer cells with little or no effect on normal cells. Human hepatoma cells, however, are resistant to TRAIL-induced apoptosis. Since interferon-a (IFN-a) is capable of enhancing TNF-a-induced apoptosis in certain cancer cells, we evaluated the effect of IFN-a on TRAIL-induced apoptosis of human hepatoma cells. IFN-a pretreatment enhanced TRAIL-induced apoptosis of HuH-7 and Hep3B cells, in which IFN-a upregulated the expression of DR5, a death receptor of TRAIL, and downregulated the expression of survivin, which has an antiapoptotic function. In contrast, IFN-a did not enhance TRAIL-induced apoptosis of HepG2 cells, in which expression of DR5 and survivin was not affected by IFN-a. On the other hand, TRAIL activated NF-?B composed of RelA-p50 heterodimer, a key transcription factor regulating cell survival, in HuH-7 and HepG2 cells. However, IFN-a pretreatment repressed the TRAIL-mediated activation of NF-?B and decreased its transcriptional activity in HuH-7 but not in HepG2 cells. Moreover, IFN-a pretreatment clearly augmented TRAIL-mediated caspase-8 activation in HuH-7 cells. Our results suggest that IFN-a could sensitize certain human hepatoma cells to TRAIL-induced apoptosis by stimulating its death signaling and by repressing the survival function in these cells.Oncogene (2003) 22, 1653-1662. doi:10.1038/sj.onc.1206139 [ABSTRACT FROM AUTHOR]

OBJECTIVES:The role of host genetic factors in chronic hepatitis B virus (HBV) infection is not fully understood. We studied the influence of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) gene promoter polymorphisms on disease progression in HBV carriers.METHODS:The sample population included 213 Japanese HBV carriers and 52 healthy volunteers. Of 213 HBV carriers, 66 were considered to be asymptomatic carriers based on the sustained normalization of serum ALT together with seropositivity for the antibody to hepatitis B e antigen (anti-HBe), and 147 were found to have chronic progressive liver disease including cirrhosis. Five biallelic polymorphisms in the TNF-α gene promoter and three biallelic polymorphisms in the IL-10 gene promoter were analyzed by polymerase chain reaction in combination with direct sequencing or restriction fragment length polymorphism assay.RESULTS:Allelic distributions of both gene promoters were not significantly different between HBV carriers and healthy volunteers. In HBV carriers, the TNF-α gene promoter polymorphisms were not linked to disease progression. In contrast, allelic frequencies of T and A at positions −819 and −592, respectively, in the IL-10 gene promoter, as well as the frequencies of ATA haplotype at positions −1082/ −819/ −592 (which is characterized with low capacity for IL-10 production), were significantly higher in asymptomatic carriers than in patients with chronic progressive liver disease. Even after adjusting for individuals positive for anti-HBe, such a relationship could be found between the two groups.CONCLUSION:In chronic HBV infection, inheritance of the IL-10 gene promoter polymorphisms is involved in a host genetic factor that is relevant to disease progression. [Copyright &y& Elsevier]

OBJECTIVES:The aim of the present study was to clarify the risk factors for nonalcoholic fatty liver in young adults.METHODS:One thousand two hundred two students, aged 18–21 yr, received matriculation health examinations, including measurements of body mass index and percent body fat and determination of serum levels of ALT at Nagasaki University in 1998. One hundred twenty-nine were found to have borderline or elevated levels of serum ALT, and 105 of the 129 students (75 men and 30 women) were subjected to further analysis for the presence of fatty liver using ultrasonography, by which both the degree of steatosis and the abdominal wall fat index (AFI) corresponding to the ratio of visceral to s.c. adipose tissue (V/S ratio) were evaluated, in addition to determination of the serum level of leptin.RESULTS:Of 105 students, 74 (70%) had fatty liver. The incidence of moderately to severely fatty liver was significantly higher in men than in women. In parameters related to obesity, the close correlation between body mass index and percent body fat was observed in both sexes. The serum level of leptin correlated well with percent body fat and AFI (V/S ratio) in women, whereas it did not correlate with AFI (V/S ratio) in men. Multiple logistic regression analysis indicated that AFI (V/S ratio) was the only independent risk factor for fatty liver in both sexes.CONCLUSIONS:These results suggest that visceral fat distribution is a key risk factor for nonalcoholic fatty liver in young adults. [Copyright &y& Elsevier]

