Acute Fulminant Hepatic Failure Research Articles

Reversible Fulminant Hepatitis with Amiodarone Therapy

Amiodarone, an iodinated benzofuranic derivative, is often used in the treatment of cardiac arrhythmias. A number of side effects have been reported in up to 74% of patients at 1 year, including pulmonary fibrosis, thyroid disease, corneal deposits and neurologic disorders. Transient asymptomatic elevation of transaminases can occur in ∼25% of patients on chronic oral therapy, however acute hepatitis, severe cholestasis and cirrhosis are rarely documented. We present a case of acute fulminant hepatic failure following initiation of amiodarone with rapid resolution on its discontinuation. The patient is a 67year old gentleman with a past medical history significant for coronary artery disease and end stage renal disease on hemodialysis. He initially presented to an outside facility with a ventricular arrhythmia that required defibrillator placement and intravenous loading of amiodarone followed by oral therapy. Shortly after discharge, the patient developed increasing confusion and profound weakness and was readmitted. On this hospitalization, he was noted to have a profound hypoglycemia with a dramatic elevation in aminotransferases, as well as total bilirubin, alkaline phosphatase and prothrombin time (ast 999, alt 1375, alkaline phosphatase 191, total bilirubin 6.8). With increasing lethargy and confusion, the patient was transferred to the intensive care unit for closer monitoring. A CAT scan of the head was unrevealing, toxicology screen and acetaminophen level negative, acute viral hepatitis panel negative. Further questioning of the patient's family did not indicate any history of heavy alcohol consumption nor the use of any herbals or other potential hepatotoxins. Amiodarone was promptly discontinued and the patient was empirically treated with n-acetylcysteine and lactulose. Over the next 5 days, the patient's liver function panel and synthetic function improved considerably with notable clearing of the patient's mentation. He was subsequently discharged to a skilled nursing facility, with almost normalization of liver tests. The absence of other causes of liver disease and the clinical course suggest that amiodarone was responsible for the development of acute hepatitis in this patient. The exact mechanism of amiodarone-related toxicity remains unknown.

Doxylamine Induced Acute Fulminant Hepatic Failure

Doxylamine Induced Acute Fulminant Hepatic Failure

Separate analysis of asialoglycoprotein receptors in the right and left hepatic lobes using 99mTc-GSA SPECT in patients with acute hepatic damage

The asialoglycoprotein receptor (ASGPR) is abundantly expressed on the sinusoidal surfaces of hepatocytes. However, regional expression and clinical significance of the ASGPR in acute hepatic damage is presently unknown. Our aim was to clarify the clinical significance of the regional expression of ASGPR in human livers with acute hepatitis (AH) and fulminant hepatic failure (FHF). Eighteen volunteers, 42 patients with AH and 10 with FHF were studied using a newly developed, conventional (99m)Tc-GSA SPECT analysis. Using Cantlie's line as a guide, ASGPR expression was analyzed separately in the right and left hepatic lobes, as well as in the whole liver, using novel indices (the liver uptake ratio [LUR] and liver uptake density [LUD], which reflect the amount and density of ASGPRs in the liver, respectively). Mean LUR and LUD values for the whole liver and the right and left lobes decreased in accordance with the severity of acute hepatic damage. In the FHF group, the reduction in LUR and LUD values in the right lobes was more significant than in the left lobes. The LUR and LUD values for the whole liver correlated well with hepatic functional reserve and total bilirubin levels. The right LUR and LUD values in particular correlated well with these parameters. A time-course observation of 13 patients with either AH or FHF revealed that the expression of ASGPRs in the right lobe recovered faster than in the left. We first evaluated the regional expression of AGSPRs by (99m)Tc-GSA SPECT analysis in both AH and FHF patients, which is a clinically useful and reliable indicator for assessing the severity of regional hepatic damage and evaluating regional liver regeneration.

Does co‐infection with multiple viruses adversely influence the course and outcome of sporadic acute viral hepatitis in children?

