Lymphoepithelioma-like cholangiocarcinoma with Epstein-Barr virus infection treated by radiofrequency ablation.

Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare intrahepatic tumor. There are usually no specific physical findings, and the tumors are often diagnosed incidentally and are frequently large-sized at diagnosis. The imaging findings of LELCC resemble those of hepatocellular carcinoma (HCC). Tumors are often found in large-sized and advanced at diagnosis, and the main treatment of the disease is surgical resection. Herein, we report treating a patient with early stage LELCC by radiofrequency ablation (RFA). We diagnosed this tumor in a 27-year-old Chinese female with a history of chronic hepatitis B (CHB). Based on the findings of blood examination, abdominal ultrasonography, and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), this tumor was diagnosed as suspected HCC. Ultrasound-guided percutaneous tumor biopsy and RFA were performed at the same time. The histopathological findings finally revealed the diagnosis of LELCC. To the best of our knowledge, this is the first report, in the English-language literature, of the treatment of LELCC by RFA; we suggest that RFA might be a candidate treatment for small-sized early stage LELCC.

Assessment of 10-year changes in liver stiffness using vibration-controlled transient elastography in non-alcoholic fatty liver disease.

AIM: Although liver biopsy is the gold standard for the diagnosis and staging of non-alcoholic fatty liver disease (NAFLD), repeated assessment of patients' liver tissue conditions are impractical. We assessed the 10-year changes in liver stiffness measurements (LSM) utilizing vibration-controlled transient elastography in NAFLD patients. METHODS: From January 2006 to September 2007, LSM was carried out for 97 biopsy-proven NAFLD patients. Of these, 34 patients underwent 10-year LSM reassessments (14 of them with paired biopsies). RESULTS: We evaluated the changes in the fibrosis stage as estimated using LSM (FS-LSM). Over a 10-year period, 32.4% had FS-LSM progression, 50% had static disease, and 17.6% had FS-LSM improvement. From among the initially diagnosed non-alcoholic steatohepatitis patients, 18% had progressed to considerable stage 4 (cirrhosis) 10 years later. In this cohort, none of the patients who had been initially diagnosed as FS-LSM stage 0 had progressed to cirrhosis 10 years later. The changes in LSM were correlated with the change in the histological fibrosis stage, the NAFLD activity score, and the change in the sum of the steatosis, activity, and fibrosis score. Improving more than 1 body mass index (kg/m2 ) and having a higher initial aspartate aminotransferase, alanine aminotransferase (ALT), or ALT responder (>30% improvement or reduction to less than 40 IU/L) were factors contributing to LSM improvements (≥2 kPa). CONCLUSIONS: Vibration-controlled transient elastography is likely to become a more clinically important tool for the long-term monitoring of NAFLD patients.

Renal vein dilation predicts poor outcome in patients with refractory cirrhotic ascites.

AIM: Renal venous hypertension is known to be associated with worsening of renal function in patients with decompensated heart failure. Intra-abdominal hypertension including cirrhotic ascites also leads to renal venous hypertension. We aimed to clarify the effect of renal venous hypertension on cirrhotic ascites. METHODS: Two hepatologists measured the left renal vein diameter in 142 consecutive patients with refractory cirrhotic ascites using non-contrast computed tomography. The renal vein diameter was measured at the renal vein main trunk and upstream of the confluence of collateral veins. RESULTS: The inter-observer agreements were high for the measurements of the left renal vein (r = 0.918, P < 0.001). The median overall survival for patients with renal vein diameter ≥11 mm was less than that for patients with renal vein diameter <11 mm (P < 0.001; 2.5 vs. 32.0 months). One-year survival rates were 15.3% versus 66.4%. Multivariate analysis revealed renal vein diameter ≥11 mm (hazard ratio, 2.94; P < 0.001; 95% confidence interval, 1.67-5.20) and a high Model for End-stage Liver Disease score combined with serum sodium level (MELD-Na) (hazard ratio, 3.39; P < 0.001; 95% confidence interval, 2.00-5.74) were significant independent predictors of mortality. CONCLUSIONS: Renal vein dilation is a risk factor of mortality in patients with refractory cirrhotic ascites, independent of the MELD-Na score.

