BUSQUEDA DE ARTICULOS Molecular characterization of hepatitis A virus in children with fulminant hepatic failure in Argentina Munne, M.S.

; Vladimirsky, S.; Moreiro, R.; Ciocca, M.; Cuarterolo, M.; Otegui, L.; Soto, S.; Brajterman, L.; Castro, R.; Sasbon, J.; Gianivelli, S.; Buamscha, D.; Quarleri, J.; Gonzalez, J.E. Vol. 28 Nr. 1 Pgina: 47 53 Fecha de publicacin: 01/01/2008 Resumen: Background: Hepatitis A infection, a vaccine-preventable disease, is an important cause of fulminant hepatic failure (FHF) in children in Argentina. Universal vaccination in 1-year-old children was implemented in June 2005. The limited studies about the correlation between the characteristics of the hepatitis A virus (HAV) and FHF have been carried out in adults. Methods: Samples from 41 children with FHF were studied from September 2003 to January 2006 and HAV RNA was detected, sequenced and analysed in the 5' non-coding region and VP1/2A region. Results: Eighteen HAV strains were characterized and found to be different at the nucleotide level from the self-limited acute infection strains that have been circulating in Argentina with no temporal or geographical pattern. They did not form a genetic cluster, but some of them were identical in the largest fragment characterized and some of them seemed to be more closely related in time and/or geographically. Conclusion: Our results suggest that viral factors could be involved in the severity of the clinical presentation of HAV infection in children in Argentina. Clinical course and consequences of hepatitis A infection Ciocca, M. Vol. 18 Nr. Suppl. 1 Pgina: S71 - S74 Fecha de publicacin: 18/02/2000 Resumen: Hepatitis A virus (HAV) is a small, non-enveloped RNA virus belonging to the Picornaviridae, for which only one serotype has been identified. Transmission is usually through the faecaloral route by person-to-person contact. The most common risk factors are household or sexual contact with a sufferer, attendance or working at a day-care centre, international travel, and association with food or waterborne outbreaks; 55% of cases have no identifiable risk factors. HAV infection may be symptomatic or asymptomatic, and shows three phases. Virus is shed during the incubation phase, anti-HAV IgM appears during the symptomatic phase and can be used for diagnosis, and anti-HAV Ige appears at the same time but persists lifelong. Unusual clinical manifestations of hepatitis A include cholestatic, relapsing and fulminant hepatitis. Hepatitis A accounts for 93% of cases of acute hepatitis in Argentina, including 7% of atypical clinical cases. Hepatitis A is the major cause of fulminant hepatitis, and has been reported to account for 10% of liver transplants in children in France and 20% in Argentina. One-year survival after liver transplantation is 64%. Prevention must be considered as the main means of averting this severe illness. (C) 2000 Published by Elsevier Science Ltd. All rights reserved. Clinical and laboratory features of viral hepatitis A in children. Blechov Z, Trojnek M, Kynl J, Cstkov J, John J, Mal M, Herrmannov K, Mareov V. Source 1st Department of Infectious Diseases, 2nd Medical Faculty, Hospital Na Bulovce Charles University in Prague, Budinova 2, 18081 Prague, Czech Republic. mtrojanek@seznam.cz Abstract Recent outbreaks of viral hepatitis A in non-endemic European countries and the potential outbreak risk in susceptible populations has led us to evaluate the clinical characteristics of children hospitalised with hepatitis A. Retrospective study included 118 children (68 boys and 50 girls) with the mean age of 8.5 years hospitalised at Hospital Na Bulovce in Prague from June 2008 to June 2009. The clinical course was symptomatic icteric in 57 (48.3

%) children, symptomatic anicteric in 23 (19.5 %), subclinical in 22 (18.6 %) and asymptomatic inapparent in 16 (13.6 %). The relapse of the disease occurred in three patients. There were no cases of fulminant hepatitis. The most frequent symptoms included jaundice (57 cases), abdominal pain/discomfort (38), vomiting (38), dark urine (37), subfebrility (29) and fever (25). Hepatic injury markers were substantially elevated in icteric patients, but moderate elevations were identified in anicteric and subclinical cases as well. Lower white blood cell and lymphocyte counts were independently associated with symptomatic and more severe clinical course. Active immunisation was provided to 22 patients, and as a post-exposure prophylaxis to 19 of them. The clinical course and laboratory parameters in vaccinated children were not significantly different from nonvaccinated children. The clinical course of hepatitis