Virus-related Acute Liver Failure Research Articles

Bioinformatics and experimental validation were combined to explore lactylation-related biomarkers in HBV-associated acute liver failure.

Currently, hepatitis B virus-related acute liver failure (HBV-ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver-related diseases. Therefore, it is essential to explore lactylation-related gene (LRGs) biomarkers in HBV-ALF to provide new information for the treatment of HBV-ALF. Two HBV-ALF-related datasets (GSE38941 and GSE14668) and 65 LRGs were used. First, the differentially expressed genes (DEGs) were derived from differential expression analysis, the key module genes from weighted gene co-expression network analysis; and LRGs were used to intersect to obtain the candidate genes. Subsequently, the feature genes obtained from least absolute shrinkage and selection operator regression analysis and support vector machine analysis were intersected to obtain the candidate key genes. Among them, genes with consistent and significant expression trends in both GSE38941 and GSE14668 were used as biomarkers. Subsequently, biomarkers were analyzed for functional enrichment, immune infiltration, and sensitive drug prediction. In this study, five candidate genes (PIGM, PIGA, EGR1, PIGK, and PIGL) were identified by intersecting 6461 DEGs and 2496 key module genes with 65 LRGs. We then screened four candidate key genes from the machine learning algorithm, among which PIGM and PIGA were considered biomarkers in HBV-ALF. Moreover, the results of enrichment analysis showed that the significant enrichment signaling pathways for biomarkers included allograft rejection and valine, leucine, and isoleucine degradation. Thereafter, 11 immune cells differed significantly between groups, with resting memory CD4+ T cells having the strongest positive correlation with biomarkers. Methylphenidate hydrochloride is a potential therapeutic drug for PIGM. Two genes, PIGM and PIGA, were identified as biomarkers related to LRGs in HBV-ALF, providing a basis for understanding HBV-ALF pathogenesis.

M6A Regulator-mediated RNA Methylation Modulates Immune Microenvironment of Hepatitis B Virus-related Acute Liver Failure.

Acute liver failure (ALF) is a rare and complicated disease with a high mortality rate. Emergency liver transplantation is the only treatment method that can improve the ALF prognosis. However, its clinical application remains limited owing to the aggressive nature of liver transplantation, limited donors, and high postoperative mortality. The study investigated the effect of m6A on the immune microenvironment of hepatitis B virus-related ALF (HBV-ALF). In this study, the gene expression data of 47 normal people and 42 HBV-ALF patients were downloaded from the Gene Expression Omnibu (GEO) database. The known 23 m6A regulators which mediated RNA modification patterns were compared and analyzed in these two groups, and the gene diagnosis model of HBV-ALF patients was established based on the analysis results. In addition, we used unsupervised clustering to identify different m6A RNA methylation modification patterns in HBV-ALF based on m6A regulators, and evaluated the immune infiltration and biological differences in these subtypes. In addition, the relationship between m6A genes and immune cell activation in HBV-ACLF patients was explored by immune infiltration analysis. Nineteen m6A regulators mediated RNA methylation (m6A regulators for short) were differentially expressed in HBV-ALF and control groups. m6A regulators could well distinguish control samples from HBV-ALF samples, and m6A regulators might be used as a basis for diagnosing HBV-ALF patients. Immune cells such as activated CD8 T cells, activated B cells, and activated CD4 T cells might play important roles in HBV-ALF, and m6A regulators were closely associated with immune cell infiltration. ALKBH15, CBLL1, IGF2BP2, IGF2BP3, and ZC3H13 were significantly associated with immune cells. Considering 23 m6A regulators, HBV-ALF patients could be classified into two subtypes (cluster 1 and cluster 2) based on different immune cell infiltration. m6A regulators of the IGFBP and YHDF families have extremely different levels in these two subtypes. Differential immune cell infiltration among these subtypes was observed, a total of 913 differentially expressed genes among different m6A modification patterns was identified, and their biological functions were explored. m6A modification might play a crucial role in the diverse and complex immune microenvironment of HBV-ALF patients.

Serum extracellular vesicle-derived ASS1 is a promising predictor for the occurrence of HEV-ALF.