This study looked at the frequency of co-infection with multiple hepatotropic viruses and the effect of such infection on the course and outcome of acute sporadic viral hepatitis (AVH) and fulminant hepatic failure (FHF) in children. Consecutive children up to 15 years of age presenting with AVH or FHF between January 1998 and July 2002 were evaluated prospectively. The following viral markers were assessed in all children: immunoglobulin M (IgM) anti-hepatitis A virus (HAV), IgM anti-hepatitis E virus (HEV), hepatitis B surface antigen (HBsAg), IgM anti-hepatitis B core (HBc), and anti-hepatitis C virus (HCV). A total of 149 children were included in the study, 122 with AVH and 27 with FHF. Co-infection with multiple viruses was detected in 30 (24.6%) AVH patients (A+E in 24, A+B in three, and E+B, A+C and A+E+B in one each) and seven (26%) FHF patients (A+E in five, and A+B and E+B in one each). The majority of single infections were due to HAV (AVH 70/92, FHF 14/20) followed by HEV (AVH 9/92, and FHF 5/20). HEV infection was associated with infection with another agent in 88% of patients with AVH (odds ratio 53, 95% confidence interval 15-186, P<0.0001). Frequency of anicteric state, prolonged cholestasis, relapsing hepatitis, ascites, hemolysis and mortality rates were similar in the single and multiple infection groups for both AVH and FHF patients. Co-infection with multiple viruses is observed in one-quarter of patients with sporadic AVH in childhood. Such infection does not produce a more severe disease. HEV positivity is a strong marker for multiple infections.

Antituberculous therapy–induced fulminant hepatic failure: Successful treatment with liver transplantation and nonstandard antituberculous therapy

Standard antituberculous therapy including isoniazid, rifampin, ethambutol, and pyrazinamide is widely used for the treatment of active tuberculosis. Its most important side effect is hepatotoxicity, ranging from asymptomatic transaminitis to fulminant hepatic failure. A 19-year-old woman was admitted to our unit due to jaundice and unconsciousness. According to her past medical history, she was diagnosed as having extrapulmonary tuberculosis and had been prescribed standard antituberculous therapy. The patient became icteric and unconscious on the fourth day after therapy initiation. She was diagnosed with drug-induced acute fulminant hepatic failure and underwent living-related liver transplantation. Nonhepatotoxic antituberculous therapy (cycloserine, ciprofloxacin, streptomycin, and ethambutol) and low-dose immunosuppressive therapy were started after transplantation. Currently the patient is very well with normal graft function 42 months after transplantation. Here we report a case of a patient with acute fulminant hepatic failure caused by isoniazid, rifampicin, or both, who was successfully treated with living-related liver transplantation and a relatively less hepatotoxic antituberculous therapy. In conclusion, liver transplantation is a feasible therapy for individuals with standard antituberculous therapy-induced hepatic failure. Nonhepatotoxic antituberculous therapy may achieve control of active tuberculosis in such individuals after transplantation.

An evidence-based update on hepatic encephalopathy

Hepatic encephalopathy (HE) is a disturbance of the central nervous system (CNS) function secondary to porto-systemic shunting. It usually occurs in the setting of advanced liver cirrhosis or acute fulminant hepatic failure. An extensive Medline search was undertaken and all relevant papers found were critically examined. Special emphasis was paid to clinical trials and meta-analyses. All guidelines and conference proceedings related to hepatic encephalopathy were also examined. HE presents with a spectrum of neuropsychiatric manifestations that may be quite subtle (minimal HE) or overt, ranging from disturbance of the sleep pattern to deep hepatic coma. Most patients with HE may be diagnosed on clinical grounds only after excluding other causes of neurological disease, but a wide variety of neuropsychological, neurophysiological, and neuroradiological tests may be utilized. The first step in the management of patients with HE should be supportive care. Following that, a significant effort must be exerted to find and correct possible exacerbating factors which may include: renal impairment, infection, constipation, drugs, gastrointestinal bleeding and other factors. Medications used to treat patients with encephalopathy aim to reduce toxin production, increase toxin elimination, and protect the brain from the harmful effects of these toxins. A critical analysis of the evidence concerning most of the available management modalities is presented. Ultimately, all patients with HE must be considered for liver transplantation. It is concluded that early recognition, positive diagnosis, and a multi-target management plan constitutes appropriate management of patients with HE.

