Anti-liver-kidney microsome antibody-positive autoimmune hepatitis presenting as fulminant liver failure

A 17-month-old girl presented with acute hepatitis, which took a fulminant course leading to death 2 months after onset. No known cause of fulminant liver failure could be identified. Postmortem examination of the liver showed massive multilobular necrosis and areas of severe piecemeal necrosis. A high level of total serum gamma-globulins raised the possibility of autoimmune hepatitis. Search for anti-liver-kidney microsome antibody in the patient's serum was positive by immunofluorescence and enzyme-linked immunosorbent assay. Western blot analysis showed reactivity of the antibody with a 50-kDa protein identical to that observed in children with autoimmune hepatitis. This patient's history strongly suggests that autoimmune hepatitis can present as fulminant liver failure in children. Early diagnosis in such a patient could lead to early immunosuppressive therapy.     

A rare case of adenoviral fulminant hepatic necrosis after chemotherapy

The authors report a rare case of fulminant adenoviral hepatic necrosis occurring after chemotherapy in a patient with a second relapse of acute myeloid leukemia. The literature is reviewed and the a role of rapid viral diagnosis in the clinical management of this complication is discussed. A 10-year-old girl with relapsed acute myeloid leukemia after allogeneic bone marrow transplant underwent re-induction chemotherapy with high-dose cytosine arabinoside and amsacrine. During induction she developed diarrhea and a marked coagulopathy, followed by fulminant hepatic failure and acute pre-renal failure. She rapidly deteriorated and died. A limited autopsy was performed. Adenovirus type 5 was cultured from ante mortem clinical samples and detected by polymerase chain reaction in postmortem samples of heart blood, lung, trachea, spleen, and liver. At autopsy, the liver demonstrated massive hepatic necrosis with positive immunofluorescence for adenovirus. Electron microscopy demonstrated intranuclear inclusions, typical of adenovirus. There was no evidence of pneumonia. Adenovirus can cause fulminant hepatic necrosis following chemotherapy in a nontransplant setting. If adenoviral disease is suspected, appropriate rapid viral studies should be undertaken, because early intervention with ribavirin or cidofovir may prevent rapid fulminant progression. Further studies on the role of antiviral therapy in this setting are warranted.     

A RARE CASE OF ADENOVIRAL FULMINANT HEPATIC NECROSIS AFTER CHEMOTHERAPY

The authors report a rare case of fulminant adenoviral hepatic necrosis occurring after chemotherapy in a patient with a second relapse of acute myeloid leukemia. The literature is reviewed and the a role of rapid viral diagnosis in the clinical management of this complication is discussed. A 10-year-old girl with relapsed acute myeloid leukemia after allogeneic bone marrow transplant underwent re-induction chemotherapy with high-dose cytosine arabinoside and amsacrine. During induction she developed diarrhea and a marked coagulopathy, followed by fulminant hepatic failure and acute pre-renal failure. She rapidly deteriorated and died. A limited autopsy was performed. Adenovirus type 5 was cultured from ante mortem clinical samples and detected by polymerase chain reaction in postmortem samples of heart blood, lung, trachea, spleen, and liver. At autopsy, the liver demonstrated massive hepatic necrosis with positive immunofluorescence for adenovirus. Electron microscopy demonstrated intranuclear inclusions, typical of adenovirus. There was no evidence of pneumonia. Adenovirus can cause fulminant hepatic necrosis following chemotherapy in a nontransplant setting. If adenoviral disease is suspected, appropriate rapid viral studies should be undertaken, because early intervention with ribavirin or cidofovir may prevent rapid fulminant progression. Further studies on the role of antiviral therapy in this setting are warranted.     

