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Donor safety is essential in living donor liver transplantation. In this study we assessed the association among perioperative factors, liver dysfunction, and complications in 251 consecutives right hepatectomies for living donation.Retrospectively collected data from a prospectively assembled cohort of 251 consecutive living donors who underwent right hepatectomy between 1999 and 2020 were evaluated.Median age was 36 years; 54% were men. There was a statistically significant relationship between standardized liver volume by body surface area and the volumes calculated by imaging, weighting, and volume displacement. (rEarly postoperative hepatic dysfunction is associated with the development of post-live liver donor complications. A thoughtful balancing of preoperative risk factors for postoperative hepatic dysfunction may indeed and by association reduce postoperative complications.

Objectives Donor-derived malignancy of the liver allograft is a rare but serious condition in the setting of necessary immunosuppression. Retransplantation after abrupt immunosuppression cessation has been performed with durable cancer-free survival. Methods We present 2 cases of patients with donor-derived malignancy who were treated with complete immunosuppression cessation, which induced rapidly progressive liver allograft rejection and failure, with a need for subsequent retransplantation. We reviewed all serial liver biopsies and explants from both patients and performed C4d immunostaining. Results Initial explants of both patients showed severe allograft rejection, with unusual features of sinusoidal obstruction syndrome and C4d positivity. Malignant tumors in the explants were necrotic, related to rejection of donor-derived cancer cells and tissue. Follow-up of both patients has shown long-term cancer-free survival but issues with recurrent allograft failure requiring a third transplant. The reasons for retransplantation in both cases were related to allograft failure from antibody-mediated rejection. Conclusions Clinicians should be aware of a potentially increased risk of rejection and recurrent allograft failure when strategizing treatment of donor-derived malignancy with immunosuppression cessation and retransplantation.

Early liver transplantation (LT) for severe alcoholic hepatitis (AH) is a rescue therapy for highly selected patients with favorable psychosocial profiles not responding to medical therapy. Given the expected increase of AH candidate referrals requiring complex care and comprehensive evaluations, increased workload and cost might be expected from implementing an early LT program for AH but have not been determined. Some centers may also view AH as a strategy to expeditiously increase LT volume and economic viability. The aim of this study was to determine the health care use and costs of an early LT program for AH. Analyses of prospective databases of AH, interhospital transfers, and the hospital accounting system at a single center were performed from July 2011 to July 2016. For 5 years, 193 patients with severe AH were evaluated at our center: 143 newly referred transfers and 50 direct admissions. Annual increases of 13% led to 2 to 3 AH transfers/month and AH becoming the top reason for transfer. There were 169 (88%) nonresponders who underwent psychosocial evaluations; 15 (9%) underwent early LT. The median cost of early LT was $297,422, which was highly correlated with length of stay (r = 0.83; P

Living donor liver transplantation (LDLT) has been increasingly embraced around the world as an important strategy to address the shortage of deceased donor livers. The aim of this guideline, approved by the International Liver Transplantation Society (ILTS), is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT. Recommendations were developed from an analysis of the National Library of Medicine living donor transplantation indexed literature using the Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care of living donor liver transplant recipients., Compared to cadaveric liver transplantation, live donor LT (LDLT) is challenged by ethical, medical and surgical considerations, many of which are still unresolved. The aim of this guideline is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT.

The following guideline represents the position of the International Liver Transplantation Society (ILTS) on key preoperative, operative, and postoperative aspects surrounding living liver donation. These recommendations were developed from experts in the field from around the world. The authors conducted an analysis of the National Library of Medicine indexed literature on "living donor liver transplantation" [Medline search] using Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). ILTS members, and many more nonmembers, were invited to comment. Recommendations have been based on information available at the time of final submission (March 2016). The lack of randomized controlled trials in this field to date is acknowledged and is reflected in the grading of evidence. Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care.

Early liver transplantation (LT) in European centers reportedly improved survival in patients with severe alcoholic hepatitis (AH) not responding to medical therapy. Our aim was to determine if a strategy of early LT for severe AH could be applied successfully in the United States. We reviewed 111 patients with severe AH at our center from January 2012 to January 2015. The primary end point was mortality at 6 months or early LT, with a secondary end point of alcohol relapse after LT. Survival was compared between those receiving early LT and matched patients who did not. Using a process similar to the European trial, 94 patients with severe AH not responding to medical therapy were evaluated for early LT. Overall, 9 (9.6%) candidates with favorable psychosocial profiles underwent early LT, comprising 3% of all adult LT during the study period. The 6-month survival rate was higher among those receiving early LT compared with matched controls (89% vs 11%, p

Background Central line-associated blood stream infections (CLABSI) have a significant impact on mortality, morbidity and length of stay. Data collected by the Infection Prevention Department revealed progressive increases in the rate of CLABSI on an Abdominal Transplant Unit. Recognizing a drift from best practice, front line staff, the IP team and vascular access specialists, collaborated to identify opportunities for improving care of patients with vascular access devices. Methods An increase in CLABSI rate was observed on the Abdominal Transplant Unit beginning in 2016. An initiative began in 2017 to evaluate whether CLABSI rate reduction was sustainable for at least 1 year and to identify key determinants of this sustainability. Interventions were aimed at infection prevention best practices, care standardization, and team-based monitoring. Interventions included (1) re-education on CLABSI reduction, (2) two RN dressing changes to validate practice during central line dressing change, (3) blood draws from central lines (during non-emergent situations) had to be approved by nurse manager, physician lead and transplant quality physician, (4) CLABSI prevention nurses were chosen as designated phlebotomists for patients with prior approval, (5) daily line review was performed to address line days, indication of line (remove latent lines) and plan of care (transition to permanent access) and this information was shared with the unit physician lead and transplant quality team. Assuring compliance with audits and timely feedback with clinician accountability were vital with compliance with best practices. Results Conclusion During the intervention, CLABSI infection rates dropped from 4.825 to 1.533 in 1,000 CVC days. The sustainability plan for this program is to continue line audits, assessing line necessity and review the effectiveness of the initiatives, review all new CLABSI data with staff and implement new changes as necessary. Joint, ongoing multidisciplinary collaboration is essential to reduce CLABSIs and optimize quality in a challenging, high-acuity patient population. Disclosures All Authors: No reported disclosures

