B cell-activating factor is associated with the histological severity of nonalcoholic fatty liver disease.

PURPOSE: B cell-activating factor (BAFF) is expressed in adipocytes and affects lipogenesis and insulin sensitivity. In addition, the BAFF receptor is expressed in visceral adipose tissue and liver. The aim of this study was to analyze serum BAFF levels in patients with nonalcoholic steatohepatitis (NASH) and simple steatosis (SS) and to compare their respective clinical and histological findings. METHODS: A total of 96 patients with nonalcoholic fatty liver disease (20 with SS and 76 with NASH) were enrolled and their serum BAFF levels were analyzed. Comprehensive blood chemistry analysis and histological examination of liver samples were also conducted. RESULTS: Serum BAFF levels were higher in patients with NASH than in those with SS (p = 0.016). NASH patients with ballooning hepatocytes and advanced fibrosis had higher levels of BAFF in sera (p = 0.016 and p = 0.006, respectively). In addition, the prevalence of NASH increased significantly as the serum BAFF level increased (p = 0.004). Higher serum BAFF levels were found to be an independent risk factor for development of NASH (OR 1.003, 95% CI 1.0003-1.006; p = 0.047). CONCLUSIONS: Nonalcoholic steatohepatitis patients had higher levels of serum BAFF than patients with SS, and higher levels were associated with the presence of hepatocyte ballooning and advanced fibrosis. The serum BAFF level may be a useful tool for distinguishing NASH from SS.

B cell-activating factor controls the production of adipokines and induces insulin resistance.

Visceral adipose tissue (VAT) inflammation has been linked to the pathogenesis of insulin resistance and metabolic syndrome. VAT has recently been established as a new component of the immune system and is involved in the production of various adipokines and cytokines. These molecules contribute to inducing and accelerating systemic insulin resistance. In this report, we investigated the role of B cell-activating factor (BAFF) in the induction of insulin resistance. We investigated BAFF levels in the sera and VAT of obese mice. In obese mice, the BAFF levels were preferentially increased in VAT and sera compared to these levels in normal control mice. Next, we treated mice with BAFF to analyze its influence on insulin sensitivity. BAFF impaired insulin sensitivity in normal mice. Finally, we investigated the mechanisms underlying insulin resistance induced by BAFF in adipocytes. BAFF also induced alterations in the expression levels of genes related to insulin resistance in adipocytes. In addition, BAFF directly affected the glucose uptake and phosphorylation of insulin receptor substrate-1 in adipocytes. We propose that autocrine or paracrine BAFF and BAFF-receptor (BAFF-R) interaction in VAT leads to impaired insulin sensitivity via inhibition of insulin signaling pathways and alterations in adipokine production.

Occupational liver injury due to N,N-dimethylformamide in the synthetics industry.

N,N-dimethylformamide (DMF) is a solvent used extensively in the chemical industry. The main toxic effect reported after exposure to DMF is hepatotoxicity. We encountered four patients with liver injury due to DMF exposure; the severity of the liver injury was related to the exposure levels. After removal of exposure, all patients recovered without specific treatment. A careful evaluation of occupational history is necessary when liver dysfunction develops in industrial workers.

Early biochemical response to ursodeoxycholic acid predicts symptom development in patients with asymptomatic primary biliary cirrhosis.

PURPOSE: Among patients with asymptomatic primary biliary cirrhosis (a-PBC), a substantial portion ultimately develop symptoms suggestive of liver injury. Prognostic variables to distinguish patients likely to become symptomatic from patients who will remain asymptomatic need to be identified. We examined the impact of biochemical response to ursodeoxycholic acid in the development of symptoms in patients with a-PBC. METHODS: Subjects comprised 83 patients with a-PBC treated using ursodeoxycholic acid (UDCA). All patients were followed regularly every 1-3 months. Response to treatment with UDCA was defined as a decrease in gamma-glutamyl transpeptidase (GGT) > or = 70% of pretreatment or normal levels from 6 months after start of treatment. RESULTS: During the follow-up period (62.1 +/- 52.7 months), 12 patients (14.5%) developed liver-related symptoms. Incidence of the development of liver-related symptoms was significantly higher in UDCA non-responders than in responders (p < 0.001). Multivariate analysis showed that response to UDCA (improvement of GGT) represents an independent factor for predicting symptom development in patients with a-PBC. CONCLUSIONS: Patients with a-PBC showing lack of biochemical response to UDCA by 6 months after treatment commencement should be considered for further treatments.

A familial case of autoimmune hepatitis.

Autoimmune hepatitis is a chronic liver disease, and both genetic background and environmental factors are related to its pathogenesis. Here, we report that out of five members of a family with similar human leukocyte antigen haplotypes, two developed autoimmune hepatitis, one was positive for antinuclear antibody, and the remaining two had no features of autoimmunity. The two patients with autoimmune hepatitis had a history of medication use, whereas the other family members did not. Our familial study suggests that in addition to genetic background, medication use and other environmental factors may be related to the onset of autoimmune hepatitis.

[A case of MALT lymphoma of the liver treated by RFA and Rituximab].

A 69 years old man was admitted to our hospital for further examinations of the liver tumor October, 2003. No underlying liver disease was found. Two tumors in the liver, 2cm in diameter respectively, were detected by abdominal ultrasonography and MRI scan. Ultrasonogram-guided needle biopsy from the liver tumor showed diffuse infiltration of CD20 positive, small lymphocytes. A distinct single band demonstrating clonal JH gene rearrangement was detected by southern blot analysis using tissues by needle biopsy. Thus, the patient was diagnosed with primary hepatic MALT lymphoma in the normal liver. These tumors were treated with percutaneus radiofrequency ablation (RFA), followed by Rituximab administration. No relapse has been noted until September, 2005.

Hepatic encephalopathy due to intrahepatic portosystemic venous shunt successfully treated by interventional radiology.

We treated a 66-year-old woman with hepatic encephalopathy secondarily induced by an intrahepatic portosystemic venous shunt (IPSVS). In serial observations, the volume of the liver became smaller and encephalopathy could not be controlled with conservative therapy. We occluded the IPSVS successfully using percutaneous transcatheter embolization with micro coils. Following embolization, encephalopathy disappeared and blood flow of all branches of portal vein improved. In cases with an IPSVS without liver cirrhosis, blood flow in the portal vein and liver volume must be followed carefully, and interventional radiology may be considered effective in those who do not show a satisfactory response to conservative therapy.

Hepatopulmonary syndrome in a patient with primary biliary cirrhosis.

A 54-year-old Japanese woman with primary biliary cirrhosis (PBC) was admitted to our hospital due to hepatic coma and refractory pleural effusion. The physical examination revealed clubbed fingers and collateral veins. The patient had an increased alveolar-arterial oxygen gas tension difference. The levels of anti-mitochondrial antibody (AMA) and AMA M2 was 80 times normal. A technetium 99m-labeled macro-aggregated human albumin scintigram showed uptake in the spleen and the kidneys. A diagnosis of hepatopulmonary syndrome (HPS) was made. HPS may be overlooked because of the lack of symptoms. We conclude that closer attention should be paid to the occurrence of HPS.