Cause Of Fulminant Hepatic Failure Research Articles

Auxiliary partial orthotopic liver transplantation (APOLT) in the treatment of acute liver failure

Auxiliary partial orthotopic liver transplantation (APOLT) has been developed in order to benefit from the efficacy of orthotopic liver transplantation (OLT) in the treatment of fulminant hepatic failure (FHF), but to avoid the negative counterpart of OLT which is to eliminate the possibility of native liver (NL) regeneration and which consequently implies a life-long immunosuppression. In our institution we performed 16 consecutive APOLTs in 15 patients between October 1992 and December 1999. Patients' mean age was 30 years (range 0.5-65 years). The causes of FHF were viral (HAV = 3; HBV = 3), drugs (n = 4), or others (n = 5). None of the patients had a history of chronic liver disease. The decision to transplant was taken when the patients met well-defined criteria. All but one of the patients were in a coma. Five patients died, 10 patients are alive (66.7%). Regeneration of the NL occurred in 11 of the 15 patients (73.3%) and in 8 of the 10 survivors. Six of these 8 patients have permanently stopped immunosuppressive therapy. These results can be favorably compared with those of OLT for FHF. In the European Transplant Registry, the survival rate is 57% at 5 years (2612 patients receiving OLT for FHF between 1988 and 1998). In our experience the survival rate is 59% at 5 years (42 patients receiving OLT for FHF between 1987 and 1999). APOLT is feasible in both adults and children; it rapidly restored liver function and reversed encephalopathy. Right APOLT seems more advisable since the right liver provides more functional hepatocytes; however, left APOLT harvested in an adult appears sufficient for a child. APOLT should be proposed only to patients with high chances of liver regeneration: age of recipient, etiology of liver failure, interval between onset of jaundice and occurrence of encephalopathy, and quality of liver graft are early prognostic indicators. Better results have been observed with younger patients (less than 40 years old) presenting with FHF (rather than subfulminant hepatic failure (SHF)) and due to HAV, HBV, or paracetamol.

Hepatic Failure as the Presenting Manifestation of Malignant Lymphoma

Fulminant hepatic failure carries a high mortality regardless of etiology. Liver transplantation may be lifesaving. Hepatic invasion by malignant lymphoma is a rare cause of liver failure, but one that is potentially responsive to treatment. Lymphoma (non-Hodgkin's or Hodgkin's) should be included in the differential diagnosis of fulminant hepatic failure so that liver transplantation is avoided and appropriate therapy can be instituted. The findings and clinical course of 4 patients with liver failure due to hepatic lymphoma, who were referred to our institution for liver transplant evaluation, are presented and discussed. Medical records, imaging studies, and histological material were examined. Review of the literature revealed less than 40 cases of lymphoma presenting as fulminant hepatic failure. The diagnosis of malignant lymphoma may be difficult. The presenting symptoms and signs are indistinguishable from other causes of fulminant hepatic failure. Early liver biopsy with adequate tissue and immunologic studies is mandatory for diagnosis. This condition may be reversible and may respond to chemotherapy if the diagnosis is made prior to multiorgan system failure. The presence of malignant lymphoma is considered a contraindication to liver transplantation, although firm data are lacking.

Herpes Simplex Type 2 Causing Fulminant Hepatic Failure

Although exceedingly rare, fulminant hepatic failure (FHF) in immunocompetent patients can develop with primary or recurrent infection due to herpes simplex virus (HSV). The diagnosis is frequently obscured by the absence of mucocutaneous involvement. Elevated transaminase values with leukopenia and a relatively low bilirubin level may provide clues to the diagnosis. We describe an immunocompetent woman who died of FHF before a definitive diagnosis of HSV type 2 hepatitis was established. Herpes simplex virus hepatitis is one of the few causes of FHF for which potentially effective therapy is available. Thus, early diagnosis is paramount and usually requires liver biopsy. Recent studies suggest that transjugular liver biopsy is safe and effective in establishing the cause of FHF. Since the diagnosis and management of FHF are frequently influenced by the results of transjugular liver biopsy, it may become a standard diagnostic tool for managing FHF in centers where such expertise exists.

