Tomoo Fujisawa

Response to interferon therapy in children with chronic hepatitis C.

We evaluated the effect of interferon therapy and investigated factors that may influence the outcome in 18 children with chronic hepatitis C. A complete response was obtained in 10 children (56%). The titer for pretreatment serum virus ribonucleic acid (< or = 10(7) copies/ml) was correlated significantly with a complete response to therapy.

Coexistence of a graft with the preserved native liver in auxiliary partial orthotopic liver transplantation from a living donor for ornithine transcarbamylase deficiency.

BACKGROUND Auxiliary partial orthotopic liver transplantation (APOLT) has recently been performed in patients with noncirrhotic metabolic liver diseases. However, long-term outcomes for the preserved native liver and the transplanted liver graft have not been clearly established yet. METHODS The recipient was a 36-month-old girl with ornithine transcarbamylase deficiency. She underwent APOLT, using her fathers left lateral segment. RESULTS Liver function was normalized soon after APOLT and the patient was able to ingest a normal diet without medication. Coexistence of the well-functioning native liver and graft was demonstrated in a computed tomography scan, Doppler ultrasonography, scintigraphy, and histological examination, during a relatively long-term follow-up period. CONCLUSIONS APOLT seems to be most useful for the treatment of noncirrhotic metabolic liver diseases.

Relationship between oxidative stress and antioxidant systems in the liver of patients with Wilson disease: Hepatic manifestation in wilson disease as a consequence of augmented oxidative stress

The role of oxidative stress in the pathogenesis of liver disease in Wilson disease (WD), a genetic disorder characterized by excess hepatic deposition of copper that generates free radicals, remains unclear. This study investigates oxidative stress on the liver and hepatic antioxidant responses in WD using liver specimens from affected patients showing mild liver damage (group I, n = 3), moderate or greater liver damage (group II, n = 5), and fulminant hepatic failure (group III, n = 5) and from asymptomatic carriers (n = 2). Decreased ratios of reduced glutathione (GSH) to oxidized glutathione (GSSG) and increased thiobarbituric acid reactive substance (TBARS), a lipid peroxidation product, were found in every affected patient, especially in group II and III patients. Activities and protein expressions of Mn-dependent superoxide dismutase (Mn-SOD), CuZn-dependent superoxide dismutase (CuZn-SOD), and catalase were decreased in all patients, especially in group III patients. Glutathione peroxidase (GPx) activity was decreased only in group III patients. Asymptomatic carriers without any clinical manifestations showed normal TBARS level and GSH/GSSG ratio with increases in both GSH and GSSG levels. Their CuZn-SOD, Mn-SOD, and catalase activities were increased. These results suggest that excessive copper-derived oxidants contribute to development and progression of liver disease in WD.

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.

Long-term outcome of chronic hepatitis B in adolescents or young adults in follow-up from childhood.

BACKGROUND It has not yet been defined whether children with chronic hepatitis B are likely to develop severe liver disease in the future. The purpose of this study was to evaluate the evolution of chronic hepatitis B acquired in childhood. METHOD Fifty-two children in the age range of 0 to 15 years who were positive for hepatitis B surface antigen and hepatitis B e antigen in serum for at least 6 months were enrolled in this study. In the majority of the 52 children, hepatitis B virus infection was acquired by perinatal transmission. All 52 showed abnormal liver function test findings for more than 6 months before enrollment, and the subjects were followed up longitudinally for 3 to 22 years (mean, 11 years). They are now more than 15 years of age (15-27 years old). RESULTS During the follow-up period, 26 (50%) children had spontaneous seroconversion to anti-hepatitis B e. Serum levels of alanine aminotransferase normalized in these 26 children. In one child of these children, hepatocellular carcinoma developed at the age of 21 years, 16 years after seroconversion, although his liver function profiles remained normal. The other 26 children remained hepatitis B e antigen positive, most with unchanged biochemical features. Sixteen (62%) children among these 26 children were treated with interferon-alpha. Eleven (69%) children had seroconversion to anti-hepatitis B e within the first year after the cessation of therapy. Hepatocellular carcinoma developed in 1 of these 11 children at the age of 16 years, 6 years after interferon therapy. Thus, hepatocellular carcinoma developed in two children in an anti-hepatitis B e positive phase. CONCLUSION All children carrying hepatitis B surface antigen should be observed carefully to monitor the possible development of hepatocellular carcinoma, especially in the antihepatitis B e-positive phase after spontaneous seroconversion or even after interferon treatment.

