Letters to the editor

913

We answer question (1) as follows. In the three patients who were diagnosed as having non-A-non-G hepatitis, all known viral markers, including hepatitis A virus (IgM anti-HAV), hepatitis B virus (IgM HB core [c] and HBV DNA, detected by polymerase chain reaction [PCR]), HCV (HCV RNA, detected by reverse transcription [RT]-PCR), hepatitis D virus (IgM anti-HDV), hepatitis E virus (HEV RNA, detected by PCR), hepatitis G virus (HGV RNA, detected by PCR), cytomegalovirus (IgM antiCMV), Epstein Barr virus (IgM anti-EBV), herpes virus (IgM anti-herpes V), and Hantaan virus (Hantaan virus RNA, detected by PCR) were confirmed to be negative. Serum ceruloplasmin, and serum and urine copper were also examined. Because we recognized that IFN was contraindicated for AIH, various autoimmune markers were closely examined and were found to be negative. All patients diagnosed as having non-A–non-G hepatitis underwent liver biopsy under laparoscopic observation. Histological findings were consistent with those of the resolving phase of acute viral hepatitis. Therefore, we presumed viral etiology in the three non-A–non-G patients. Aplastic anemia, which sometimes develops after viral FHF,2 developed in one patient with non-A–non-G hepatitis 4 weeks after discharge. He was readmitted to our hospital, and showed full recovery with cyclosporin A treatment. Regarding question (2), one patient was found to have HCV RNA in serum by PCR, and was diagnosed with acute hepatitis C. The genotype was 1b and the initial viral load was 190 KIU/ml. The route of infection was not ascertained. The acute severe hepatitis resolved rapidly with a decrease of the HCV RNA level. The prevalence of HCV infection in adult patients with FHF at our hospital during the late 1980s was as high as 60% in non-A–non-B FH,3 and the rate dropped to 4% after the introduction of blood-donor screening for anti-HCV by the Japanese Red Cross. Regarding question (3), the four patients were followed up for 60 months (range, 54–71 months) and liver function test results were continuously within the normal range. All patients enjoyed normal lives without any medication. In Japan, at present, in 70% of children who undergo livingrelated liver transplantation (Ltx) the etiology of of the underlying disease is not known, and Kyoto University Hospital, one of the centers for LTx, has reported that they often experience graft dysfunction probably attributable to unidentified viral infection.3 The use of IFN combined with immunosuppressive drugs is warranted for non-A–non-G hepatitis in school-aged patients with FHF in areas where viral infection is endemic.

Kazuaki Inoue, Makoto Yoshiba Department of Gastroenterology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama 227-8501, Japan

References 1. Yoshiba M, Yamada M, Inoue K, Watanabe T, Kanesaka S, Isoyama K. Possible prevention of fulminant hepatic failure in four children with acute severe hepatitis. J Gastroerterol 2004;39:399–400. 2. Tung J, Hadzic N, Layton M, Baker AJ, Dhawan A, Rela M, et al. Bone marrow failure in children with acute liver failure. J Pediatr Gastroenterol Nutr 2000;31:557–61. 3. Yoshiba M, Sekiyama K, Sugata F, Okamoto H, Mayumi M. Persistence of HCV replication in non-A, non-B fulminant viral hepatitis. Gastroenterol Jpn 1991;26:235. 4. Uemoto S, Inomura Y, Sakurai T, Egawa H, Fujita S, Kiuchi T, et al. Living donor liver transplantation for fulminant hepatic failure. Transplantation 2000;70:152–7. Received: February 8, 2005 / Accepted: February 14, 2005 Reprint requests to: K. Inoue DOI 10.1007/s00535-005-1657-1

Prevalence of noncardiac chest pain in Japanese patients with recurrent chest pain To the Editor: The prevalence of gastroesophageal reflux disease (GERD), which is mainly caused by the reflux of acidic gastric contents into the esophagus, has been steadily increasing in Japanese patients, partly because of recent increases in gastric acid secretion as well as decreased rates of Helicobacter pylori infection. Typical symptoms reported by patients with GERD are heartburn and acid regurgitation, though some also complain about various atypical symptoms, such as chest pain, chronic cough, asthma-like dyspnea, globus, and otalgia. Among these extraesophageal atypical symptoms, chest pain has recently received increasing attention. Recurrent anterior chest pain is a worrisome symptom for patients with ischemic coronary heart disease, and those who frequently visit emergency units with such complaints and require medical examinations for coronary diseases consume large amounts of medical resources. In Western

Table 1. Clinical and laboratory data of patients with CCP and those with NCCP

Number of patients Male/Female Age (years) Height (cm) Body weight (kg) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Habitual alcohol drinker (%) Habitual smoker (%) LDL-cholesterol (mg/dl) HDL-cholesterol (mg/dl) HbA1C NS, not significant

CCP

NCCP

P value

633 447/186 68.3 ± 0.4 157.5 ± 0.7 58.6 ± 0.5 133.8 ± 1.0 75.3 ± 0.6 29.9 49.1 151.3 ± 2.0 48.3 ± 0.8 6.1 ± 0.1

319 (34%) 175/144 66.0 ± 0.6 158.1 ± 0.6 60.0 ± 0.6 139.1 ± 1.2 79.8 ± 0.5 33.9 27.9 145.6 ± 2.7 57.7 ± 1.3 5.7 ± 0.1