A broad-spectrum caspase inhibitor blocks concanavalin A-induced hepatitis in mice.

Fulminant hepatic failure (FHF) is a clinical syndrome resulting from massive death of liver cells or sudden and severe impairment of liver function. The causes of FHF are diverse and the overall mortality is very high. Recently, it became clear that apoptosis of hepatocytes is the critical cause of acute hepatic failure in FHF. It is well known that a family of cysteine proteases called caspase is one of the key mediators of the apoptotic pathway. Thus, caspases are attractive potential targets for the treatment of disorders resulting from excessive apoptosis. In this report, we examined the activity of a new caspase inhibitor, Xyz 033 mp. This nonpeptide inhibitor showed broad-spectrum caspase-inhibiting activity and protected primary rat hepatocytes from apoptotic death. In a mouse model of FHF induced by concavalin A (Con A), Xyz 033 mp suppressed elevated AST and ALT and specifically reduced IL-1 beta concentration. Also, Xyz 033 mp rescued mice from lethal experimental hepatitis induced by Con A. In addition, histological examinations indicated that Xyz 033 mp protected hepatocytes from the fatal apoptogenic effect of Con A. These results suggest that Xyz 033 mp may be a candidate therapeutic agent for FHF caused by massive apoptotic death of hepatocytes.

HEPATITIS B

The hepatitis B virus is a hepatotropic virus that can produce a variety of clinical syndromes in patients ranging in age from infants to elderly adults. Worldwide, it is among the leading causes of fulminant hepatic failure, cirrhosis, and hepatocellular carcinoma. Recent advances have led to effective antiviral treatments using interferon and nucleoside analogues. Highly effective vaccinations also are used widely and ultimately may lead to eradication of this life-threatening virus.

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

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. 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. No evidence of hepatitis G virus infection was found in these patients. Hepatitis G virus is unlikely to be a common cause of fulminant hepatic failure in pediatric patients from the upper midwestern United States.

An institutional review of fulminant hepatic failure in an urban Canadian centre

This study describes the demographic, etiologic, biochemical, and outcome features of 20 adult patients admitted to an urban intensive care unit with fulminant hepatic failure (FHF) from January 1989 to November 1994. The mean age of the group was 46±16 years (range: 18–70) with the majority (12/20, 60%) female. Fifteen (75%) of the 20 patients were encephalopathic prior to admission to the ICU while the remaining five (25%) developed encephalopathy during their ICU stay. The mean ICU stay was 5±4.6 days (range: 1–17 days). Acetaminophen toxicity was the most common cause of FHF (9/20, 45%) followed by hepatic ischemia (5/20, 25%), viral hepatitis (2/20, 10%), and miscellaneous or undiagnosed causes (4/20, 20%). The mortality rate was 95%. These findings indicate that in this Canadian centre the most common cause of FHF admissions to the intensive care unit is acetaminophen toxicity rather than viral hepatitis (British rather than American pattern) and is associated with an unexpectedly high mortality rate.

Living-related liver transplantation and neurological outcome in children with fulminant hepatic failure.

Fulminant hepatic failure (FHF) in children is associated with high mortality under medical management. Living-related liver transplantation (LRLT) is an accepted measure to treat the children with end-stage liver disease. Reversibility of hepatic encephalopathy is crucial for the quality of life among the survivors after transplantation. A retrospective review was made of the records of children undergoing LRLT at this hospital between May 1992 and November 1996. Eleven children with FHF underwent emergency LRLT. The mean age was 5 years (range, 2 months to 15 years). The indication for transplantation was persistent or worsening hepatic encephalopathy and severe coagulopathy, despite repeated plasma exchanges or exchange transfusions. The cause of FHF was non-A, non-B hepatitis in seven children, hepatitis B in two children, herpes simplex virus hepatitis in one child, and fulminant Wilson's disease with intravascular hemolysis in one child. The grade of hepatic encephalopathy was II in four children, III in two, and IV in five. The actuarial survival rate was 73% after a mean follow-up of 28 months (range, 13-67 months). Short-term neurological morbidity was present in two children with grade IV encephalopathy who also showed brain edema on cranial computed tomography. Eight survivors exhibited no long-term neurological deficit; the mean intelligence or developmental quotient was 97 (range, 86-110) at the end of the follow-up period. LRLT is an effective option for the treatment of FHF in children. The long-term neurological status is satisfactory among survivors.