To determine the safety profile of new hepatitis C virus (HCV) treatments in liver transplant (LT) recipients with recurrent HCV infection.Forty-two patients were identified with recurrent HCV infection that underwent LT at least 12 mo prior to initiating treatment with a Sofosbuvir-based regimen during December 2013-June 2014. Cases were patients who experienced hepatic decompensation and/or serious adverse events (SAE) during or within one month of completing treatment. Controls had no evidence of hepatic decompensation and/or SAE. HIV-infected patients were excluded. Cumulative incidence of decompensation/SAE was calculated using the Kaplan Meier method. Exact logistic regression analysis was used to identify factors associated with the composite outcome.Median age of the 42 patients was 60 years [Interquartile Range (IQR): 56-65 years], 33% (14/42) were female, 21% (9/42) were Hispanic, and 9% (4/42) were Black. The median time from transplant to treatment initiation was 5.4 years (IQR: 2.1-8.8 years). Thirteen patients experienced one or more episodes of hepatic decompensation and/or SAE. Anemia requiring transfusion, the most common event, occurred in 62% (8/13) patients, while 54% (7/13) decompensated. The cumulative incidence of hepatic decompensation/SAE was 31% (95%CI: 16%-41%). Risk factors for decompensation/SAE included lower pre-treatment hemoglobin (OR = 0.61 per g/dL, 95%CI: 0.40-0.88, P0.01), estimated glomerular filtration rate (OR = 0.95 per mL/min per 1.73 m(2), 95%CI: 0.90-0.99, P = 0.01), and higher baseline serum total bilirubin (OR = 2.43 per mg/dL, 95%CI: 1.17-8.65, P0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for cases.Sofosbuvir/ribavirin will continue to be used in the post-transplant population, including those with HCV genotypes 2 and 3. Management of anemia remains an important clinical challenge.

The number of liver donors has not measurably increased since 2004 and has begun to decrease. Although many waitlisted patients may be suitable candidates to receive a living donor graft, they are often reticent to discuss living donation with close friends and family, partly because of a lack of knowledge about donor health and quality of life outcomes after donation. The objective of this study was to test the effectiveness of an educational intervention that uses testimonials and self-report data from living donors in New York State. The study had an independent sample pretest (n = 437) and posttest (n = 338) design with posttest, between-subjects comparison for intervention exposure. All waitlisted patients at 5 liver transplant centers in New York were provided a peer-based educational brochure and DVD either by mail or at the clinic. The outcome measures were liver candidates' knowledge and self-efficacy to discuss living donation with family and friends. The number and proportion of individuals who presented to centers for living liver donation evaluation were also measured. Liver transplant candidates' self-efficacy to discuss living donation and their knowledge increased from the pretest period to the posttest period. Those exposed to the peer-based intervention reported significantly greater knowledge, a greater likelihood of discussing donation, and increased self-efficacy in comparison with those not exposed to the intervention. The results did not differ by age, length of time on the waiting list, education, or ethnicity. In comparison with the preintervention period, living donation increased 42%, and the number of individuals who presented for donation evaluation increased by 74%.

Introduction Prior to transplantation of segmental liver grafts to adult recipients, it is crucial to confirm that the graft size is safe for the donor, yet adequate for the recipient's metabolic needs. Computed tomography (CT) and magnetic resonance imaging (MRI) are the current best standards. We applied a new formula to estimate right liver lobe weight in living donors and compared our results with CT and MRI. Methods Between August 1998 and December 20, 91 adults received right lobes from living donors. Donor liver volumes were assessed by CT or MRI. Actual weights of right lobe grafts were determined after back table flushing. We estimated whole liver weights using the formula: 772 × body surface area (BSA). Right lobe liver weight was calculated as 57% of the estimated whole liver weight (R-57). Results Mean actual right lobe weight ( n = 90) was 855.83 ± 183.4 g. Estimated right lobe weight was 858.08 ± 90.80 (R-57, P = NS); 1077.35 ± 263.07 mL for CT ( P = .0001), and 1185.07 ± 350.10 mL for MRI ( P = .0001). Mean graft–recipient weight ratio (GRWR) was 1.23%; there was no significant difference with R-57 GRWR but there was a difference from CT and MRI-GRWR ( P = .001). The proportion of cases of estimated right lobe weight and GRWR within 20% of the corresponding actual value were 80% and 90%, respectively, for R-57 versus 36% and 43% for the imaging studies ( P = .0001). Conclusion With readily available software to calculate BSA, physicians can predict right lobe weight knowing only the donor's height and weight. CT and MRI will only be necessary for anatomic liver mapping.

Acute cellular rejection (ACR) after liver transplantation occurs in as much as 70% of patients within the first year. There is very little known about ACR that occurs more than 1 yr after transplant, and it is generally believed that late occurring ACR may be more resistant to medical treatment and is associated with a higher rate of chronic ductopenic rejection and graft loss. A total of 532 recipients with more than 1000 d follow-up and who did not have hepatitis C were identified. Forty-three (8.1%) had biopsy proven late ACR at a mean of 1545 ± 441 d post-transplant. Additionally, 38 of the 43 (88.4%) patients with late ACR had earlier episodes of ACR before 1000 d post-transplant vs. only 295 of the 488 patients (60.5%) that did not have late ACR (p

Posttransplantation allograft malignancy of donor origin is a rare complication after liver transplantation. In the case described, subjective fevers and nonspecific abdominal complaints nearly 6 months following cadaveric liver transplantation in a young woman prompted an evaluation which was remarkable for a large central liver mass. A poorly differentiated squamous cell carcinoma was diagnosed, but was unresectable at exploration. The tumor was confined to the liver. Histocompatibility testing using polymerase chain reaction (PCR) amplification techniques identified both donor and recipient HLA alleles. The patient was treated with chemoembolization, systemic chemotherapy and cessation of immunosuppression. Repeat biopsy 2 months later showed the tumor to be completely necrotic. With decompensated liver disease, she was relisted and retransplanted. More than 2 years later she remains disease-free with complete pathological remission. This is the only reported case of squamous cell carcinoma of donor origin arising in a transplanted liver.