Our experience with fulminant hepatic failure in Turkish children: etiology and outcome

Fulminant hepatic failure is a rare and devastating event during childhood. The etiology of liver failure is reported to change according to age and geographical location. We aimed to investigate, retrospectively, causes and outcome of fulminant hepatic failure in Turkish children. Thirty-four children with fulminant hepatic failure were analysed by means of etiology and outcome. Etiological factor, clinical presentation, encephalopathy stage and biochemical parameters were correlated with outcome. Acute viral hepatitis was detected in 12 cases (35.2 per cent) and hepatitis A was the most commonly detected cause among cases with fulminant hepatic failure (n = 9, 26.4 per cent). Hepatitis B and non A-E infection were diagnosed in two (5.8 per cent) and one (2.9 per cent) cases, respectively. Wilson's disease was defined in four patients (12.5 per cent). Budd-Chiari syndrome (2.9 per cent), autoimmune hepatitis (2.9 per cent) and mushroom poisoning (2.9 per cent) were other detected causes of fulminant hepatic failure in this group. No viral, metabolic, toxic or anatomic reason could be detected in the remaining 15 (44.1 per cent) patients and they were evaluated as cryptogenic. Mortality was 67.6 per cent (23 cases). Encephalopathy grade, total and indirect bilirubin levels were found to be significantly higher in patients who died (p = 0.004, p = 0.03, p = 0.04). Seven patients could have been transplanted (two cadavaric, five living related) and the mortality of this group was 28.5 per cent (n = 2). It was concluded that fulminant hepatitis A virus (HAV) infection is the most common detectable cause of fulminant hepatic failure in Turkish children.     

Orthotopic liver transplantation for acute liver failure secondary to autoimmune hepatitis in a child with autoimmune polyglandular syndrome type 1

Autoimmune polyglandular syndrome type 1 (APS-1) is an autosomal-recessive condition characterized by hypoparathyroidism, autoimmune Addison's disease, and chronic mucocutaneous candidiasis. Autoimmune hepatitis develops in 10-20% of affected patients and has a variable course ranging from asymptomatic chronic liver disease to lethal fulminant hepatic failure. Liver transplantation has been documented previously in only two patients. We report a 14-yr-old boy with APS-1 who developed acute liver failure secondary to associated autoimmune hepatitis. He did not respond to corticosteroid therapy and was successfully treated with an orthotopic liver transplant.     

Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United kingdom

OBJECTIVE: To study the etiology, outcome and prognostic indicators in children with fulminant hepatic failure in the United Kingdom. DESIGN: Retrospective review of all patients <17 years with fulminant hepatic failure from 1991 to 2000. Fulminant hepatic failure was defined as presence of coagulopathy (prothrombin time >24 seconds or International Normalized Ratio >2.0) with or without hepatic encephalopathy within 8 weeks of the onset of symptoms. SETTING: Liver Unit, Birmingham Children's Hospital, United Kingdom. RESULTS: Ninety-seven children (48 male, 49 female; median age, 27 months; range, 1 day-192.0 months) were identified with fulminant hepatic failure. The etiologies were: 22 metabolic, 53 infectious, 19 drug-induced, and 3 autoimmune hepatitis. The overall survival rate was 61%. 33% (32/97) recovered spontaneously with supportive management. Fifty-five children were assessed for liver transplantation. Four were unstable and were not listed for liver transplantation; 11 died while awaiting liver transplantation. Liver transplantation was contraindicated in 10 children. Of the 40 children who underwent liver transplantation, 27 survived. Children with autoimmune hepatitis, paracetamol overdose or hepatitis A were more likely to survive without liver transplantation. Children who had a delay between the first symptom of liver disease and the onset of hepatic encephalopathy (median, 10.5 days versus 3.5 days), higher plasma bilirubin (299 micromol/L versus 80 micromol/L), higher prothrombin time (62 seconds versus 40 seconds) or lower alanine aminotransferase (1288 IU/L versus 2929 IU/L) levels on admission were more likely to die of fulminant hepatic failure or require liver transplantation (P < 0.05). On multivariate analysis, the significant independent predictors for the eventual failure of conservative therapy were time to onset of hepatic encephalopathy >7 days, prothrombin time >55 seconds and alanine aminotransferase 相似文献   

No evidence of hepatitis G virus in fulminant hepatic failure in children

BACKGROUND: The cause of fulminant hepatic failure in children remains unknown, but a viral origin has been suspected in most cases. The recently discovered blood-borne virus, hepatitis G, has been suggested as a possible causative agent. METHOD: Six consecutive children who underwent liver transplantation for fulminant hepatic failure were studied. The children were tested for hepatitis G virus antibodies and hepatitis G virus RNA by polymerase chain reaction after excluding other causes of fulminant hepatic failure. RESULTS: No evidence of hepatitis G virus infection was found in these patients. CONCLUSION: Hepatitis G virus is unlikely to be a common cause of fulminant hepatic failure in pediatric patients from the upper midwestern United States.     