A was largely self-limiting and benign. Asymptomatic infections are frequent, representing risk for disease spread; however, they are associated with elevations of hepatic injury markers. The inclusion of significant proportion of asymptomatic cases that were identified and investigated only because of active epidemiological surveillance in the outbreak focus represents the particular asset of this study. Virol J. 2011 May 23;8:254. doi: :10.1186/1743-422X-8-254. Immunological and molecular epidemiological characteristics of acute and fulminant viral hepatitis A. Hussain Z, Husain SA, Almajhdi FN, Kar P. Source PCR Hepatitis Laboratory, Department of Medicine, Maulana Azad Medical College, New Delhi, India. hussainzahep@gmail.com Abstract BACKGROUND: Hepatitis A virus is an infection of liver; it is hyperendemic in vast areas of the world including India. In most cases it causes an acute self limited illness but rarely fulminant. There is growing concern about change in pattern from asymptomatic childhood infection to an increased incidence of symptomatic disease in the adult population. OBJECTIVE: In-depth analysis of immunological, viral quantification and genotype of acute and fulminant hepatitis A virus. METHODS: Serum samples obtained from 1009 cases of suspected acute viral hepatitis was employed for different biochemical and serological examination. RNA was extracted from blood serum, reverse transcribed into cDNA and amplified using nested PCR for viral quantification, sequencing and genotyping. Immunological cell count from freshly collected whole blood was carried out by fluorescence activated cell sorter. RESULTS: Fulminant hepatitis A was mostly detected with other hepatic viruses. CD8+ T cells count increases in fulminant hepatitis to a significantly high level (P = 0.005) compared to normal healthy control. The immunological helper/suppressor (CD4+/CD8+) ratio of fulminant hepatitis was significantly lower compared to acute cases. The serologically positive patients were confirmed by RT-PCR and total of 72 (69.2%) were quantified and sequenced. The average quantitative viral load of fulminant cases was significantly higher (P < 0.05). There was similar genotypic distribution in both acute and fulminant category, with predominance of genotype IIIA (70%) compared to IA (30%). CONCLUSIONS: Immunological factors in combination with viral load defines the severity of the fulminant hepatitis A. Phylogenetic analysis of acute and fulminant hepatitis A confirmed genotypes IIIA as predominant against IA with no preference of disease severity.

Pediatr Int. 2008 Oct;50(5):624-7. doi: 10.1111/j.1442-200X.2008.02626.x. Detection of hepatitis A virus RNA from children patients with acute and fulminant hepatitis of unknown etiology in Vietnam: Genomic characterization of Vietnamese HAV strain. Hoang PL, Trong KH, Tran TT, Huy TT, Abe K. Source Department of Gastroenterology, Children's Hospital No 1, Ho Chi Minh City, Vietnam. Abstract BACKGROUND: Although it is thought that Vietnam is a high endemic region of hepatitis A virus (HAV) infection, there is no report on genomic characterization of HAV spread in Vietnam. The purpose of the present paper was therefore to identify various virus infections from 33 children with acute or fulminant hepatitis of unknown etiology admitted to Children's Hospital No.1 in Ho Chi Minh City, Vietnam. METHODS: Anti-HAV IgM and IgG were assayed by ELISA. Viral RNA and DNA were determined by PCR method. HAV genes isolated by PCR were sequenced and characterized by phylogenetic analysis. RESULTS: Anti-HAV IgM was detected in 18 of 26 acute hepatitis (69.2%) and one of seven (14.3%) fulminant hepatitis patients. Furthermore, HAV-RNA in serum was identified in five of 26 acute (19.2%) and two of seven (28.6%) fulminant hepatitis patients, respectively, on nested reverse transcription-polymerase chain reaction. Among the seven HAV-RNApositive patients tested, two (28.6%) were negative for anti-HAV IgM. We also obtained seven isolates containing the HAV genome with the viral protein 1 (VP1) region sequence. All Vietnamese HAV isolates formed a cluster and belonged to genotype IA according to phylogenetic analysis based on the short sequences of VP1-2A junction region. CONCLUSION: HAV is an important agent with regard to fulminant hepatitis among children in Vietnam. To the authors' knowledge this is the first report on Vietnamese HAV strain confirmed on sequencing. Korean J Hepatol. 