Liver transplantation for the treatment of metastatic neuroendocrine tumors (NETs) is radical. Although cure is not impossible, it is improbable. The reported experience with transplantation for NETs is limited to less than 150 cases with widely varying results and few 5-year disease-free survivors. We reviewed our experience with transplantation for patients with NETs. Fourteen symptomatic patients with unresectable NET liver metastases who had failed medical management were listed for transplantation. Two patients listed for transplantation underwent prior right lobectomies. Three patients were listed but did not undergo transplantation: one was lost to follow-up, one died 14 months after listing, and one remains waiting over 4 years. Eleven patients underwent liver transplantation, three with living donor grafts. There were four men (36.4%) and seven women (63.6%) who had a mean age of 51.2+/-6.3 years. Three patients had distal pancreatectomies and one patient had a Whipple procedure at the time of transplantation. There were six nonfunctioning tumors (54.6%), three carcinoid tumors (27.3%), and two (18.2%) Vipomas. In one patient, with fulminant hepatic failure, the NET was an incidental finding in the explant. The 1- and 5-year survival among transplanted patients is 73% and 36%, respectively, with a mean follow-up of 34+/-40 months (range 0 to 119 months). Of the three patients surviving more than 5 years, only one was disease free. In carefully selected patients with metastatic NETs, liver transplantation may be an appropriate option.

A 57-year-old male with a history of hypercholesterolemia and anxiety but otherwise in good health volunteered to donate the right lobe of his liver to his brother. The operation was performed uneventfully, without transfusion. Postoperatively he did well, until he developed tachycardia, profound hypotension, and coffee ground emesis on postoperative day 3. Despite resuscitative measures, he arrested and expired. Autopsy demonstrated gas gangrene of the stomach as the underlying cause of the hemorrhage and numerous colonies of Gram-positive bacilli were identified. Subsequent polymerase chain reaction (PCR) analysis identified these bacteria to be Clostridium perfringens (C. perfringens) type D. This patient's death was devastating, both to his family and his medical team. The impact of his death has transcended that of an individual occurrence. In conclusion, herein we present the facts and discuss this extraordinary example of florid clostridial infection and toxin-mediated shock. It was completely unexpected and probably unpreventable, and its cause was almost inconceivable. (Liver Transpl 2004;10:1315–1319.)

Introduction. Adult-to-adult living donor liver transplants are being increasingly performed. Although considerable data are available on the quality of life after kidney donation, there is little comparable information on liver donors. Methods. Between August 1998 and July 2000, 48 adults received liver grafts from living donors. At least 2 months after donation, donors were mailed a structured questionnaire and the standardized Medical Outcomes Study Short-Form Health Survey (SF-36), a generic measure assessing health-related quality of life outcomes using eight scales: mental health, emotional limits, vitality, social function, physical function, physical limits, pain, general health. Results. Thirty donors (62.5%) responded at a mean of 280±157 days after donation. Fifteen (50%) of their recipients had major complications (two deaths, four retransplants, nine biliary complications). Regarding overall satisfaction, all said they would donate again. Compared to published U.S. norms (n=2474), our group of donors scored higher than the general population in seven of eight domains on the SF-36. Donors whose recipients had no complications scored significantly higher in mental health (P

Due to the current regionally based allocation system, some patients list for and are transplanted away from home in regions with shorter waits and higher transplant rates. Of 147 included patients, 120 died waiting and 27 received transplants at outside centers during the study (32.5 months). Those transplanted elsewhere had higher median incomes than patients dying on the waitlist ($84 946 vs. $55 250, p = 0.0001). Those with median incomes$60 244 were more likely to die than those with incomes$60 244 (94% vs. 70%, RR: 1.35, 95% CI: 1.14-1.59). Patients with Medicaid were more likely to die waiting than those with other insurance (100% vs. 77%, RR: 1.30, 95% CI: 1.18-1.44). Our analysis demonstrates that those who died waiting were more likely to have lower incomes and Medicaid compared with those transplanted elsewhere. Even when we controlled for Medicaid status, patients who died waiting had lower incomes compared with those transplanted elsewhere. Increased organ sharing over geographically broader regions, as recommended by the Institute of Medicine in 1999, may reduce incentives for patients to travel to receive a liver and reduce inequities. Current efforts to address this disparity continue to fall short of the Institute of Medicine recommendations, United States Department of Health and Human Services regulations and the Final Rule.

The aim of this study is to analyze the impact of the recipient's disease severity on graft size requirements and outcome in adult-to-adult living donor liver transplantation. A limiting factor in adult-to-adult living donor liver transplantation has been adequacy of graft size. A minimal graft-recipient weight ratio (GRWR) of 0.8% to 1% has been suggested, without taking the recipient's disease into account. Forty adults underwent liver transplantation using left (n = 10; mean weight, 481 +/- 83 g) or right lobes (n = 30; mean weight, 845 +/- 182 g). We recorded graft survival, Child-Turcotte-Pugh score, and occurrence of small-for-size syndrome (poor bile production, prolonged postoperative prothrombin time, and cholestasis without ischemia markers). Small grafts were defined as GRWR of < or =0.85%. Large grafts were defined as GRWR greater than 0.85%. Six patients died within 6 months of transplantation (early patient survival rate, 85%); two patients died late of tumor recurrence. Among transplant recipients with normal liver function or Child's class A, there was no significant difference with the use of small (n = 6) or large (n = 9) grafts (graft survival rates, 83% v 88%, respectively; P =.65). Among patients with Child's class B or C, graft survival rates were 74% in recipients of large grafts (n = 19) and 33% in recipients of small grafts (n = 6; P =.023). Five of 6 patients with Child's class B or C who received small grafts developed small-for-size syndrome; 2 patients died (1 patient after retransplantation) and 3 patients survived (2 patients after retransplantation). Graft function and survival are influenced not only by graft size, but also by pretransplantation disease severity. GRWR as low as 0.6% can be used safely in patients without cirrhosis or in patients with Child's class A. Transplant recipients with Child's class B or C require a GRWR greater than 0.85% to avoid small-for-size syndrome and related complications.

