Pretreatment prediction of virological response to peginterferon plus ribavirin therapy in chronic hepatitis C patients using viral and host factors.

The interferon sensitivity determining region (ISDR) of the hepatitis C virus (HCV) and T-helper type 1 and type 2 (Th1/Th2) ratio were analyzed along with other host and viral factors for their ability to predict the response of patients with chronic hepatitis C to pegylated interferon alpha-2b (Peg-IFN) and ribavirin (RBV) combination therapy. A total of 120 chronic hepatitis C patients with genotype 1 HCV and high baseline viral loads who were to undergo combination therapy scheduled for 48 weeks were enrolled. Sustained virologic response (SVR) was achieved in 54 (45%) of the 120 patients. The pretreatment factors significantly associated with SVR by logistic regression analysis were ISDR mutant [odds ratio (OR) = 86.0, P = 0.0008], Th1/Th2 ratio

Insulin resistance and hepatitis C virus: a case-control study of non-obese, non-alcoholic and non-steatotic hepatitis virus carriers with persistently normal serum aminotransferase.

BACKGROUND/AIMS: Recent studies using transgenic mouse models have demonstrated that the presence of hepatitis C virus (HCV) singularly induces insulin resistance (IR). When evaluated in humans, the exclusion of other factors influencing IR, such as obesity, alcohol intake, hepatic inflammation and steatosis is needed, but only few studies have been performed to these ends. Therefore, we aimed at exploring the singular effects of HCV on glucose metabolism through analysis of HCV carriers with persistently normal serum aminotransferase. METHODS: Non-obese, non-diabetic and non-alcoholic HCV carriers (n=30) were enrolled with 30 hepatitis B virus carriers matched by age, gender, body mass index and waist-to-hip ratio. All patients maintained normal serum aminotransferase (<30 U/L), hyaluronic acid (<50 ng/ml) and platelet count (>150 x 10(3)/microl) for more than 5 years without additional treatments, and had no signs of steatosis. We then compared fasting plasma glucose, serum insulin and adiponectin, and homoeostasis model assessment of IR (HOMA-IR) and HOMA-beta indices between the groups. RESULTS: There were no significant differences in IR/secretion-associated markers or serum adiponectin. Multivariate analysis demonstrated that the presence of HCV was not an independent predictor of IR. HOMA-IR was strongly correlated with waist circumferences and serum gamma-glutamyltransferase in HCV carriers, but not with serum aminotransferase, high-sensitivity C-reactive protein, hyaluronic acid or HCV core antigen. CONCLUSIONS: These results suggest that the presence of HCV alone does not affect IR. Coexistence of hepatitis, steatosis and/or fibrosis may be important to the pathogenesis of IR induced by chronic HCV infection.

De novo autoimmune hepatitis following living-donor liver transplantation for primary biliary cirrhosis.

Since first being described in 1998, de novo autoimmune hepatitis (AIH) after liver transplantation has been reported in several cases suffering from non-autoimmune liver diseases and primary biliary cirrhosis (PBC). Glutathione S-transferase (GST) T1 genotype mismatches between donor and recipient have also been suggested to constitute a risk factor for de novo AIH. Here, we report a 33-yr-old woman who presented complaining of marked fatigue and jaundice four yr after living-donor liver transplantation for PBC. On examination, transaminase levels were highly elevated and ANA and antimitochondrial antibody M2 were positive. Histological findings showed zonal necrosis with lymphoplasmacytic infiltration closely resembling AIH. She had pretreatment AIH score of 16 and 19 points after relapse of de novo AIH. Two color fluorescence in situ hybridization with X and Y chromosome-specific probes clearly revealed that the hepatocytes were of donor origin and lymphocytes were of patient origin. The GSTT1 genotype of the patient and the donor were the same null type, suggesting that mechanisms other than GSTT1 mismatches may exist in de novo AIH development. In conclusion, recipient immune cells attacked the allogeneic transplanted liver of the patient via de novo AIH, although the exact participation of autoimmune mechanisms is unclear.

POEMS syndrome caused refractory ascites in a polycystic disease patient undergoing hemodialysis.

A 60-year-old man with polycystic disease (PCD) undergoing hemodialysis was admitted to our hospital because of refractory ascites in September 2000. He had been diagnosed with probable chronic inflammatory demyelinating polyradiculopathy 6 months before admission. Though the ascites was bloody and exudative, the cytology was normal and cultures of bacteria and acid-fast bacillus were both negative. Hepatic venous outflow obstruction was excluded by several radiological examinations. Because of the presence of polyneuropathy, organomegaly, endocrine abnormality, M-protein, plasma cell dyscrasia, and skin lesions, POEMS, syndrome was diagnosed; this had caused the refractory ascites. Initial prednisolone therapy was effective for the refractory ascites, but it was not effective in preventing recurrence. He died due to cachexia in December 2000. This is a very rare case of the presence of both PCD and POEMS syndrome in a patient.