Development of biomarkers for predicting the occurrence of hepatitis E virus related-acute liver failure (HEV-ALF) is conducive to prevention and early intervention. Serum samples from 250 HEV-ALF patients, 250 patients with acute hepatitis E (AHE) and 250 health controls (HCs) were collected. We assessed the predictive ability of extracellular vesicle (EV)-derived argininosuccinate synthase 1 (ASS1) levels for HEV-ALF occurrence. Serum EVs were successfully isolated. EV-derived ASS1 levels in the HEV-ALF patients were significantly higher than those in the AHE patients and HCs. In HEV-ALF patients, EV-derived ASS1 levels were positively correlated with the number of failed organs and disease progression. The logistical regression showed that EV-derived ASS1 level is an independent risk factor for HEV-ALF, and orthogonal partial least squares discriminant analysis (OPLS-DA) also suggested that EV-derived ASS1 level has high predictive capability. Besides, the area under the curve (AUC) of EV-derived ASS1 level to predict HEV-ALF occurrence was 0.728 (0.684-0.772) with the sensitivity and specificity being 72.80% and 64.80%, which had a high decision-making ability. Furthermore, there existed no significant difference between the age ≥60 and age <60 groups in EV-derived ASS1 levels. Serum EV-derived ASS1 level is a promising predictor for the occurrence of HEV-ALF.

Low platelets: a new and simple prognostic marker for patients with hepatitis E virus-related acute liver failure.

Hepatitis E virus-related acute liver failure (HEV-ALF) rapidly worsens and has a high mortality. However, no simple and specific parameters for predicting short-term mortality are available. A derivation cohort including 97 patients with HEV-ALF and another validation cohort were enrolled. Laboratory and clinical parameters were recorded. Platelet count, model for end-stage liver disease (MELD), and King's College criteria (KCC) were separately used for predicting mortality, and the levels of cytokines associated with systemic inflammation, platelet production, and plateletactivation were measured. Platelet counts were significantly lower in patients with HEV-ALF, and nonsurvivors had lower platelet counts than survivors (p < 0.001). Platelet count was an independent risk factor forpredicting 28- and 90-day mortality in patients with HEV-ALF. The AUROC of the baseline platelet count (cutoff, 131 × 109/L) for 28- and 90-day mortality was 0.786 and 0.764, respectively, which was superior to KCC score (p < 0.05) and comparable to MELD score. Furthermore, the platelet counts at 3 and 7days after ALF diagnosis had similar predictive power for 28- and 90-day mortality. The value of platelet count was also confirmed in the validation cohort. Moreover, platelet-associated cytokines, including thrombopoietin, platelet factor 4, and P-selectin, were increased in patients with HEV-ALF. Decreased platelet count is a simple and reliable indicator for predicting 28- and 90-day mortality in patients with HEV-ALF. Overactivation of platelets is an important risk for platelet countsdecrease, and treatment aiming at platelet count recovery may be considered.

The Immune Landscape of Hepatitis B Virus-Related Acute Liver Failure by Integration Analysis.

Hepatitis B virus-related acute liver failure (HBV-ALF) is a common type of liver failure, associated with high short-term mortality and morbidity rates. However, the immune landscape of HBV-ALF and its correlation with cell death are currently unknown. Based on 3 Gene Expression Omnibus data sets, infiltrated immune cells were quantified by single-sample gene set enrichment analysis method. The expression levels of immune genes and the abundance of immune cells in liver failure were compared with those in normal liver. The enrichment scores of cell death gene sets from Kyoto Encyclopedia of Genes and Genomes (KEGG) were calculated by gene set variation analysis method, and a protein-protein interaction (PPI) network was constructed using Cytoscape. Besides 21 differentially expressed immune genes, we identified 11 types of differentially infiltrated immune cells in HBV-ALF compared with normal liver. Enriched pathways of these immune genes mainly consisted of chemokine receptors, chemokine binding, interleukin-10 signaling, and TNFs bind their physiological receptors by Reactome pathway analysis. In addition, the enrichment scores of apoptosis and necroptosis pathway instead of autophagy and ferroptosis were increased in liver failure compared with normal liver. PPI network and gene cluster analysis of immune genes and apoptosis and necroptosis genes suggested that hub genes were mainly related to immune response and apoptosis. In summary, our study offers a conceptual framework to understand the immune landscape of HBV-ALF, which might help to improve prognosis.