Fabry disease results from deficient alpha-galactosidase A (alpha-Gal A) activity and the pathologic accumulation of the globotriaosylceramide (GL-3) and related glycosphingolipids, primarily in vascular endothelial lysosomes. Treatment is currently palliative, and affected patients generally die in their 40s or 50s. Preclinical studies of recombinant human alpha-Gal A (r-halphaGalA) infusions in knockout mice demonstrated reduction of GL-3 in tissues and plasma, providing rationale for a phase 1/2 clinical trial. Here, we report a single-center, open-label, dose-ranging study of r-halphaGalA treatment in 15 patients, each of whom received five infusions at one of five dose regimens. Intravenously administered r-halphaGalA was cleared from the circulation in a dose-dependent manner, via both saturable and non-saturable pathways. Rapid and marked reductions in plasma and tissue GL-3 were observed biochemically, histologically, and/or ultrastructurally. Clearance of plasma GL-3 was dose-dependent. In patients with pre- and posttreatment biopsies, mean GL-3 content decreased 84% in liver (n=13), was markedly reduced in kidney in four of five patients, and after five doses was modestly lowered in the endomyocardium of four of seven patients. GL-3 deposits were cleared to near normal or were markedly reduced in the vascular endothelium of liver, skin, heart, and kidney, on the basis of light- and electron-microscopic evaluation. In addition, patients reported less pain, increased ability to sweat, and improved quality-of-life measures. Infusions were well tolerated; four patients experienced mild-to-moderate reactions, suggestive of hypersensitivity, that were managed conservatively. Of 15 patients, 8 (53%) developed IgG antibodies to r-halphaGalA; however, the antibodies were not neutralizing, as indicated by unchanged pharmacokinetic values for infusions 1 and 5. This study provides the basis for a phase 3 trial of enzyme-replacement therapy for Fabry disease.

Background Short-term outcomes of liver transplantation are well reported. Little is known, however, about long-term results in liver recipients surviving > or =5 years. We sought to analyze long-term complications in liver recipients surviving > or =5 years after transplant, to assess their medical condition and to compare findings to the general population. Methods We analyzed the chart and database records of all patients (n=139) who underwent liver transplantation at a major transplant center before January 1, 1991. Outcome measures included the presence of diabetes, hypertension, heart, renal or neurological disease, osteoporosis, incidence of de novo malignancy or fracture, or other pathology, body mass index, serum cholesterol and glucose, liver function, blood pressure, frequency of laboratory and clinic follow-up, current pharmacological regimen, and late rejection episodes. Results Ninety-six patients (70%) survived > or =5 years. Compared to numbers expected based on U.S. population rates, transplant recipients had significantly higher overall prevalences of hypertension (standardized prevalence ratio [SPR]=3.07, 95% confidence interval [CI], 2.35-3.93) and diabetes (SPR=5.99, 95% CI, 4.15-8.38), and higher incidences of de novo malignancy (standardized incidence ratio [SIR]=3.94, 95% CI, 2.09-6.73), non-Hodgkin's lymphoma (SIR=28.56, 95% CI, 7.68-73.11), non-melanoma skin cancer (estimated SIR> or =3.16) and fractures in women (SIR=2.05, 95% CI, 1.12-3.43). Forty-one of 87 (47.1%) patients were obese, and 23 patients (27.4%) had elevated serum cholesterol levels (> or =240 mg/dl, 6.22 mmol/L), compared to 33% and 19.5% of U.S. adults, respectively. Prevalences of heart or peptic ulcer disease were not significantly higher. Conclusions Liver transplantation is being performed with excellent 5-year survival. Significant comorbidities exist, however, which appear to be related to long-term immunosuppression.

When tacrolimus side effects persist despite dose reduction, conversion to cyclosporine-based immunosuppression (CyA) is necessary. We characterized tacrolimus side effects that warranted discontinuation of the drug, and outcomes after conversion. Of 388 liver recipients who received tacrolimus as primary immunosuppression, 70 required conversion to CyA. We recorded indication for conversion, whether conversion was early or late after transplantation, tacrolimus dose and trough blood level at conversion, and incidence of rejection after conversion. Conversion was early in 29 patients (41.4%) and late in 41 (58.6%). Indications for early conversion were neurotoxicity (20), (insulin-dependent) diabetes mellitus (IDDM) (5), nephrotoxicity (3), gastrointestinal (GI) toxicity (6), and cardiomyopathy (1), and for late conversion were neurotoxicity (15), IDDM (12), nephrotoxicity (3), GI toxicity (5), hepatotoxicity (6), post-transplant lmphoproliferate disease (PTLD) (2), cardiomyopathy (1), hemolytic anemia (1), and pruritus (1). All early-conversion patients showed improvement/resolution of symptoms. Among late-conversion patients, 37 (90.2%) had improvement/resolution; in 4 (9.8%), adverse effects persisted. The overall rejection rate was 30%. Sixty-two patients (88.6%) are alive with functioning grafts 686 +/- 362 days (range, 154-1433 days) after conversion. When tacrolimus side effects are unresponsive to dose reduction, conversion to CyA can be accomplished safely, with no increased risk of rejection and excellent long-term outcome.