2010 Mar;16(1):19-28. doi: 10.3350/kjhep.2010.16.1.19. [Clinical features of patients with fulminant hepatitis A requiring emergency liver transplantation: comparison with acute liver failure due to other causes]. [Article in Korean] Kim JD, Choi JY, Park CH, Song MJ, Jang JW, Bae SH, Yoon SK, Lee YS, You YK, Kim DG. Source Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea. Abstract BACKGROUND/AIMS: According to recent prevalence of hepatitis A virus (HAV) infection, acute liver failure (ALF) due to HAV infection is observed frequently in parallel. The aim of this study was to elucidate the clinical, laboratory, and pathologic features of patients who have undergone emergency liver transplantation (LT) due to fulminant HAV infection. METHODS: Clinical, laboratory, and pathologic data of 11 transplant recipients with anti-HAV IgMpositive ALF between December 2007 and May 2009 were analyzed, and compared with data of 10 recipients who underwent LT for the management of ALF due to other causes. RESULTS: The median age of the patients with HAV-related ALF was 34 years (range: 15-43 years). The levels of hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine were higher and the level of bilirubin was lower in the HAV-related

ALF group than in the other group (P=0.005, 0.001, 0.001, 0.010, and 0.003, respectively). The time from the onset of initial symptoms to the development of encephalopathy was shorter in the HAV-related ALF group than in the other group (median 5 days, range: 4-13 days; P<0.001). In patients with HAV-related ALF, laboratory findings and clinical prognostic parameters including the Acute Liver Failure Study Group prognostic index, King's College criteria, and model for endstage liver disease (MELD) and Child-Pugh scores were not associated with the grade of hepatic encephalopathy or time of progression to encephalopathy. CONCLUSIONS: The results of this study indicate that the clinical condition of patients with HAV-related ALF requiring emergency LT aggravates rapidly. Prognostic parameters are not sufficient for discriminating transplant candidates in patients with fulminant hepatitis A. J Pak Med Assoc. 2010 Mar;60(3):175-8. Risk factors for fulminant hepatic failure and their relation with outcome in children. Latif N, Mehmood K. Source Department of Paediatrics, Civil Hospital, Karachi. Abstract OBJECTIVE: To identify the risk factors for fulminant hepatic failure (FHF) and their relation with the outcome in children. METHODS: Descriptive case study was conducted at National Institute Of Child Health. Fifty patients having clinical and biochemical markers suggestive of FHF were included in this study and data was extracted from files, retrospectively. Their outcome was noted as expiry or recovery during hospital stay. RESULTS: The most common etiology found was viral in origin present in thirty-seven (74%) cases. Out of them twenty-eight (56%) had HAV and nine (18%) had HBV. Thirteen (26%) patients were negative for acute serology of hepatrophic viruses, out of them four (8%) had Wilson's disease and one (2%) had autoimmune hepatitis. Etiology could not be established in eight (16%) cases. Thirty (60%) patients expired and twenty (40%) patients recovered. CONCLUSION: FHF is not uncommon in children. Hepatitis A is most common cause in paediatric age group. Age less than 4 years, higher degree of encephalopathy, INR >4, higher serum bilirubin with lower SGPT has poor outcome and mortality is high without liver transplantation. Intervirology. 2010;53(1):15-9. doi: 10.1159/000252779. Epub 2010 Jan 5. Hepatitis A: clinical manifestations and management. Jeong SH, Lee HS. Source Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea. Abstract Due to improved living conditions and subsequent changes in hepatitis A epidemiology, the disease burden of hepatitis A is increasing in many regions. Recently, Korea has faced a large, community-wide outbreak of hepatitis A, which has prompted a vaccination program. The clinical spectrum of hepatitis A virus infection ranges from asymptomatic infection to fulminant hepatitis. Clinical manifestations depend on the age of the host: less than 30% of infected young children are symptomatic, while about 80% of infected adults manifest severe hepatitis with remarkably elevated serum

