Roshan Shrestha

Liver transplantation for acute liver failure from drug induced liver injury in the United States

Studies of acute liver failure from drugs have included cases mostly attributed to acetaminophen (APAP) but have reported limited data on other drugs. We used the United Network for Organ Sharing (UNOS) liver transplant database from 1990 to 2002 to identify recipients and estimate a U.S. population‐based rate of liver transplantation due to acute liver failure from drugs. Patients were identified if their diagnosis was acute hepatic necrosis from an implicated drug at the time of transplant. Liver transplantation for drug hepatotoxicity accounted for 15% of liver transplants for acute liver failure over the study period. In our cohort (n = 270), 206 (76%) recipients were female. APAP alone, or in combination with another drug, accounted for 133 (49%) cases. In the non‐acetaminophen (non‐APAP) group (n = 137), the most frequently implicated drugs were: isoniazid, n = 24 (17.5%); propylthiouracil, n = 13 (9.5%); and phenytoin and valproate in 10 (7.3%) cases each. One‐year patient and graft survival for the entire cohort was 77 and 71%, respectively. Among Caucasians (n = 206) and African‐Americans (n = 48), APAP only was implicated in 110 (53%) patients and 12 (25%) patients, respectively, and non‐APAP drugs were implicated in 96 (47%) patients and 36 (75%) patients, respectively (P = .0004). Among African‐Americans in the non‐APAP group, 28 (78%) were women. In conclusion four drugs were implicated in 42% of patients undergoing liver transplantation for acute liver failure due to drugs other than APAP. The increased frequency of African‐American women undergoing liver transplantation for non‐APAP drug induced liver injury warrants further study. (Liver Transpl 2004;10:1018–1023.)

Adult living donor liver transplantation using a right hepatic lobe

BACKGROUND Living donor liver transplantation has gained wide acceptance as an alternative for children with end-stage liver disease. The standard left lateral segment used in this operation does not provide adequate parenchymal mass to broaden its application to larger children or adults. METHODS We report two cases of adult to adult living donor liver transplantation using a right hepatic lobe in patients with chronic liver disease. RESULTS Both recipients experienced excellent initial graft function and have normal liver function 4 and 9 months postoperatively. Both donors are alive and well and returned to normal life 4 weeks postoperatively. CONCLUSIONS Our initial experience suggests that this technique is a safe and reliable option for adults with chronic end-stage liver disease. A conservative application of this procedure in the adult population could significantly reduce the mortality on the adult waiting list.

Prednisone withdrawal 14 days after liver transplantation with mycophenolate: a prospective trial of cyclosporine and tacrolimus.

BACKGROUND The long-term complications of immunosuppressive therapy such as diabetes, hypercholesterolemia, and hypertension are a major source of morbidity in liver transplant recipients. In this prospective, randomized, open-label study we completely withdrew prednisone (PRED) 14 days after liver transplantation in an effort to decrease these metabolic complications. Patients were maintained on mycophenolate mofetil (MMF) in combination with either cyclosporine (CsA; Neoral formulation) or tacrolimus (TAC). Thus, we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy, toxicity, and effect on posttransplant metabolic complications. METHODS A total of 71 patients were randomized to receive either TAC-MMF (n=35) or CsA-MMF (n=36) after liver transplantation and were analyzed for patient and graft survival. Fifty-eight patients continued the immunosuppressive protocol for at least 6 months after transplantation and were analyzed for the incidence of acute rejection and the prevalence of diabetes, hypertension, and hypercholesterolemia. RESULTS The 6-month patient survival rates were 94.4% for CsA-MMF and 88.6% for TAC-MMF. Corresponding 6-month graft survival rates were 88.7% and 85.71% with no immunologic graft losses in either group. The incidence of biopsy-proven acute rejection was 46% for CsA-MMF and 42.3% for TAC-MMF. Six patients were converted from CsA to TAC (four for recurrent rejection) and seven patients were converted from TAC to CsA (four for neurotoxicity). Only one patient (in the TAC-MMF group) developed new-onset posttransplant diabetes. In contrast, four of eight patients in the CsA-MMF group who were diabetic before transplant became nondiabetic in the first 3 months after transplant. The mean serum cholesterol level was significantly lower in the TAC-MMF group than in the CsA-MMF group (145.2+/-41.8 mg/dl and 190.3+/-62.2, respectively; P<0.001) and the incidence of hypertension was lower in the TAC-MMF group (12% vs. 30.3% in the CsA-MMF group, P<0.01). Both groups had a lower incidence of metabolic complications compared with a historical group (n=100) maintained on CsA and PRED (10 mg/day at 6 months). CONCLUSIONS MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver transplantation with a moderate rejection rate and no immunologic graft losses. Early PRED withdrawal decreases posttransplant diabetes, hypercholesterolemia, and hypertension, but patients maintained on TAC have lower serum cholesterol levels and a lower incidence of hypertension than CsA-treated patients.

