Article

The Effect of Ursodeoxycholic Acid in Children With Prolonged Hepatitis A Virus Infection That May Be A Trigger Factor for Autoimmune Hepatitis

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Abstract

The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. www.amjgastro.com, *2007 Journal Citation Report (Thomson Reuters, 2008)

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Tanreqing Injection (TRQ) has been used primarily in treating infections of the upper respiratory tract and serious influenza in China, as a classical compound herbal recipe. TRQ had been demonstrated its effects of clearing heat, eliminating phlegm, detoxification, reducing inflammation and alleviating cough. The survival rate, histopathology of lungs and viral titers in mice were evaluated in this study to verify the curative effect of TRQ. However, there is not enough information about the components. In the present study, a high-performance and practical LC/QTOF/MS method was developed for characterization and identification of the natural ingredients in TRQ. A total of 60 compounds, including 10 amino acids, 10 iridoid glucosides, 14 flavonoids, 13 other phenolic compounds, 10 steroid acids and 3 other compounds were characterized and identified. And we confirmed the material basis of Anti-influenza A active ingredients in TRQ. Therefore, we have developed an accurate analytical method. LC/QTOF/MS could be applied for identification the complex components in Traditional Chinese Medicine.
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Unlabelled: Hepatitis A infection is known to induce autoimmune hepatitis and autoimmune hemolytic anemia. Here we present a case with autoimmune hepatitis type I and autoimmune hemolytic anemia following hepatitis A virus (HAV) infection. Case: M.A., a male patient, was brought to the hospital with complaints of jaundice and malaise. Physical examination revealed paleness and icterus. The liver was palpable 5 cm below the costal margin in the midclavicular line; the spleen was palpable 2 cm from the costal margin. Laboratory examination revealed severe anemia, reticulocytosis and direct Coombs' IgG positivity. Liver enzymes, total and conjugated bilirubin and alkaline phosphates levels, total protein and immunglobulin levels were high and prothrombin time elongated. Hepatitis A IgM antibody was found positive, while other hepatitis serologic markers were negative. Anti-smooth muscle antibody (ASMA) was positive in 1/80 titer. With these laboratory findings, the case was diagnosed as autoimmune hepatitis and autoimmune hemolytic anemia induced by hepatitis A infection. Liver histology also supported the diagnosis. Steroid therapy resulted in clinical and laboratory remission. In conclusion, it is important to vaccinate children against hepatitis A infection to protect them from its complications and also from autoimmune diseases induced by this infection.
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Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis in the world. Rarely, acute infection may persist for a long time. Autoimmune hepatitis (AIH) may provide anti-HAV IgM positivity detection for a prolonged time. On the other hand, HAV as an infectious agent may also trigger AIH. Here we presented a case which seemed like a simple acute viral hepatitis A infection at the beginning but turned out to be an AIH according to the International Autoimmune Hepatitis Group's system. A 21-year-old female was diagnosed as symptomatic acute HAV infection with anti-HAV IgM positivity and elevated aminotransferase levels. The other viral serological tests were negative. On the 6th, 12th and 18th months of the follow up, her anti-HAV IgM positivity still continued and transaminase levels were also 3 to 7 times high of the upper limit of normal. In addition, antinuclear antibody was positive. However, on the 19th month anti-HAV IgM could be detected as negative. Liver histology was prominent. The patient had a score of 16 according to the International Autoimmune Hepatitis Group's system. She was given prednisolone (10 mg/day) and azathioprine (100 mg/day). The aminotransferase levels were detected within normal ranges at the end of the first month of therapy. She was in remission during follow up for 6 years. In conclusion, prolonged HAV infection and AIH may not only trigger each other but also deteriorate the liver histology. AIH should be investigated in cases of long-lasting HAV infection in order to begin the treatment earlier. On the other hand, AIH patients should also be vaccinated for both HBV and HAV to avoid more severe diseases.