Since the 1970s, there has been dramatic growth in the annual number of liver transplants, with improving survival. We review indications for liver transplantation for fulminant hepatic failure (FHF), cholestatic liver disease, and hepatocellular liver disease. A decreased factor V level appears to be a sensitive indicator of FHF requiring transplantation, with a factor V level of less than 20% (less than 30% for age greater than 30 years) suggested as the main indication in encephalopathic patients. The King's criteria are also useful for identifying patients with FHF who require transplantation. FHF from Wilson's disease is universally fatal without transplantation. Any patient with FHF who is unlikely to recover spontaneously should be referred to a transplant center. In patients with primary biliary cirrhosis (PBC), the Mayo Clinic model is widely used to calculate a risk score (based on age, bilirubin, albumin, prothrombin time, and edema). PBC patients with a rapidly rising Mayo risk score and/or a rising bilirubin should be listed for transplantation. The Mayo Clinic survival model for primary sclerosing cholangitis is based on bilirubin, histological stage, age, and presence or absence of splenomegaly, but this model is limited by the emergence of recurrent bacterial cholangitis, dominant strictures, and cholangiocarcinoma. Patients with hepatitis C should be referred for transplantation upon onset of ascites, variceal bleeding, encephalopathy, and/or jaundice with decreasing synthetic function. In patients with autoimmune hepatitis, prognostic indicators that herald the need for transplantation include variceal bleeding, encephalopathy, ascites, hyperbilirubinemia, and worsening synthetic function. Patients with Budd–Chiari syndrome who have end-stage complications of cirrhosis are candidates for transplantation, but clotting disorders must be treated to minimize the risk of recurrent thrombosis. Although hepatocellular carcinoma was once a contraindication, the presence of a small tumor without vascular or distant metastasis is now an indication for liver transplantation. In summary, liver transplantation remains a lifesaving procedure for individuals with end-stage liver disease due to a variety of causes.

Clinical recurrence of hepatitis C after liver transplantation can lead to cirrhosis, liver failure, and death. In patients undergoing liver transplantation for hepatitis C, we assessed the efficacy of interferon alfa-2b (IFN) in preventing recurrent hepatitis. We randomized 86 patients to either an IFN group (3 MU three times a week starting within 2 weeks after transplantation and continued for 1 year) or a control (no IFN) group. Recurrence, the primary end point, was diagnosed on biopsy performed at 1 year or for abnormal biochemistries. HCV RNA levels were measured by branched-chain DNA (bcDNA) assay and arbitrarily defined as low, moderate, or high (10 x 10(5), 10-100 x 10(5), or100 x 10(5) Eq/mL, respectively). Data on 30 IFN patients and 41 no-IFN patients who survivedor = 3 months were reviewed. Mean follow-up was 669 +/- 228 days for IFN patients and 594 +/- 254 days for no-IFN patients. IFN patients were less likely to develop recurrent hepatitis (8 IFN vs. 22 no-IFN patients, P = .017, log rank analysis). IFN and 1-month HCV RNA level were independent predictors of recurrence. IFN reduced the risk of recurrence by a factor of 0.4 (P = .04, Cox proportional hazards model); HCV RNA level100 x 10(5) Eq/mL at 1 month after transplantation increased the risk by a factor of 3.1 (P = .01). Low, moderate, and high viral levels at 1 and 3 months were associated with significantly different rates of recurrence in IFN patients (P = .05 at 1 month and P = .003 at 3 months) but not in untreated patients (P = .28 at 1 month and P = .25 at 3 months). In patients with two or more rejections, the risk of recurrence was increased by a factor of 2.17 (P = .05). On 47 1-year biopsies (24 IFN; 23 no IFN), piecemeal necrosis was more common in untreated patients (P.02). One- and 2-year patient survival, respectively, was 96% and 96% with IFN and 91.2% and 87.2% without (P = NS). Prophylactic IFN reduced the incidence of recurrent hepatitis after transplant. Although IFN was most effective in patients with low HCV RNA levels, we also noted an effect in patients with moderate levels. IFN did not prevent viremia, suggesting that it may work through alternative mechanisms.

We report the case of a 22-year-old man who developed fulminant hepatic failure 3 days after an intentional acetaminophen overdose. The patient had a history of a seizure disorder for which he was taking phenytoin. The acetaminophen level at presentation was in the "nontoxic" range. Emergent liver transplantation was performed 4 days after the ingestion. This is the first reported case of successful liver transplantation for acetaminophen-induced fulminant hepatic failure in the setting of phenytoin therapy.

Recurrent hepatitis C causes significant morbidity after liver transplantation. Because immunosuppression is associated with enhanced viral replication, we postulated that clinical recurrence of the disease may be associated with augmented immunosuppression for rejection. In 96 patients with hepatitis C who received liver transplants, we recorded the interval from transplantation to recurrence, the episodes of steroid-resistant rejection (SRR) requiring OKT3, the number of rejection episodes, and the use of OKT3 induction. Recurrence was diagnosed based on elevated transaminases and characteristic histology. Hepatitis C recurred in 43 of 96 patients. Fifteen of 21 patients (71.4%) who previously had SRR had recurrence, versus 28 of 75 patients (37.3%) who either had no SRR (72 patients) or had it after recurrence was diagnosed (3 patients) (P

BACKGROUND This series compares outcomes of patients with hepatocellular carcinoma (HCC) listed for orthotopic liver transplantation (OLT) within and outside Milan criteria, and determines the impact of extended criteria liver allografts (ECD). METHODS Records of patients listed for liver transplantation at a single center from 1998 to 2007 were reviewed retrospectively. RESULTS Ninety-seven HCC patients were listed for OLT, 77 underwent transplantation; 47 received ECDs and 30 standard organs. ECDs were more frequently allocated to outside Milan recipients. Wait time for OLT was shorter for outside Milan patients (4 vs. 7 months P=0.04) but hazard rate of dropout was higher (26%, 46%, and 73% at 6,12, and 24 months compared with 2%, 14%, and 60% P