Mutations in the nonstructural protein 5A gene and response to interferon therapy in young patients with chronic hepatitis C virus 1b infection

A region associated with sensitivity to interferon (IFN) has been identified previously in the nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) genotype 1b. A study was undertaken to determine whether the presence of mutations in the NS5A2209–2248 sequence could serve as a predictor of response to IFN therapy in children and adolescents with chronic HCV‐1b infection. Sixteen children (M/F ratio = 11:5; mean age 11.7 years, range 5 to 19 years) with chronic HCV‐1b infection who received IFN‐α for 6 months (total dose: 8 MU/kg) were enrolled in this study. Twelve of the children (75%) had an underlying malignant disease. Pretreatment NS5A gene sequences were detected by reverse transcription–nested polymerase chain reaction (RT‐nested PCR). PCR products were subjected to direct sequencing by the dideoxy chain termination method. The amino acid sequences of NS5A2209–2248 were compared with the published NS5A2209–2248 sequences of HCV‐J. The NS5A2209–2248 sequences were detected in 10 (63%) of the 16 children. Eight patients had the wild‐type sequences, with no amino acid changes; and two patients had the intermediate type, with only one amino acid change. Four (25%) of the 16 patients responded completely to IFN therapy. Three of the four patients had the wild‐type sequences, while none of the patients with the mutant type had a complete response. Serum HCV RNA levels in children with the wild type did not differ from those in patients with the mutant type. This study shows that there is no significant correlation between response to IFN and mutations in NS5A2209–2248. The amino acid sequences in NS5A2209–2248 in young patients with chronic HCV‐1b infection appear to be conserved. J. Med. Virol. 53:361–365, 1997.

Helicobacter pylori infection prevents the occurrence of the tolerance phenomenon of histamine H2 receptor antagonists

Background : The attenuated anti‐secretory activity of H2 receptor antagonists (H2RA) during continuous administration is referred to as the tolerance phenomenon. However, it is not clarified whether Helicobacter pylori infection affects the occurrence of tolerance to H2RA. It is also not clarified whether the tolerance phenomenon occurs to a new H2RA, lafutidine.

Utility of Simplified Criteria for the Diagnosis of Autoimmune Hepatitis in Children

Background and Aim: Although the diagnostic scoring system of autoimmune hepatitis (AIH) has been used, these criteria are intended mainly as research tools and are complicated to apply. To resolve these difficulties and allow quick diagnosis, a simplified scoring system was proposed in 2007. We retrospectively compared the simplified AIH scoring system with the 1999 revised original AIH scoring system in children. Patients and Methods: Twenty children (boys/girls 10/10, age 1–15 years, mean age ± SD 8.4 ± 4.4 years) who were diagnosed with AIH based on clinical, biochemical, immunological, and histological data were enrolled in this study. In addition, 36 children with non-AIH liver diseases (boys/girls 22/14, age 1–16 years, mean age ± SD 7.8 ± 4.4 years) were available for evaluation of both the simplified and the 1999 revised scoring system. Results: The sensitivity and specificity of the 1999 revised scoring system were 100% and 81%, respectively. In contrast, the sensitivity and specificity of the simplified scoring system were 55% and 86%, respectively. Of the 20 children with AIH, 9 (45%) were classified as not having AIH using the simplified scoring system. Of the 9 children, 2 and 7 were classified as having definite AIH and probable AIH using the 1999 revised scoring system, respectively. All 5 children with primary sclerosing cholangitis were graded as having AIH using the simplified AIH criteria and the 1999 revised criteria. Conclusions: Although the simplified AIH scoring system has low sensitivity for the diagnosis of AIH in children, the specificity of the simplified AIH scoring system is high. However, the simplified AIH scoring system could not differentiate between AIH and primary sclerosing cholangitis. Therefore, the simplified AIH scoring system does not seem to be a reliable diagnostic tool in children.

Selective portal blood flow diversion in auxiliary partial orthotopic liver transplantation to induce regeneration of the graft

Experience with auxiliary partial orthotopic liver transplantation (APOLT) is still very limited and many questions remain to be solved. In this article, we present the case of a 5-year-old girl with ornithine transcarbamylase deficiency who initially did well after APOLT. During a severe rejection episode 16 months after transplantation, she developed encephalopathy and hyperammonemia. Despite a good clinical and histopathological response to antirejection therapy, the graft had become smaller and the native liver had undergone compensatory hypertrophy. After we surgically ligated the right portal branch, the graft recovered and the patient was able to stop her medication 1 month after surgery. We have estimated that the minimum volume of normal liver required to correct the metabolic defect in ornithine transcarbamylase deficiency is 8 cm3/kg. The ligation of the right portal branch was a safe and effective method of inducing a gradual and progressive involution of the hypertrophic native liver and regeneration of the atrophic graft.

Assessment of degree of health of the stomach by concomitant measurement of serum pepsinogen and serum Helicobacter pylori antibodies

The stomach was assessed by measuring serum pepsinogen (PG) and Helicobacter pylori (Hp) antibodies by immunoassay, based on the findings of upper gastrointestinal endoscopy performed on the same day. The assessment involved 1,636 individuals who visited the hospital for general medical checkups. Those negative for Hp antibodies and PG were grouped in group A, Hp-positive/PG-negative subjects were included in group B, and PG-positive subjects in group C. Group A comprised 660 subjects (40.3%), group B 514 (31.4%), and group C 462 (28.2%). Gastric cancer was detected in 0.87% (4/462) in group C, 0.19% (1/514) in group B, and 0% (0/660) in group A. All four patients with gastric adenoma were in group C. Hyperplastic polyps were detected most frequently in group C followed by group B, while there were no cases in group A. By contrast, most fundic gland polyps were found in group A. The detection rate of peptic ulcers was highest in group B, while that of reflux esophagitis was highest in group A. These findings suggest that the “degree of health” of the stomach can be assessed by measuring serum PG and Hp antibodies.