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Ursodeoxycholic acid (UDCA) is able to improve biochemical markers of cholestasis, with a parallel decrease in transaminases, in various cholestatic liver diseases. To evaluate the effects of UDCA administration on acute viral hepatitis-related cholestasis and the course of acute viral hepatitis. Seventy-nine consecutive patients with acute viral hepatitis (HBV: 43, HCV: 11, HAV: 15, HEV: 3, Non A-E: 7) were randomized to receive either UDCA for 3 weeks or no treatment. Liver biochemistry and serum bile acid determinations were run at weekly intervals. No significant differences were observed in mean percentage decreases in transaminases between treated and untreated patients. By contrast, cholestatic indexes decreased significantly more quickly in patients treated with UDCA than in controls, and this effect was more evident in patients with increasing alanine transaminase levels at admission. After a peak at the end of the first week of therapy, serum levels of conjugated ursodeoxycholic acid (CUDCA) showed a gradual decrease. Conjugated cholic acid (CCA) and chenodeoxycholic acid (CCDCA) showed a progressive decrease with the resolution of viral hepatitis, but no influence of UDCA administration was observed. Our study demonstrates that UDCA significantly improves cholestatic indices in patients with acute viral hepatitis, but this effect does not seem to affect the course of the illness.
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In a prospective investigation the sensitivity of conventional radiography, sonography, color Doppler flow imaging (CDFI) and CT in the detection of hepatic portal venous gas (HPVG) was compared in 7 patients with different diagnoses. For the identification of HPVG sonography, CDFI and CT have a higher sensitivity than conventional radiography. CT, however, was the most suitable method to identify the underlying cause of HPVG. Patients with iatrogenic HPVG as a result of diagnostic or therapeutic intervention had a good prognosis. In contrast, in all cases with a sudden appearance of HPVG and a noniatrogenic cause, exitus ensued within 1 week.
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The roentgenographic finding hepatic--portal venous gas (HPVG) has been reported extensively in the pediatric and radiology literature. The surgical implications and clinical significance have yet to be fully defined. This study reviews the 60 reported cases in the literature and adds four new cases. HPVG appears as a branching radiolucency extending to within 2 cm of the liver capsule. HPVG is associated with necrotic bowel (72%), ulcerative colitis (8%), intra abdominal abscess (6%), small bowel obstruction (3%), and gastric ulcer (3%). Mucosal damage, bowel distention and sepsis predispose to HPVG. The current mortality rate of 75% represents an improvement from previous experience. Analysis of survivors indicates that the finding of HPVG requires urgent surgical exploration except when it is observed in patients with stable ulcerative colitis.
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In a prospective investigation the sensitivity of conventional radiography, sonography, color Doppler flow imaging (CDFI) and CT in the detection of hepatic portal venous gas (HPVG) was compared in 7 patients with different diagnoses. For the identification of HPVG sonography, CDFI and CT have a higher sensitivity than conventional radiography. CT, however, was the most suitable method to identify the underlying cause of HPVG. Patients with iatrogenic HPVG as a result of diagnostic or therapeutic intervention had a good prognosis. In contrast, in all cases with a sudden appearance of HPVG and a noniatrogenic cause, exitus ensued within 1 week.
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A study of the clinical profile of 59 patients who presented with hepatitis A virus infection showed that dark urine, fatigue, gastrointestinal complaints, and fever were the most common presenting symptoms. The most frequent physical findings were hepatomegaly and jaundice. The mean presenting laboratory tests included total bilirubin of 5 mg/dl., alkaline phosphatase of 269 units/L, and serum aspartate aminotransferase and alanine aminotransferase levels of 1442 mIU/mL and 1952 mIU/mL, respectively. Atypical manifestations included relapse, cholestasis, rash, and arthralgia. Two patients presented with hepatitis A and concomitant type I autoimmune chronic hepatitis, and both required immunosuppressive therapy. Five patients who presented with hepatitis A were pregnant, and during follow-up, none of their infants developed elevated serum transaminase values or had detectable IgM anti-HAV antibody. All 59 patients experienced complete clinical and biochemical recovery within 6 months after onset of illness.
Article
In previously published studies ursodeoxycholic acid (UDCA) showed beneficial effect on the course of chronic hepatitis. We investigated the effect of UDCA on the course of acute viral hepatitis in a prospective double-blind study. Seventy-eight consecutive patients were randomly assigned either to the UDCA group or to placebo. At 12 months of follow-up 76 patients were available for the final assessment. The analysis of all cases and of the patients with hepatitis B (n = 59) showed a comparable rate of decline of the alanine aminotransferase and other liver function tests in the treatment group and in the placebo group. However, the elevation of alanine aminotransferase persisted more frequently in the placebo group (all cases, p = 0.05; hepatitis B group, p = 0.03). Persistence of the hepatitis B virus infection, measured by the presence of hepatitis B early antigen and hepatitis B virus DNA (polymerase chain reaction and hybridization) at 12 months of follow-up, was observed in I of 33 patients in the UDCA group and in 6 of 25 patients in the placebo group (p = 0.02). Gallstones detected by entry ultrasound dissolved in four of eight cases in the UDCA group and in none of six in the placebo group. We conclude that UDCA has a beneficial effect on the course of the acute viral hepatitis. It may enhance the clearance of the hepatitis B virus and thus prevent the development of chronic hepatitis.