Successful, Combined Long-term Treatment of Cerebral Candidiasis and Aspergillosis in a Liver Transplant Recipient: A Case Report

Invasive fungal infections, of which the most common are candidiasis and aspergillosis, are among the most important and fatal complications in solid organ transplantation. They continue to be a significant cause of morbidity and mortality in patients with involvement of the central nervous system (CNS) because of the poor CNS penetration of antifungal medications. Voriconazole yields fungicidal drug concentrations in the CNS, but its use is limited in solid organ transplant patients because of its metabolic interactions with immunosuppression. Here we report a case of invasive fungal infection in the CNS after an emergency liver transplantation due to hepatitis B virus-related acute liver failure. The patient was managed successfully with a long-term conservative medical treatment.

Prognostic Nomogram for Patients with Hepatitis E Virus-related Acute Liver Failure: A Multicenter Study in China.

Background and AimsTimely and effective assessment scoring systems for predicting the mortality of patients with hepatitis E virus-related acute liver failure (HEV-ALF) are urgently needed. The present study aimed to establish an effective nomogram for predicting the mortality of HEV-ALF patients.MethodsThe nomogram was based on a cross-sectional set of 404 HEV-ALF patients who were identified and enrolled from a cohort of 650 patients with liver failure. To compare the performance with that of the model for end-stage liver disease (MELD) scoring and CLIF-Consortium-acute-on-chronic liver failure score (CLIF-C-ACLFs) models, we assessed the predictive accuracy of the nomogram using the concordance index (C-index), and its discriminative ability using time-dependent receiver operating characteristics (td-ROC) analysis, respectively.ResultsMultivariate logistic regression analysis of the development set carried out to predict mortality revealed that γ-glutamyl transpeptidase, albumin, total bilirubin, urea nitrogen, creatinine, international normalized ratio, and neutrophil-to-lymphocyte ratio were independent factors, all of which were incorporated into the new nomogram to predict the mortality of HEV-ALF patients. The area under the curve of this nomogram for mortality prediction was 0.671 (95% confidence interval: 0.602–0.740), which was higher than that of the MELD and CLIF-C-ACLFs models. Moreover, the td-ROC and decision curves analysis showed that both discriminative ability and threshold probabilities of the nomogram were superior to those of the MELD and CLIF-C-ACLFs models. A similar trend was observed in the validation set.ConclusionsThe novel nomogram is an accurate and efficient mortality prediction method for HEV-ALF patients.

Systematic analysis on multiple Gene Expression Omnibus data sets reveals fierce immune response in hepatitis B virus-related acute liver failure.

Acute liver failure (ALF) caused by hepatitis B virus (HBV) is common type of liver failure in the world, with high morbidity and mortality rates. However, the prevalence, genetic background and factors determining the development of HBV‐related ALF are rarely studied. In this study, we examined three Gene Expression Omnibus (GEO) data sets by bioinformatics analysis to identify differentially expressed genes (DEGs), key biological processes and pathways. Immune infiltration analysis showed high immune cells infiltration in HBV‐related ALF tissue. We then confirmed natural killer cells and macrophages infiltration in clinical samples by immunohistochemistry assay, implying these cells play a significant role in HBV‐ALF. We found 1277 genes were co‐up‐regulated and that 1082 genes were co‐down‐regulated in the 3 data sets. Inflammation‐related pathways were enriched in the co‐up‐regulated genes and synthetic metabolic pathways were enriched in the co‐down‐regulated genes. WGCNA also revealed a key module enriching in immune inflammation response and identified 10 hub genes, differentially expressed in an independent data set. In conclusion, we identified fierce immune inflammatory response to elucidate the immune‐driven mechanism of HBV‐ALF and 10 hub genes based on gene expression profiles.

Changing epidemiology of acute liver failure in Italy: a single-center experience over 25 years.

Acute liver failure (ALF) is a rare but often lethal syndrome. In Italy, recent data on its incidence and causes are lacking. We report here the epidemiological analysis of ALF cases observed in Campania, a Southern Italian region, over the last 25 years. Medical records of ALF cases hospitalized from 1992 to 2018 were retrospectively analyzed. Two hundred ten ALF cases occurred during 1992-2018: 103 (49%) hepatitis B virus (HBV)-related (including 5 cases also infected with Delta virus), 39 (19%) from undetermined cause, 36 (17%) drug-induced, 11 (5%) Wilson's disease-associated, 8 (4%) hepatitis A virus (HAV)-related and 12 (6%) from other causes. Separate time-periods analysis of data showed a significant progressive decrease in ALF incidence mainly attributable to a decline of HBV and other viruses etiology. Already before 2010, HAV or Delta virus-related cases have no longer been observed. No hepatitis C or E virus-related ALF was detected through the study period. A progressive decrease in frequency of ALF due to undetermined causes or drug was also evident. A decrease in ALF incidence and a changing in its etiology were observed in Campania during 1992-2018. Both results were likely mainly due to 1991 introduction of HBV universal vaccination and may be considered generalizable nationwide.