Onset of Tuberculosis from a Pulmonary Latent Tuberculosis Infection during Antiviral Triple Therapy for Chronic Hepatitis C.

A 62-year-old man was diagnosed with the onset of tuberculosis (Tb) from a pulmonary latent tuberculosis infection (LTBI) during triple therapy with pegylated interferon α2a, ribavirin, and telaprevir for a chronic hepatitis C infection in 2013 before interferon (IFN)-free anti-viral therapy was introduced in Japan. A liver biopsy before IFN treatment revealed the presence of epithelioid cell granulomas (ECGs). IFN may also be employed for chronic hepatitis B infection and malignant tumors, thus, special attention must be paid to the development of Tb from a LTBI when ECGs are observed before treatment. It is also necessary to review the significance of the liver biopsy.

Pathological evidence of the cause of spontaneous regression in a case of resected hepatocellular carcinoma.

A 67-year-old man presented for an evaluation after experiencing right hypochondrial pain lasting for two months. Abdominal ultrasonography showed a hepatic tumor in the right liver and extremely mild hepatic steatosis. The imaging findings indicated that the tumor (43 mm in size) was ischemic, and the lesion was surgically resected and examined. The histopathological findings demonstrated 95% necrosis with moderately differentiated hepatocellular carcinoma (HCC). The diagnosis was HCC with spontaneous regression. There was also pathological evidence of thrombus formation in the peripheral arteries and portal veins. In addition, the non-cancerous regions of the liver were diagnosed as exhibiting non-alcoholic steatohepatitis. The pathological findings obtained after resection of the HCC lesion showed spontaneous regression.

[A case of phlegmonous gastritis which resolved with medical treatment].

A 70-year-old man visited our outpatient clinic with chief complaints of severe upper abdominal pain and fever. Blood tests revealed a markedly enhanced inflammatory reaction. He was hospitalized and diagnosed with phlegmonous gastritis based on findings of esophagogastroduodenoscopy and multidrug-resistant streptococcus detected by gastric juice culture. The clinical symptoms promptly resolved after starting concomitant treatment with vancomycin hydrochloride and levofloxacin. Administration of vancomycin hydrochloride for phlegmonous gastritis was not found in our literature search and the present case is thus considered to provide a valuable example of such use.

A case of asymptomatic intraductal papillary neoplasm of the bile duct without hepatolithiasis.

A 65-year-old woman was found to have dilatation of the intrahepatic bile duct in the right anterior segment during a general health. Laboratory data were within normal ranges and no solid mass was detected in her abdominal computer tomography (CT) or nuclear magnetic resonance imaging (MRI). However, endoscopic retrograde cholangiopancreatography (ERCP) demonstrated an obstruction of the right bile duct. Intraoperative cholangiography showed stenosis of the intrahepatic bile duct in the anterior inferior segment (B5) and narrowness of the intrahepatic bile duct in the anterior superior segment (B8), so that we strongly suspected intrahepatic cholangiocarcinoma (ICC). Histologically, surgically resected liver specimens, without tumor mass by macroscopic observation, showed intraductal papillary proliferation with fibrovascular cores and intraductal spreading of carcinoma in situ throughout a considerable area, especially in bile ductules around the peripheral small portal area. Furthermore, the immunohistochemical profile of the tumor (MUC5AC+/CK7+) was compatible with an intraductal papillary neoplasm of the bile duct (IPN-B). Consequently, this case was diagnosed as IPN-B with spreading CIS, stage I (pT1, pN0, P0, H1, M0). We report a case of IPN-B with interesting histopathological findings and emphasize that cholangiography is especially helpful for the diagnosis of bile duct dilatation due to infiltration of carcinoma cells.

