Yoshinori Kushiyama

SEROLOGICALLY SILENT HEPATITIS B VIRUS COINFECTION IN PATIENTS WITH HEPATITIS C VIRUS-ASSOCIATED CHRONIC LIVER DISEASE: CLINICAL AND VIROLOGICAL SIGNIFICANCE

Frequent coinfection of surface antigen‐negative hepatitis B virus (silent HBV) in hepatitis C virus (HCV)‐associated chronic liver disease (CLD) has been reported. The clinical and virological significance of silent HBV infection was investigated in 65 patients with HCV‐associated CLD who subsequently received interferon (IFN) therapy. HBV DNA was detected in 34 (52.3%) patients by a nested polymerase chain reaction (PCR). Virologically, all of the 34 patients were found to have HBV with an eight‐nucleotide deletion in the core promoter. Coinfection of silent HBV was more frequent with HCV genotype 1b than in 2a (64.3% vs 28.6%, P < .01). With HCV genotype 1b, the serum RNA level was significantly higher (≥106 copies per milliliter vs ≤105 copies per milliliter) in patients with silent HBV than those without coinfection (P < .01). Clinically, silent HBV was associated with a higher level of serum alanine aminotransferase (158.5 ± 104.8 vs 121.8 ± 78.6 IU/l; mean ± SD) and a greater histological activity of hepatitis as evaluated by histological activity index score (9.4 ± 3.8 vs 8.6 ± 4.5; mean ± SD), although it was not statistically significant. Silent HBV was also associated with poor efficacy of IFN therapy (P < .01). The results suggest that silent HBV has some promoting effect for HCV replication, at least for HCV genotype 1b, and may affect the histological activity of hepatitis and IFN response in HCV‐associated CLD. J. Med. Virol. 58:201–207, 1999.

Hepatitis B Virus with X Gene Mutation Is Associated with the Majority of Serologically "Silent" Non-B, Non-C Chronic Hepatitis

Hepatitis B virus (HBV) with X gene mutations has been a putative pathogen of chronic hepatitis without serological markers of known hepatitis viruses. The aim of this study was to reconfirm whether the HBV with the X gene mutation is associated with these serologically “silent” non‐B, non‐C (NBNC) chronic hepatitis, alcoholic liver disease (ALD) and autoimmune hepatitis (AIH). HBV DNA was amplified from serum and sequenced in 30 patients with NBNC chronic hepatitis in comparison with 20 patients with ALD and 5 patients with AIH. HBV DNA was identified in 21 patients (70%) in NBNC chronic hepatitis by nested polymerase chain reaction while only one patient (5%) in ALD and none in AIH showed HBV DNA. Eighteen (85.7%) of the 21 identified HBV DNAs had an identical 8‐nucleotide deletion mutation at the distal part of the X region. This mutation affected the core promoter and the enhancer II sequence of HBV DNA and created a translational stop codon which truncated the X protein by 20 amino acids from the C‐terminal end. All the HBV DNAs had a precore mutation at the 83rd nucleotide resulting in disruption of HBe antigen synthesis. These results indicate that HBV mutants are closely associated with the majority of serologically “silent” NBNC chronic hepatitis cases and the population of such mutant HBV DNAs is not uniform.

Crystal Violet Chromoendoscopy with Mucosal Pit Pattern Diagnosis is Useful for Surveillance of Short-Segment Barrett's Esophagus