Article
Ursodeoxycholic acid (UDCA) improves liver enzymes and in many instances liver histology in cholestatic liver diseases such as primary biliary cirrhosis and primary sclerosing cholangitis. Besides classic cholestatic diseases, UDCA also improves liver biochemistry in alcoholic liver disease and in chronic viral hepatitis C. The main target of UDCA treatment, however, is cholestasis, and consequently the mechanisms responsible for the beneficial effects in these diseases are of interest, and are discussed in detail in this article.
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The pathogenic mechanisms for autoimmune hepatitis (AIH) are not completely known. Susceptibility to AIH is associated with the human leukocyte antigens (HLA) class II: DR3 and DR4. Nevertheless, AIH does not have a strong genetic predisposition, suggesting that other factors are involved. Perhaps the strongest evidence of a viral cause for AIH exists for hepatitis C virus. AIH has been reported to develop rarely after acute infection with hepatitis A virus. We report on a 55-year-old woman in whom AIH developed during the convalescence period of serologically proven acute viral hepatitis type A. HLA class II DRB1*0401, which was reported to be associated with AIH with a moderate coarse and late appearance in life, was found in this patient. Steroid therapy was followed by a complete clinical remission. Our case supports the possibility that acute hepatitis A may trigger the development of AIH in a genetically susceptible subject.
Article
The beneficial effect of ursodeoxycholic add have been documented in adults but experience with this agent is limited in the pediatric population. The objective of this study was to evaluate ursodeoxycholic acid treatment in children with cholestatic liver disease. Twenty-four patients with intrahepatic cholestasis (neonatal hepatitis 7, Byler disease 7, idiopathic intrahepatic cholestasis 10) whose ages ranged from 1.5 months to 15 years were treated with ursodeoxycholic acid (15-20 mg/kg/day) for 12 months. Liver biopsy was performed initially on all patients and on 17 at the end of the twelve months. The outcome was evaluated by monitoring clinical and biochemical markers of cholestasis, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, cholesterol, total serum tasting bile acids and total and conjugated bilirubin at entry and every three months of treatment. Pruritus was ameliorated in all patients; there was complete disappearance of itching in 16.7 percent. There were significant decreases in mean serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin and gamma-glutamyl transpeptidase. Liver biopsy specimens showed a significant improvement in the cholestasis but not in fibrosis. No adverse effects of therapy were noted. The improvements in the clinical and biochemical parameters and tolerability of the drug suggest that ursodeoxycholic acid is a safe and effective treatment in children with intrahepatic cholestasis.
Acute hepatitis A virus (HAV) Association with fulminant hepatic failure (FHF) and autoimmune hepatitis (AIH) in pediatric population
  • Ramonet Md S Gomez
  • S Morise
Ramonet MD, Gomez S, Morise S, et al. Acute hepatitis A virus (HAV). Association with fulminant hepatic failure (FHF) and autoimmune hepatitis (AIH) in pediatric population. JPGN 2000;31(suppl 2):s116 –7.
Hepatic-portal venous gas in adults: Etiology, pathophysiology and clinical significance
  • Pr Liebman
  • Mt Patten
  • J Manny
Liebman PR, Patten MT, Manny J, et al. Hepatic-portal venous gas in adults: Etiology, pathophysiology and clinical significance. Ann Surg 1978;187:281–7.
Department of Gastroenterology, Iwate Prefectural Central Hospital
  • Reprint Requests
  • M D Ikehata
Reprint requests and correspondence: Atsushi Ikehata, M.D., Department of Gastroenterology, Iwate Prefectural Central Hospital, 1-4-1 Ueda, Morioka, Iwate 020-0066, Japan. Received Sep. 14, 2000; accepted Sep. 25, 2000.
Association with fulminant hepatic failure (FHF) and autoimmune hepatitis (AIH) in pediatric population
  • M D Ramonet
  • S Gomez
  • S Morise
Ramonet MD, Gomez S, Morise S, et al. Acute hepatitis A virus (HAV). Association with fulminant hepatic failure (FHF) and autoimmune hepatitis (AIH) in pediatric population. JPGN 2000;31(suppl 2):s116 -7.