Patient and graft survival in hepatitis C recipients after adult living donor liver transplantation in the United States

End stage liver disease from chronic hepatitis C is the leading indication for liver transplantation in the United States. Small studies suggest that recurrent hepatitis C may be more common and occur earlier after living donor liver transplantation compared to deceased donor liver transplantation. The objective of our study was to analyze the United Network for Organ Sharing liver transplant database to compare patient and graft survival in recipients transplanted for chronic hepatitis C who received a living donor organ and deceased donor organ between 1999 and 2002. We identified 279 living donor recipients and 3,955 deceased donor recipients. Living donor recipients were less ill at the time of transplant, more likely to be female, and received grafts from younger donors. In the living donor group and deceased donor group, 1‐year graft survival was 77% and 82%, respectively, and 2‐year graft survival was 72% and 75%, respectively, P = .11. One‐year patient survival was 87% in both groups and 2‐year patient survival was 83% and 81% in the living donor group and deceased donor group, respectively, P = .68. Short‐term patient and graft survival are similar between living donor and deceased donor liver transplant recipients with hepatitis C suggesting that recurrent hepatitis C does not seem to affect short‐term outcomes. (Liver Transpl 2004;10:340–346.)

Social stigmatization and hepatitis C virus infection.

Goal Our aim was to assess stigmatization by evaluating the impact of hepatitis C virus (HCV) on social interactions, feelings of rejection, internalized shame, and financial insecurity, and behavior. Background HCV patients suffer from slowly progressive disease. Although much research has improved the long-term prognosis of chronic HCV, quality of life may be affected by perceived social stigmatization. Study In a cross-sectional study, HCV patients without cirrhosis or significant comorbidities were recruited from the University of North Carolina viral hepatitis clinic. Subjects completed a questionnaire administered by a trained interviewer that assessed changes in sexual behavior, personal hygiene habits, social function, and interactions. Additionally, subjects completed validated, standardized questionnaires, the Health Status Questionnaire, and the SCL-90-R. Frequencies were calculated for the prevalence of stigmatization and altered social interaction. Correlations between education and behavior changes were assessed. A series of multivariate analyses controlling for age, sex, and education were performed to assess the association between HCV acquisition risk and stigmatization. Results One hundred seventy-five of 217 potential subjects (81%) participated in the survey. The average age was 45.2±7.7 years. Fifty-five percent were men and 53% were single. Twenty-nine percent had some college education. Risk factors for HCV acquisition included transfusion (21%) and injection drug use (29%), whereas 32% had an unknown mode of infection. Among common activities, 47% were less likely to share drinking glasses, 14% were less likely to prepare food, and one-third of subjects were less likely to share a towel. Thirty-five percent of respondents reported changes in their sexual practices. Decreased frequency of kissing and sexual intercourse was reported in 20% and 27% of individuals, respectively. Almost half of the single subjects reported increased use of condoms compared with only 20% among married couples. The majority of subjects perceived financial insecurity, internalized shame, and social rejection. Only 39% reported health impairment. Education level did not influence behavior change. Conclusion The majority of HCV subjects alter common behaviors and report financial insecurity, internalized shame, and social rejection, regardless of the method of HCV acquisition or socioeconomic status. These findings indicate that all HCV individuals be counseled and encouraged to participate in educational programs at the time of diagnosis to reduce unnecessary behavioral changes and stigmatization perceptions to improve quality of life.