To investigate the association of hepatitis B virus (HBV) with core promoter mutation (T1762A1764) or precore mutation (A1896) with the clinical course of illness, we analyzed serial core promoter and precore sequences in 22 patients with HBV-associated chronic liver disease who were followed for 12+/-4 years (mean +/- SD). Sixteen of 22 patients were positive for HBeAg at baseline, and 15 of the 16 patients seroconverted to anti-HBe during the observation period. T1762A1764 mutation was detected in 16 of 22 patients, including 11 patients positive for HBeAg, at baseline. During the follow-up period, A1896 mutation emerged in 7 of 16 patients who had the wild-type HBV or only the T1762A1764 mutation at baseline. Sustained remission of hepatitis correlated with the low level of viremia, but did not with type of mutations. These results indicate that HBV with T1762A1764 mutation tends to precede A1896 mutation during the course of infection in Japanese patients with chronic liver disease. [ABSTRACT FROM AUTHOR]

Annual mass examination was performed between 1972 and 1997 in Tomie-town, Goto Islands, Japan, where hepatitis B virus (HBV) infection is very prevalent. In the present study, the incidence of spontaneous loss of hepatitis B surface antigen (HBsAg) in HBsAg carriers was determined in this area. Three thousand and nineteen inhabitants were tested for HBsAg two or more times in our annual surveys. Among them, 131 (4.3%) were defined as chronic HBsAg carriers based on the persistence of HBsAg for 1 or more years. These 131 subjects were followed for 12.2 +/- 7.6 years. During the follow-up period, spontaneous loss of HBsAg occurred in 38 (29%) of the 131 carriers, with a yearly incidence of 2.5%. This loss was seen more frequently in carriers aged 40 years or more on enrollment than in those aged less than 40 years during the same observation periods (P = 0.0141), irrespective of sex or the results of liver function tests. The values for liver function test results were similar before and after loss of HBsAg in these carriers. Stored serum samples were available for later analysis of HBV-DNA by polymerase chain reaction in 32 carriers with loss of HBsAg. The HBV-DNA sequence was detected in 26 (81%) and 2 of the 32 carriers (6%) before and after loss of HBsAg, respectively. These results indicate that spontaneous loss of HBsAg, largely attributable to clearance of viremia, occurs age-dependently in chronic carriers. [ABSTRACT FROM AUTHOR]

A 66-year-old cirrhotic woman was referred to our hospital for evaluation of refractory pleural effusion and dyspnea. Massive right sided-pleural effusion but no ascites was detected. She had been treated with diuretics and albumin, repeated thoracenteses, and pleural drainage with an intercostal catheter, all of which had failed to relieve her symptoms. The diagnosis of hepatic hydrothorax without ascites was made by injection of technetium-99m-sulfur colloid into the peritoneal cavity. A transjugular intrahepatic portosystemic shunt was placed and successfully reduced the pleural effusion, resulting in complete relief of her symptoms. The patient has been free of symptoms for 18 months after the procedure. [ABSTRACT FROM AUTHOR]

A case of surgically confirmed primary malignant fibrous histiocytoma of the liver is presented. A 35-year-old man was admitted to hospital with an epigastric mass. No abnormal laboratory findings, including tumor markers, were detected. Ultrasound and computed tomography showed the main tumor in the left lateral segment and a daughter nodule in the posterior segment of the liver. Arteriography demonstrated a slightly hypervascuIar mass in the left lateral segment. Histological examination of the resected tumor showed bundles of spindle cells with a focal storiform pattern, which were intermingled with bizarre giant cells, therefore a diagnosis of malignant fibrous histocytoma was made. [ABSTRACT FROM AUTHOR]