Dengue induced acute liver failure:A meta summary of case reports

BACKGROUND Dengue fever is the most common cause of viral hemorrhagic fever,with more than 400 million cases being reported annually,worldwide.Even though hepatic involvement is common,acute liver failure(ALF)is a rare complication of dengue fever.AIM To analyze the demographic profile,symptomology,hospital course and outcomes of patients presenting with ALF secondary to dengue infection by reviewing the published case reports.METHODS A systematic search was performed from multiple databases including PubMed,Reference Citation Analysis,Science Direct,and Google Scholar.The search terms used were"dengue"OR"severe dengue"OR"dengue shock syndrome"OR"dengue haemorrhagic syndrome"OR"dengue fever"AND"acute liver failure"OR"hepatic failure"OR"liver injury".The inclusion criteria were:(1)Case reports or case series with individual patient details;(2)Reported acute liver failure secondary to dengue infection;and(3)Published in English language and on adult humans.The data were extracted for patient demographics,clinical sympto-matology,clinical interventions,hospital and intensive care unit course,need for organ support and clinical outcomes.RESULTS Data from 19 case reports fulfilling the predefined inclusion criteria were included.The median age of patients was 38 years(inter quartile range:Q3-Q126.5 years)with a female preponderance(52.6%).The median days from diagnosis of dengue to development of ALF was 4.5 d.The increase in aspartate aminotransferase was higher than that in alanine aminotransferase(median 4625 U/L vs 3100 U/L).All the patients had one or more organ failure,with neurological failure present in 73.7%cases.42.1%patients required vasopressor support and hepatic enceph-alopathy was the most reported complication in 13(68.4%)cases.Most of the patients were managed conser-vatively and 2 patients were taken up for liver transplantation.Only 1 death was reported(5.3%).CONCLUSION Dengue infection may rarely lead to ALF.These patients may frequently require intensive care and organ support.Even though most of these patients may improve with supportive care,liver transplantation may be a therapeutic option in refractory cases.

Viral etiologies of acute liver failure

Acute liver failure(ALF)is a rare cause of liver-related mortality worldwide,with an estimated annual global incidence of more than one million cases.While drug-induced liver injury,including acetaminophen toxicity,is the leading cause of ALF in the Western world,viral infections remain a significant cause of ALF and the most common cause in many developing nations.Given the high mortality rates associated with ALF,healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis,rapid treatment initiation when possible,and optimal management,which may include liver transplantation.This review aims to provide a summary of viral causes of ALF,diagnostic approaches,treatment options,and expected outcomes.

Roles of hepatic stellate cells in acute liver failure: From the perspective of inflammation and fibrosis

Acute liver failure(ALF)usually results in hepatocellular dysfunction and coagulopathy and carries a high mortality rate.Hepatic stellate cells(HSCs)are famous for their role in liver fibrosis.Although some recent studies revealed that HSCs might participate in the pathogenesis of ALF,the accurate mechanism is still not fully understood.This review focuses on the recent advances in understanding the functions of HSCs in ALF and revealed both protective and promotive roles during the pathogenesis of ALF:HSC activation participates in the maintenance of cell attachment and the architecture of liver tissue via extracellular matrix production and assists liver regeneration by producing growth factors;and HSC inflammation plays a role in relaying inflammation signaling from sinusoids to parenchyma via secretion of inflammatory cytokines.A better understanding of roles of HSCs in the pathogenesis of ALF may lead to improvements and novel strategies for treating ALF patients.

An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.

Arterial steroid injection therapy can inhibit the progression of severe acute hepatic failure toward fulminant liver failure

AIM: To utilize transcatheter arterial steroid injection therapy (TASIT) via the hepatic artery to reduce hepatic macrophage activity in patients with severe acute hepatic failure.METHODS: Thirty-four patients with severe acute hepatic failure were admitted to our hospital between June 2002 to June 2006 providing for the possibility of liver transplantation (LT). Seventeen patients were treated using traditional liver supportive procedures, and the other 17 patients additionally underwent TASIT with 1000 mg methylprednisolone per day for 3 continuous days. RESULTS: Of the 17 patients who received TASIT, 13 were cured without any complications, 2 died, and 2 underwent LT. Of the 17 patients who did not receive TASIT, 4 were self-limiting, 7 died, and 6 underwent LT. Univariate logistic analysis revealed that ascites, serum albumin, prothrombin time, platelet count, and TASIT were significant variables for predicating the prognosis. Multivariate logistic regression analysis using stepwise variable selection showed that prothrombin time, platelet count, and TASIT were independent predictive factors. CONCLUSION: TASIT might effectively prevent the progression of severe acute hepatic failure to a fatal stage of fulminant liver failure.

