Polyenephosphatidylcholine prevents alcoholic liver disease in PPARalpha-null mice through attenuation of increases in oxidative stress.

BACKGROUND/AIMS: Alcoholic liver disease (ALD) is one of the leading causes of cirrhosis and yet efficient therapeutic strategies are lacking. Polyenephosphatidylcholine (PPC), a major component of essential phospholipids, prevented alcoholic liver fibrosis in baboons, but its precise mechanism remains uncertain. We aimed to explore the effects of PPC on ALD using ethanol-fed peroxisome proliferator-activated receptor alpha (Ppara)-null mice, showing several similarities to human ALD. METHODS: Male wild-type and Ppara-null mice were pair-fed a Lieber-DeCarli control or 4% ethanol-containing diet with or without PPC (30 mg/kg/day) for 6 months. RESULTS: PPC significantly ameliorated ethanol-induced hepatocyte damage and hepatitis in Ppara-null mice. These effects were likely a consequence of decreased oxidative stress through down-regulation of reactive oxygen species (ROS)-generating enzymes, including cytochrome P450 2E1, acyl-CoA oxidase, and NADPH oxidases, in addition to restoration of increases in Toll-like receptor 4 and CD14. PPC also decreased Bax and truncated Bid, thus inhibiting apoptosis. Furthermore, PPC suppressed increases in transforming growth factor-beta1 expression and hepatic stellate cell activation, which retarded hepatic fibrogenesis. CONCLUSIONS: PPC exhibited anti-inflammatory, anti-apoptotic, and anti-fibrotic effects on ALD as a result of inhibition of the overexpression of ROS-generating enzymes. Our results demonstrate detailed molecular mechanisms of the anti-oxidant action of PPC.

[Internal iliac artery aneurysm rupture with aorto-enteric fistula after reconstruction of abdominal aortic aneurysm: report of a case].

An 84-year-old male was admitted to our hospital due to diarrhea. Fourteen years ago, he underwent a graft replacement for an abdominal aortic aneurysm. Three years ago, he was pointed out left internal iliac artery aneurysm about 8cm in diameter. During the hospital stay, he experienced sudden massive hematochezia. Colonoscopic examination revealed a fistula at the rectum. Abdominal CT showed left internal iliac artery aneurysm with aorto-enteric fistula (AEF). An emergent aneurysmectomy and Hartmann's procedure was performed and the patient recovered. This case might show the usefulness of colonoscopy and CT for early diagnosis of secondary AEF. Early diagnosis and surgical treatment are necessary to recover from secondary AEF.

Adenovirus fulminant hepatic failure: disseminated adenovirus disease after unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia.

Adenovirus is one of the major causes of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation for hematological malignancy. Fulminant hepatic failure is a rare manifestation of post-transplant complication with adenovirus. Extremely high mortality and aggressiveness of the clinical course have been posing clinical challenges for the diagnosis as well as for the treatment. Here, we report a case with disseminated adenovirus disease presenting with fulminant hepatic failure after bone marrow transplantation for acute lymphoblastic leukemia.

Useful parameters for distinguishing nonalcoholic steatohepatitis with mild steatosis from cryptogenic chronic hepatitis in the Japanese population.

BACKGROUND/AIMS: As detecting mild steatosis is difficult by abdominal ultrasonography (US), nonalcoholic steatohepatitis (NASH) with mild steatosis may sometimes be confused with cryptogenic chronic hepatitis. We aimed to test this possibility and to isolate factors that may indicate NASH. METHODS: First, 53 Japanese patients diagnosed as having cryptogenic chronic hepatitis by laboratory examination and US were enrolled. These patients were histologically divided into NASH and non-NASH groups, and their clinical features were compared. Second, the diagnostic accuracy of predictors of NASH was examined prospectively. RESULTS: Fifteen patients (28%) were histologically diagnosed as having NASH with mild steatosis. Multivariable analysis revealed that body mass index (BMI) and serum ferritin level were independent predictors of NASH. The best cutoff values to detect NASH were assessed by using receiver-operating characteristic curves: BMI>25.2 kg/m(2) and serum ferritin level >142 ng/ml. When both markers were concomitantly negative, the negative predictive value to detect NASH was 100%. CONCLUSIONS: In cases of mild steatosis, US is not a perfect tool for the accurate diagnosis of NASH. BMI and serum ferritin level are useful discriminators of NASH from cryptogenic chronic hepatitis, and might be helpful markers for diagnosing NASH more accurately in Japanese patients.

Severe alcoholic hepatitis with extremely high neutrophil count successfully treated by granulocytapheresis.

We report a severe alcoholic hepatitis (SAH) patient with an extremely high WBC count, high serum bilirubin and low prothrombin time (PT) successfully treated with granulocytapheresis. After neutrophil-elastase inhibitor failed to reduce WBC count, methylprednisolone pulse therapy was performed. However, WBC count continued to be elevated to 97,190/microl (neutrophils 97.0%) despite improvement of total bilirubin and PT. After 5 sessions of granulocytapheresis and ulinastatin administration, increased serum IL-6, IL-8, neutrophil-elastase and WBC count gradually decreased. We could conclude that granulocytapheresis and ulinastatin can be very effective in reducing cytokines and neutrophil-elastase, and in improving the general status of SAH patients.

Laparoscopic findings in patients with nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Laparoscopic observation of the liver is important to diagnose liver conditions accurately. However, the laparoscopic findings of nonalcoholic steatohepatitis (NASH) have not been characterized. The aim of this study was to clarify the laparoscopic characteristics of NASH. METHODS: Twenty-four patients were enrolled. The degrees of hepatomegaly, color and irregularity of the liver surface, and the presence of depressions, patches, and vesicles were investigated. These laparoscopic findings were compared among NASH, alcoholic liver disease (ALD), and autoimmune hepatitis (AIH). RESULTS: Mild hepatomegaly, dullness of the liver edge, increased fat accumulation of the round ligament, and whitish markings were found in most of the patients with NASH. Small depressions were observed in approximately 70% of the patients. As fibrosis developed, the liver surface became whiter and more uneven. Compared with patients with ALD and AIH, increased fat accumulation of the round ligament and dullness of the liver edge were observed more frequently in those with NASH. However, coarse and groove-like depressions were rare in NASH patients. CONCLUSIONS: Several findings, including mild hepatomegaly, increased fat accumulation of the round ligament, rounded liver edge, whitish markings, and small depressions were common in patients with NASH. However, coarse and groove-like depressions were rare. These findings may be helpful for confirming a diagnosis of NASH.