Aetiology of lcteric Hepatitis and Fulminant Hepatic Failure in Children and the Possible Predisposition to Hepatic Failure by Sickle Cell Disease

ABSTRACT. The aetiological agents of acute icteric hepatitis and fulminant hepatic failure were investigated in 47 children less than 12 years of age presenting at our hospital during the period January to December 1987. Hepatitis A virus was the aetiological agent in 72 %, hepatitis B virus in 11 %, cytomegalovirus in 2 % and non A non B in 15 %. These results confirm the endemicity of these viruses in the Saudi population and that they can be contracted in early life and could lead to severe hepatitis. Three of the patients who had hepatitis A virus infection developed fulminant hepatic failure and two of them died. Two of the patients who developed fulminant hepatic failure were also suffering from sickle cell disease. This raises the question of a possible predisposition to hepatic failure in sickle cell disease upon infection with hepatitis A virus.     

Aetiology of icteric hepatitis and fulminant hepatic failure in children and the possible predisposition to hepatic failure by sickle cell disease

The aetiological agents of acute icteric hepatitis and fulminant hepatic failure were investigated in 47 children less than 12 years of age presenting at our hospital during the period January to December 1987. Hepatitis A virus was the aetiological agent in 72%, hepatitis B virus in 11%, cytomegalovirus in 2% and non A non B in 15%. These results confirm the endemicity of these viruses in the Saudi population and that they can be contracted in early life and could lead to severe hepatitis. Three of the patients who had hepatitis A virus infection developed fulminant hepatic failure and two of them died. Two of the patients who developed fulminant hepatic failure were also suffering from sickle cell disease. This raises the question of a possible predisposition to hepatic failure in sickle cell disease upon infection with hepatitis A virus.     

Variability of clinical presentation of hepatic artery thrombosis in pediatric liver transplantation: Role of imaging modalities

Among a series of 90 pediatric liver transplantations, 9 cases of hepatic artery thrombosis (HAT) in 8 patients are reported. All cases were diagnosed in the first two weeks and confirmed angiographically and surgically. Clinical presentation was often unreliable with only 2 cases showing the typical pattern of massive hepatic necrosis. Five cases presented with biliary complications and in 2 cases, HAT was discovered fortuitously on duplex sonography. The role of imaging modalities is emphasized. Duplex sonography is the best non-invasive screening method and we recommend a routine daily examination in the first 2 weeks. CT is the most useful method to assess the extension of liver infarction. PTC remains necessary to evaluate biliary complications and to plant the best therapeutic approach in this devastating event. Two patients died, 2 had to be retransplanted (one patient twice) and are doing well, 2 are on a waiting list for re-transplantation and one underwent an emergency surgical arterial desobstruction and is completely asymptomatic.Presented at the ESPR meeting in Dublin 1989. Selected for publication by an International Group of the ESPR     

Fulminant hepatitis in Kala-azar

One hundred and fifty cases of Kala-azar were studied for evidence of hepatic involvement. The hepatic function was mildly affected in 25 cases and 3 cases had fulminate hepatitis. Most of the cases were cured after anti-Kala-azar therapy except 2 cases, who died of hepatic failure. This study suggests that fulminant hepatitis may be the outcome of Kala-azar, itself.     

Successful tenofovir treatment for fulminant hepatitis B infection in an infant

Fulminant hepatic failure is defined by the presence of severe impairment of liver function, with or without encephalopathy, in patients with no underlying chronic liver disease. We report the case of a 4-month-old infant who developed fulminant hepatitis B infection and recovered concomitant with tenofovir therapy without liver transplantation.     

Adenovirus necrotizing hepatitis complicating atypical teratoid rhabdoid tumor

Adenovirus‐induced fulminant hepatitis is rare. It has been reported in children with primary immunodeficiency, following transplantation or while receiving chemotherapy for hematological malignancy. We present the case of an infant recovering from chemotherapy for atypical teratoid rhabdoid tumor (ATRT) in whom a diagnosis of hepatic necrosis due to adenovirus was made.     