BACKGROUND:Because of a rapid increase in the incidence of Barretts cancer, the appropriate surveillance method for Barretts esophagus is of interest. Methylene blue chromoendoscopy has been reported to be an effective and inexpensive method to improve biopsy surveillance of Barretts epithelium. However, the usefulness of this method in short-segment Barretts esophagus cases is still controversial.AIMS:This study was undertaken to evaluate the abilities of crystal violet and methylene blue chromoendoscopy to detect potentially dysplastic Barretts epithelium in cases with short-segment columnar-appearing epithelium of the esophago-gastric junction.PATIENTS AND METHODS:Four hundred patients with endoscopically suspected short-segment Barretts esophagus were enrolled and randomly assigned to receive chromoendoscopy with 0.05% crystal violet, 0.1% crystal violet, 0.5% methylene blue, or 1.0% methylene blue. During crystal violet and methylene blue chromoendoscopy, biopsy specimens were obtained from stained and unstained columnar-appearing epithelium of the esophago-gastric junction, and the detection rates of Barretts epithelium were evaluated. The value of pit pattern diagnosis was also evaluated as a possible way to detect dysplastic Barretts epithelium.RESULTS:Chromoendoscopy with 0.05% crystal violet detected histologically confirmed Barretts epithelium with the highest sensitivity (89.2%) and specificity (85.7%). Crystal violet clearly stained both dysplastic and nondysplastic Barretts epithelia and made the surface pit pattern easy to observe without using magnifying endoscopy.CONCLUSIONS:The combination of crystal violet chromoendoscopy and pit pattern diagnosis is considered to be useful for the surveillance of short-segment Barretts esophagus.

Effectiveness of interferon-alpha therapy in chronic hepatitis C is associated with the amount of interferon-alpha receptor mRNA in the liver

BACKGROUND/AIMS This study aimed to investigate the relationship between interferon-alpha receptor mRNA in the liver and the response to interferon therapy in chronic hepatitis C. METHODS Interferon-alpha receptor mRNA was quantified by reverse transcription polymerase chain reaction using liver biopsies from 40 patients, comprising 20 responders and 20 non-responders to subsequent interferon therapy. RESULTS The amount of interferon-alpha receptor mRNA was significantly larger in interferon-responders (0.72+/-0.12) than non-responders (0.26+/-0.08) (p<0.01). Regardless of the response to interferon, histological activity index scores and the amount of HCV-RNA showed significant inverse correlation to the amount of interferon-alpha receptor mRNA, whereas the HCV-RNA genotype was not associated with the amount of interferon-alpha receptor mRNA. Logistic analysis and multiple regression analysis showed that the amount of interferon-alpha receptor mRNA was significantly associated with the efficacy of interferon (p=0.0275), but not with fibrosis of the liver (p= 0.2726). CONCLUSIONS Our results suggest that the amount of interferon-alpha receptor mRNA is an important factor determining the response to interferon, and may be a new predictor of interferon response in chronic hepatitis C.

Prevalence of and risk factors for Barrett's esophagus with intestinal predominant mucin phenotype

Objective. Barretts esophagus with the intestinal predominant mucin phenotype is considered to have a higher malignant potential than that with the gastric predominant mucin phenotype. The purpose of this prospective study was to investigate the prevalence of and risk factors for Barretts esophagus with the intestinal predominant mucin phenotype in patients undergoing endoscopy. Material and methods. A total of 1699 consecutive patients undergoing esophagogastroduodenoscopy were enrolled in the study. A targeted biopsy was performed when endoscopically observed columnar-appearing esophagus was stained with crystal violet. The sample, histologically evidenced as Barretts esophagus, was immunohistochemically evaluated and categorized as of either gastric or intestinal predominant mucin phenotype. All the patients were requested to complete the structured questionnaire indicating their symptoms and food consumption patterns. Prevalence of and risk factors for Barretts esophagus with and without the intestinal predominant mucin phenotype were investigated. Results. Out of 1668 patients, 629 (37.7%) were found to have endoscopic Barretts esophagus. In 333 out of 1668 patients (19.9%), histological studies were diagnostic of Barretts esophagus. One hundred and six of these 333 patients (31.8%) had the intestinal predominant mucin phenotype. Age, male gender and the presence of hiatal hernia were confirmed by multivariate analysis as the independent predictors for the presence of Barretts esophagus with the intestinal predominant mucin phenotype. Conclusions. Barretts esophagus with the intestinal predominant mucin phenotype was immunohistochemically found in 6.4% of all study patients. Older age, male gender and the presence of hiatal hernia were the risk factors for the presence of Barretts esophagus with the intestinal predominant mucin phenotype.

Difference in localization of esophageal mucosal breaks among grades of esophagitis

Background:  Gastroesophageal reflux occurs mainly during the daytime in patients with Los Angeles grade A esophagitis, but predominantly during the night in patients with grade C and D esophagitis. The purpose of the present paper was to investigate whether this difference in the pattern of gastroesophageal reflux influences the circumferential localization of erosions in the esophageal wall.