Values of Doppler sonography predicts high risk variceal bleeding in patients with viral cirrhosis.

BACKGROUND/AIMS: Gastrointestinal bleeding such as rupture of esophagogastric varices remains one of the leading causes of death in patients with liver cirrhosis. As a critical issue, assessment of the bleeding risk of esophageal varices is extremely important. In the present study, by determining the relationship between several parameters measured by pulsed Doppler sonography and the bleeding risk of esophageal varices assessed by upper endoscopy, we investigated what is the most valuable parameter as a supplement to the bleeding risk. METHODOLOGY: A total of 158 patients with hepatitis virus-infected liver cirrhosis (56 positive for HBs antigen and 102 positive for HCV antibody) were studied. As controls, 171 normal subjects were used. The flow volumes of the portal trunk and the splenic vein, the Congestion Index, and the S/P ratio were measured by pulsed Doppler sonography. Based on upper endoscopic findings, we classified the patients into two groups based on bleeding risk of esophageal varices: high-risk and low-risk. Logistic regression analysis was employed to identify the most valuable parameter as a supplement to the bleeding risk. RESULTS: The flow volume of the splenic vein, the Congestion Index, and the S/P ratio in cirrhotic patients with esophageal varices were significantly higher than those in normal subjects (P = 0.000). The mean flow volumes of the portal trunk and splenic vein and the mean of the S/P ratio in the high-risk group for bleeding of esophageal varices were significantly higher than those in the low-risk group (P = 0.000-0.005). Based on logistic regression analysis, the flow volume of the splenic vein was found to be the most valuable parameter for bleeding risk (P < 0.001). CONCLUSIONS: The flow volume of splenic vein with pulsed Doppler sonography was the most valuable parameter for the bleeding risk of esophageal varices.

Acute liver dysfunction complicated with uncontrollable glycemia due to insulin antibody: successful treatment with glucocorticoid and lispro insulin.

Here, we report a case of acute liver dysfunction complicated with uncontrollable glycemia due to insulin antibody. The patient was admitted to our hospital due to diabetic ketoacidosis. He was administered insulin immediately, however, his fasting plasma glucose level remained unstable despite the insulin treatment. Blood biochemistry revealed severe liver dysfunction, although no markers including hepatitis virus or autoantibodies associated with autoimmune liver diseases were detected. The 125I-insulin binding rate was high (54%). The characteristics of insulin antibody in this patient were similar to the antibodies of IAS patients, therefore we administered oral glucocorticoid against insulin antibody. The reduction in the 125I-insulin binding rate and the binding capacity of the high affinity site of insulin antibodies were balanced after oral glucocorticoid therapy. In addition, preprandial subcutaneous regular insulin was switched to lispro insulin. Postprandial plasma glucose levels were relatively improved by lispro insulin. The etiology of acute liver dysfunction was unknown, however, we believe that the combination of oral glucocorticoid and lispro insulin was suitable and useful for preventing recurrent liver dysfunction in this patient.

Low frequency of anti-SLA/LP autoantibody in Japanese adult patients with autoimmune liver diseases: analysis with recombinant antigen assay.

Anti-soluble liver antigen/liver pancreas (SLA/LP) autoantibody has been proposed to be one of the autoantibodies characterizing autoimmune hepatitis (AIH). Recently, one of the autoantigens to anti-SLA/LP was identified as a UGA suppressor tRNA-associated protein. Although the function of this protein remains unknown, the recombinant protein has been prokaryotically expressed. Using this protein as an antigen, a recombinant immunoassay for anti-SLA/LP autoantibody has been established and the frequency and significance of this autoantibody have been discussed in European countries. So, in the present study, we investigated anti-SLA/LP autoantibodies in Japanese patients with autoimmune liver diseases using the recombinant antigen ELISA and Western blot assay. Seventy-five patients with AIH type 1, 5 with AIH type 2, 46 with primary biliary cirrhosis, 10 with primary sclerosing cholangitis, 47 with chronic hepatitis C, 48 with systemic lupus erythematosus, 3 with cryptogenic hepatitis, and 40 normal controls were the subjects of the present study. Anti-SLA/LP autoantibodies were detected in only 5 of 75 (6.7%) patients with AIH type 1, but in none of the other 159 patients or 40 normal controls. The clinicopathologic features of anti-SLA/LP-positive AIH type 1, including carriers of HLA DR locus variations, were not significantly different from anti-SLA/LP-negative patients except for the mortality rate. Anti-SLA/LP autoantibody was detected at a low frequency in Japanese patients with AIH type 1 and did not significantly influence clinical features. However, since it has high disease-specificity to AIH type 1, further analysis of SLA/LP may contribute to help clarify the pathogenesis of AIH type 1.