Prognostic evaluation of early indicators in fulminant hepatic failure by multivariate analysis.

Viral hepatitis is the commonest cause of fulminant hepatic failure (FHF) in developing countries. We evaluated the early indicators of prognosis in these patients by multivariate analysis. The records of 204 consecutive patients with acute liver failure admitted with hepatic encephalopathy over five years were studied. The etiology of these patients included virus related in 186 (91.1%), drug induced in 15 (7.4%), Wilson's disease in one (0.5%), acute Budd-Chiari syndrome in one (0.5%), and malignant infiltration in one (0.5%). Patients with FHF complicating viral hepatitis were analyzed by univariate and multivariate analysis. These patients were further subclassified depending upon the interval between the onset of jaundice and the onset of encephalopathy into hyperacute (HALF; interval 0-7 days), acute (ALF; interval 8-28 days) and subacute liver failure (SALF; interval 4-12 weeks). Sixty (32.3%) patients with viral hepatitis survived. Univariate analysis showed that the interval between onset of encephalopathy and onset of jaundice, grade of encephalopathy, raised intracranial pressure, prothrombin time, and serum bilirubin levels on admission were related to outcome in these patients. Multivariate logistic regression analysis showed that the presence of raised intracranial pressure at the time of admission, prothrombin time >100 sec on admission, age (>50 yr), and onset of encephalopathy seven days after onset of jaundice were associated with poor prognosis. Forty seven (37.0%) of 129 patients with HALF survived compared with 9 (22.5%) of 40 with ALF and 4 (21.1%) of 19 with SALF (P = NS). Raised intracranial pressure was more frequent in patients with HALF (48.8%) than in patients with ALF (32.5%) and SALF (15.8%; P = 0.01), while clinically detectable ascites was more frequent in patients with SALF (78.9%) compared with HALF (19.7%) and ALF (37.5%; P < 0.0001). The factors adversely affecting the outcome in our patients with FHF complicating viral hepatitis include presence of overt clinical features of raised ICP at the time of hospitalization, prothrombin time (>100 sec) on admission, age (>50 yr), and onset of encephalopathy seven days after onset of jaundice.

LACK OF EVIDENCE FOR HEPATITIS G VIRUS AND FULMINANT HEPATIC FAILURE IN CHILDREN

Background An apparent increase in the number of fulminant hepatic failure (FHF) cases in infants and children has been reported over the past several years. The majority of patients with FHF have no identifiable etiology. The recently discovered parenterally transmitted virus, hepatitis G (HGV), has been suggested as a possible etiologic agent. Aim: To assess the prevalence of active infection and past exposure to HGV in our children who underwent orthotopic liver transplantation (OLT) for idiopathic fulminant hepatic failure. Methods: Six children, 5 at the Mayo Clinic between 1994-97 and one at the University of Minnesota, underwent OLT for FHF. Drugs, toxins, and metabolic disorders were excluded in all patients. Serology tests for hepatitis A and B, cytomegalovirus, EBV, herpes and Parvovirus B19 were performed in all patients. Polymerase chain reaction (PCR) for the detection of hepatitis C RNA, hepatitis E RNA and HBV DNA was performed. Active HGV viremia was detected in serum and liver tissue by RT-PCR using published primers to the NS5 region of the viral genome with detection by a PCR ELISA technique. Serum was also tested for anti-HGV E2 antibodies using a capture ELISA to assess past exposure to HGV. Results: Serologic markers for hepatitis A IgM, anti-HBc, anti-HCV, EBV IgM, CMV, HSV and Parvovirus B19 IgM were negative in all patients. PCR for HBV and HCV was negative. Five of the explanted liver tissues were cultured and were negative for bacteria and viruses. The mean time from the onset of jaundice to transplantation was 24 days. Two children had aplastic anemia on bone marrow biopsy after OLT, 2 had pancytopenia with normal bone marrow cellularity and 2 had normal white and red blood cell counts. All six pretransplant sera were negative for HGV RNA by PCR. The five explanted livers tested for HGV RNA were also negative by PCR. Pretransplant serum was negative for HGV E2 antibodies in all patients. Conclusions: 1. None of our children transplanted for FHF had evidence for HGV RNA. 2. None of the FHF patients had evidence of anti-HGV E2. 3. HGV is an unlikely cause of FHF with or without aplastic anemia in children.