The number of liver donors has not measurably increased since 2004 and has begun to decrease. Although many waitlisted patients may be suitable candidates to receive a living donor graft, they are often reticent to discuss living donation with close friends and family, partly because of a lack of knowledge about donor health and quality of life outcomes after donation. The objective of this study was to test the effectiveness of an educational intervention that uses testimonials and self-report data from living donors in New York State. The study had an independent sample pretest (n = 437) and posttest (n = 338) design with posttest, between-subjects comparison for intervention exposure. All waitlisted patients at 5 liver transplant centers in New York were provided a peer-based educational brochure and DVD either by mail or at the clinic. The outcome measures were liver candidates' knowledge and self-efficacy to discuss living donation with family and friends. The number and proportion of individuals who presented to centers for living liver donation evaluation were also measured. Liver transplant candidates' self-efficacy to discuss living donation and their knowledge increased from the pretest period to the posttest period. Those exposed to the peer-based intervention reported significantly greater knowledge, a greater likelihood of discussing donation, and increased self-efficacy in comparison with those not exposed to the intervention. The results did not differ by age, length of time on the waiting list, education, or ethnicity. In comparison with the preintervention period, living donation increased 42%, and the number of individuals who presented for donation evaluation increased by 74%.

Background The optimal role of surgery in the management of hepatocellular carcinoma (HCC) is in continuous evolution. Objective The objective of this study was to analyse survival rates after liver resection (LR) and orthotopic liver transplantation (OLT) for HCC within and outwith Milan criteria in an intention-to-treat analysis. Methods During 1997–2007, 179 patients with cirrhosis and HCC either underwent LR ( n = 60) or were listed for OLT ( n = 119). Patients with incidental HCC after OLT, preoperative macrovascular invasion before LR, non-cirrhosis and Child–Pugh class C cirrhosis prior to OLT were eliminated, leaving 51 patients primarily treated with LR and 106 patients listed for primary OLT (84 of whom were transplanted) to be included in this analysis. A total of 66 patients fell outwith Milan criteria (26 LR, 40 OLT) and 91 continued to meet Milan criteria (25 LR, 66 OLT). Results The median length of follow-up was 26 months. The mean waiting time for OLT was 7 months. During that time, 21 patients were removed from the waiting list as a result of tumour progression. Probabilities of dropout were 2% and 13% at 6 and 12 months, respectively, for patients within Milan criteria, and 34% and 57% at 6 and 12 months, respectively, for patients outwith Milan criteria ( P 3 cm was found to be the independent factor associated with dropout (hazard ratio [HR] 6.0). Postoperative survival was slightly higher after OLT, but this was not statistically significant (64% for OLT vs. 57% for LR). Overall survival from time of listing for OLT or LR did not differ between the two groups ( P = 0.9); for patients within Milan criteria, 1- and 4-year survival rates after LR were 88% and 61%, respectively, compared with 92% and 62%, respectively, after OLT ( P = 0.54). For patients outwith Milan criteria, 1- and 4-year survival rates after LR were 69% and 54%, respectively, compared with 65% and 40%, respectively, after OLT ( P = 0.42). Tumour size >3 cm was again found to be an independent factor for poor outcome (HR 2.4) in the intention-to-treat analysis. Conclusions Survival rates for patients with HCC are similar in LR and OLT. Liver resection can potentially decrease the dropout rate and serve as a bridge for future salvage LT, particularly in patients with tumours >3 cm.

The liver is the primary site of synthesis for the majority of coagulation factors. There are published accounts of liver donor-to-recipient transmission of protein C deficiency with dysfibrinogenemia and factor XI deficiency. In this article, we report what we believe to be the first observation, of transmission of factor VII deficiency, a rare, autosomal recessive coagulation disorder, from an affected liver donor to a naive liver recipient. At 300 days after transplantation, the recipient remains with an isolated prolongation of the prothrombin time and a below-normal level of factor VII, and has had no bleeding complications.

Background. Transplantation of blood type A subgroup 2 (A2) livers into non-A recipients has not been reported previously. A2 to O renal transplantation has been reported, with early results including some accelerated rejections and graft losses. This has led some to selectively offer A2 renal transplantation only for patients with low anti-A titers. Given the different clinical behavior of liver allografts to preformed antibody, we felt that such restriction was unnecessary. Methods. We performed six cases of A2 to O liver transplantation with no augmented immunomodulation or restriction with regard to antibody titers. Clinical courses, anti-A titers, rejection rates, and graft and patient survival were evaluated. Results. All six patients had high pretransplant anti-A titers (>1:8), and all six grafts functioned normally. There were nine rejections in the six patients, of which three were severe (steroid-resistant) and five were late (>90 days). No rejection was vascular, and no grafts were lost, with mean follow-up of 665 days. In one patient who had anti-A antibody measured at the time of rejection IGM titers increased from baseline. Currently all patients are home with normal function. Conclusions. We found that transplantation of blood group A2 livers into blood group O recipients is safe and can be performed without graft loss and without regard to anti-A titer level. The rate of acute cellular rejection is high in this small series, and a significant proportion of these events were late or required OKT-3. We did not rely on plasmapheresis or anti-A titer determinations. However, the potential for late rejection prompts us to consider the addition of a third immunosuppressive agent. The transplantation of A2 livers into O recipients can partially compensate for the more frequent use of O livers in recipients from other blood groups.

