Successful immunosuppression withdrawal should benefit the natural history of organ transplantation patients. To identify the clinical hazards of removing drug treatment and possible characteristics that predict a favorable outcome in long-term liver recipients, immunosuppression was withdrawn completely and the clinicopathological outcome documented in 18 liver recipients. Indication for transplantation, HLA matching, early rejection history, and presence of microchimerism were examined as predictors of outcome. Chimerism was determined by polymerase chain reaction-based examination for donor-specific HLA-DRB1 alleles and Y-gene-specific nucleotide sequences. At 3 years, 5 patients (28%) remained completely off immunosuppression; 12 patients (67%) experienced histological graft changes: acute rejection in 4, portal tract inflammation/ hepatitis in 7, and necrosis in 1. Hepatitis B or C viral infections did not account for the nonrejection patterns. Unmasking of systemic disorders occurred. Chimerism, demonstrated in 7 patients (39%), with skin the optimal tissue, was not associated with tolerance. Parameters associated with successful drug withdrawal were transplantation for non-immune-mediated liver disorders, fewer donorrecipient HLA A, B, and DR mismatches, and a low incidence of early rejection. Immunosuppression withdrawal is a feasible option in a proportion of selected liver recipients, but identification of tolerant patients remains imprecise. (HEPATOLOGY 1998;27:926-933.)

No abstract

Sarcoidosis can cause end-stage chronic liver disease, which is often unrecognized until examination of the explanted liver. Response to conventional immunosuppression is variable and unpredictable. Transplantation is feasible and safe in this population but recurrence is possible.

Hepatocellular carcinoma (HCC) has traditionally been considered a rare complication of cirrhosis secondary to autoimmune hepatitis (AIH), yet the true incidence remains unknown due to a lack of published data. Consequently, some professional guidelines do not mandate routine surveillance for HCC in this condition. Our aims were to evaluate the rate at which HCC develops among a large, prospectively obtained cohort of patients with AIH at a single center. Demographic, clinical, and laboratory indices associated with the development of HCC were also identified. HCC was discovered in 15 of 243 patients with AIH, all of whom had type 1 AIH equating to 1090 cases per 100,000 patient follow-up years. HCC occurred in the same proportion of females as males, 6.1% versus 6.4%, P ‫؍‬ 0.95. HCC occurred more frequently in patients who had cirrhosis at presentation, 9.3% versus 3.4%, P ‫؍‬ 0.048, or who had a variceal bleed as the index presentation of AIH, 20% versus 5.3%, P ‫؍‬ 0.003. The median duration from time of confirmed cirrhosis to a diagnosis of HCC was 102.5 months, range 12-195 months. Median survival in patients whose HCC was diagnosed on surveillance was 19 months (range 6-36 months) compared with 2 months (range 0-14 months) for patients presenting symptomatically (P ‫؍‬ 0.042). Conclusion: Cirrhosis in AIH is the sine qua non for HCC development, which subsequently occurs at a rate of 1.1% per year and affects men and women in equal proportions. (HEPATOLOGY 2008;48:863-870.)

Autoimmune hepatitis (AIH) typically responds to treatment in 90% of patients. Early prediction of treatment outcome would be advantageous in clinical practice. We evaluated whether parameters at initiation of therapy or changes in these parameters at day 3 and day 7 following corticosteroid initiation predicted treatment failure. Treatment-naive, jaundiced patients presenting to our tertiary unit between 1999-2009 were identified and mathematical models of prognosis in liver disease scores calculated at day 0, day 3, and day 7. Overall, 72 patients were identified (48 women, 24 men). Treatment failure occurred in 18% (13/72) of patients. At diagnosis, higher median bilirubin (451 lmol/L versus 262 lmol/L, P 5 0.02), INR (1.62 versus 1.33, P 5 0.005), model for endstage liver (MELD) score (26 versus 20, P 5 0.02), MELD-sodium (Na) score (27 versus 22, P 5 0.03) and United Kingdom endstage liver disease score (UKELD) score (59 versus 57, P 5 0.01) significantly correlated with treatment failure. Analysis of area under the receiver operator characteristic curve (AUROC) values at day 7 identified change (D) bilirubin (AUROC 0.68), D creatinine (0.69), D MELD (0.79), D MELD-Na (0.83) and D UKELD (0.83) best predicted treatment failure. Specifically, a fall in UKELD of less than 2 points predicted treatment failure with a sensitivity of 85% and specificity of 68%. Of 13 treatment failures, nine required second-line immunosuppression, three required emergency transplant, and one died of sepsis. In total, four patients died in the treatment failure group compared with one in the responder group (4/13 5 31% versus 1/59 5 1.7%, P 5 0.003). Conclusion: Approximately 20% of icteric AIH presentations fail corticosteroid therapy. This is associated with significant mortality and the need for emergency transplantation. Treatment failure is best predicted by change in MELD-Na and UKELD at day 7. Early identification of nonresponders may allow timely escalation of immunosuppression to prevent clinical deterioration. (HEPATOLOGY 2011;53:926-934)

No abstract

Objectives: Uncontrolled hemorrhage remains one of the leading causes of trauma deaths and one of the most challenging problems facing emergency medical professionals. Several hemostatic agents have emerged as effective adjuncts in controlling extremity hemorrhage. However, a review of the current literature indicates that none of these agents have proven superior under all conditions and in all wound types. This study compared several hemostatic agents in a lethal penetrating groin wound model where the bleeding site could not be visualized.Methods: A complex groin injury with a small penetrating wound, followed by transection of the femoral vessels and 45 seconds of uncontrolled hemorrhage, was created in 80 swine. The animals were then randomized to five treatment groups (16 animals each). Group 1 was Celox-A (CA), group 2 was combat gauze (CG), group 3 was Chitoflex (CF), group 4 was WoundStat (WS), and group 5 was standard gauze (SG) dressing. Each agent was applied with 5 minutes of manual pressure. Hetastarch (500 mL) was infused over 30 minutes. Hemodynamic parameters were recorded over 180 minutes. Primary endpoints were attainment of initial hemostasis and incidence of rebleeding.Results: Overall, no difference was found among the agents with respect to initial hemostasis, rebleeding, and survival. Localizing effects among the granular agents, with and without delivery mechanisms, revealed that WS performed more poorly in initial hemostasis and survival when compared to CA.

Benign recurrent intrahepatic cholestasis (BRIC) is characterized by episodic cholestasis and pruritus without anatomical obstruction. Effective medical treatment is not available. We report complete and long-lasting disappearance of pruritus and normalization of serum bile salt concentrations in cholestatic BRIC patients within 24 hours after endoscopic nasobiliary drainage (NBD). Relative amounts of phospholipids and bile salts in bile collected during NBD appeared to be normal, but phospholipids other than phosphatidylcholine (especially sphingomyelin) were increased. In conclusion, we propose that temporary endoscopic nasobiliary drainage should be considered in cholestatic BRIC patients. (HEPATOLOGY 2006;43:51-53.)