Mushroom Poisoning: An Indication for Liver Transplantation

There are numerous causes of fulminant hepatic failure including acetaminophen, viral etiologies, acute fatty liver of pregnancy, ischemic hepatitis, and acute Budd-Chiari syndrome. One of the rare causes of fulminant hepatic failure is toxic mushroom poisoning. This article describes one case in which ingestion of a toxic mushroom, Amanita phalloides, caused a patient severe liver damage ultimately requiring organ transplantation. Early identification of liver dysfunction and referral to a liver transplant center for evaluation may be critical to save such a patient's life.

Azathioprine-Induced Lymphoma Manifesting as Fulminant Hepatic Failure

Azathioprine-Induced Lymphoma Manifesting as Fulminant Hepatic Failure

Posttransplantation chronic hepatitis in fulminant hepatic failure.

Non-A, non-B or seronegative hepatitis is the leading indication for liver transplantation in patients with fulminant hepatic failure (FHF). We examined protocol annual review liver allograft biopsy specimens in consecutive adult patients transplanted for FHF in an attempt to determine the extent of the histological changes. One hundred eleven biopsy specimens from 41 patients transplanted for fulminant seronegative hepatitis and 34 from a comparison group of 16 patients transplanted for other causes of FHF (11 paracetamol overdose, 2 idiosyncratic drug reaction, 3 Wilson's disease) were available. Specimens were analyzed using standard proforma without knowledge of the original diagnosis. Chronic hepatitis was present in 29 patients (71%) transplanted for fulminant seronegative hepatitis (23 mild, 3 moderate, and 3 severe) compared with 5 patients (31%, all mild) transplanted for other causes of FHF. Twenty-five patients (61%) grafted for seronegative FHF had fibrosis (13 mild, 9 moderate, and 3 severe) in contrast to 4 fibrosis (25%) (all mild) in the comparison group. Excluding early allograft failure because of primary graft nonfunction or vascular complications, six patients with seronegative FHF required retransplantation (2 = chronic rejection; 1 = severe hepatitis with panacinar necrosis, resembling original liver; and 3 = chronic hepatitis with precirrhotic fibrosis and prominent cholestasis of unknown cause). One patient in the comparison group had a second graft (chronic rejection). Posttransplantation chronic hepatitis is more frequent and severe in patients transplanted for seronegative hepatitis. Graft survival may be adversely influenced by the development of chronic hepatitis, which may represent persistent or recurrent disease.

Fulminant Hepatitis in A Tropical Population: Clinical Course, Cause, and Early Predictors of Outcome