Influence of acid suppressants on gastric emptying: Cross‐over analysis in healthy volunteers

Background:  Gastric emptying plays an important role in gastroesophageal reflux disease. Acid suppressants such as H2 receptor antagonists and/or proton pump inhibitors are often used in patients with gastroesophageal reflux disease. However, it remains controversial whether H2 receptor antagonists and proton pump inhibitors delay or accelerate gastric emptying. Here, the influence of acid suppressants on gastric emptying was evaluated via a cross‐over study using the [13C]‐labeled acetate breath test.

Reliability of Symptoms and Endoscopic Findings for Diagnosis of Esophageal Eosinophilia in a Japanese Population

Background/Aims: The clinical characteristics of esophageal eosinophilia (EE), which is essential for diagnosis of eosinophilic esophagitis (EoE), have not been fully clarified in a Japanese population. The aim of this study was to analyze the reliability of symptoms and endoscopic findings for diagnosing EE in Japanese individuals. Methods: We prospectively enrolled subjects who complained of esophageal symptoms suggesting EoE and/or those with endoscopic findings of suspected EoE at the outpatient clinics of 12 hospitals. Diagnostic utility was compared between the EE and non-EE groups using logistic regression analysis. Results: A total of 349 patients, including 319 with symptoms and 30 with no symptoms but endoscopic findings suggesting EoE were enrolled. Of those with symptoms, 8 (2.5%) had EE, and 3 were finally diagnosed with EoE. Of those without symptoms but endoscopic findings, 4 had EE. Among 8 symptomatic patients, 7 had abnormal endoscopic findings suspicious of EoE. Although dysphagia was a major symptom in EE, none of the presenting symptoms was useful for diagnosis of EE. Among the endoscopic findings, linear furrow was the most reliable (OR = 41.583). Conclusion: EE is uncommon among patients with esophageal symptoms in Japanese individuals. The most useful endoscopic finding for diagnosis of EE was linear furrow, whereas subjective symptoms were not supportive.

Barrett's oesophagus with predominant intestinal metaplasia correlates with superficial cyclo-oxygenase-2 expression, increased proliferation and reduced apoptosis: changes that are partially reversed by non-steroidal anti-inflammatory drugs usage.

Background : Cyclo‐oxygenase‐2 expression has been reported to play an important role in the metaplasia‐dysplasia‐carcinoma sequence in Barretts oesophagus. However, the existence of cyclo‐oxygenase‐2 expressing cells in Barretts epithelium is still uncertain.

Prevalence of irritable bowel syndrome-like symptoms in ulcerative colitis patients with clinical and endoscopic evidence of remission : prospective multicenter study

Abstract Objective. Irritable bowel syndrome (IBS)-like symptoms are often found in ulcerative colitis (UC) patients in remission. However, the prevalence of those symptoms in UC patients with endoscopic evidence of remission shown by mucosal healing remains unknown. Material and methods. IBS diagnosis was evaluated by questionnaire results according to the Rome III criteria. Clinical remission was assessed by clinical activity index (CAI), whereas endoscopic remission was evaluated by endoscopic index (Matts grade). Results. We enrolled 172 patients in clinical remission (CAI ≤ 4), after excluding 36 for incomplete questionnaire results or nonremission findings, as well as 330 control subjects. Of the 172 UC patients, 46 (26.7%) met the Rome III criteria, which was a significantly higher rate as compared with the controls (4.8%). The prevalence rate of IBS-like symptoms in UC patients with endoscopic remission findings (Matts grade ≤2) was 25.6%, which was similar to that of those with clinical remission. When endoscopic remission was defined as Matts grade 1, the prevalence rate of IBS-like symptoms was decreased to 15.4%, although the prevalence rate remained higher than that of the control subjects. Conclusions. The prevalence of IBS-like symptoms in UC patients with clinical and endoscopic remission findings was significantly higher than that of control subjects. Furthermore, the prevalence rate in patients with complete endoscopic remission was decreased. These findings suggest that residual low-grade inflammation may influence the presence of IBS-like symptoms in UC patients in remission.