aminotransferases. Fulminant hepatitis is rare, with a reported incidence from 0.015 to 0.5%. Atypical manifestations include relapsing hepatitis and prolonged cholestasis, and complicated cases with acute kidney injury have been reported. Extrahepatic manifestations, such as autoimmune hemolytic anemia, aplastic anemia, pure red cell aplasia, pleural or pericardial effusion, acute reactive arthritis, acute pancreatitis, acalculous cholecystitis, mononeuritis, and Guillain-Barr syndrome, have been rarely reported. Management of hepatitis A includes general supportive care, and critical decisions regarding liver transplantation await further studies on prognostic predictors. Fundamental management ofhepatitis A is active vaccination. However, a vaccination program should be adapted to the regional situation, according to differing epidemiology and disease burden. Copyright 2010 S. Karger AG, Basel. J Med Virol. 2010 Aug;82(8):1318-26. doi: 10.1002/jmv.21822. Atypical manifestations of hepatitis A infection: a prospective, multicenter study in Korea. Jung YM, Park SJ, Kim JS, Jang JH, Lee SH, Kim JW, Park YM, Hwang SG, Rim KS, Kang SK, Lee HS, Yun HS, Jee YM, Jeong SH. Source Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea. Abstract The clinical outcome of symptomatic hepatitis A and the incidence and clinical characteristics of atypical presentation of hepatitis A were studied using prospective, multicenter design. The atypical presentation included delayed anti-hepatitis A virus (HAV) immunoglobulin M (IgM) seroconversion defined as positive anti-HAV IgM on the repeated test within 7 days of hospital admission after the initially negative result, prolonged cholestasis, and acute kidney injury (AKI). A total of 595 patients with symptomatic hepatitis A requiring hospital admission were enrolled prospectively from September 2006 to August 2008 in four major hospitals in a Korean city with a population of approximately 1 million. Clinical outcomes of symptomatic hepatitis A showed a case fatality rate of 0.2%, and fulminant hepatitis in 0.5%. Delayed anti-HAV IgM seroconversion was found in 6.4%, and was significantly associated with shorter intervals from symptom onset to hospital admission, higher body mass index, and lower alanine aminotransferase (ALT) level at admission. Prolonged cholestasis was found in 4.7% of patients, and could be predicted by preexisting chronic hepatitis B viral infection, prolonged prothrombin time, and higher total bilirubin level. AKI was complicated in 1.5%, which could be predicted by lower albumin level, higher ALT level, and higher white blood cell (WBC) count. More than half of the patients required hemodialysis. Substantial occurrence of delayed anti-HAV IgM seroconversion, prolonged cholestasis, and AKI was confirmed with various predictable factors, which could be helpful for accurate diagnosis and management of hepatitis A patients. (c) 2010 Wiley-Liss, Inc. PMID: 20572083 [PubMed - indexed for MEDLINE] Eur J Radiol. 2009 Nov;72(2):327-34. doi: 10.1016/j.ejrad.2008.07.020. Epub 2008 Sep 4. Fulminant hepatic failure in children: etiology, histopathology and MDCT findings. Cakir B, Kirbas I, Demirhan B, Tarhan NC, Bozkurt A, Ozcay F, Coskun M. Source Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara, Turkey. banutopcu@yahoo.com Abstract INTRODUCTION:

The purpose of this study is to determine the etiologies, histopathology and MDCT findings of children with fulminant hepatic failure admitted to our institution. MATERIALS AND METHODS: Between June 2004 and November 2006, 15 children with fulminant hepatic failure who underwent MDCT were included retrospectively in this study. Twelve patients had liver biopsies. The patients were divided into three groups as hyperacute (Group I), acute (Group II) and subacute (Group III) depending on onset of hepatic encephalopathy. RESULTS: Hepatitis A in 4 patients, non-A, non-E hepatitis in 4; mushroom poisoning in 3; fulminant Wilson's disease in 2; autoimmune hepatitis in 1; and both hepatitis B and toxic hepatitis (with leflunomide treatment) in 1 patient were detected. MDCT of all three groups revealed diffuse reduction in hepatic attenuation in 11 patients; ascites in 9; periportal edema in 6; edema of gallbladder wall in 6; splenomegaly in 6; heterogeneous hepatic parenchyma in 6; hepatomegaly in 3; irregular contours of liver in 2; multiple micronodules in 1 and necrotic areas and regeneration in liver parenchyma in 2 patients. Histopathologic evaluation of liver biopsies showed massive hepatic necrosis, inflammatory cell infiltration and ductular proliferation in 8 patients, periportal edema in 6, edema of gallbladder wall in 5, regenerating nodules and fibrous septa consistent with cirrhotic pattern in 2, and regenerating nodules and necrotic areas in 2 patients. CONCLUSION: The most common MDCT findings in fulminant hepatic failure were diffuse reduction in hepatic attenuation and ascites. Massive hepatic necrosis was the most common histopathologic finding. PMID:18771870 [PubMed - indexed for MEDLINE] Korean J Gastroenterol. 