The profiles of patients with fulminant hepatic failure (FHF) from developing countries have not been reported earlier. The current study was conducted prospectively, at a single tertiary care center in India, to document the demographic and clinical characteristics, natural course, and causative profile of patients with FHF as well as to define simple prognostic markers in these patients. Four hundred twenty-three consecutive patients with FHF admitted from January 1987 to June 1993 were included in the study. Each patient's serum was tested for various hepatotropic viruses. Univariate Cox's regression for 28 variables, multivariate Cox's proportional hazard regression, stepwise logistic regression, and Kaplan-Meier survival analysis were done to identify independent predictors of outcome at admission. All patients presented with encephalopathy within 4 weeks of onset of symptoms. Hepatotropic viruses were the likely cause in most of these patients. Hepatitis A (HAV), hepatitis B (HBV), hepatitis D (HDV) viruses, and antitubercular drugs could be implicated as the cause of FHF in 1.7% (n= 7), 28% (n= 117), 3.8% (n= 16), and 4.5% (n= 19) patients, respectively. In the remaining 62% (n= 264) of patients the serological evidence of HAV, HBV, or HDV infection was lacking, and none of them had ingested hepatotoxins. FHF was presumed to be caused by non-A, non-B virus(es) infection. Sera of 50 patients from the latter group were tested for hepatitis E virus (HEV) RNA and HCV RNA. In 31 (62%), HEV could be implicated as the causative agent, and isolated HCV RNA could be detected in 7 (19%). Two hundred eighty eight (66%) patients died. Approximately 75% of those who died did so within 72 hours of hospitalisation. One quarter of the female patients with FHF were pregnant. Mortality among pregnant females, nonpregnant females, and male patients with FHF was similar (P > .1). Univariate analysis showed that age, size of the liver assessed by percussion, grade of coma, presence of clinical features of cerebral edema, presence of infection, serum bilirubin, and prothrombin time prolongation over controls at admission were related to survival (P < .01). The rapidity of onset of encephalopathy and cause of FHF did not influence the outcome. Cox's proportional hazard regression showed age > or = 40 years, presence of cerebral edema, serum bilirubin > or = 15 mg/dL, and prothrombin time prolongation of 25 seconds or more over controls were independent predictors of outcome. Ninety-three percent of the patients with three or more of the above prognostic markers died. The sensitivity, specificity, positive predictive value, and the negative predictive value of the presence of three or more of these prognostic factors for mortality was 93%, 80%, 86%, and 89.5%, respectively, with a diagnostic accuracy of 87.3%. We conclude that most of our patients with FHF might have been caused by hepatotropic viral infection, and non-A, non-B virus(es) seems to be the dominant hepatotropic viral infection among these patients. They presented with encephalopathy within 4 weeks of the onset of symptoms. Pregnancy, cause, and rapidity of onset of encephalopathy did not influence survival. The prognostic model developed in the current study is simple and can be performed at admission.

Fulminant hepatitis in a tropical population: Clinical course, cause, and early predictors of outcome

The profiles of patients with fulminant hepatic failure (FHF) from developing countries have not been reported earlier. The current study was conducted prospectively, at a single tertiary care center in India, to document the demographic and clinical characteristics, natural course, and causative profile of patients with FHF as well as to define simple prognostic markers in these patients. Four hundred twenty-three consecutive patients with FHF admitted from January 1987 to June 1993 were included in the study. Each patient's serum was tested for various hepatotropic viruses. Univariate Cox's regression for 28 variables, multivariate Cox's proportional hazard regression, stepwise logistic regression, and Kaplan-Meier survival analysis were done to identify independent predictors of outcome at admission. All patients presented with encephalopathy within 4 weeks of onset of symptoms. Hepatotropic viruses were the likely cause in most of these patients. Hepatitis A (HAV), hepatitis B (HBV), hepatitis D (HDV) viruses, and antitubercular drugs could be implicated as the cause of FHF in 1.7% (n= 7), 28% (n= 117), 3.8% (n= 16), and 4.5% (n= 19) patients, respectively. In the remaining 62% (n= 264) of patients the serological evidence of HAV, HBV, or HDV infection was lacking, and none of them had ingested hepatotoxins. FHF was presumed to be caused by non-A, non-B virus(es) infection. Sera of 50 patients from the latter group were tested for hepatitis E virus (HEV) RNA and HCV RNA. In 31 (62%), HEV could be implicated as the causative agent, and isolated HCV RNA could be detected in 7 (19%). Two hundred eighty eight (66%) patients died. Approximately 75% of those who died did so within 72 hours of hospitalisation. One quarter of the female patients with FHF were pregnant. Mortality among pregnant females, nonpregnant females, and male patients with FHF was similar (P > .1). Univariate analysis showed that age, size of the liver assessed by percussion, grade of coma, presence of clinical features of cerebral edema, presence of infection, serum bilirubin, and prothrombin time prolongation over controls at admission were related to survival (P < .01). The rapidity of onset of encephalopathy and cause of FHF did not influence the outcome. Cox's proportional hazard regression showed age > or = 40 years, presence of cerebral edema, serum bilirubin > or = 15 mg/dL, and prothrombin time prolongation of 25 seconds or more over controls were independent predictors of outcome. Ninety-three percent of the patients with three or more of the above prognostic markers died. The sensitivity, specificity, positive predictive value, and the negative predictive value of the presence of three or more of these prognostic factors for mortality was 93%, 80%, 86%, and 89.5%, respectively, with a diagnostic accuracy of 87.3%. We conclude that most of our patients with FHF might have been caused by hepatotropic viral infection, and non-A, non-B virus(es) seems to be the dominant hepatotropic viral infection among these patients. They presented with encephalopathy within 4 weeks of the onset of symptoms. Pregnancy, cause, and rapidity of onset of encephalopathy did not influence survival. The prognostic model developed in the current study is simple and can be performed at admission. (Hepatology 1996 Jun;23(6):1448-55)