There is no clear consensus regarding the best treatment strategy for patients with advanced hepatocellular carcinoma (HCC). Patients with cirrhosis and HCC beyond Milan who had undergone liver resection (LR) or primary orthotopic liver transplantation (OLT) between November 1995 and December 2005 were included in this study. Pathological tumor staging was based on the American Liver Tumor Study Group modified Tumor-Node-Metastasis classification. A total of 23 HCC patients were primarily treated by means of LR, 5 of whom eventually underwent salvage OLT. An additional 32 patients underwent primary OLT. The overall actuarial survival rates at 3 and 5 years were 35% after LR, and 69% and 60%, respectively, after primary OLT. Recurrence-free survival at 5 years was significantly higher after OLT (65%) than after LR (26%). Of the patients who underwent LR, 11 (48%) experienced HCC recurrence only in the liver; 6 of these 11 presented with advanced HCC recurrence, poor medical status, or short disease-free intervals and were not considered for transplantation. Salvage OLT was performed in 5 patients with early stage recurrence (45% of patients with hepatic recurrence after LR and 22% of all patients who underwent LR). At a median of 18 months after salvage OLT, all 5 patients are alive, 4 are free of disease, and 1 developed HCC recurrence 16 months after salvage OLT. For patients with HCC beyond Milan criteria, multimodality treatment—including LR, salvage OLT, and primary OLT—results in long-term survival in half of the patients. When indicated, LR can optimize the use of scarce donor organs by leaving OLT as a reserve option for early stage HCC recurrence.

AIM: To describe our experience using a low-accelerating-dose regimen (LADR) with pegylated interferon alpha-2a and ribavirin in treatment of hepatitis C virus (HCV) recurrence. METHODS: From 2003, a protocolized LADR strategy was employed to treat liver transplant (LT) recipients with recurrent HCV at our institution. Medical records of 182 adult patients with recurrent HCV treated with LADR between 1/2003 and 1/2011 were reviewed. Histopathology from all post-LT liver biopsies were reviewed in a blinded fashion. Paired recipient and donor IL28B status were assessed. A novel technique was employed to ascertain recipient and donor IL28B (rs12979860) Gt data using DNA extracted from archival FFPE tissue from explanted native livers and donor gallbladders respectively. The primary endpoint was SVR; secondary endpoints examined include (1) patient and graft survival; (2) effect of anti-viral therapy on liver histology (fibrosis and inflammation); (3) incidence of on-treatment development of ACR, CDR, or PCH; (4) association of recipient and donor IL28B genotype with SVR; and (5) incidence of anti-viral therapy-associated adverse events (anemia, leukopenia, thrombocytopenia, depression) and hepatic decompensation. RESULTS: The overall SVR rate was 38% (29% Gt1, 67% Gt2, 86% Gt3 and 58% Gt4). HCV Gt (P < 0.0001), donor age (P = 0.003), cytomegalovirus mismatch (P = 0.001), baseline serum bilirubin (P = 0.002), and baseline viral load (P = 0.04) were independent predictors for SVR. SVR rates were significantly higher in the recipient-CC/donor-non CC pairs (P = 0.007). Neither baseline fibrosis nor change in fibrosis stage after anti-viral therapy were associated with SVR. Fibrosis progressed in 72% of patients despite SVR. Median graft survival was 91 mo. Five-year patient survival was superior in patients who achieved SVR (97% vs 82%, P = 0.001). Pre-treatment ALP ≥ 150 U/L (P = 0.01), total bilirubin ≥ 1.5 mg/dL (P = 0.001) and creatinine ≥ 2 mg/dL (P = 0.001) were independently associated with patient survival. Only 13% of patients achieving SVR died during the follow-up period. Treatment discontinuation and treatment-related mortality occurred in 35% and 2.2% of patients, respectively. EPO, G-CSF and blood transfusion were needed in 89%, 40% and 23% of patients, respectively. Overall hospitalization rate for treatment-related serious adverse events was 21%. Forty-six (25%) of the patients were deceased; among those who died, 25 (54%) were due to liver-related complications, and 4 deaths (9%) occurred while receiving therapy (2 patients experienced hepatic decompensation and 2 sepsis). CONCLUSION: LADR strategy remains relevant in managing post-LT recurrent HCV where access to DAAs is limited. SVR is associated with improved survival, but fibrosis progression still occurs.

To determine gynecologic symptoms and sexual function in a group of patients awaiting liver transplantation and a second group after liver transplantation.A questionnaire was mailed to 524 women. Of these, 233 had had transplants, and 291 were on a waiting list. The Transplant Database was used to obtain demographic information regarding these patients, and data were analyzed based on population age, Child's classification, type of liver disease, and pretransplant or posttransplant status.The response rate was 53%. There was no difference in ethnic or age distribution between pretransplant and posttransplant patients. There were no significant differences in rates of amenorrhea, but there was a greater prevalence of amenorrhea in patients with hepatocellular vs. cholestatic diseases (60% vs. 19%, p = 0.009). There was a higher incidence of pad use for urinary incontinence in pretransplant vs. posttransplant patients (14% vs. 7%, p = 0.04). There was no difference in availability of a sexual partner, sexual activity, orgasm experience, dyspareunia, satisfaction with sex life, symptoms of organ prolapse or dysmenorrhea based on transplant status, disease etiology or Child's classification.Liver failure patients differed in some of their gynecologic symptoms depending on their disease etiology and transplant status, but sexuality remained unchanged.

We investigated the prevalence of intrapulmonary shunts in 82 patients with hepatic cirrhosis referred for echocardiography as part of liver transplantation evaluation. Intrapulmonary shunts were present in 49 of 82 patients (60%). Baseline characteristics were similar in patients with and without intrapulmonary shunts. Mean follow up was 41 ± 15 months in patients with intrapulmonary shunts and 42 ± 15 months in patients without intrapulmonary shunts (P not significant). At follow up, 8 of 49 patients (16%) with intrapulmonary shunts and 4 of 33 patients (12%) without intrapulmonary shunts had died (P not significant).

Acute cellular rejection (ACR) after liver transplantation occurs in as much as 70% of patients within the first year. There is very little known about ACR that occurs more than 1 yr after transplant, and it is generally believed that late occurring ACR may be more resistant to medical treatment and is associated with a higher rate of chronic ductopenic rejection and graft loss. A total of 532 recipients with more than 1000 d follow-up and who did not have hepatitis C were identified. Forty-three (8.1%) had biopsy proven late ACR at a mean of 1545 +/- 441 d post-transplant. Additionally, 38 of the 43 (88.4%) patients with late ACR had earlier episodes of ACR before 1000 d post-transplant vs. only 295 of the 488 patients (60.5%) that did not have late ACR (p0.01). The incidence of primary sclerosing cholangitis (PSC) was 32.6% among patients with late ACR and 11.1% among patients without late ACR (p0.01). The overall patient survival for patients who had late ACR (n = 43) is 81.4% while for patients without late ACR (n = 488) it is 82.0% (p = ns). Patients remain at risk for ACR even after 1000 d post-transplant, particularly those with PSC.