2008 Nov;52(5):298-303. [Clinical features of acute hepatitis A in recent two years]. [Article in Korean] Lee EJ, Kwon SY, Seo TH, Yun HS, Cho HS, Kim BK, Choe WH, Lee CH, Kim JN, Yim HJ. Source Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea. Abstract BACKGROUND/AIMS: The purpose of this study was to characterize the clinical features of acute hepatitis A in Seoul and Gyeonggi province during the recent 2 years. METHODS: We reviewed the medical records of 222 patients who were diagnosed as acute hepatitis A between August 2005 and March 2007 at the Konkuk University Hospital and Korea University, Ansan Hospital. The clinical manifestation, serological tests, and image findings were analyzed. RESULTS: Median age of the patients was 28.1 years and the age groups of highest incidence were the second and third decade. The frequent symptoms were anorexia (66.4%), fatigue (49.2%), fever (47.7%), and abdominal discomfort (42.5%). Fourteen cases (6.3%) showed renal insufficiency, and hemodialysis was performed in one. Cholestatic hepatitis in 2 cases, relapsing hepatitis in 4 cases and prolonged hepatitis in 13 cases were observed. However, there was no case of fulminant hepatitis or death. The underlying diseases including chronic hepatitis B, diabetes mellitus and thyroid disorder did not affect the disease severity of hepatitis A. IgM anti-HAV was not detected initially in 6.7% of the patients. Anti-HEV (IgM) was detected simultaneously in 3 of 150 patients. CONCLUSIONS: The age of patients with acute hepatitis A has been increased in the recent years. Most patients recovered uneventfully. However, unusual patterns of severe hepatitis and renal

insufficiency occurred in considerable number of cases. Follow-up serologic test for IgM anti-HAV is needed in seronegative cases with hepatitis A. PMID: 19077476 [PubMed - indexed for MEDLINE] Med Princ Pract. 2006;15(4):266-9. Epidemiology and outcome of severe hepatitis A infection in children in Kuwait. Husain E, Al-Tawfiq JA, Husain K. Source Department of Pediatrics, Infectious Diseases Hospital, Kuwait. entesar@qualitynet.net Abstract OBJECTIVE: To describe the epidemiology, clinical features and outcome of hepatitis A virus (HAV) infection in children in Kuwait. SUBJECTS AND METHOD: The medical records of 350 patients (age 0-16 years) admitted to the Infectious Diseases Hospital, Kuwait, between January 2000 and December 2002, with hepatitis A infection were reviewed. RESULTS: The mean age was 8.6 +/- 3.8 years and 47% of patients were between 7 and 12 years old. Kuwaiti children comprised 44% of admitted patients. The largest proportion of children with hepatitis A (34%) were from the northern part of the country. HAV infection was prevalent throughout the year with a peak during the months of August to October. Of the Kuwaiti children, 31% reported a history of contact with jaundiced patients, while 52% of the non-Kuwaiti children had a history of recent travel prior to their illness. Patients had symptoms for a mean of 6 +/- 3.6 days prior to presentation. The mean length of hospitalization was 5.8 +/- 2.9 days. The rate of complications of HAV infection was 6% and only one child required admission to the intensive care unit for fulminant hepatitis. None of the patients had permanent sequelae. CONCLUSIONS: HAV infection is a significant cause of morbidity for children in Kuwait. The disease is mostly prevalent in preschool and school agechildren. Despite the excellent outcome of all patients, a considerable number of patients tend to have a complicated course and prolonged hospitalization. In view of these data, hepatitis A vaccine should be considered as a part of routine childhood immunization in Kuwait. Copyright 2006 S. Karger AG, Basel. Acta Medica (Hradec Kralove). 2005;48(3-4):173-5. Two siblings with fulminant viral hepatitis A: case report. Yalniz M, Ataseven H, Celebi S, Poyrazolu OK, Sirma N, Baheitolu IH. Source Firat University, Department of Gastroenterology, Faculty of Medicine, Turkey. mehmetyalniz@hotmail.com Abstract Fulminant hepatitis is a rare complication of acute hepatitis A infection. Nevertheless, the seroepidemiology of the infection is rapidly changing with the developing world, rendering more adults susceptible to the infection, in particular with more severe course. We report here fulminant hepatitis Ainfection with a mortal course during an epidemic period in two siblings. Although it causes a self-limited mild disease, hepatitis A virus may have a severe course including fulminant hepatitis and may lead to mortality, especially in older ages. Hence, the risk of hepatitis A virus infection and its complications should be reduced with measures of immunization and sanitation. Med J Aust. 2000 Jan 3;172(1):19-21.