Management of hepatitis B virus-related acute liver failure.

Hepatitis B virus (HBV) is the most important cause of acute liver failure (ALF) in Eastern countries. HBV-related ALF may occur after acute HBV infection (A-ALF) or during acute exacerbation (flare) of chronic HBV infection (C-ALF). C-ALF may occur spontaneously or as a result of the effect of immunosuppression due to chemotherapeutic or immunosuppressive agents. The definition of HBV-related ALF is uncertain, because different diagnostic criteria are used in C-ALF, which may present as acute-on-chronic liver failure. Although the pathogenesis differs in the two subgroups of ALF, the symptoms and biochemical parameters can be similar. High titers of immunoglobulin M hepatitis B core antibody and lower viral loads are frequent in A-ALF as compared with C-ALF. The prognosis of C-ALF is significantly poor as compared with that of A-ALF. In C-ALF, most immunosuppression-mediated reactivation of hepatitis B results in fatality. Many case series or case-control studies have not demonstrated the survival benefit of nucleos(t)ide treatment. This treatment failure is probably related to delayed initiation of nucleos(t)ide treatment and viral suppression. Treatment with nucleos(t)ide analogs should be started immediately and should be continued regardless of subgroups of HBV-related ALF. Liver transplantation is the only treatment option that improves the prognosis of HBV-related ALF. Patients under consideration for transplantation should be given nucleos(t)ide analogs as prophylaxis to reduce the likelihood of post-transplant HBV recurrence.

Serum from patients with hepatitis E virus-related acute liver failure induces human liver cell apoptosis

The pathogenesis of acute liver failure has not been fully elucidated. The present study investigated the effects of the serum from patients with hepatitis E virus (HEV)-related acute liver failure on human liver cell survival and apoptosis, and evaluated the protective effects of anti-lipopolysaccharide(LPS) antibody recognizing core polysaccharide against acute liver failure serum-induced apoptosis. Serum was collected from patients with HEV-related acute liver failure. The levels of endotoxin (LPS) in the serum were measured using a quantitative tachypleus amebocyte lysate endotoxin detection kit with a chromogenic endpoint. Serum with a mean concentration of LPS was incubated with L02 human liver cells and the rate of apoptosis was detected by flow cytometry. The apoptotic rate was also evaluated in liver cells incubated with antibody and the HEV-related acute liver failure serum. The results indicated that the concentration of LPS in the serum of patients with HEV-related acute liver failure was 0.26±0.02 EU/ml, which was significantly higher than that of the control group (P<0.05). The rate of apoptosis in the human liver cells induced by acute liver failure serum was 5.83±0.42%, which was significantly increased compared with that in the cells treated with the serum of healthy individuals (P<0.05). The apoptotic rate of the cells incubated with antibody and the acute liver failure serum was 5.53±0.51%, which was lower than that of the cells incubated with acute liver failure serum alone (P>0.05). These results indicate that the serum of patients with HEV-related acute liver failure induces the apoptosis of human liver cells. LPS may be directly involved in the apoptosis of human liver cells. Moreover, the presence of the antibody did not significantly reduce the level of apoptosis of liver cells exposed to HEV-related acute liver failure serum.

Hepatobiliary Quiz-6 (2013)