Effect of naked eukaryotic expression plasmid encoding rat augmenter of liver regeneration on acute hepatic injury and hepatic failure in rats

AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intravenously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals.RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the most effective group after four times of injection of recombinant pcDNA3-ALR plasmid. The indexes of PCNA significantly increased in the recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The level of serum AST and ALT remarkably reduced in recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The results showed that the effect of 200 μg/kg recombinant pcDNA3-ALR plasmid in the rats with acute liver injury was stronger than that of 50μg/kg pcDNA3-ALR DNA.The effect of intravenous injection of recombinant pcDNA3ALR plasmid was better. After the rats with acute hepatic failure were treated with recombinant pcDNA3-ALR plasmid,the survival rate (40%) significantly increased in treatment groups compared to control group (15%, P＜0.01).CONCLUSION: The ALR gene may play an important role in relieving acute hepatic injury and hepatic failure by promoting hepatic cell proliferation and reducing level ofAST and ALT in CCl4-intoxicated rats.

Are heat stroke and physical exhaustion underestimated causes of acute hepatic failure?

While cardiopulmonary symptoms are common in patients undergoing dassical or, due to physical exercise, exertional heat stroke, the failure of other organs is a rarely described phenomenon. Here we present two cases of acute hepatic failure, one due to classic heat shock, while the other occurred while the patient was doing a marathon-type running. Both cases presented with very high transaminases and significantly elevated international normalized ratio （INR）. No other causes for liver failure could be identified but physical exhaustion and hyperthermia.

Hepatoprotective effects of cathepsin B inhibitor on acute hepatic failure induced by lipopolysaccharide/D-galactosamine in mice

BACKGROUND:Increasing evidence suggests that the inactivation of cathepsin B attenuates hepatocyte apoptosis and liver damage.This study aimed to investigate the protective effects of a cathepsin B inhibitor(CA-074me) on lipopolysaccharide(LPS)/D-galactosamine(D-GalN)-induced acute hepatic failure(AHF) in mice.METHODS:Mice were intraperitoneally injected with a combination of LPS/D-GalN to induce AHF with or without CA-074me pretreatment.The cumulative survival rates were calculated 48 hours after the induction of AHF.As well as changes in biochemical indicators and liver histology,hepatocyte apoptosis was assessed using a TUNEL method.Serum tumor necrosis factor-α(TNF-α) production,caspase-3,caspase-8,and caspase-9 activity was evaluated.Cytosolic cytochrome c and Bcl-2 expression were measured by Western blotting.RESULTS:The marked elevation in serum aminotransferase activity and prothrombin time found in LPS/D-GalN-treated mice was significantly improved by pretreatment with CA074me.The efficacy of CA-074me was also confirmed by histological analysis and TUNEL assay.The survival rate significantly improved in LPS/D-GalN-induced mice given CA-074me compared with untreated mice.LPS/D-GalNinduced caspase-3 and caspase-9 activation was remarkably suppressed by CA-074me.However,the increased levels of serum TNF-α and elevated caspase-8 activity in AHF mice were not significantly reduced by CA-074me.Moreover,CA074me sharply reduced the increased expression of cytosolic cytochrome c and markedly augmented Bcl-2 expression.CONCLUSION:These results suggest that CA-074me has a protective effect in acute hepatic failure induced by LPS/D-GalN.