Fulminant hepatitis A in indigenous children in north Queensland. Hanna JN, Warnock TH, Shepherd RW, Selvey LA. Source Queensland Health, Cairns. md1@health.qld.gov.au Abstract Since 1993, three Indigenous children in north Queensland have died of fulminant hepatitis A. Even if the children had been able to undergo liver transplantation, prolonged immunosuppressant therapy and the likelihood of opportunistic infections would inevitably have jeopardised any chance of long-term survival. As hepatitis A has become a leading infectious cause of death in young Indigenous children in north Queensland, hepatitis Avaccine has recently been introduced into the vaccination schedule for these children. Hepatology. 1997 Oct;26(4):1018-22. Liver failure in children with hepatitis A. Debray D, Cullufi P, Devictor D, Fabre M, Bernard O. Source Service d'Hpatologie Pdiatrique, Hpital de Bictre, Le Kremlin-Bictre, France. Abstract There have been very few reports dealing with liver failure related to hepatitis A in children. Moreover, the criteria usually used for selecting patients with fulminant hepatitis A for liver transplantation have not been evaluated in children. Therefore, the current study was conducted retrospectively in a single French urban pediatric liver transplantation center to serve as a reminder of the potential severity of hepatitis A in children and to identify predictors of outcome. Children were selected by chart review using a data base system and were grouped according to outcome for analyses purposes. Over a 15-year period, 24 children with hepatitis A showed evidence of liver failure, including 6 children who did not develop hepatic encephalopathy, 7 children in whom encephalopathy occurred but resolved spontaneously, and 11 children in whom death or liver transplantation was the outcome. The mean age at onset was 6.5 years. Those with the most rapid onset of liver failure from onset of jaundice had the best chance of recovery without developing encephalopathy. Otherwise, no predictive factors of outcome were found at onset of liver failure. Among the 18 childrenwho developed encephalopathy, the best early prognostic indicator of a poor outcome irrespective of the grade of encephalopathy, appeared to be a prothrombin time level below 21% of normal combined with a serum bilirubin level above 400 micromol/L. Therefore, these two prognostic indicators may be helpful in deciding liver transplantation in children with hepatitis A-induced fulminant liver failure. Gastroenterol Clin Biol. 1997;21(4):327-30. [Hematologic manifestations related to hepatitis A virus. 3 cases]. [Article in French] Maiga MY, Oberti F, Rifflet H, Ifrah N, Cals P. Source Service d'Hpato-Gastroentrologie, CHU, Angers. Abstract We report 3 cases of acute hepatitis A infection with haematological manifestations. In the first case, severe aplastic anemia occurred in a 6 year-oldchild, who underwent 3 bone marrow grafts before responding favourably. In the second and third cases, severe anemia and thrombocytopenia occurred in a 42 year-old man with cholestatic hepatitis, and in a 66 year-old man with fulminant hepatitis; there was a favourable outcome in both cases. These cases demonstrate that haematological manifestations in hepatitis A can be severe, independent of the severity of liver disease. Although these manifestations seem to be rare, we suggest performing systematic haematological evaluations in cases of viral hepatitis A with unusual outcomes.

J Clin Gastroenterol. 1993 Sep;17(2):158-62. Fulminant hepatic failure with massive necrosis as a result of hepatitis A infection. Masada CT, Shaw BW Jr, Zetterman RK, Kaufman SS, Markin RS. Source Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135. Abstract Fulminant hepatic failure as a result of hepatitis A is a rarely diagnosed complication entity in developed countries. With the advent of specific serologic markers for acute hepatitis A virus infection, the incidence and pathology of fulminant hepatitis A can be more clearly defined. We describe four patients (one adult, three children; two males and two females, ages 2 1/2-58 years) referred to our institution for orthotopic liver transplantation subsequent to fulminant hepatic failure following hepatitis A infection. All of these patients had a history of residence in or travel to hepatitis Aendemic areas. Hepatitis A infection was documented by the presence of serum IgM against hepatitis A virus prior to transplantation. Infection with hepatitis B virus, cytomegalovirus, Epstein-Barr virus, and herpes simplex virus was excluded by clinical and specific serologic examinations. All patients presented with varying degrees of encephalopathy, progressing to coma. Coagulopathy in the form of prolonged prothrombin time and partial thromboplastin time was present in all patients. Peak liver parenchymal enzymes increased to greater than ten times the upper limit of the normal range. Total and direct bilirubin levels increased to > 20 and 10 mg/dl, respectively. Histologic evaluation of the explanted livers showed a spectrum of changes ranging from periportal hepatocellular necrosis with focal parenchymal collapse and prominent bile duct proliferation to massive necrosis with complete loss of hepatic architecture. Vaccine. 