1.Regarding anti-tubercular therapy (ATT) related hepatotoxicity the following are TRUE:1.Transient asymptomatic rise of transaminases is common and settles spontaneously with continuation of isoniazid.2.Most common pattern of ATT induced hepatotoxicity is cholestatic.3.ATT induced acute liver failure has worse prognosis virus related acute liver failure.4.Combination therapy increases the risk of hepatotoxicity.5.Daily dosing regimen increases risk of hepatotoxicity.2.Regarding the mechanisms of ATT related hepatotoxicity the following are TRUE:1.Slow acetylators have less risk of isoniazid induced hepatotoxicity.2.Rifampicin increases isoniazid induced hepatotoxicity by inducing cytochrome P450 enzymes.3.Rifampicin can cause both conjugated and unconjugated hyperbilirubinemia without hepatocellular damage.4.Pyrazinamide induced hepatotoxicity is dose dependent.5.Women have lower risk of ATT induced hepatotoxicity due to lower cytochrome P450 enzyme activity.3.Regarding model for end stage liver disease (MELD) the following are TRUE EXCEPT:1.MELD was initially developed as a score to predict survival following surgical porto-systemic shunting for refractory ascites or variceal bleeding.2.Upper value of serum creatinine is capped at 4 mg/dl.3.Addition of etiology of liver disease improves the predictive ability of the MELD score.4.MELD scores are also predictive of post transplant morbidity, length of ICU stay and cost of transplantation.5.Addition of other recipient and donor criteria to MELD may be useful in optimizing transplant risk in patients with high MELD scores.4.Regarding use of MELD for applications other than liver transplantation the following are TRUE EXCEPT:1.MELD score does not predict occurrence of infection and mortality in hospitalized patients with cirrhosis.2.MELD score can be used to estimate mortality after surgery in patients with cirrhosis.3.MELD score can be used to estimate hepatic failure after hepatic resection for hepatocellular carcinoma.4.MELD score does not predict mortality after hepatic resection for hepatocellular carcinoma.5.MELD is a predictor of rebleeding and mortality after variceal hemorrhage.5.Regarding development of non-alcoholic fatty liver disease (NAFLD) after liver transplant the following are TRUE:1.Recurrence of NAFLD in patients transplanted for cryptogenic cirrhosis is almost universal.2.De-novo development of NAFLD in patients transplanted for other indications is rare.3.NAFLD post liver transplant is an insidious process requiring months to years to develop.4.Risk factors for recurrent or de-novo NAFLD after transplant are similar to those for NAFLD in native liver.5.Well defined evidence based paradigms are available for treatment of NAFLD after liver transplant.6.Regarding hepatitis C virus (HCV) infection in patients of end stage renal disease (ESRD) on regular hemodialysis the following are TRUE:1.The prevalence of HCV infection is higher in ESRD patients than in the general population.2.Duration of hemodialysis is not a risk factor for HCV positivity.3.Guidelines routinely recommend use dedicated dialysis machines, patient isolation, and a ban on reuse of dialyzer in patients with HCV infection.4.Routine screening for HCV infection should be done in all ESRD patients on hemodialysis.5.HCV positive patients have worse outcome after renal transplant.7.Regarding gastric varices in patients with portal hypertension the following are TRUE EXCEPT:1.Gastric varices account for only 5–10% of all upper digestive bleeds.2.Bleeding from gastric varices is correlated with hepatic venous pressure gradient.3.Patients with extrahepatic portal vein obstruction are more likely to have isolated gastric varices than patients with cirrhosis.4.Transjugular intrahepatic porto-systemic shunt is the first line treatment of gastric varices.5.Balloon occluded retrograde transvenous obliteration is a newer modality for treatment of gastric varices.8.Regarding the mechanisms responsible for progression of steatosis to steatohepatitis in NAFLD the following are TRUE EXCEPT:1.Hepatic triglyceride is directly toxic to the liver and degree of steatosis is correlated with inflammation.2.Free fatty acids cause liver injury directly as well as via lipid peroxidation.3.Patients with steatohepatitis have higher oxidative stress compared with chronic viral hepatitis.4.Levels of inflammatory cytokines are similar in steatohepatitis and simple steatosis.5.Iron overload and hemochromatosis gene mutations are important cause of oxidative stress in Asian patients with steatohepatitis.9.Regarding primary cholestatic liver diseases the following are TRUE:1.Specific anti-nuclear antibodies directed against nuclear body or envelope proteins are useful for diagnosis of primary biliary cirrhosis (PBC).2.The Barcelona and Paris criteria are used to asses response to therapy in primary sclerosing cholangitis (PSC).3.Ursodeoxycholic acid decreases risk of colonic neoplasia in PSC.4.Colectomy prior to liver transplantation decreases risk of recurrence of PSC after transplantation.5.Immunoglobulin G4-associated cholangitis is steroid unresponsive.10.Regarding evaluation of a patient with ascites the following are TRUE EXCEPT:1.Bedside inoculation of ascitic fluid into blood culture bottles increases bacterial detection.2.Yield of malignant cytology improves if multiple samples of fluid are tested.3.CA 125 is a useful investigation in a patient with suspected malignant ascites.4.Serum-ascites albumin gradient (SAAG) ≥ 1.1 is has good accuracy for underlying portal hypertensive ascites even in cases of mixed ascites.5.Pro-brain natriuretic peptide cannot differentiate ascites due to heart failure from ascites due to cirrhosis.

