Impact of race-neutral eGFR calculations on African American kidney transplant candidate wait time: A single center retrospective analysis.

Race-inclusive estimated glomerular filtration rate (eGFR) could contribute to racial disparity in access to kidney transplantation. The Organ Procurement and Transplantation Network (OPTN) issued a policy allowing waiting time modification for candidates affected by race-inclusive eGFR calculations. Implementation of the new OPTN policy at the kidney transplant program of the Mount Sinai Hospital involved review of 921 African American candidates, of whom 240 (26%) candidates gained a median of 1 year and 10 months. The duration of time candidates gained varied from a minimum of 5 days to a maximum of 12 years and 3 months; 45.4% gained at least 2 years, and 12% gained at least 4 years of wait time. Among those who gained wait time, 20 (8.3%) candidates received deceased donor kidney transplants. Candidates who gained wait time had similar sociodemographic characteristics as those who did not, except that the median age for the former was higher by 3 years (59 vs. 56). Our early data suggest that the current policy on waiting time modification for candidates affected by race-inclusive estimation of GFR has the potential to improve racial disparity in access to kidney transplantation. However, the generalizability of our findings to other centers requires further study.

Extensive Health Care Utilization and Costs of an Early Liver Transplantation Program for Alcoholic Hepatitis.

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 < 0.001). Total net revenue of the program from LT admission to 90 days after LT was -$630,305 (-5.0% revenue), which was inversely correlated with MELD score (r = -0.70; P = 0.004) and yielded lower revenue than a contemporaneous LT program for acute-on-chronic liver failure (ACLF; $118,168; 1.4% revenue; P = 0.001). The health care use and costs of an early LT program for AH are extensive and lifesaving with marginally negative net revenue. Significantly increasing care of severe AH patients over 5 years resulted in increased LT volume, but at a lower rate than ACLF, and without improving economic outcomes due to high MELD and prolonged length of stay.

Segment 4 and the left lateral segment regeneration pattern after resection of the middle hepatic vein in a living donor right hepatectomy.

BACKGROUND: Inclusion of the middle hepatic vein (MHV) with a right hepatectomy (RH) in live donor liver transplantation improves venous drainage of the anterior sector of the graft. Its long-term effects on donor left liver (LL) regeneration are not well described. METHODS: Donors who underwent RH with MHV (MHV+, n = 12) were compared with donors who underwent RH with preservation of the MHV (MHV-, n = 24). Peri-operative complications and volume of the entire liver and individual segments were evaluated at 1 year post-donation. RESULTS: There was a trend towards a higher complication rate in the MHV+ group (41% versus 25%), without reaching statistical significance (P = 0.3). Males, high body mass index (BMI) and a smaller residual liver volume (RLV) were predictors for greater LL regeneration. MHV+ donors had impaired regeneration of segment 4 (S4) at 1 year, and compensatory greater left lateral segment regeneration. The absence of venous drainage of S4 (V4) to left hepatic vein (LHV) was a predictor of impaired S4 regeneration. CONCLUSIONS: Regeneration of S4 is impaired in MHV+ donors. Caution should be taken when considering MHV removal on donors with dominant S4, especially on those with potential increased demand for liver regeneration, such as males, higher BMI and a smaller RLV.

Geographic disparity: the dilemma of lower socioeconomic status, multiple listing, and death on the liver transplant waiting list.

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.

Age added to MELD or ACLF predicts survival in patients with alcohol-associated hepatitis declined for liver transplantation.

BACKGROUND: Severe alcohol-associated hepatitis (AH) that is nonresponsive to corticosteroids is associated with high mortality, particularly with concomitant acute-on-chronic liver failure (ACLF). Most patients will not be candidates for liver transplantation (LT) and their outcomes are largely unknown. Our aim was to determine the outcomes of these declined candidates and to derive practical prediction models for transplant-free survival applicable at the time of the waitlist decision. METHODS: We analyzed a database of patients with severe AH who were hospitalized at a LT center from January 2012 to July 2021, using the National Death Index for those lacking follow-up. Clinical variables were analyzed based on the endpoints of mortality at 30, 60, 90, and 180 days. Logistic and Cox regression analyses were used for model derivation. RESULTS: Over 9.5 years, 206 patients with severe AH were declined for LT, mostly for unfavorable psychosocial profiles, with a mean MELD of 33 (±8), and 61% with ACLF. Over a median follow-up of 521 (17.5-1368) days, 58% (119/206) died at a median of 21 (9-124) days. Of 32 variables, only age added prognostic value to MELD and ACLF grade. CLIF-C ACLF score and 2 new models, MELD-Age and ACLF-Age, had similar predictability (AUROC: 0.73, 0.73, 0.72, respectively), outperforming Lille and Maddrey's (AUROC: 0.63, 0.62). In internal cross-validation, the average AUROC was 0.74. ACLF grade ≥2, MELD score >35, and age >45 years were useful cutoffs for predicting increased 90-day mortality from waitlist decision. Only two patients initially declined for LT for AH subsequently underwent LT (1%). CONCLUSIONS: Patients with severe AH declined for LT have high short-term mortality and rare rates of subsequent LT. Age added to MELD or ACLF grade enhances survival prediction at the time of waitlist decision in patients with severe AH declined for LT.

