Ryan M. Taylor

Fulminant Hepatitis A Virus Infection in the United States: Incidence, Prognosis, and Outcomes

Acute liver failure (ALF) due to hepatitis A virus (HAV) infection is an uncommon but potentially lethal illness. The aim of this study was to identify readily available laboratory and clinical features associated with a poor prognosis among ALF patients with HAV infection. The presenting features of 29 adults with anti‐HAV IgM positive ALF enrolled in the ALFSG_between 1998 and 2005 were reviewed. The HAV patients listed for transplantation by UNOS were also reviewed. Acute HAV accounted for 3.1% of patients enrolled in the ALFSG. At 3 weeks follow‐up, 16 had spontaneously recovered (55%), 9 underwent transplantation (31%), and 4 had died (14%). A prognostic model incorporating 4 presenting features (serum ALT <2,600 IU/L, creatinine >2.0 mg/dL, intubation, pressors) had an AUROC for transplant/death of 0.899 which was significantly better than the Kings College criteria (0.623, P = .018) and MELD scores (0.707, P = .0503). Between 1988 and 2005, the frequency of patients requiring liver transplantation for HAV in the UNOS database significantly decreased from 0.7 % to 0.1% (P < .001). In addition, the proportion of HAV cases enrolled in the ALFSG significantly decreased from 5% to 0.8% (P = .007). In conclusion, the frequency of HAV patients enrolling in the ALFSG and being listed for liver transplantation in the United States has declined in parallel. A prognostic index consisting of 4 clinical and laboratory features predicted the likelihood of transplant/death significantly better than other published models suggesting that disease specific prognostic models may be of value in non‐acetaminophen ALF. (HEPATOLOGY 2006;44:1589–1597.)

Fulminant hepatitis A virus infection in the United States: Incidence, prognosis, and outcomes See Editorial on Page 1397 Potential conflict of interest: Nothing to report. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Acute liver failure (ALF) due to hepatitis A virus (HAV) infection is an uncommon but potentially lethal illness. The aim of this study was to identify readily available laboratory and clinical features associated with a poor prognosis among ALF patients with HAV infection. The presenting features of 29 adults with anti‐HAV IgM positive ALF enrolled in the ALFSG_between 1998 and 2005 were reviewed. The HAV patients listed for transplantation by UNOS were also reviewed. Acute HAV accounted for 3.1% of patients enrolled in the ALFSG. At 3 weeks follow‐up, 16 had spontaneously recovered (55%), 9 underwent transplantation (31%), and 4 had died (14%). A prognostic model incorporating 4 presenting features (serum ALT <2,600 IU/L, creatinine >2.0 mg/dL, intubation, pressors) had an AUROC for transplant/death of 0.899 which was significantly better than the Kings College criteria (0.623, P = .018) and MELD scores (0.707, P = .0503). Between 1988 and 2005, the frequency of patients requiring liver transplantation for HAV in the UNOS database significantly decreased from 0.7 % to 0.1% (P < .001). In addition, the proportion of HAV cases enrolled in the ALFSG significantly decreased from 5% to 0.8% (P = .007). In conclusion, the frequency of HAV patients enrolling in the ALFSG and being listed for liver transplantation in the United States has declined in parallel. A prognostic index consisting of 4 clinical and laboratory features predicted the likelihood of transplant/death significantly better than other published models suggesting that disease specific prognostic models may be of value in non‐acetaminophen ALF. (HEPATOLOGY 2006;44:1589–1597.)

Immune thrombocytopenic purpura following liver transplantation: a case series and review of the literature.

Thrombocytopenia is common among liver transplant candidates and recipients. The aim of our study was to determine the incidence and outcome of new‐onset immune‐mediated thrombocytopenic purpura (ITP) following liver transplantation at a single center. Among the 256 liver transplant recipients with an International Classification of Diseases, Ninth Edition code for thrombocytopenia, 8 cases of new‐onset ITP were identified, leading to an overall incidence of 0.7% in 1,105 consecutive liver transplant recipients over a 15‐year period. All 8 patients were Caucasian, 5 (63%) were male, and the median age at ITP onset was 54 years (range, 15‐63). The median platelet count at presentation was 3,500 cells/mL (range, 1,000‐12,000) and liver disease was due to hepatitis C (38%), primary sclerosing cholangitis (38%), and cryptogenic cirrhosis (25%). The median time from transplant to ITP onset was 53.5 months (range, 1.9‐173). Three of the 6 patients tested (50%) had cell‐bound antiplatelet antibodies, 1 patient had an underlying hematological malignancy, and none of the organ donors had a history of ITP. Corticosteroids and/or immunoglobulin infusions were effective in 4 patients. However, serial rituximab infusions were required in 4 patients with persistent thrombocytopenia, and 3 of them eventually required splenectomy to induce disease remission. At a median follow‐up of 19.7 months, 7 long‐term survivors remain in remission with a median platelet count of 267,000 cells/mL. In conclusion, new‐onset ITP is an infrequent but important cause of severe thrombocytopenia in liver transplant recipients. Corticosteroids and immunoglobulin infusions were effective in 50% while the remainder of patients required rituximab infusions or eventual splenectomy for long‐term disease remission. Liver Transpl 12:781–791, 2006.