1992;10 Suppl 1:S18-20. Atypical clinical manifestations of hepatitis A. Schiff ER. Source Division of Hepatology, University of Miami School of Medicine, FL. Abstract Viral A hepatitis is a self-limited infection occurring predominantly among children usually as an anicteric often subclinical illness. Adults afflicted with this virus are more likely to develop icteric hepatitis. This is exemplified in developed countries when a common source outbreak occurs among non-immune adults. Fulminant hepatitis is uncommon in the USA and hepatitis A has never been documented to evolve into chronic hepatitis. However, prolonged cholestasis and relapsing hepatitis are well described. The usual features of cholestatic viral hepatitis A are pruritus, fever, diarrhoea, and weight loss. Serum bilirubin levels are > 10 mg/dl and the clinical course lasts at least 12 weeks. Cholestasis will spontaneously resolve, although corticosteroids will hasten the resolution but may predispose the patient to develop a relapse of the hepatitis. A biphasic or relapsing form of viralhepatitis A occurs in 6 to 10% of cases. The initial episode lasts 3 to 5 weeks and is followed by a period of remission characterized by normal liver chemistries lasting 4 to 5 weeks. Relapse may mimic the initial episode of the acute hepatitis. The full duration of the illness ranges from 16 to 40 weeks from the onset and immunoglobulin M antibody to hepatitis A virus persists throughout the clinical course. Hepatitis A virus has been recovered from stools during the relapse. Extrahepatic manifestations of hepatitis A include evanescent skin rash and transient arthralgias. Documented cases of arthritis and cutaneous vasculitis have been associated with cryoglobulinaemia and are rare.

Ann Trop Paediatr. 1991;11(3):207-11. Fulminant hepatitis in children: report of 12 cases. Friedland IR, Zuckerman M, Kala UK, Parbhoo KB. Source Department of Paediatrics, Baragwanath Hospital, Johannesburg, South Africa. Abstract Twelve cases of childhood fulminant hepatitis seen over a 4-year period are described. Six had hepatitis A, five hepatitis B and one non-A non-B hepatitis. Encephalopathy, the cardinal feature of fulminant hepatitis, was usually evident within 2 weeks of onset of illness, and the median duration of illness in fatal cases was 19 days. Deep jaundice, prolongation of the prothrombin time and raised serum ammonia were invariable. Eight childrendied and the four survivors were critically ill before recovering. Acute viral hepatitis is generally a benign illness in childhood. Although infrequently recorded, fulminant hepatitis may, however, ensue and is associated with a high mortality. Nihon Shokakibyo Gakkai Zasshi. 1990 Jun;87(6):1383-91. [Clinical and epidemiological study on factors of serious development of viral hepatitis type A]. [Article in Japanese] Muraoka H. Source Second Department of Medicine, Kurume University School of Medicine. Abstract In order to investigate the factors that make viral hepatitis type A serious, clinical pictures were analyzed in 269 patients with viral hepatitis type A broken out during the past 8 years. In 1986 incidence of patients with severe hepatic dysfunction was higher and the average age of them was as high as 36.8 +/- 12.8 years old. The percentage of patients over 40 years of age was increasing from 1979 to 1986. Moreover in 6 patients with fulminanthepatitis type A, 4 of them (66.7%) were older than 50 years. Analysis of the clinical courses of 9 patients associated with underlying chronic liver disease disclosed serious hepatic dysfunctions in 7 out of 9. And the prolonged course of abnormal transaminase levels was observed in one of them. Therefore, aging and underlying chronic liver disease were considered as main factors that make viral hepatitis type A severe. Rev Inst Med Trop Sao Paulo. 1989 Jul-Aug;31(4):213-20. Fulminant hepatitis: a clinical review of 11 years. Levin AS, Barone AA, Shiroma M. Abstract 24 cases of fulminant hepatitis (FH) hospitalized in the Clnica de Doenas Infecciosas e Parasitrias do Hospital das Clnicas da Faculdade de Medicina da Universidade de So Paulo during the period from January 1976 to December 1986 were reviewed from their clinical, epidemiological and laboratorial aspects. 88% of the patients died; 20 patients (83%) presented hemorrhages and, of these, 19 died. Bacterial infections occurred in 14 patients (58%) all of whom died. Ascitis was noted in 3 cases; cerebral edema was present