Mesenchymal stem cells rescue acute hepatic failure by polarizing M2 macrophages

AIM To investigate whether M1 or M2 polarization contributes to the therapeutic effects of mesenchymal stem cells(MSCs) in acute hepatic failure(AHF).METHODS MSCs were transfused into rats with AHF induced by D-galactosamine(DGal N). The therapeutic effects of MSCs were evaluated based on survival rate and hepatocyte proliferation and apoptosis. Hepatocyte regeneration capacity was evaluated by the expression of the hepatic progenitor surface marker epithelial cell adhesion molecule(Ep CAM). Macrophage polarization was analyzed by M1 markers [CD68,tumor necrosis factor alpha(TNF-α),interferon-γ(IFN-γ),inducible nitric oxide synthase(INOS)] and M2 markers [CD163,interleukin(IL)-4,IL-10,arginase-1(Arg-1)] in the survival and death groups after MSC transplantation.RESULTS The survival rate in the MSC-treated group was increased compared with the DPBS-treated control group(37.5% vs 10%). MSC treatment protected rats with AHF by reducing apoptotic hepatocytes and promoting hepatocyte regeneration. Immunohistochemical analysis showed that MSC treatment significantly increased the expression of Ep CAM compared with the control groups(P < 0.001). Expression of Ep CAM in the survival group was significantly up-regulated compared with the death group after MSC transplantation(P = 0.003). Transplantation of MSCs significantly improved the expression of CD163 and increased the gene expression of IL-10 and Arg-1 in the survival group. IL-4 concentrations were significantly increased compared to the death group after MSC transplantation(88.51 ± 24.51 pg/m L vs 34.61 ± 6.6 pg/m L,P < 0.001). In contrast,macrophages showed strong expression of CD68,TNF-α,and INOS in the death group. The concentration of IFN-γ was significantly increased compared to the survival group after MSC transplantation(542.11 ± 51.59 pg/m L vs 104.07 ± 42.80 pg/m L,P < 0.001).CONCLUSION M2 polarization contributes to the therapeutic effects of MSCs in AHF by altering levels of anti-inflammatory and pro-inflammatory factors.

Efficacy of liver transplantation for acute hepatic failure:asingle-center experience

BACKGROUND:Acute hepatic failure (AHF) is a devastating clinical syndrome with a high mortality rate.The outcome of AHF varies with etiology,but liver transplantation (LT) can significantly improve the prognosis and survival rate of such patients.This study aimed to detect the role of LT and artificial liver support systems (ALSS) for AHF patients and to analyze the etiology and outcome of patients with this disease.METHODS:A retrospective analysis was made of 48 consecutive patients with AHF who fulfilled the Kings College Criteria for LT at our center.We analyzed and compared the etiology,outcome,prognosis,and survival rates of patients between the transplantation (LT) group and the non-transplantation (N-LT) group.RESULTS:AHF was due to viral hepatitis in 25 patients (52.1%;hepatitis B virus in 22),drug or toxic reactions in 14 (29.2%;acetaminophen in 6),Wilson disease in 4 (8.3%),unknown reasons in 3 (6.3%),and miscellaneous conditions in 2 (4.2%).In the LT group,36 patients (7 underwent living donor LT,and 29 cadaveric LT) had an average model for endstage liver disease score (MELD) of 35.7.Twenty-eight patients survived with good graft function after a follow-up of 27.3± 4.5 months.During the waiting time,6 patients were treated with ALSS and 2 of them died during hospitalization.The 30-day,12-month,and 18-month survival rates were 77.8%,72.2%,and 66.7%,respectively.In the N-LT group,12 patients had an average MELD score of 34.5.Four patients were treated with ALSS and all died during hospitalization.The 90-day and 1-year survival rates were only 16.7% and 8.3%,respectively.CONCLUSIONS:Hepatitis is the most prominent cause of AHF at our center.Most patients with AHF,who fulfill the Kings College Criteria for LT,did not survive longer without LT.ALSS did not improve the prognosis of AHF patients,but may extend the waiting time for a donor.Currently,LT is still the most effective way to improve the prognosis of AHF patients.

Differential Gene Expression Profiles in Acute Hepatic Failure Model in Mice Infected with MHV-3 Virus Intervened by Anti-hepatic Failure Compound