Acute fulminant hepatitis B in a patient with diabetic nephropathy treated successfully with concomitant lamivudine and molecular adsorbents recirculating system

A 36-year-old man with type 2 diabetes and diabetic nephropathy treated with hemodialysis developed hepatitis B virus (HBV)-induced acute fulminant hepatic failure (FHF). Despite supportive treatment, the condition rapidly progressed as manifested by severe jaundice, coagulopathy and hepatic coma. He was placed on the waiting list for liver transplantation and was treated with lamivudine and extracoporeal liver support with the molecular adsorbent recirculating system (MARS). After three 8-h sessions of MARS treatment in 1 week, he had remarkable improvement in clinical symptoms and serum biochemistry. On the 14th hospital day, surface antigen seroconversion was noted with undetectable hepatitis B virus surface antigen (HBs Ag) and low titre of anti-HBs antibody, indicating a complete recovery from acute fulminant hepatitis B. MARS treatment has been reported to benefit patients with liver failure from different causes including acute exacerbation of chronic hepatitis B, poisoning, post transplantation and Wilson's disease. The present case suggests its potential benefit when combined with lamivudine in treating uremic patients with acute fulminant hepatitis B.

Levofloxacin-Induced Acute Fulminant Hepatic Failure in a Patient with Chronic Hepatitis B Infection

To report a case of possible levofloxacin-induced acute fulminant hepatic failure. An unconscious 55-year-old woman was hospitalized with the diagnosis of hepatic encephalopathy. The patient had received levofloxacin 500 mg daily for 10 days because of an upper respiratory infection. Her past medical history revealed hepatitis B surface antigen positivity as an asymptomatic hepatitis B virus carrier for 10 years. After hospitalization, treatment included plasmapheresis and supportive care. The patient's consciousness improved on the second day of treatment. Other etiologies of fulminant hepatic failure were ruled out, suggesting levofloxacin-induced fulminant hepatic failure. Although the patient received supportive treatment, her condition gradually deteriorated and she died 12 weeks after admission to our hospital. An objective causality assessment revealed that the adverse event was possibly related to levofloxacin. Levofloxacin is widely used because of its broad spectrum of antimicrobial activity. As of August 9, 2005, to our knowledge, only one case of fulminant hepatic failure in relation to levofloxacin has previously been published. We believe that, in our patient, the relationship between levofloxacin and her illness is clear because of the negative results in the etiological studies, the short time between the drug's administration and the development of disease, and the pathologic findings suggestive of drug-induced hepatitis. Clinicians should be aware of the possibility of severe hepatic injury associated with levofloxacin when prescribing this drug.

Role of transfusion-transmitted virus in acute viral hepatitis and fulminant hepatic failure of unknown etiology.

The role of the newly described transfusion-transmitted virus (TTV), a circular single-stranded DNA virus, has been investigated in acute liver disease, comprising 36 patients with acute viral hepatitis (AVH) and 25 with fulminant hepatic failure (FHF), including 50 volunteer blood donors as controls. Detection of TTV DNA sequences was carried out by polymerase chain reaction (PCR) using primers derived from the UTR(A) region of the TTV genome. The clinical course and biochemical profile when infected with TTV alone or coinfected with other classical hepatotropic viruses were analyzed. All patients were first evaluated for liver function profile and for the presence of various hepatotropic viruses using serological tests and PCR in serologically negative patients. Transfusion-transmitted virus DNA was detected in 80.6% (29/36) of the AVH cases and in 76% (19/25) of the FHF cases, which were significantly higher levels (P < 0.05) than the 52% (26/50) observed in volunteer blood donors. No significant difference in symptoms, clinical course, liver function and risk factor profile between TTV-positive and TTV-negative patients could be observed in both AVH and FHF patients. TTV was found to coexist with both parenterally and non-parenterally transmitted hepatotropic viruses in similar frequency in both AVH and FHF patients. Further, there was no significant difference in the mortality rates between TTV-positive and TTV-negative FHF patients. Also, there was no difference between patients coinfected by TTV and other hepatotropic viruses and those with TTV infection alone. Thus, it appears that TTV, although it exists in a very high frequency in the Indian population, appears to have no significant etiological role in AVH and FHF.

MELD/PELD and the allocation of deceased donor livers for status 1 recipients with acute fulminant hepatic failure, primary nonfunction, hepatic artery thrombosis, and acute Wilson's disease.

1. Historical perspective of donor allocation to patients with fulminant hepatic failure (FHF). 2. Predicting prognosis in patients with FHF using the London and Clichy criteria. 3. Model for end-stage liver disease (MELD) is a predictor of mortality in patients with FHF. 4. Outcomes of adults listed as Status 1 in the United States. 5. Outcomes of pediatric candidates listed as Status 1 in the United States. 6. Proposed redefinition for Status 1 in adult and pediatric candidates.

