Yasushi Uchida

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.

Co-infection by serologically-silent hepatitis B virus may contribute to poor interferon response in patients with chronic hepatitis C by down-regulation of type-I interferon receptor gene expression in the liver

Intrahepatic mRNA levels of type‐I interferon (IFN) receptor genes have been shown to correlate with the clinical efficacy of IFN therapy in patients with chronic hepatitis C. Recently, co‐infection by serologically‐silent hepatitis B virus (HBV) has been assumed to be associated with the poor IFN response in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between the co‐infection of serologically‐silent HBV and type‐I IFN receptor gene expression in the liver of patients with chronic hepatitis C. The intrahepatic mRNA levels of IFNAR2, one of the two subunits of the type‐I IFN receptor, were quantified and compared with both the prevalence of HBV DNA and the hepatitis C virus (HCV) genotype in 45 patients with chronic hepatitis C, who were negative for hepatitis B surface antigen. Co‐infection, as evaluated by a nested polymerase chain reaction, was present in 22 patients (48.9%), with dominance of the HCV genotype 1b (65.2%) over genotype 2a (31.8%). Co‐infection was associated with lower IFNAR2 mRNA levels, higher levels of serum HCV RNA, and a poor IFN response, regardless of the HCV genotype. The findings suggest the possibility that co‐infection by serologically‐silent HBV is one of the factors that can lead to an unfavorable IFN response in chronic hepatitis C by down‐regulation of IFN receptor gene expression in the liver. J. Med. Virol. 63:220–227, 2001.

Helicobacter pylori infection influences nocturnal gastric acid breakthrough.

Nocturnal gastric acid breakthrough is defined as night‐time periods when gastrin pH falls below 4.0 for greater than 1h during administration of a proton pump inhibitor. This phenomenon is a serious problem for patients who require strict control of their gastric acid secretions.

Expression rate of cytokine mRNA in the liver of chronic hepatitis C: comparison with chronic hepatitis B.

This study was carried out to test the hypothesis that, in chronic hepatitis (CH), inflammatory processes, including viral replication, host immune response, and hepatocyte destruction, are regulated by a cytokine network in the liver. Expression of the mRNA of the cytokines IL1-beta, IL2, IL4, IL5, IL6, TNF-alpha, and IFN-gamma, the lymphocyte markers CD4 and CD8, and the HLA class I molecule, beta 2-microglobulin (B2MG) in the liver tissue of 20 CH(C) cases and 9 CH(B) patients was investigated by the reverse transcription polymerase chain reaction (RT-PCR) method. TNF-alpha, CD4, and B2MG mRNA were detected in 100% of cases of in both CH(B) and CH(C). The expression rates of IL1-beta, IL2, IL4, IFN-gamma, and CD8 mRNA were 80%, 40%, 25%, 40%, and 80% in CH(C) and 88.9%, 44.5%, 30%, 55.6%, and 100% in CH(B). IL6 mRNA was detected only in CH(B), in 22.2% of cases, IL5 mRNA was not detected in either CH(B) or CH(C). IL2, IL4, and IFN-gamma mRNA were expressed significantly more frequently in patients who had high serum ALT and a high histological activity index (HAI) score. There was no difference in cytokine expression between CH(B) and CH(C), except in IL6, suggesting the existence of a common immunopathogenesis for CH(B) and CH(C). In chronic viral hepatitis, IL1-beta and TNF-alpha appear to play a major role in immune responses and IL2, IL4, and IFN-gamma seem to be associated with increased cytotoxic T cell response. Our results give partial support to the hypothesis that the cytokine network is important in the inflammatory process in chronic viral hepatitis in vivo.

Changes in serum lipid concentrations in patients with chronic hepatitis C virus positive hepatitis responsive or non-responsive to interferon therapy.

Background: Changes in serum lipid concentrations during the administration of interferon to patients with chronic hepatitis C virus (HCV) infection have not been fully investigated. The present study was designed to compare changes in serum lipid concentrations before, during and after interferon therapy in responders and non‐responders to treatment.

Lymphoepithelial cyst of the pancreas.

A case of lymphoepithelial cyst (LEC) of the pancreas is presented. A 48-year-old man complaining of general fatigue was found to have a heterogeneous water-dense mass protruding from the surface of the pancreas on plain computed tomography (CT). Dynamic CT disclosed septa within the mass. Magnetic resonance imaging (MRI) showed a hypoiintense mass on T1-weighted imaging, and a hyperintense mass on T2-weighted imaging. MRI with gadolinium enhancement revealed septa within the mass. Endoscopic ultrasonography showed septa and fine echogenic structures within the cystic echoic lesion. Endoscopic retrograde pancreatecraphy showed a normal duct system. Distal pancreatectomy with splenectomy was performed, with a suspected diagnosis of cystic neoplasms of the pancreas. Histopathologic examination disclosed LEC of the pancreas. Our case suggests that LEC should be considered in the differential diagnosis of cystic neoplasms of the pancreas.

Plasma endothelin-1 concentrations are elevated in acute hepatitis and liver cirrhosis but not in chronic hepatitis

SummaryWe measured plasma endothelin-1 (ET-1) concentrations in 20 healthy controls and 63 patients with liver diseases including 9 cases of acute hepatitis (AH), 14 cases of chronic hepatitis (CH), 24 cases of liver cirrhosis (LC), 11 cases of hepatocellular carcinoma with LC (HCC), 3 of primary biliary cirrhosis and 2 of idiopathic portal hypertension. ET-1 levels in AH (5.07±2.54 pg/ml, mean±SD), LC (3.71 ±1.17) and HCC (3.08±0.93) were significantly higher than those in healthy controls (2.18±0.37). ET-1 levels in AH, LC and HCC were also significantly higher than those in CH (2.05±0.61). ET-1 levels showed negative correlations with serum albumin levels and Ch-Ease activities, and positive correlations with serum bilirubin levels, AST and ALT activities. However, there was no correlation between plasma ET-1 concentrations and concentrations of serum thrombomodulin which is known to be a marker of injured vascular endothelial cells. In cirrhotic patients, ET-1 levels were significantly influenced by the presence of ascites. The results of the present study suggest that plasma ET-1 concentrations may be a useful clinical indicator for use in the follow-up of patients with chronic liver diseases, e.g., progression from CH to LC, and change in grade of portal hypertension and decompensation in LC.