Intestinal cryptosporidiosis as an initial manifestation in a previously healthy Japanese patient with AIDS.

BACKGROUND: Cryptosporidium parvum infection has been recognized as one of the pathogens causing severe and persistent diarrhea in immunodeficient patients, such as those with AIDS, worldwide. However, in Japan, the frequency of this infection has been rare, except for environmental contamination through the water supply. In this communication, we describe a Japanese patient with AIDS presenting with intestinal Cryptosporidiosis as an initial manifestation. METHODS: The oocysts of Cryptosporidium parvum in his stool were detected by the Ziehl-Neelsen method and electron microscopy. The antigen-specificity was proved by immunostaining, using a fluorescein isothiocyanate (FITC)-labeled monoclonal antibody and enzyme-linked immunosorbent assay (ELISA), using Cryptosporidium-specific antibody. RESULTS: A 28-year-old Japanese homosexual man was admitted to our hospital because of severe watery diarrhea of 1-week duration. Numerous oocysts of Cryptosporidium parvum were observed in his stool. Cryptosporidium parvum antigen was detected in stool samples. Serological examinations revealed that anti-HIV-1 antibody was positive, and HIV RNA was positive at a high level. He was diagnosed as having AIDS associated with intestinal Cryptosporidiosis. The circulating CD4+ T-cell count was 152/microl. His diarrhea was not alleviated by administration of loperamide and an ordinary antibiotic agent, but ultimately resolved by the administration of the macrolide antibiotic agent, clarithromycin. CONCLUSIONS: We emphasize that the presence of Cryptosporidium parvum infection should be kept in mind in searching for pathogens causative of severe diarrhea in AIDS patients.

Association of single nucleotide polymorphisms of the interleukin-10 promoter gene and susceptibility to primary biliary cirrhosis: immunogenetic differences in Italian and Japanese patients.

Several lines of data suggest that genetic factors play an important role in the onset and/or progression of primary biliary cirrhosis (PBC). Since PBC is an autoimmune disease, it is reasoned to assume that genes encoding cytokines may confer susceptibility to disease. Amongst these factors, interleukin-10 (IL-10) has received significant attention. The promoter region of IL-10 gene has three single nucleotide polymorphisms (SNPs) at positions -1082, -819 and -592. To elucidate the association of the three SNPs of IL-10 promoter region with susceptibility of PBC in two different genetic populations, 159 unrelated patients with PBC (94 Italian and 65 Japanese) and 143 local controls (72 Italian and 71 Japanese) were enrolled. SNPs were determined using allele-specific PCR/RFLP. In Italian PBC patients, the frequency of homozygosity for G/G at position -1082 was significantly higher than that of local controls (p < 0.041, OR = 2.44, 95% C.I.; 1.02-5.86). The frequencies of haplotype GCC in PBC patients, possibly linked to higher IL-10 production, were also significant higher than local controls (p < 0.033). However, in Japanese population, there were no significant differences in the three SNPs and haplotypes between PBC patients and controls. Excessive production of IL-10 may play an important role in some populations in modulating the onset of PBC. Further, immunogenetic studies of PBC should take into account ethnic and geographic variations; this makes such studies in heterogeneous population, like the USA, more difficult.