Role of TIPS as a Bridge to Hepatic Transplantation in Budd-Chiari Syndrome☆

PURPOSE To investigate the role of transjugular intrahepatic portosystemic shunt (TIPS) as a bridge to transplantation for patients with Budd-Chiari syndrome (BCS). MATERIALS AND METHODS Eight patients (five women, three men) with a mean age of 49.8 years (range, 20-61 years) were diagnosed with BCS by means of computed tomography, hepatic venography, and liver biopsy. One patient had acute liver failure, with subacute or chronic failure in seven. TIPS placement was attempted in all eight patients. Clinical follow-up and portograms were obtained in all patients until death or transplantation. RESULTS TIPS placement was completed in seven of eight patients (87.5%). During the follow-up period, TIPS occlusion occurred in four patients. TIPS revision in this patient, although successful, was complicated by hemorrhage and multiorgan failure, and the patient died. Assisted patency rate, excluding the technical failure, was 100%. Mean follow-up in the six survivors with TIPS was 342 days (range, 19-660 days). All six survivors had complete resolution of their ascites. Albumin levels improved an average of 0.43 g/dL (range, 0.3-1.4 g/dL). Bilirubin levels improved in five of six patients (83%), decreasing by an average of 5.6 mg/dL (range, 3.0-15.2 mg/dL). Of the six survivors, three underwent elective liver transplantation, one is awaiting transplantation, and one has been removed from the transplantation list because of clinical improvement. One patient was a candidate for transplantation but declined to be put on the list. CONCLUSION Hepatic synthetic dysfunction improves markedly after TIPS placement in patients with BCS. Significant improvement in ascites can also occur. TIPS can be an effective bridge to transplantation for patients with BCS.

Early hepatic stellate cell activation is associated with advanced fibrosis after liver transplantation in recipients with hepatitis C

Recurrent hepatitis C after liver transplantation is a serious problem faced by liver transplant recipients. Activation of hepatic stellate cells is an early step in hepatic fibrogenesis. The aim of this study was to evaluate hepatic stellate cell activation, early after liver transplantation, as a predictor for the subsequent development of advanced fibrosis. Forty‐six patients who underwent liver transplantation for hepatitis C and protocol liver biopsies were divided into rapid fibrosers (n = 21), defined as recipients who developed bridging fibrosis or cirrhosis within 2 years of liver transplantation, and slow fibrosers (n = 25). The protocol liver biopsy obtained 4 months after transplantation was stained and quantitated for hepatic stellate cell activation with antibody to alpha smooth muscle actin. Hepatic stellate cell activity was independently associated with rapid fibrosis (odds ratio: 1.6 [95% CI: 1.1,2.2], P = 0.013). The c‐statistics for the receiver operating characteristic curve for stellate cell activity and fibrosis were 0.78 and 0.67, respectively, P = 0.36. The receiver operating characteristic curve for a model including stellate cell activity, histology activity index, and alanine aminotransferase. obtained at month 4 had the best c‐statistic (0.88). In recipients with stage 0 or 1 fibrosis on the month 4 liver biopsy who subsequently developed advanced fibrosis, the c‐statistic for the receiver operating characteristic curves was significantly better for stellate cell activity than for stage of fibrosis (0.77 and 0.51, respectively; P = 0.004). In conclusion, hepatic stellate cell activation early after liver transplantation complements traditional testing for identifying liver transplant recipients with hepatitis C at greatest risk for developing advanced fibrosis. (Liver Transpl 2005;11:1235–1241.)