<0.01 <0.01 NS NS <0.01 <0.01 NS <0.01 NS <0.01 <0.01

914 countries, 61% to 89% of the patients who complained of recurrent chest pain have been reported to not have organic coronary heart disease, but rather, noncardiac chest pain (NCCP), which has been found to be caused by gastroesophageal acid reflux in up to 60% of NCCP patients.1 Therefore, we consider that, in at least 35% of patients with recurrent chest pain, the pain may be easily controlled by the administration of acid-suppressing drugs. In Japan, there are no data available concerning the prevalence of NCCP in patients with recurrent chest-pain symptoms. Therefore, we conducted a retrospective multicenter study to determine the number of patients with NCCP among those with recurrent chest pain who required an investigation by coronary angiography. All patients with recurrent chest pain and investigated by coronary angiography for the first time in 2003 and 2004 at four medical centers in Japan (Kasai Municipal Hospital, Awaji Prefectural Hospital, Tottori Municipal Hospital, and Shimane Central Prefectural Hospital) were enrolled in the study. Clinical and laboratory data were collected from the medical records. The presence or absence of organic coronary heart disease was also confirmed from the coronary angiography radiomorphological records. Patients with organic coronary arterial diseases were designated as having cardiac chest pain (CCP), while those without organic coronary disease were designated as having NCCP. Statistical analyses were performed using the Mann-Whitney U-test and the c2 test as appropriate. After receiving their consent, we enrolled 952 patients in this study, with 633 found to have organic coronary artery disease. Therefore, 34% of all patients with recurrent chest pain were diagnosed as having NCCP. When the clinical characteristics were compared between patients with CCP and those with NCCP, there were significant differences in age, blood pressure, smoking habit, high-density lipid (HDL)-cholesterol, and hemoglobin (Hb)A1C. Further, the NCCP patients showed a higher proportion, of females than the CCP patients, while CCP patients more frequently had a smoking habits. As for risk factors of arteriosclerosis, HbA1C was higher and HDL-cholesterol was lower in patients with CCP, while blood pressure was slightly higher in the NCCP patients. These results indicate that a significant percentage of patients with recurrent chest pain in Japan are diagnosed with NCCP. The pathogenesis of chest pain observed in patients with NCCP has been reported to be multifactorial, and musculoskeletal pain and pain with an esophageal origin are considered to be the major causes of NCCP.2 Because the number of patients with GERD has been steadily increasing, future investigations of the prevalence of patients with GERD-related chest pain among those with NCCP are necessary. Tomonori Imaoka, Youichi Miyaoka Department of Gastroenterology, Shimane Central Prefectural Hospital, Shimane, Japan Katsuhisa Nishi, Akira Takarada Department of Medicine, Awaji Prefectural Hospital, Awaji, Japan Hirohumi Fujishiro Department of Gastroenterology, Tottori Municipal Hospital, Tottori, Japan

Letters to the editor Shunji Ohara, Toshiharu Takashima Department of Medicine, Kasai Municipal Hospital, Kasai, Japan Kyoichi Adachi, Yoshikazu Kinoshita Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo 693-8501, Japan

References 1. Eslick GD, Fass R. Noncardiac chest pain: evaluation and treatment. Gastroenterol Clin North Am 2003;32:531–52. 2. Fang J, Bjorkman D. A critical approach to noncardiac chest pain: pathophysiology, diagnosis, and treatment. Am J Gastroenterol 2001; 96:958–68. Received: December 10, 2004 / Accepted: December 17, 2004 Reprint requests to: Y. Kinoshita DOI 10.1007/s00535-004-1658-5

Crohn’s disease in Turner’s syndrome with X-chromosomal mosaicism of 45 XO and 47 XXX To the Editor: Crohn’s disease is characterized by a chronic relapsing intestinal inflammation and typically occurs from a young age. Although the etiology of this disease has not been fully clarified, genetic analysis has recently revealed several susceptibility genes for inflammatory bowel disease (IBD).1 One of the representive susceptibility genes for Crohn’s disease in Western populations is NOD2, located at chromosome 16;1 however, this disease susceptibility gene has not been confirmed in Japanese.2 Therefore, other genetic analysis is needed in Japan. X-chromosomal abnormality is associated with a number of somatic abnormalities, referred to as Turner’s syndrome, and characterized by short stature and ovarian dysgenesis, with failure of secondary sexual development. Patients with this syndrome cannot grow maturely from childhood. The risk of certain autoimmune diseases, such as hypothyroidism, in patients with Turner’s syndrome is higher than that in subjects with a normal X chromosome.3 A 16-year-old woman was admitted to our hospital with a 1-year history of diarrhea, fever, and general fatigue. In her past history, she was diagnosed as having Turner’s syndrome at the age of 11 years. Chromosomal analysis of peripheral lymphocytes disclosed a mosaic pattern with 60% of the cells having 45 XO and 40% with 47 XXX (Fig 1a,b). She had received hormonal replacement of growth hormone since age 11 years. Physical examination was notable for short stature but no other signs of Turner’s syndrome. On laboratory data, her erythrocyte sedimentation rate was 75 mm/h and C-reactive protein level was 1.44 mg/dl. Colonoscopy revealed a longitudinal deep ulcer in the transverse colon (Fig. 2a) and multiple erosions in the sigmoid colon (Fig. 2b). Microscopic findings of biopsy specimens obtained from the erosive lesions showed inflammatory cell infiltration and the presence of granuloma in the mucosa (Fig. 2c). Upper gastrointestinal endoscopy and barium contrast radiography of the small intestine