Protein arginine methyltransferase 1 modulates innate immune responses through regulation of peroxisome proliferator-activated receptor γ-dependent macrophage differentiation

Arginine methylation is a common posttranslational modification that has been shown to regulate both gene expression and extranuclear signaling events. We recently reported defects in protein arginine methyltransferase 1 (PRMT1) activity and arginine methylation in the livers of cirrhosis patients with a history of recurrent infections. To examine the role of PRMT1 in innate immune responses in vivo, we created a cell type-specific knock-out mouse model. We showed that myeloid-specific PRMT1 knock-out mice demonstrate higher proinflammatory cytokine production and a lower survival rate after cecal ligation and puncture. We found that this defect is because of defective peroxisome proliferator-activated receptor γ (PPARγ)-dependent M2 macrophage differentiation. PPARγ is one of the key transcription factors regulating macrophage polarization toward a more anti-inflammatory and pro-resolving phenotype. We found that PRMT1 knock-out macrophages failed to up-regulate PPARγ expression in response to IL4 treatment resulting in 4-fold lower PPARγ expression in knock-out cells than in wild-type cells. Detailed study of the mechanism revealed that PRMT1 regulates PPARγ gene expression through histone H4R3me2a methylation at the PPARγ promoter. Supplementing with PPARγ agonists rosiglitazone and GW1929 was sufficient to restore M2 differentiation in vivo and in vitro and abrogated the difference in survival between wild-type and PRMT1 knock-out mice. Taken together these data suggest that PRMT1-dependent regulation of macrophage PPARγ expression contributes to the infection susceptibility in PRMT1 knock-out mice.

Su1069 Esophageal Variceal Bleeding in Hospitalized Patients With Cirrhosis: Results From the NIS Database 2002 - 2012

BACKGROUND: Esophageal variceal bleeding (EVB) is a frequent complication in cirrhotic patients resulting in considerablemortality andmorbidity. However, recent large-scale studies are lacking. We AIMS: To conduct a retrospective analysis using a national U.S. database to study the differences in demographic characteristics, rate of complications, and outcomes, and temporal trends in hospitalized cirrhotic patients with and without EVB. METHODS: We interrogated data from the Nationwide Inpatient Sample 2002 2012. Utilizing International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, we studied hospital discharges for cirrhosis and related EVB in adult patients. Cases were queried for complications well-recognized in cirrhotic patients. These included infections including Clostridium difficile infection and spontaneous bacterial peritonitis, hepatic encephalopathy and hepatorenal syndrome. Comorbid conditions were assessed using the Elixhauser comorbidity. We used high-dimensional propensity scores in a 1:5 matching ratio with a greedy matching algorithm generated by regression analysis. For trend analysis, we used the Cochrane-Armitage test. RESULTS: Patients with EVB suffered a significantly higher rate of alcohol abuse (63.90% versus 48.80%; p<0.01). EVB was also associated with an overall lower incidence of infection (13.50% versus 24.10%; p<0.01). EVB in cirrhotic patients was independently associated with overall worse outcomes with respect to in-hospital mortality (10.00% versus 5.00%; p<0.01) and hospital charges (median

RS738409 SNP of PNPLA3 Gene Predicts Clinical Recovery in Patients with Decompensated Hepatitis C Cirrhosis After Attaining Sustained Virological Response

41,000 versus

Approach to the Patient with Acute Liver Failure

26,000; p<0.01). In the period from 2002 2012, the number of cirrhosis-related hospitalizations increased from 337,956 to 570,220 (p<0.01). Concurrently, the incidence of EVB declined from 8.60% to 5.78% with an overall decreased trend (p<0.01). CONCLUSION: EVB in cirrhotic patients was associated with a significantly higher mortality and increased hospital charges. The incidence of EVB in hospitalized cirrhotic patients declined significantly from 2002 2012. This is consistent with earlier trends from 1988 2002 and likely reflects the effectiveness of primary and secondary prophylaxis.