Acute fulminant hepatic failure and toxic epidermal necrolysis associated with the use of moxifloxacin

Acute fulminant hepatic failure and toxic epidermal necrolysis associated with the use of moxifloxacin

Acute fulminant hepatic failure associated with the use of rosiglitazone

Acute fulminant hepatic failure associated with the use of rosiglitazone

Rapid fulminant liver failure after anal exposure to genital herpes: a case report

Fulminant hepatic failure from herpes simplex virus (HSV) in immunocompetent individuals has been reported but is quite rare. We present an unusual case of acute HSV infection transmitted anally causing fatal hepatitis in a young individual with no apparent immunosuppressive illness. A 44 year-old previously healthy female with a past history significant only for asthma and shingles presented with a five day history of diarrhea, anorexia, arthralgias, diffuse abdominal pain and high grade fever (105F). Three days prior to her becoming ill the patient had anal intercourse with her boyfriend who had active genital herpes. Her primary care physician started the patient on oral ciprofloxacin. Her symptoms worsened and she was admitted. Diagnostic work-up revealed WBC of 5.0 103/ul, ALT- 221 IU/L, AST-527 IU/L, total bilirubin of 2.3mg/dl, alkaline phosphatase (ALK) of 189-IU/L, Albumin of 2.5g/dl, INR of 1.7, negative serologies or titers for hepatitis A, B, C; CMV, HIV, syphilis and ANA. Microbiologic work-up was unremarkable. The patient began to deteriorate clinically and developed acute respiratory distress syndrome as well as abdominal ascites. Transjugular liver biopsy was performed which revealed subacute hepatocyte necrosis involving 15–20% of the submitted tissue with marked polymorphonuclear infection and inclusion bodies. The patient was transferred to our facility. On examination, the patient was tachypneic and was found to have a scattered discrete vesicular rash on her face/torso/extremities as well as a protuberant abdomen with percussion tenderness in the right upper quadrant. Labs revealed a total bilirubin of 8.8 (direct 8.7), AST- 296, ALT-430, ALK- 190, creatinine of 4.2mg/dl and an INR of 2.3. The liver biopsy was re-evaluated and immunostains for HSV I and II were positive. The patient was intubated and aggressive supportive care in the ICU was initiated including therapy with acyclovir. She developed multi-organ failure and expired after 2 weeks. Thus we present an unusual case of acute fulminant hepatic failure secondary to genital herpes infection after anal exposure. Hepatitis caused by HSV infection carries a very high mortality, which is unchanged with institution of acyclovir (except if it is started very early) and even worsened by liver transplantation, which is therefore contraindicated.

PREVALENCE AND SEVERITY OF ACUTE VIRAL HEPATITIS AND FULMINANT HEPATITIS DURING PREGNANCY: A PROSPECTIVE STUDY FROM NORTH INDIA

The present study aimed to find out the prevalence and severity of acute viral hepatitis and fulminant hepatitis during pregnancy in North India. The study was conducted on 97 consecutive pregnant patients in third trimester with acute viral hepatitis (AVH) or fulminant hepatic failure (FHF). The patients were evaluated on the basis of history, examination, liver function profile and serological markers for hepatitis A,B,C and E viruses. Hepatitis E virus (HEV) was the causative agent in 47.4% of the cases of viral hepatitis and 52.6% were caused by non-E viruses(HAV-5.2%,HBV-7.2%,HCV-0%,non A-E 47.4%). HEV was responsible for 36.2% of the cases of AVH and 75% of the cases of FHF. The mortality was 24.7% (24/97). All of them had FHF. Eighteen of 24 cases (75%) who expired were HEV positive. The mortality rate was 39.1% in HEV group and 11.7% in non HEV group. Majority of patients (87.5%) who expired had died undelivered. Hepatitis E was the commonest etiological agent in those who had fulminant disease during pregnancy and was associated with high mortality rate.

Histopathological features of L-asparaginase-induced liver disease.

We studied the histopathological changes of liver in four patients who developed hepatomegaly and abnormal liver chemistry tests 2 to 20 days following administration of L-asparaginase as a part of a combination chemotherapy regimen for treatment of acute lymphoblastic leukemia. The severity of the liver disease due to L-asparaginase was unpredictable. One patient developed acute fulminant hepatic failure and required liver transplantation. The most consistent pathological change, observed in all four cases, was diffuse steatosis. Other changes included patchy hepatocyte necrosis, mixed inflammatory cell infiltrates in the portal tracts, and variable degrees of hepatocellular, or canalicular cholestasis, or a combination of these.