Is a computerized bowel sound auscultation system useful for the detection of increased bowel motility

pylori positive status indicated a weak correlation (r 0.267, p 0.05) between the bacterial burden of gastric mucosa and the GUA ratio. However, we failed to find any significant correlation between the GUA ratio and colonization density of H. pylori in children with peptic ulcers (r 0.454, p 0.05) and in the H. pylori positive children without ulcers (r 0.174, p 0.05). Significant correlation was observed between GUA ratio and gastric inflammation score (r 0.406, p 0.01) in the total H. pylori positive group. However, the GUA ratio did not correlate with gastritis severity in the patients with peptic ulceration (r 0.358, p 0.05) and in the H. pylori negative patients (r 0.02, p 0.05). Nevertheless, there was a significant positive correlation between GUA ratio and the gastritis score in the ulcer-free group of children with H. pylori positive status (r 0.416, p 0.05). It is well known that H. pylori produce large amounts of the enzyme urease. Unusually high urease activity of H. pylori may allow consideration of urease as a specific marker of the infection (1, 2). The standard biopsy-dependent urease tests are very specific but moderately sensitive because of patchy dissemination of H. pylori on the gastric mucosa (4). Noninvasive C urea breath tests have great sensitivity and safety, but they are very expensive techniques. In the present study we propose a sensitive, cheap, and biopsy-independent minimally invasive method for rapid H. pylori detection. The present procedure is more suitable for pediatric practice because it is a safer technique than the standard local biopsy-dependent methods. The presented data on the diagnostic importance of the GUA ratio are comparable with the results obtained by the noninvasive C urea breath test (5). Therefore, the GUA measurement method is an excellent surrogate marker that reflects the total urease activity in the stomach but does not predict density of the bacterial load on the gastric mucosa. Finally, the current findings are mainly in agreement with our previous data on the lack of a relationship between the H. pylori urease activity and duodenal ulceration in childhood (2, 6).

Congenital anomalies in a child born from a mother with interferon-treated chronic hepatitis B

refused to participate was male) and 12/13 (92%) were anorexic. The patients had a median age of 26 yr. Eight patients (62%) had sought out a gastroenterologist or primary care physician with a GI complaint. Of these eight patients, six (46%) had sought treatment for their GI complaintsbefore ever seeking treatment for their eating disorder.Five patients (38%) had had an endoscopy, an upper GI barium contrast radiograph, or a lower GI barium contrast radiograph. Six patients (46%) had been prescribed some form of medication for a GI problem. Seven of the patients (54%) experienced frequent heartburn or reflux. They experienced these symptoms an average of 2.7 times/day. Six of the patients had a history of laxative abuse. All of these patients had previously sought help for a GI problem. Gastroenterologists would serve their patients well by learning the early signs and symptoms of anorexia and bulimia. Because they are in a unique position to make an early diagnosis, they can refer these patients in a timely fashion to mental health professionals who specialize in the treatment of eating disorders. The earlier these problems are treated, the better the prognosis. Our study also suggests that gastroenterologists would benefit their patients by learning the signs and symptoms of surreptitious laxative abuse. A series of open-ended questions for the initial interview of patients suspected of anorexia or bulimia has been advocated and could be useful not only for this patient population, but for all young, female patients if used routinely (6). Clearly, further studies are warranted to confirm and expand these findings. We propose an ongoing follow-up study to survey 100 consecutive inpatients on the eating disorders unit. The study should include a control group to determine the incidence of similar physician visits by an ageand sex-matched population. Our hypothesis is that a matched control group would have a significantly lower incidence of visits to a gastroenterologist than would a population of eating-disordered patients.

Laparoscopic observations of hepatic capsular abnormalities: non-postoperative adhesions and hepatic capsular thickening.

BACKGROUND Hepatic capsular abnormalities (adhesions or thickening) are often striking at laparoscopy. However, their diagnosis is difficult because capsular abnormalities can also be caused by several pathologic conditions. The aim of this study was to systematically investigate the associated factors and prevalence of laparoscopically observed non-postoperative adhesions and hepatic capsular thickening. METHODS We reviewed all data and studied laparoscopically observed hepatic capsular abnormalities (non-postoperative adhesions and thickening) in 2500 consecutive patients who underwent laparoscopy from 1981 to 1997. RESULTS Non-postoperative adhesions were observed in 14.6% of cases and their frequency increased with age. Although several types of adhesions, from band-like to membrane-like, were seen, there were no correlations between type and underlying pathologic conditions, except tuberculous peritonitis with membrane-like adhesions and Fitz-Hugh-Curtis syndrome with violin string-like adhesions. Hepatic capsular thickening was observed in 9.7% of cases. The main associated factor was viral hepatitis followed by other liver diseases. CONCLUSIONS Hepatic capsular abnormalities are observed relatively frequently (21.5%) during laparoscopy. Initial laparoscopic diagnosis of non-postoperative adhesions may help in selecting patients with tuberculous peritonitis and Fitz-Hugh-Curtis syndrome for appropriate treatment.