Differential gene expression profiles in Balb/cJ mouse model of acute hepatic failure infected with MHV-3 virus intervened by anti-hepatic failure compound （AHFC） and the changes of cytokines regulated by genes were investigated. The Balb/cj mice were divided into AHFC-intervened group and control group randomly. Acute hepatic failure model of Balb/cJ mice infected with MHV-3 virus was established. The survival rate in the two groups was observed. It was found that the survival rate in the AHFC-intervened group and control group was 90% and 50% respectively 48 h after intraperitoneal injection of MHV-3 （P〈0.05）. Before and after the experiment, the cytokines in peripheral blood of the survival mice were determined, and RNA was extracted from survival mouse liver tissue for the analysis of the differential gene expression by a 36 kb mouse oligonuleotide DNA array. In all the genes of microarray there were 332 genes expressed differently in the two groups, in which 234 genes were up-regulated and 78 genes down-regulated. Through clustering analysis, the differential expression of immune related genes, including TNF receptor superfamily, Kctd9, Bcl-2, Fgl2, IL-8, IL-6, IFN-7, TNF-α etc. might be related with the curative effectiveness of AHFC. It was suggested that AHFC can balance the immune state of mouse model of acute hepatic failure infected with MHV-3 virus mainly through regulating the expression of immune related genes, decrease the immune damage and inhibit liver cell apoptosis of mouse acute hepatic failure model obviously so as to increase the survival rate of mouse models of acute hepatic failure.

Hepatoprotective effect of nitric oxide in experimental model of acute hepatic failure

AIM: To evaluate the effect of nitric oxide (NO) on the development and degree of liver failure in an animal model of acute hepatic failure (AHF).

A rat model for acute hepatic failure

OBJECTIVE: To develop a surgical model of acute hepatic failure.METHODS: Hepatectomy was performed in rats according to the method described by Higgins andAnderson. Ninety percent liver resection (removing the left lateral, median, and right lateral lobes)(n=7) and 95% liver resection leaving only half of the caudate lobe (n=13) were performed.Hypoglycemia was corrected by giving 20% glucose in the drinking water, coupled with repeatedintraperitoneal injection of 5% glucose adapted to glycemia. While the survival rate, alanine transaminase(ALT) and bilirubin were observed.RESULTS: 95% liver resection decreased survival rates of the rats from 86% (90% liver resection) to23% (P【0. 05), and increased bilirubin levels (4.04±2.84 mg/dL vs. 1.25±1.85 mg/dL [90%liver resection]).CONCLUSION: 95% liver resection is a good rat model for acute hepatic failure.

Hepatic angiosarcoma presenting as acute liver failure in young adults. Report of two cases and review of literature

Background: Hepatic angiosarcoma is a rare tumor of endothelial origin that accounts for up to 2% of all primary neoplasms of the liver. It is uncommon in young adults and acute liver failure is a very unusual presentation of this disease. Case Presentation: We report the cases of two young male adults who presented with acute liver failure. One of them was diagnosed with primary hepatic angiosarcoma after transplantation based on the complete evaluation of the heaptectomy specimen;while the other was diagnosed through a liver biopsy which was done as part of the work-up for transplantation. Both patients had a rapidly worsening clinical course and died within 2 months of diagnosis. Conclusion: Hepatic angiosarcoma is a poor prognosis disease with high and early mortality. Therefore, a high level of suspicion should be present to promptly diagnose it, especially when dealing with patients with a rapidly worsening liver disease.

Subacute fulminant hepatic failure with intermittent fever

BACKGROUND: Viral hepatitis B accounts for over 80% of acute hepatic failures in China and the patients die mainly of its complications. A patient with hepatic failure and fever is not uncommon, whereas repeated fever is rare. METHODS: A 32-year-old female was diagnosed with subacute hepatic failure and hepatitis B viral infection because of hyperbilirubinemia, coagulopathy, hepatic encephalopathy, serum anti-HBs-positive without hepatitis B vaccination, and typical intrahepatic pathological features of chronic hepatitis B. Plasma exchange was administered twice and she awoke with hyperbilirubinemia and discontinuous fever. RESULTS: Urethritis was confirmed and medication-induced fever and/or spontaneous bacterial peritonitis (Gram-negative bacillus infection) was suspected. The patient was treated with antibiotics, steroids and a Chinese herbal medicine, matrine, for three months and she recovered. CONCLUSION: The survival rate of patients with hepatic failure might be improved with comprehensive supporting measures and appropriate, timely management of complications.