Serum gamma-interferon-inducing factor (IL-18) and IL-10 levels in patients with acute hepatitis and fulminant hepatic failure.

The aim was to determine the role of T-helper (Th)1/Th2 cytokine responses in the clinical outcome of patients with acute liver injury. The serum levels of the cytokines, interleukin (IL)-18, gamma-interferon (IFN-gamma), IL-10 and IL-4 were measured in 20 fulminant hepatic failure (FHF), 18 acute hepatitis (AH), 30 chronic viral hepatitis and 20 liver cirrhosis (LC) patients. Thirteen cases were from the intensive care unit (ICU) and there were 21 healthy volunteers. Immunohistochemical staining of liver biopsies for IL-18 expression was also performed. Serum IL-18 levels in patients with FHF were significantly more elevated than in patients with other liver diseases, ICU cases and healthy volunteers. Furthermore, serum IFN-gamma levels in patients with FHF were also significantly higher than in patients with chronic viral hepatitis, LC and healthy volunteers. We found a positive correlation between the levels of IL-18 and IFN-gamma. However, no relationship was observed between these and clinical outcome. In immunohistochemical staining, CD68+ macrophage cells and IL-18-positive cells were observed in portal zones. Elevated serum IL-10 levels were restricted to patients presenting with FHF, and were significantly higher in surviving cases (P < 0.01). Furthermore, serum IL-10 levels, but not IL-4 levels, were inversely correlated with serum total bilirubin concentrations (P = 0.045) and the death rate (p) outlined in Japan (P = 0.030). These results suggest that IL-18 and IFN-gamma are involved in the pathogenesis of acute hepatic injury in humans, and that, in particular, elevated serum levels of IL-10 may be predictive of improved outcomes for these patients.

Bioartificial liver support anno 2001.

Despite maximal intensive care, mortality of acute fulminant hepatic failure is high: 60%-75% in several studies. In addition patients with chronic liver insufficiency suffer from a bad quality of life: all patients suffer from fatigue; symptoms of hepatic encephalopathy, jaundice, and itching are often present. Analogous to artificial kidney treatment in patients with renal failure, an artificial liver assist device is needed not only to bridge patients with fulminant hepatic failure to liver transplantation or own liver regeneration, but also to improve the quality of life of patients with chronic liver insufficiency. Several modalities of artificial liver support are under investigation, like plasma exchange, haemodialysis, haemadsorption, albumin dialysis, liver cell transplantation, and the bioartificial liver. Artificial livers based on only supportive detoxification function do not show significant improvement of survival in controlled studies. Bioartificial liver support systems have also the potential to support hepatic synthetic functions. Bioreactors can be charged with freshly isolated or cryopreserved porcine hepatocytes, but also by human hepatoma cell lines. Several uncontrolled studies in humans show safety of such a treatment, even by using porcine cells. Transmission of porcine endogenous retrovirus to recipients has not been found. Furthermore, beneficial effects have been reported on symptoms of hepatic encephalopathy, on the height of intracranial pressure and on hemodynamic parameters. By using porcine cells immunological problems (e.g., serum sickness) can be expected during treatments longer than one week. However, "proof of the pudding" in the sense of improvement of survival is not yet available. The creation of a "liver dialysis unit" in the near future depends mainly on the development of well-differentiated immortalized human hepatocytes. Some progress in this field has already been obtained.

Significance of Fas antigen-mediated apoptosis in human fulminant hepatic failure

OBJECTIVE: The aim of this study was to elucidate the role of apoptosis in human fulminant hepatic failure. We studied the expression of Fas antigen on liver tissues, Fas ligand in lymphocytes, and soluble Fas ligand in patients’ serum. METHODS: On finding apoptotic cells in fulminant hepatic failure liver, we first examined them using the TUNEL method. Subsequently, the expression of Fas was studied by immunostaining. Simultaneously, Fas ligand presenting on both liver-infiltrated cells and peripheral lymphocytes was studied by reverse transcription-polymerase chain reaction, and soluble Fas ligand in sera was measured by ELISA. RESULTS: By using the TUNEL method, we first demonstrated that many apoptotic cells existed in fulminant hepatic failure but not in normal ones. Our immunohistochemistry study showed that many hepatocytes in fulminant hepatic failure strongly expressed Fas. In addition, Fas ligand on both liver-infiltrating lymphocytes and peripheral lymphocytes in fulminant hepatic failure patients was detected. The serum level of soluble Fas ligand was significantly increased in fulminant hepatic failure (mean value, 2.91 ng/ml in fulminant hepatic failure [n = 10], 1.62 ng/ml in acute hepatitis [n = 10], and 0.27 ng/ml in healthy controls [n = 10]). Furthermore, this serum level of sFas ligand was significantly associated with prothrombin time both in acute hepatitis and fulminant hepatic failure. CONCLUSIONS: The present results indicate that Fas-mediated apoptosis may be one of the triggers for the induction of fulminant hepatic failure.

