Validation of fatty liver index as a predictor of hepatic steatosis in Asian populations: Impact of alcohol consumption and sex.

AIM: This study was undertaken to investigate the utility of the fatty liver index (FLI) as a noninvasive tool for predicting hepatic steatosis based on alcohol consumption and sex in a large Asian population. METHODS: We carried out a single-center observational cohort study at the HITO Medical Center in Japan and enrolled 1976 Asian subjects. The subjects were categorized into nondrinkers and light drinkers (0-19 g/day) and moderate drinkers (20-59 g/day) based on their self-reported alcohol intake. We used physical examinations, laboratory tests, and a questionnaire to collect information on various factors related to the FLI, including body mass index, waist circumference, and levels of γ-glutamyl transferase and triglycerides. RESULTS: The diagnostic accuracy of the FLI was assessed by calculating the area under the receiver operating characteristic curve (AUROC), and optimal cut-off values were determined using Youden's index. The FLI had an acceptable performance index of >0.7 both overall and in all subgroups, with an overall AUROC of 0.844. The AUROCs were higher in women and moderate drinkers of both sexes. We also compared the cut-off values obtained in the present study with the previously reported values of 30 and 60. Optimal cut-off values for the FLI were calculated for the total population and subgroups and were found to differ from the previously established values in other countries. CONCLUSIONS: Our study suggests that the FLI is a useful noninvasive marker for predicting hepatic steatosis in a large Asian population, irrespective of alcohol consumption and sex.

Cholecystocolic fistula closed using endoscopic therapy alone: A case report.

BACKGROUND: Cholecystocolic fistula (CCF) is a known but rare complication of cholelithiasis. Treatment for CCF is generally surgical. As the number of elderly patients has increased in recent years, many cases require non-surgical treatment; therefore, endoscopic treatment has gained importance. PATIENT CONCERNS AND DIAGNOSIS: An 87-year-old woman presented with impaired consciousness and symptoms of anorexia. Computed tomography showed cholecystitis and a fistula between the gallbladder and transverse colon. Colonoscopy revealed a CCF. The condition was diagnosed as CCF caused by acute cholecystitis. INTERVENTIONS AND OUTCOMES: The patient declined surgery due to her age. Endoscopic fistula closure was performed using a through-the-scope clip after endoscopic naso-gallbladder drainage. Successful closure of the fistula resulted in improvement of cholecystitis and anorexia. The patient was discharged after one month. It has been more than 18 months since the procedure, there has been no recurrence. CONCLUSION: This report on successful endoscopic closure of a CCF indicates that it may be useful for patients who decline surgery.

Adenoendocrine carcinoma of the accessory papilla of the duodenum: report of a case.

This report describes a very rare case of an adenoendocrine carcinoma of the accessory papilla of the duodenum. A 70-year-old woman was admitted to the hospital complaining of epigastralgia. Gastrointestinal endoscopy showed a protruding tumor with ulceration at the accessory papilla of the duodenum. A biopsy revealed a small-cell carcinoma. Computed tomography showed a highly enhanced tumor in the early phase. No metastatic lesions were shown. Magnetic resonance cholangiopancreatography showed dilatation of the pancreatic duct, but a normal common bile duct. A pyloruspreserving pancreaticoduodenectomy was performed with lymph node dissection. Microscopically, the tumor was a small-cell neuroendocrine carcinoma with adenomatous differentiation. An immunohistochemical analysis showed positive staining for synaptophysin, chromogranin A, CD56, and carbohydrate antigen 19-9. The final diagnosis was an adenoendocrine carcinoma with lymph node metastasis. The postoperative course was uneventful and the patient is now doing well as an outpatient after 14 months of follow-up.

Molecular analysis of antigenicity and immunogenicity of a vaccine-induced escape mutant of hepatitis B virus.

BACKGROUND: To analyze the mechanisms of mutant escape, we established a murine model of hepatitis B virus (HBV) infection and studied the interaction of the envelope protein of the virion with various kinds of anti-hepatitis B antibody. METHODS: Mutation from glycine to arginine at aa145 was introduced into replication-competent DNA of HBV. The resulting mutant HBV DNA was transfected into cultured hepatoma cells and livers of mice using liposome-mediated gene transfer. Then, interactions between the antigenic envelope protein (in culture or in circulation) and anti-hepatitis B antibody were examined. RESULTS: Mutant envelope protein escaped human hepatitis B immunoglobulin, rabbit polyclonal anti-hepatitis B surface antigen (HBsAg) antibody, and monoclonal anti-a antibody in vitro and in vivo. There was a difference in the degree of inhibition between hepatitis B immunoglobulin and the other two antibody types in vitro. Transfection with an HBV construct containing a mutation in the a-loop resulted in levels of HBsAg in circulation and seroconversion to anti-HBs antibody that were similar to those produced by a wild-type construct. CONCLUSIONS: The degree of escape by the mutant envelope protein differed according to antibody type. Of the three types of antibody used in this study, HBV immunoglobulin was least affected by mutation in the a-loop. There appears to be no correlation between antigenicity and immunogenicity of the escape mutant, and the a-loop mutant may cause hepatitis with the usual serum viral markers.