in 16 cases. Maximal ALT levels for each patient during hospitalization ranged widely from 81 to 4,460 UI/l. Thirteen patients presented high creatinine levels (54%). Prothrombin time activity ranged from 2.1% to 67%. Fever was present in 20 cases (83%). Encephalopathy occurred within the first 2 weeks of illness in 72% of the cases. In 7 cases other illnesses were present. The etiology could not be determined in 13 cases. In 3 cases it was due to yellow fever and 6 cases were caused by viruses other than yellow fever. In one case the cause was drug usage and in another case, possibly alcohol. The authors believe that the clinical definition of FH requires further discussion before it is established. In this study FH is a young person's disease. The mortality found was similar to that by other authors. Factors that contributed to death were: hemorrhages and bacterial infection. Factors that worsened the prognosis of hepatitis were: associated illnesses and surgical procedure. The levels of ALT during hospitalization did not correlate well with the severity of the hepatitis. Pediatrie. 1987;42(1):37-40. [Fulminating hepatitis A in children. Apropos of 4 cases]. [Article in French] Rayet I, Teyssier G, Damon G, Frappaz D, Colmant A, Pozzetto B. Abstract We report four cases of fulminant hepatitis in children (4 to 15 years) who developed an hepatic encephalopathy grade III to IV, 4 to 13 days after the onset of their illness. Three patients recovered without sequelae. The complications were neurological: one child showed elevation of the intracranial pressure, successfully treated after monitoring of extra-dural pressure; one suffered from cerebral death. Hepatitis A was diagnosed by the presence in serum of the IgM component of hepatitis A antibody, but another etiologic factor was present in two cases: an halothane anesthesia and an Epstein Barr virus infection which could explain the severity of the hepatitis. Acta Paediatr. 2011 Sep;100(9):e132-4. doi: 10.1111/j.1651-2227.2011.02231.x. Epub 2011 Mar 17. Fulminant hepatitis and glomerulonephritis--a rare presentation of hepatitis A virus infection. Pal RB, Saha P, Das I, Sinha MK. Source Department of Pediatrics, rbinod100@gmail.com Medical College and Hospital, Kolkata, India.

Abstract AIM: We report a case of fulminant hepatitis and glomerulonephritis by Hepatitis A virus infection. METHODS: We observed the patient's clinical course and analyzed his data retrospectively. RESULTS: The three-year-old boy presented with features of acute renal failure and stage 2 hepatic encephalopathy. Renal biopsy showed diffuse mesangioproliferative glomerulonephritis with immunoglobulin M and complement 3 deposition. After receiving supportive

treatment for over 6 weeks, the hepatic and renal function became normal. Renal biopsy after 3 months was normal. CONCLUSION: Acute renal failure is a rare complication of Hepatitis A virus infection. Physicians should be aware of the potential renal involvement of Hepatitis A virus infection as the prognosis is not always favourable. 2011 The Author(s)/Acta Paediatrica 2011 Foundation Acta Paediatrica. Med Arh. 2005;59(6):339-42. [Pathological aspects of the prolonged forms of the hepatitis "A"]. [Article in Bosnian] Dautovi-Krki S, Radovi S. Source Klinika za Infektivne Bolesti, Klinicki Centar Univerziteta U Sarajevu. Abstract Prolonged forms of the hepatitis "A" have been examined during the three year multicentric prospected study. AIMS: Of the study from patohistological aspect was: 1) Determinate stage and type of liver damage during the differentiate phase of prolonged HAV infection; 2) The resultats of the researches compared with duration of persistance activity of serum ALT, circulating immune complexes (CIC) and persistence length IgM anti-HAV. MATERIAL AND METHODS: In 21 patients with prolonged Hepatitis "A" have been done Biopsy of Liver with Menhginy needle by intercostal approach. We put the material into formalin and it was processed by standard procedure. Biopsy of liver was preformed between 50-60 days, 60-180 days, 180210 days of illness. Anti-HAV IgM was determined by ELISE method. CIC have determined photometrically in the poliethylenglycole sediment. RESULTS: of the researches showed that in 21 patients with biopsy Hepatitis acuta was faund in 20%, 55 % residue posthepatitis, 10% patients had nonspecifical finding, 10 % reported hronical persistence hepatitis and 5% chronical active hepatitis. CONCLUSIONS: Authors conclused that during the prolonged HAV infection, all stages of liver damage can be find from acute to chronic illness. There is positive correlation between persistance of maintaince of CiC and IgM anti-HAV in patients sera and staging of patohistological lesions in liver. There is no correlation between activity of CIC, activity ALT in sera and study of liver lesions.