Auxiliary liver transplantation: Regeneration of the native liver and outcome in 30 patients with fulminant hepatic failure-a multicenter European study

Auxiliary liver transplantation (LT) is a special procedure of LT which could be proposed to patients with fulminant hepatic failure (FHF) and has for aim that complete regeneration of the native liver (NL) left in place will allow the graft recipient to resume normal liver function after allograft withdrawal. We report 30 cases of auxiliary LT performed for FHF in 12 European centers. Twenty-five of 30 patients were younger than 50 years. The cause of FHF was hepatitis A virus (HAV) in 4 patients, hepatitis B virus (HBV) in 7, paracetamol overdose in 5, ecstasy in 2, hepatotoxic drugs in 4, autoimmune hepatitis in 2, liver lesions of preeclampsia in 1 and unknown in 5. A postoperative, both clinical and histological follow-up of more than 3 weeks was obtained in 22 patients, enabling us to look for indicators predictive of NL regeneration and outcome. Histological changes observed in the NL included complete regeneration in 68%, incomplete regeneration with obvious fibrous sequelae in 14% and severe liver fibrosis or cirrhosis in 18%, of the 22 patients studied. The percentage and distribution of necrosis observed in tissue samples of the NL at the time of transplantation was not related to the final outcome. Complete NL regeneration was observed in 15 patients, out of whom 14 were younger than 40 years. Patients with complete regeneration were mainly affected by FHF due to HAV, HBV, or paracetamol overdose. After a follow-up of 18/11 (mean/median) months (range, 3 to 67 months), 19 of the 30 patients (63%) survived and 13 of them (68%), i.e., 43% of the 30 patients, had resumed normal NL function, with interrupted immunosuppression, the ultimate goal of emergency auxiliary LT. We conclude that, in patients with FHF, auxiliary LT is a procedure feasible in a number of centers and is associated with a complete regeneration capability of the NL in a majority of survivors, especially in those younger than 40 years. Confirmation of these encouraging preliminary results by large-scale prospective studies is required.

Auxiliary liver transplantation: Regeneration of the native liver and outcome in 30 patients with fulminant hepatic failure–a multicenter European study

Auxiliary liver transplantation (LT) is a special procedure of LT which could be proposed to patients with fulminant hepatic failure (FHF) and has for aim that complete regeneration of the native liver (NL) left in place will allow the graft recipient to resume normal liver function after allograft withdrawal. We report 30 cases of auxiliary LT performed for FHF in 12 European centers. Twenty-five of 30 patients were younger than 50 years. The cause of FHF was hepatitis A virus (HAV) in 4 patients, hepatitis B virus (HBV) in 7, paracetamol overdose in 5, ecstasy in 2, hepatotoxic drugs in 4, autoimmune hepatitis in 2, liver lesions of preeclampsia in 1 and unknown in 5. A postoperative, both clinical and histological follow-up of more than 3 weeks was obtained in 22 patients, enabling us to look for indicators predictive of NL regeneration and outcome. Histological changes observed in the NL included complete regeneration in 68%, incomplete regeneration with obvious fibrous sequelae in 14% and severe liver fibrosis or cirrhosis in 18%, of the 22 patients studied. The percentage and distribution of necrosis observed in tissue samples of the NL at the time of transplantation was not related to the final outcome. Complete NL regeneration was observed in 15 patients, out of whom 14 were younger than 40 years. Patients with complete regeneration were mainly affected by FHF due to HAV, HBV, or paracetamol overdose. After a follow-up of 18/11 (mean/median) months (range, 3 to 67 months), 19 of the 30 patients (63%) survived and 13 of them (68%), i.e., 43% of the 30 patients, had resumed normal NL function, with interrupted immunosuppression, the ultimate goal of emergency auxiliary LT. We conclude that, in patients with FHF, auxiliary LT is a procedure feasible in a number of centers and is associated with a complete regeneration capability of the NL in a majority of survivors, especially in those younger than 40 years. Confirmation of these encouraging preliminary results by large-scale prospective studies is required. (Hepatology 1996 May;23(5):1119-27)