Acute pancreatitis and fulminant hepatic failure

Background: The association of acute pancreatitis with fulminant hepatic failure (FHF) was first recognized in 1973. Since then, few studies have described the clinical profile of the FHF patient with acute pancreatitis. Identification of the distinguishing attributes of pancreatitis in combination with FHF will provide a more sound basis for clinical management. The purposes of this study were to identify distinguishing clinical characteristics of acute pancreatitis in FHF and to compare outcomes with those of patients with acutely decompensated chronic liver disease and acute pancreatitis (DECOMP). Study Design: This was a retrospective survey of 30 patients with FHF and 30 with DECOMP admitted during the period July 1995 to July 1997. Results: The prevalence of acute pancreatitis in FHF and DECOMP was 33% and 23%, respectively. Acute pancreatitis was associated with severe hepatocellular synthetic dysfunction, renal insufficiency, requirement for endotracheal intubation, increased acuity of illness at the time of ICU admission, more rapid decompensation during the disease, and significantly greater mortality in both the FHF and DECOMP groups. Conclusions: In both FHF and DECOMP, acute pancreatitis increases disease acuity and mortality. Acute pancreatitis does not occur with significantly greater frequency in FHF. Implementation of orthotopic liver transplantation may not be warranted in this setting.

Detection of hepatitis C and E virus genomes in sera of patients with acute viral hepatitis and fulminant hepatitis by their simultaneous amplification in PCR.

A study was undertaken to investigate the role of hepatitis C virus (HCV) and hepatitis E virus (HEV), either alone or together, in the causation of sporadic acute viral hepatitis (AVH) and fulminant hepatitis (FH) by simultaneous detection of their genomes in serum samples using the reverse transcription and nested polymerase chain reaction (RT-PCR). A total of 50 patients were enrolled in the study of which 34 had AVH and 16 had sporadic FH. The serum samples were first tested for hepatitis B surface antigen (HBsAg) and immunoglobulin (Ig)M antibodies against hepatitis A virus (HAV), hepatitis B core antigen (HBcAg) and HEV and also antibodies against HCV using commercially available enzyme-linked immunosorbent assay (ELISA) kits. All samples were then subjected to RT-PCR using primers for both HCV and HEV simultaneously in the same reaction mixture. Hepatitis C or hepatitis E was diagnosed when either the antibodies or PCR or both were positive for the respective viruses. Evidence of hepatitis C was present in six of the 34 (17.6%) cases of AVH and two out of 16 (12.5%) cases of FH. Four patients in the AVH group and one of the fulminant hepatic failure (FHF) group were found to be positive by PCR and the rest by serology. But as a sole aetiological agent, HCV infection was found in only one (2.9%) case of AVH and in none of the FHF cases. Evidence of HEV infection was found in 22/34 (64.7%) and 8/16 (50%) cases of AVH and FHF, respectively. Excluding co-infection with other viruses, HEV was found to be the sole aetiological agent in 15/34 (44.1%) of AVH and 7/16 (43.7%) cases of FHF. In five (10%) (four AVH and one FHF) of the 50 cases, evidence of infection with both HCV and HEV was present. But only in two of these five cases, genomes of both HCV and HEV were co-amplified. In seven (four AVH and three FHF) out of 50 (14%) cases, no known viral agent could be detected. Our results suggest that HEV is the most common aetiological agent for both acute viral hepatitis and fulminant hepatic failure and that HCV is a rare cause of acute liver diseases although along with other viruses, evidence of either present or past HCV infection may be present in a substantial number of cases. Furthermore, advanced-stage pregnancy appears to be a potential risk factor for HEV infection and high rate of mortality in women. The study suggests that the method of simultaneous amplification of both HCV and HEV genomes could reduce the time, labour and cost involved in diagnostic work up of acute liver disease patients.