Noncirrhotic Portal Hypertension in Patients With Human Immunodeficiency Virus–1 Infection

BACKGROUND & AIMS Noncirrhotic portal hypertension (NCPH) is unusual in North American patients. This study characterized patients with NCPH and human immunodeficiency virus-1 (HIV-1) infection to identify potential risk factors for this association. METHODS Eleven consecutive patients from our urban hepatology clinic with HIV-1 infection and NCPH were the subject of this series. Case histories, including medication lists and laboratory data, were analyzed. RESULTS Age at diagnosis was 51 +/- 7 years. CD4 count was 303 +/- 185 cells/mL, and HIV viral load was <75 copies/mL in 9 patients. Didanosine was the only medication taken by all patients; 10 each had taken lamivudine and zidovudine. In the 10 patients tested, 8 had at least 1 thrombophilic abnormality; 6 were deficient in protein S, and 2 had multiple abnormalities. Nodular regenerative hyperplasia was observed in all 11 and portal venulopathy in 5 patients. All patients had esophageal varices; 3 developed variceal bleeding. Six patients had ascites; 2 required transjugular intrahepatic portal systemic shunt. CONCLUSIONS Exposure to didanosine and/or a hypercoagulable tendency might predispose patients infected with HIV-1 to vascular changes resulting in NCPH.

Impact of Donor Age and Year of Transplant on Graft Survival in Liver Transplant Recipients with Chronic Hepatitis C

Studies suggest donor age and year of transplantation are associated with low graft survival in liver transplant recipients with hepatitis C. We sought to determine if advanced donor age and recent year of transplantation are associated with graft survival in hepatitis C recipients and to determine if the effect of donor age on graft survival is specific to hepatitis C. We analyzed the United Network for Organ Sharing liver transplant database from 1994 to 2002. Six thousand four hundred and four subjects transplanted for end‐stage liver disease from chronic hepatitis C met our criteria. One‐year graft survival in hepatitis C recipients with organs from donors <40 years old and ≥60 years old was 84% and 73%, p = 0.003, respectively. These rates in recipients with cholestatic liver disease and alcoholic liver disease were 85% and 82%, respectively, p = 0.11 and 82% and 78%, respectively, p = 0.14. Three‐year graft survival in hepatitis C recipients transplanted from 1994 to 1995 and 1996 to 1999 was 67% and 69%, respectively, p = 0.10. Graft survival in hepatitis C recipients has not declined in recent years. Older donor age is associated with lower short‐term graft survival in recipients with hepatitis C, but not in recipients with cholestatic or alcoholic liver disease.

Endoscopic stent insertion into the gallbladder for symptomatic gallbladder disease in patients with end-stage liver disease

BACKGROUND Endoscopic stent insertion into the gallbladder entails placement of a double-pigtail polyethylene stent between the gallbladder and the duodenum at ERCP. This procedure may be an effective temporary measure in patients with severe comorbid conditions, especially end-stage liver disease, that subsequently allows more definitive therapy, including liver transplantation. METHODS The records for 29 patients who underwent attempted endoscopic gallbladder stent insertion between May 1999 and May 2004 were reviewed retrospectively. RESULTS Mean patient age was 47 years; 86% of the patients were listed for liver transplantation, with a mean model for end-stage liver disease score of 15; 72% had Childs class B cirrhosis. Indications for gallbladder stent placement included recurrent biliary colic (69%), acute cholecystitis (17%), acalculous cholecystitis (7%), and gallstone pancreatitis (7%). Of the 29 patients who underwent ERCP, stent placement was successful in 26 (90%). Median follow-up was 9.4 months (range 0.1-40.5 months). Of those who had a stent placed, 6 (22%) subsequently underwent liver transplantation and another 15 (56%) were alive, most awaiting liver transplantation. Only 3 patients had late a complication or recurrence of biliary symptoms after stent placement. CONCLUSIONS Endoscopic stent placement in the gallbladder is a safe and an effective palliative treatment for patients with symptoms caused by gallbladder disease who are poor surgical candidates.