Hepatitis E Virus: Another Addition to the Existing Alphabet of Human Hepatitis Viruses

Hepatitis E Virus: Another Addition to the Existing Alphabet of Human Hepatitis Viruses

Fulminant hepatic failure caused by ecarazine hydrochloride (a hydralazine derivative)

The cause of fulminant hepatic failure is reported to be unknown in more than half the cases in Japan. We recently reviewed 23 cases of fulminant hepatic failure that had been treated at our hospital. The cause of disease had been regarded as unknown before this study. It was found that seven of these patients had been under ecarazine hydrochloride therapy when they developed fulminant hepatic failure. We examined the reasons why fulminant hepatic failure in these seven patients had not been previously attributed to ecarazine, and found that it could be explained by the following factors: (1) the time from the start of ecarazine therapy to the onset of hepatic failure was long; (2) in all cases, hepatic failure developed more than 10 days after the clinical recognition of hepatitis; and (3) characteristic signs of drug-induced hepatic failure such as a skin rash and positive lymphocytes stimulation test with the drug were absent in all cases. Fulminant hepatic failure in these cases could be characterized by: (1) rapid decrease in serum alanine transaminase (ALT) level after discontinuation of ecarazine, (2) prolonged jaundice despite discontinuation of ecarazine, (3) high incidence of anti-nuclear antibody (ANA) (57%), and (4) histological findings of extensive hepatocellular necrosis ranging from bridging necrosis to massive necrosis. Of the seven patients, four died of fulminant hepatic failure. These four patients had received high doses of ecarazine hydrochloride for prolonged periods. Our data suggest that there may be many cases in which the cause of fulminant hepatic failure or acute hepatitis was not previously determined that can be attributed to long- term drug therapy for chronic diseases.

Fulminant hepatic failure caused by ecarazine hydrochloride (a hydralazine derivative)

The cause of fulminant hepatic failure is reported to be unknown in more than half the cases in Japan. We recently reviewed 23 cases of fulminant hepatic failure that had been treated at our hospital. The cause of disease had been regarded as unknown before this study. It was found that seven of these patients had been under ecarazine hydrochloride therapy when they developed fulminant hepatic failure. We examined the reasons why fulminant hepatic failure in these seven patients had not been previously attributed to ecarazine, and found that it could be explained by the following factors: (1) the time from the start of ecarazine therapy to the onset of hepatic failure was long; (2) in all cases, hepatic failure developed more than 10 days after the clinical recognition of hepatitis; and (3) characteristic signs of drug-induced hepatic failure such as a skin rash and positive lymphocytes stimulation test with the drug were absent in all cases. Fulminant hepatic failure in these cases could be characterized by: (1) rapid decrease in serum alanine transaminase (ALT) level after discontinuation of ecarazine, (2) prolonged jaundice despite discontinuation of ecarazine, (3) high incidence of anti-nuclear antibody (ANA) (57%), and (4) histological findings of extensive hepatocellular necrosis ranging from bridging necrosis to massive necrosis. Of the seven patients, four died of fulminant hepatic failure. These four patients had received high doses of ecarazine hydrochloride for prolonged periods. Our data suggest that there may be many cases in which the cause of fulminant hepatic failure or acute hepatitis was not previously determined that can be attributed to long- term drug therapy for chronic diseases. (Hepatology 1996 Mar;23(3):465-70)