Mitsuhiko Aiso

The Clinical Significance of IgA Antimitochondrial Antibodies in Sera and Saliva in Primary Biliary Cirrhosis

Abstract:  It still remains unclear how antimitochondrial autoantibodies (AMA) are involved with immunopathogenesis of primary biliary cirrhosis (PBC). We have suggested the potential role of IgA‐AMA in damage to epithelial cells in PBC. In the current study, we investigated whether IgA‐AMA were detectable in sera and saliva of PBC patients, to examine the association between detectable IgA‐type autoantibodies in sera or saliva and progression of liver diseases. Fifty‐three patients with PBC were enrolled, and IgA‐AMA in sera and saliva were sought by immunoblotting using pork heart mitochondria as antigens. The progression of PBC was determined as Scheuers classification consisting of four histological stages. We found IgA‐AMA, IgA‐anti‐PDC‐E2, and IgA‐anti‐E3BP in 43/53 (81%), 37/53 (70%), and 35/53 (66%) sera of patients with PBC, but none of controls. The progression of PBC was statistically associated with presence of IgA‐anti‐PDC‐E2 (P= 0.0124), but neither with IgA‐AMA (P= 0.1296) nor anti‐IgA‐E3BP (P= 0.5973). In saliva, detectable IgA‐AMA, IgA‐anti‐PDC‐E2, and IgA‐anti‐E3BP were noted in 12/26 (46%), 6/26 (23%), and 11/26 (42%), respectively. Detection of IgA‐anti‐PDC‐E2 was strongly associated with progression of PBC (P= 0.0002), whereas detection of IgA‐AMA and IgA‐anti‐E3BP were not associated (P= 0.2145 and P= 0.5118). The current findings suggest that the presence of IgA‐anti‐PDC‐E2 in sera or saliva might be associated with progression of PBC, although a prospective study with PBC patients with detectable IgA‐anti‐PDC‐E2 at early stages will be required to conclude the contribution of IgA‐anti‐PDC‐E2 to the progression of PBC.

Benefit of cystatin C in evaluation of renal function and prediction of survival in patients with cirrhosis.

The assessment of renal function is of vital importance in management of patients with cirrhosis. While serum creatinine (Cr) is routinely used for this purpose, Cr‐based estimated glomerular filtration rate (eGFR) does not reflect true renal function because of muscle wasting and impaired liver function. By contrast, cystatin C (CysC) is unrelated to muscle volume and liver function. In this study, we examined whether CysC‐based GFR estimation is beneficial in assessment of renal function in patients with cirrhosis.

Validation of the Japanese version of the Chronic Liver Disease Questionnaire for the assessment of health‐related quality of life in patients with chronic viral hepatitis

Patients with chronic liver diseases (CLD) suffer from a variety of subjective symptoms, and the assessment of health‐related quality of life (HRQOL) is crucial. The Chronic Liver Disease Questionnaire (CLDQ) is the first liver disease‐specific instrument for this purpose. In this study we aimed to develop the Japanese version of CLDQ and to assess its validity and reliability in Japanese patients with chronic viral hepatitis.

Gene expression profiling in whole liver of bile duct ligated rats: VEGF-A expression is up-regulated in hepatocytes adjacent to the portal tracts.

Background and Aim:  It would be of clinical importance to clarify molecular mechanisms of cholangiocytes proliferation for the treatment of intractable cholestatic diseases. The aim of this study was to elucidate gene expression profiling in the whole liver of bile duct ligated (BDL) rats using microarray analysis. In addition, the localization and time course of up‐regulated expression of vascular endothelial growth factor (VEGF) was investigated.

Effect of tauro‐α‐muricholate and tauro‐β‐muricholate on oestradiol‐17β‐glucuronide‐induced cholestasis in rats

The effect of tauro‐β‐muricholate (βMC‐tau) and tauro‐α‐muricholate (αMC‐tau) on oestradiol‐17β‐glucuronide (E217G)‐induced cholestasis was compared with that of taurourso‐deoxycholate (UDC‐tau) in rats. Like UDC‐tau, αMC‐tau and βMC‐tau infused at the rate of 0.2 μmol/min per 100 g bodyweight (BW) completely inhibited the cholestasis induced by E217G infused at the rate of 0.06 μmol/min per 100 g BW for 20 min. These findings indicate that βMC‐tau and αMC‐tau are useful in protecting against various types of experimental cholestasis, as well as against bile acid‐induced cholestasis.

Effect of lithocholate-3-sulfate and its amides on biliary excretion of glutathione and phospholipid

Some organic anions and lithocholate-3-O-glucuronide have been reported to inhibit biliary glutathione excretion. In this study the effect of lithocholate-3-sulfate on biliary glutathione excretion was examined in rats. Furthermore, the effects of its amides on biliary glutathione and phospholipid excretion were also studied. Intravenously injected lithocholate-3-sulfate (3 μmol/100 g body wt.) depressed biliary glutathione excretion to 15% of the basal value, which corresponded to biliary lithocholate-3-sulfate excretion. The same dose of glyco- and taurolithocholate-3-sulfate also inhibited biliary glutathione excretion, and its inhibition was more marked with glycolithocholate-3-sulfate. In contrast, taurolithocholate-3-sulfate increased the bile acid/phospholipid ratio in the bile more markedly than glycolithocholate-3-sulfate did. These findings indicate that the mechanisms for inhibition by lithocholate-3-sulfate amides of biliary excretion of glutathione and phospholipid are different.

Gilbert Syndrome with Concomitant Hereditary Spherocytosis Presenting with Moderate Unconjugated Hyperbilirubinemia

We experienced a case of a 19-year-old man with Gilbert syndrome with concomitant hereditary spherocytosis. The patient presented with moderate unconjugated hyperbilirubinemia, and inherited etiology was strongly suspected. The diagnosis of Gilbert syndrome was confirmed by the genetic analysis of the UGT1A1 gene, demonstrating UGT1A1*28 and compound heterozygote UGT1A1*6. In addition, since the laboratory findings and imaging studies revealed lysemia as well as gallstone and splenomegaly, a diagnosis of hereditary spherocytosis was made as a comorbidity. Both Gilbert syndrome and hereditary spherocytosis are hereditary diseases with a high frequency, and the hyperbilirubinemia may be exacerbated when these two diseases are concomitant.

Autoimmune neutropenia due to antineutrophil antibodies in a patient with primary sclerosing cholangitis.

Autoimmune neutropenia (AIN) is defined as a decrease in the circulating absolute neutrophil count (ANC) to less than 1500/μl caused by serum antineutrophil antibodies. Secondary AIN is associated with various autoimmune diseases. Herein we present the case of a patient with primary sclerosing cholangitis (PSC) who developed secondary AIN. A 19-year-old man was admitted due to liver injury, and a diagnosis of PSC was established by cholangiogram and liver biopsy. Severe neutropenia, with the ANC down to 130/μl, developed during his hospital course. No medications had been given at that time and bone marrow aspiration revealed no abnormality. Therefore we suspected secondary AIN as a causative etiology and examined whether antineutrophil antibodies were detectable in the patient’s sera by flow cytometric analysis of the granulocyte indirect immunofluorescence test. We found that antineutrophil antibody was strongly positive on admission, and the titer decreased along with recovery from neutropenia. This is the first reported case of a patient with PSC who developed AIN, with detection of serum antineutrophil antibodies.