For patients with hepatocellular carcinoma (HCC), the only hope for cure lies in physical removal or destruction of the tumor prior to spread outside the liver.1,2 In most patients with HCC, however, cirrhosis and multicentricity preclude resection, leaving liver transplantation as the only approach with the potential to cure both the cirrhosis and the tumor. Results of liver transplantation in patients with early unresectable HCC are comparable to results of liver transplantation for other indications.3 On the basis of these findings, UNOS prioritizes patients with a single tumor ≤ 5 cm or with 2–3 tumors all ≤ 3 cm. Patients with larger tumors, however, receive no priority and are thus in effect barred from receiving a cadaveric donor liver. We recently reviewed our experience in 43 patients with HCC ≥ 5 cm who underwent cadaveric liver transplantation. At a mean follow-up of 55 months, 44% were alive and 48% were free of recurrence.4 By contrast, 3-year survival in patients with HCC treated only with chemotherapy is less than 25%.5,6 Over recent years, however, longer waiting times have severely limited cadaveric transplantation for HCC. At our center, the average waiting time among HCC patients is in excess of 1 year, and 16–23% of HCC patients who are listed for transplant eventually drop off the waiting list due to tumor progression.7,8 Living donor liver transplantation (LDLT) provides an alternative source of donor livers for transplantation, the allocation of which is independent of waiting time or UNOS criteria. For the patient who has a living donor, a donor organ is not a scarce resource.7,9 In patients who undergo transplantation for HCC, the median interval to recurrence is 12 months.3,4,6 Previously we reported our initial results in 27 patients with HCC who underwent LDLT, for whom the median follow-up was 236 days.7 In that series, 2 recurrences were noted. Here we report our extended results in these and other patients with HCC who underwent living donor liver transplantation, with a median follow-up > 1 year.

Background and aims Isolated intestinal transplantation has been limited by poor patient and graft survival. If high survival could be achieved and if parenteral nutrition-associated liver disease were reversible, this procedure could be more widely applied, with early liver dysfunction indicating the need for transplant evaluation. Methods Twenty-six patients who had failed parenteral nutrition received 28 isolated intestinal transplants. We analyzed patient and graft survival, the effect of sirolimus on the severity and frequency of rejection, and the reversibility of liver dysfunction after transplant. Results Three-year actuarial patient and primary graft survival were 88% and 71%, respectively. Two patients underwent successful retransplants. Twenty-two patients are alive at a mean of 21+/-15 (median 18; range 3-51) months. Actuarial survival with freedom from parenteral support is 81% at 3 years (21 of 26 patients). Actuarial freedom from parenteral support among survivors is 95.5% at 3 years (21 of 22 patients). Early rejection was less frequent with sirolimus (34% vs. 70% without sirolimus) (P=0.007). Moderate and severe rejection was less frequent with sirolimus (1/11 episodes vs. 9/17 episodes without sirolimus) (P=0.05). No grafts were lost after introduction of sirolimus. In all four patients with advanced liver dysfunction, fibrosis and cholestasis regressed within 1 year. Conclusions High patient survival and parenteral nutrition-free survival can be achieved after isolated intestinal transplantation. Sirolimus treatment has eliminated graft loss. Parenteral nutrition-associated liver disease is reversible with intestinal transplantation. Refractory liver dysfunction in patients receiving parenteral nutrition should prompt consideration for isolated intestinal transplantation.

Transplantation between monozygotic twins has been successfully performed using the kidney, small intestine, and pancreas. Identical HLA matching has enabled these individuals to be transplanted without the need for immunosuppressive medication. Liver transplantation without immunosuppression would lessen the risk of recurrent viral hepatitis and eliminate much of the morbidity associated with long-term use of immunosuppressive medication. Living-donor liver transplantation (LDLT) has been performed with increasing success in recent years without an opportunity arising to use a monozygotic twin as a donor. We report 2 cases of LDLT between identical twins wherein perfect haploidentity has allowed these recipients to be transplanted without the need for immunosuppression. Although HLA matched genotypically, there may be differences in anatomy between donor and recipient. Mild liver chemistry test abnormalities may occur after transplant despite the absence of immunosuppression. GASTROENTEROLOGY 2002;123:1341-1345

Adult-to-adult living donor liver transplants are being increasingly performed. Although considerable data are available on the quality of life after kidney donation, there is little comparable information on liver donors.Between August 1998 and July 2000, 48 adults received liver grafts from living donors. At least 2 months after donation, donors were mailed a structured questionnaire and the standardized Medical Outcomes Study Short-Form Health Survey (SF-36), a generic measure assessing health-related quality of life outcomes using eight scales: mental health, emotional limits, vitality, social function, physical function, physical limits, pain, general health.Thirty donors (62.5%) responded at a mean of 280+/-157 days after donation. Fifteen (50%) of their recipients had major complications (two deaths, four retransplants, nine biliary complications). Regarding overall satisfaction, all said they would donate again. Compared to published U.S. norms (n=2474), our group of donors scored higher than the general population in seven of eight domains on the SF-36. Donors whose recipients had no complications scored significantly higher in mental health (P0.007) and general health (P0.008) compared with U.S. norms. Donors whose recipients had major complications scored significantly lower on the mental health scale than those with recipients without major complications.Donors did not regret their decision to donate; several felt the experience had changed their lives for the better. Donors scored as well as or better than U.S. norms in general health. Quality of life after donation must remain a primary outcome measure when we consider the utility of living-donor liver transplants.