Xenogeneic hepatic progenitor cell transplantation ameliorate CCl_4 /partial hepatectomy-induced rat acute liver failure

Objective： Hepatic progenitor cell transplantation has shed light on the treatment of liver failure. The present study was designed to evaluate whether xenogeneic liver epithelial progenitor cells （LEPCs） transplantation could promote liver recovery in a rat model of acute liver failure. The engraftment and hepatocytic differentiation of transplanted hepatic progenitor cells in the rat spleen was also investigated. Methods： LEPCs were propagated in vitro for long and transduced with lentiviral vector carrying mCherry gene. Intraperitoneal injection of CC14 followed by 2/3 partial hepatectomy three days later were used to establish rat models of acute liver failure. Rats were intrasplenically injected with mCherry modified LEPCs （n=20, 1× 107 cells/0.5 mL） or the same volume of medium （n=20）. Serum liver enzymes （ALT, AST） and liver histology were evaluated for 21 days after transplantation. The engraftment of transplanted LEPCs in the spleens was tested by polymerase chain reaction （PCR） amplification targeting mCherry gene. The differentiation into hepatocytic lineage of transplanted LEPCs was investigated usingimmunohistochemistry staining against Alb. Results： LEPCs were effectively transduced with lentiviral vector showing a transduction efficiency of 90%. Compared with control, cell-injected group displayed significantly lower levels of ALT and AST （P〈0.05） and better histological features including less swelling change and hepatocyte death. PCR amplification of mCherry sequences confirmed the engraftment of LEPCs in the spleens. Alb-positive cells first appeared 5 days after cell transplantation and the number of Alb-positive cells increased substantially （P〈0.05）, which revealed the hepatocytic differentiation process Conclusion： Xenogeneic hepatic progenitor cells can engraft and differentiate into hepatocytes in the splenic parenchyma. Intrasplenic delivery of hepatic progenitor cells ameliorates CCh/partial hepatectomy-induced liver injury in rats

Intracranial pressure monitoring in the perioperative period of patients with acute liver failure undergoing orthotopic liver transplantation

Acute liver failure(ALF)may result in severe neurological complications caused by cerebral edema and elevated intracranial pressure(ICP).Multiple pathogenic mechanisms explain the elevated ICP,and newer hypotheses have been described.While invasive ICP monitoring(ICPM)may have a role in ALF management,these patients are typically coagulopathic and at risk for intracranial hemorrhage.ICPM is the subject of much debate,and significant heterogeneity exists in clinical practice regarding its use.Contemporary ICPM techniques and coagulopathy reversal strategies may be associated with a lower risk of hemor-rhage;however,most of the evidence is limited by its retrospective nature and relatively small sample size.

Risk factors for progression to acute-on-chronic liver failure during severe acute exacerbation of chronic hepatitis B virus infection

BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.

Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation

Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.

Potential triggering factors of acute liver failure as a first manifestation of autoimmune hepatitis-a single center experience of 52 adult patients

AIM To investigate potential triggering factors leading to acute liver failure(ALF) as the initial presentation of autoimmune hepatitis(AIH).METHODS A total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients(9.2%) fulfilled the criteria for ALF defined by the "American Association for the Study of the Liver(AASLD)". According to this definition, patients with "acute-on-chronic" or "acute-on-cirrhosis" liver failure were excluded. Following parameters with focus on potential triggering factors were evaluated: Patients' demographics, causation of liver failure, laboratory data(liver enzymes, MELD-score, autoimmune markers, virus serology), liver histology, immunosuppressive regime, and finally, outcome of our patients.RESULTS The majority of patients with ALF were female(84.6%) and mean age was 43.6 ± 14.9 years. Interestingly, none of the patients with ALF was positive for antiliver kidney microsomal antibody(LKM). We could identify potential triggering factors in 26/52(50.0%) of previously healthy patients presenting ALF as their first manifestation of AIH. These were drug-induced ALF(57.7%), virus-induced ALF(30.8%), and preceding surgery in general anesthesia(11.5%), respectively. Unfortunately, 6 out of 52 patients(11.5%) did not survive ALF and 3 patients(5.7%) underwent liver transplantation(LT). Comparing data of survivors and patients with non-recovery following treatment, MELDscore(P < 0.001), age(P < 0.05), creatinine(P < 0.01), and finally, ALT-values(P < 0.05) reached statistical significance. CONCLUSION Drugs, viral infections, and previous surgery may trigger ALF as the initial presentation of AIH. Advanced age and high MELD-score were associated with lethal outcome.