Propylthiouracil-associated liver failure presenting as probable autoimmune hepatitis in a child with Graves' disease

This case describes a young girl with Graves' disease, who presented with fulminant hepatic failure 9 months into propylthiouracil (PTU) therapy. Her clinical presentation was consistent with 'probable autoimmune hepatitis,' as defined by the International Autoimmune Hepatitis Group scoring system. Despite discontinuation of PTU and high-dose steroid therapy, she required liver transplantation. Subsequent pathology could not definitively rule out autoimmune hepatitis. PTU is an important cause of drug-related liver failure in children, and clinicians should be mindful that it is frequently used in patients who already have an underlying risk of autoimmune liver disease.     

CD8 + T-LYMPHOCYTE INFILTRATION AND APOPTOSIS IN FULMINANT EPSTEIN-BARR VIRUS HEPATITIS IN A PREVIOUSLY HEALTHY GIRL

A previously healthy 9-month old girl presented with fulminant hepatitis caused by the Epstein Barr virus (EBV). The patient developed fever, coma, and jaundice, and laboratory examination demonstrated acute liver failure. She did not respond sufficiently to conservative treatment and underwent liver transplantation with a graft from her father. Her condition improved transiently, but she died several weeks after surgery from a recurrence of liver failure. Histologic examination of the excised liver revealed massive panacinar necrosis and infiltration of mononuclear cells. Immunohistochemical staining identified these cells as CD8 + T-lymphocytes. A small number of apoptotic cells were observed, the nuclei of which were clearly labeled by terminal-deoxyribosyl-transferase-mediated deoxyuridine nick-end labeling. Tests for anti-EBV antibodies gave negative results, and EBV infection was diagnosed by in situ hybridization of liver tissue. CD8 + T-lymphocytes induced by the viral infection and apoptosis may have played an important role in damaging the hepatocytes of this patient.     

Chronic active hepatitis with a favorable course, after fulminant hepatitis]

The case reported here is that of a girl with presumably viral non A, non B, acute hepatitis with a very unusual course. Fulminant hepatitis with submassive and bridging hepatic necrosis and a 17-day coma began during the 7th week of evolution. Prolonged chronic active hepatitis followed. Treatment was initiated 6 months after the beginning of the affection and was maintained for more than 2 years, with an apparent cure persisting after follow-up period of 6 months; fibrous scars were the only abnormalities demonstrable on histologic examination of liver biopsy. It is possible that such type of fulminant hepatitis with unusual course will become more frequent, as survival of the initial acute episode increase.     

Extensive hepatic necrosis in a premature infant.

A fatal case of fulminant hepatic failure that occurred in the neonatal period is reported in a premature infant born after 27 4/7-weeks' gestation. Immediately after birth the infant had severe hypoxia and hypotension resulting from birth asphyxia, hypovolemic shock, and septicemia. At autopsy, histological appearance of the liver showed virtually total hepatocellular necrosis without features of fibrosis. Although the exact cause of hepatocellular injury cannot be fully ascertained, it is assumed that hypoxia and hypotension must have been the predominant factors leading to massive hepatic necrosis.     

Fulminating hepatitis A in children. Apropos of 4 cases

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.     

Perinatal cytomegalovirus hepatitis: to treat or not to treat with ganciclovir

OBJECTIVE: The use on ganciclovir for perinatal cytomegalovirus (CMV) infection is controversial. We aim to evaluate the use of ganciclovir treatment for neonatal CMV hepatitis. METHODS: We present five infants with perinatally-acquired CMV hepatitis as a single organ manifestation of CMV infection. The three more severely affected children, i.e. those with cholestasis and elevation of serum hepatic enzymes to more than twice the normal values, were treated for 15 days with intravenous ganciclovir. RESULTS: The three treated infants improved clinically and CMV DNA in the blood disappeared during treatment. After cessation of ganciclovir treatment all of the patients had a relapse of the infection. The two untreated patients recovered completely. CONCLUSION: The long-term outcome of infants with CMV hepatitis is unpredictable. Some patients have persistent liver injury despite ganciclovir therapy. Ganciclovir therapy did not prevent chronic liver disease in any of the patients in our study. Owing to the possible serious side-effects the cost-benefit of ganciclovir treatment should be carefully evaluated.