Specificity of an anti-capsid antibody associated with Hepatitis B Virus-related acute liver failure

Previously, the livers of patients suffering from acute liver failure (ALF), a potentially fatal syndrome arising from infection by Hepatitis B Virus (HBV), were found to contain massive amounts of an antibody specific for the core antigen (HBcAg) capsid. We have used cryo-electron microscopy and molecular modeling to define its epitope. HBV capsids are icosahedral shells with 25Å-long dimeric spikes, each a 4-helix bundle, protruding from the contiguous "floor". Of the anti-HBcAg antibodies previously characterized, most bind around the spike tip while one binds to the floor. The ALF-associated antibody binds tangentially to a novel site on the side of the spike. This epitope is conformational. The Fab binds with high affinity to its principal determinants but has lower affinities for quasi-equivalent variants. The highest occupancy site is on one side of a spike, with no detectable binding to the corresponding site on the other side. Binding of one Fab per dimer was also observed by analytical ultracentrifugation. The Fab did not bind to the e-antigen dimer, a non-assembling variant of capsid protein. These findings support the propositions that antibodies with particular specificities may correlate with different clinical expressions of HBV infection and that antibodies directed to particular HBcAg epitopes may be involved in ALF pathogenesis.

Two distinct subtypes of hepatitis B virus–related acute liver failure are separable by quantitative serum immunoglobulin M anti-hepatitis B core antibody and hepatitis B virus DNA levels

Hepatitis B virus (HBV)-related acute liver failure (HBV-ALF) may occur after acute HBV infection (AHBV-ALF) or during an exacerbation of chronic HBV infection (CHBV-ALF). Clinical differentiation of the two is often difficult if a previous history of HBV is not available. Quantitative measurements of immunoglobulin M (IgM) anti-hepatitis B core antibody (anti-HBc) titers and of HBV viral loads (VLs) might allow the separation of AHBV-ALF from CHBV-ALF. Of 1,602 patients with ALF, 60 met clinical criteria for AHBV-ALF and 27 for CHBV-ALF. Sera were available on 47 and 23 patients, respectively. A quantitative immunoassay was used to determine IgM anti-HBc levels, and real-time polymerase chain reaction (rtPCR) was used to determine HBV VLs. AHBV-ALFs had much higher IgM anti-HBc titers than CHBV-ALFs (signal-to-noise [S/N] ratio median: 88.5; range, 0-1,120 versus 1.3, 0-750; P < 0.001); a cut point for a S/N ratio of 5.0 correctly identified 44 of 46 (96%) AHBV-ALFs and 16 of 23 (70%) CHBV-ALFs; the area under the receiver operator characteristic curve was 0.86 (P < 0.001). AHBV-ALF median admission VL was 3.9 (0-8.1) log10 IU/mL versus 5.2 (2.0-8.7) log10 IU/mL for CHBV-ALF (P < 0.025). Twenty percent (12 of 60) of the AHBV-ALF group had no hepatitis B surface antigen (HBsAg) detectable on admission to study, wheras no CHBV-ALF patients experienced HBsAg clearance. Rates of transplant-free survival were 33% (20 of 60) for AHBV-ALF versus 11% (3 of 27) for CHBV-ALF (P = 0.030). AHBV-ALF and CHBV-ALF differ markedly in IgM anti-HBc titers, in HBV VLs, and in prognosis, suggesting that the two forms are, indeed, different entities that might each have a unique pathogenesis.

Atypical Acute Leukemia Early After Liver Transplantation

Acute myeloid leukemia (AML) has been rarely reported after transplantation, namely seven cases described so far. The putative mechanism of action is long-standing immunosuppression, even though no clear correlation with the type of drug has ever been demonstrated. We report the case of a 28-year-old male patient who presented with a early onset of AML after liver transplantation for hepatitis B virus-related acute liver failure. The AML was characterized by aggressive clinical features with extrahematologic sites of involvement and an atypical immunophenotype; the laboratory findings were consistent with the diagnosis of monocytic acute leukemia.

815 Molecular epidemiology of hepatitis B virus-related acute liver failure in the United States: a multicenter case control study

815 Molecular epidemiology of hepatitis B virus-related acute liver failure in the United States: a multicenter case control study