Recurrent Liver Allograft Injury in Patients With Donor-Derived Malignancy Treated With Immunosuppression Cessation and Retransplantation.

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.

Two hundred and fifty-one right hepatectomies for living donation: Association between preoperative risk factors, hepatic dysfunction, and complications.

BACKGROUND: 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. METHODS: Retrospectively collected data from a prospectively assembled cohort of 251 consecutive living donors who underwent right hepatectomy between 1999 and 2020 were evaluated. RESULTS: 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. (r2 = 0.40, r2 = 0.34, and r2 = 0.34, respectively), with the relationship between standardized liver volume and liver volume by imaging being the strongest. The median remnant liver volume was 35%. Fifty-eight donors (23%) developed postoperative hepatic dysfunction, which was associated with increased length of stay (P = .04), and complications (P < .01). Men had a 2.5 times higher chance of developing postoperative hepatic dysfunction. Age >50 years was an independent predictor of increased bilirubin at postoperative day 4 (P < .01), and remnant liver volume was inversely associated with higher peak international normalized ratio (P < .01). Eighty-one donors (32%) experienced complications. Postoperative hepatic dysfunction was associated with 2.4 times higher chances of complications (odds ratio = 2.4, P < .01). CONCLUSION: Early 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.

A peer-based intervention to educate liver transplant candidates about living donor liver transplantation.

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%.

Surgical treatment of hepatocellular carcinoma beyond Milan criteria. Results of liver resection, salvage transplantation, and primary liver transplantation.

BACKGROUND: There is no clear consensus regarding the best treatment strategy for patients with advanced hepatocellular carcinoma (HCC). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Hepatitis in association with rickettsialpox.

Rickettsialpox is an acute, self-limited, febrile illness caused by Rickettsia akari and transmitted by Liponyssoides sanguineus, a mite that infests the common house mouse, Mus musculus. Liver involvement in rickettsialpox has received little attention, although hepatitis has been reported in several other rickettsial infections. In this report, we describe two patients with rickettsialpox who had acute hepatitis that resolved completely. In the appropriate clinical setting, rickettsialpox should be considered in the differential diagnosis of hepatitis.

Prevalence and prognosis of intrapulmonary shunts in patients with hepatic cirrhosis.

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).

Gynecologic symptoms and sexual function before and after liver transplantation.

OBJECTIVE: To determine gynecologic symptoms and sexual function in a group of patients awaiting liver transplantation and a second group after liver transplantation. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: Liver failure patients differed in some of their gynecologic symptoms depending on their disease etiology and transplant status, but sexuality remained unchanged.

The International Liver Transplant Society Guideline on Living Liver Donation.

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.

Hepatic decompensation/serious adverse events in post-liver transplantation recipients on sofosbuvir for recurrent hepatitis C virus.

AIM: To determine the safety profile of new hepatitis C virus (HCV) treatments in liver transplant (LT) recipients with recurrent HCV infection. METHODS: 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. RESULTS: 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, P < 0.01), 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, P < 0.01). The sustained virological response rate for the cohort of 42 patients was 45%, while it was 31% for cases. CONCLUSION: 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.

Tumors with intrahepatic bile duct differentiation in cirrhosis: implications on outcomes after liver transplantation.

BACKGROUND: The role of liver transplantation (LT) in the management of cirrhotic patients with tumors exhibiting intrahepatic bile duct differentiation remains controversial. The objective of this study was to characterize the spectrum of these tumors and analyze post-LT outcomes. METHODS: Retrospective pathology database search of explant histology analysis of liver transplants between April 1993 and November 2013. RESULTS: Thirty-two patients were analyzed, 75% were men with a mean age of 60 years. Seven patients had nodules demonstrating intrahepatic cholangiocarcinoma (I-CCA), nine had I-CCA nodules occurring concomitantly with hepatocellular carcinoma (HCC), and 16 had mixed HCC-CCA nodules. The median number of tumors was 1 and size was 2.5 cm. Overall patient survival post-LT at 1 and 5 years was 71% and 57%, respectively. Patients within Milan criteria, especially with I-CCA features, showed a 5-year tumor recurrence rate (10%) and 5-year survival rate (78%) comparable with other patients having HCC within Milan criteria. CONCLUSION: This series showed that patients with CCA within Milan criteria may be able to achieve acceptable long-term post-LT survival.

Utility of the low-accelerating-dose regimen in 182 liver recipients with recurrent hepatitis C virus.

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.

Isolated intestinal transplantation: proof of clinical efficacy.

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.