Prevalence of herpesviridae and hepatitis virus sequences in the livers of patients with fulminant hepatitis of unknown etiology in Japan.

BACKGROUND: Fulminant non-A, non-B, non-C hepatitis has a high mortality rate, making the identification of its causative agent imperative. Cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, and herpes simplex virus are all members of the herpesviridae family that are associated with fatal hepatic failure. We investigated the involvement of herpesviridae and hepatitis virus in the pathogenesis of fulminant hepatitis. METHODS: The study participants consisted of 11 patients with fulminant hepatitis and 11 with acute hepatitis negative for known hepatitis viral markers and any other liver diseases. Viral DNA was extracted from liver tissues and amplified. In situ hybridization was then performed for 1 patient to detect viral DNA and RNA, and viral protein was localized by monoclonal antibodies. RESULTS: Human herpesvirus-6 was detected in liver tissues from seven patients, (five children and two adults) with fulminant hepatitis and two patients with acute hepatitis. Two patients with fulminant hepatitis also had cytomegalovirus in the liver. Although Epstein-Barr virus and herpes simplex virus were detected in the patients with fulminant hepatitis, they were not specific to these patients. In situ hybridization in one of the patients localized DNA and RNA of human herpesvirus-6 in hepatocyte nuclei, and an envelope antigen of this virus was detected in hepatocyte cytoplasm. CONCLUSIONS: Human herpesvirus-6 was frequently detected in Japanese pediatric patients with fulminant non-A, non-B, non-C hepatitis. Although the significance of human herpesvirus-6 in liver pathogenesis remains unclear, this virus may replicate in hepatocytes in some patients with acute onset hepatitis.

Genotypic analysis of hepatitis B virus from patients with fulminant hepatitis: comparison with acute self-limited hepatitis.

AIM/BACKGROUND: There is an increasing evidence that certain hepatitis B virus (HBV) strains may contribute to the pathogenesis of fulminant hepatitis B (FHB). Recently, we reported that genotypes of HBV influence the clinical course of acute self-limited hepatitis B (AHB). In this study, we compared clinical features of FHB between different HBV genotypes and compared the prevalence of each genotype between FHB and AHB patients. METHODS: The subjects consisted of seven patients with FHB and 25 patients with AHB. The core promoter and precore region were directly sequenced following polymerase chain reaction, and genotype was determined by restriction fragment length polymorphism analysis of the S gene. RESULTS: Of the seven FHB patients, one had genotype A, one had genotype B, four had genotype C, and one had genotype D. Six of the seven FHB patients were infected by heterosexual contact; one FHB patient who was not infected by heterosexual contact had genotype C. All four FHB patients with genotype C had a short duration clinical course. In one patient with genotype A, the time from onset of hepatitis to hepatic coma was 30 days. These results are similar to those of the patients with AHB, in which clinical course was longer in patients with genotype A than in patients with genotype C. CONCLUSION: Viral genotype can be used to predict the clinical course of both FHB and AHB.

Repeated jaundice due to YMDD mutant in a patient with prolonged lamivudine therapy for chronic hepatitis B under prednisolone treatment for Still's disease.

A 50-year-old woman patient began receiving lamivudine because of acute exacerbation of chronic hepatitis B. She also suffered from adult-onset Still's disease and had received prednisolone for 5 years. Lamivudine was effective for treatment of the first flare. Fifteen months after lamivudine treatment was started, a breakthrough due to lamivudine-resistant strain M5521 occurred. Between 10 and 12 months after the breakthrough, flare with jaundice occurred 3 times. We decided interferon would not be suitable, because it could induce activation of Still's disease. Prolonged lamivudine therapy is only recommended in cases of hepatitis B in which there is no alternative treatment.

Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) replication and transcription factor activates the K9 (vIRF) gene through two distinct cis elements by a non-DNA-binding mechanism.

The replication and transcription activator (RTA) of Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, a homologue of Epstein-Barr virus BRLF1 or Rta, is a strong transactivator and inducer of lytic replication. RTA acting alone can induce lytic replication of KSHV in infected cell lines that originated from primary effusion lymphomas, leading to virus production. During the lytic replication process, RTA activates many kinds of genes, including polyadenylated nuclear RNA, K8, K9 (vIRF), ORF57, and so on. We focused here on the mechanism of how RTA upregulates the K9 (vIRF) promoter and identified two independent cis-acting elements in the K9 (vIRF) promoter that responded to RTA. These elements were finally confined to the sequence 5'-TCTGGGACAGTC-3' in responsive element (RE) I-2B and the sequence 5'-GTACTTAAAATA-3' in RE IIC-2, both of which did not share sequence homology. Multiple factors bound specifically with these elements, and their binding was correlated with the RTA-responsive activity. Electrophoretic mobility shift assay with nuclear extract from infected cells and the N-terminal part of RTA expressed in Escherichia coli, however, did not show that RTA interacted directly with these elements, in contrast to the RTA responsive elements in the PAN/K12 promoter region, the ORF57/K8 promoter region. Thus, it was likely that RTA could transactivate several kinds of unique cis elements without directly binding to the responsive elements, probably through cooperation with other DNA-binding factors.