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INTRODUCTION AND OBJECTIVES: Sarcopenia is a common complication of end-stage liver disease (ESLD), but its exact relationship to myosteatosis and frailty remains unclear. In this pilot study, we tested the feasibility of a specialized MRI protocol and automated image analysis in patients with ESLD. MATERIALS AND METHODS: In a single-center prospective study, adult liver transplant candidates with ESLD underwent assessment of muscle composition between 3/2022 and 6/2022 using the AMRA® MAsS Scan. The primary outcome of interest was feasibility of the novel MRI technique in patients with ESLD. We also tested if thigh muscle composition correlated with validated measures of frailty and sarcopenia. RESULTS: Eighteen subjects (71 % male, mean age 59 years) were enrolled. The most common etiologies of cirrhosis were alcohol-related liver disease (44 %) and non-alcohol-associated fatty liver disease (33 %), with a mean MELD-Na of 13 (± 4). The mean time needed to complete the MRI protocol was 14.9 min and only one patient could not complete it due to metal hardware in both knees. Forty-one percent of patients had adverse muscle composition (high thigh fat infiltration and low-fat free muscle volume) and these patients were more likely to have undergone a recent large volume paracentesis (43 % vs. 0 %, p < 0.02). The adverse muscle composition group performed significantly worse on the 6-minute walk test compared to the remainder of the cohort (379 vs 470 m, p < 0.01). CONCLUSIONS: The AMRA® MAsS Scan is feasible to perform in patients with ESLD and can be used to quantify myosteatosis, a marker of muscle quality and potentially muscle functionality in ESLD.
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Doença Hepática Terminal , Estudos de Viabilidade , Imageamento por Ressonância Magnética , Sarcopenia , Humanos , Projetos Piloto , Pessoa de Meia-Idade , Masculino , Feminino , Doença Hepática Terminal/diagnóstico por imagem , Doença Hepática Terminal/complicações , Estudos Prospectivos , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Idoso , Transplante de Fígado , Fragilidade/diagnóstico por imagem , Fragilidade/complicações , Músculo Esquelético/diagnóstico por imagemRESUMO
OBJECTIVE: To compare textbook outcomes (TO) of open live donor right hepatectomy (RH) versus open right hepatic lobectomy for cancer in a single Western center and to identify clinical factors associated with failure to achieve a TO. BACKGROUND: TO, a composite quality measure that captures multiple aspects of perioperative care, has not been thoroughly studied in open RH. We hypothesized that TO rates after RH for live donor transplant could represent the "best-achievable" results of this operation and could serve as the benchmark for RH performed for an oncologic indication. METHODS: A prospective database was reviewed to compare TO rates after RH for live donor purposes versus RH for cancer at a single center from 2010 to 2020. A TO was defined as achieving 7 metrics: no perioperative transfusion, no major postoperative complications, no significant bile leak, no unplanned transfer to the ICU, no 30-day mortality, no 30-day readmission, and no R1 margins for cancer cases. RESULTS: Among 686 RH patients (371 live donor and 315 cancer cases), a TO was achieved in 92.2% of RH donors and 53.7% of RH cancer cases. Live donor patients tended to be younger, healthier, and thinner. Among donors, increased intraoperative blood loss, and in cancer cases, male sex, tumor size, and increased intraoperative blood loss were associated with TO failure. CONCLUSIONS: A TO can be achieved in over 90% of patients undergoing living donor RH and in approximately half of RH cancer cases. These metrics represent a new benchmark for "real-world" TO after open RH.
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Transplante de Fígado , Neoplasias , Humanos , Masculino , Hepatectomia/métodos , Doadores Vivos , Benchmarking , Perda Sanguínea Cirúrgica , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologiaRESUMO
BACKGROUND: Living donor liver transplantation (LDLT) continues to be the primary modality of liver transplantation in Asia, but it accounts for about 5% of all liver transplantations in the US. ABO incompatibility is the primary reason motivated donors are declined. Although kidney paired exchanges are common, liver paired exchange (LPE) is still evolving in the US. STUDY DESIGN: This is a retrospective review (between January 1, 2019, and July 31, 2021) of our initial experience with LPE. RESULTS: A total of 10 LPEs (20 LDLTs) were performed during the study period. Seven LPEs were initiated by a nondirected O donor. The other 3 pair sets involved 1 ABO compatible and 1 ABO incompatible pair. Transplantations in a pair set were completed within a mean of 4.8 (range 1-14) days of each other. All 20 donors are doing well with no major complications at 12.7 (range 1-20) months. Seventeen of 20 recipients are alive and have good allograft function. One recipient died in the early postoperative period. Two late deaths of patients with functioning allografts were due to COVID-19 (at 8 months) and peritoneal carcinomatosis and gram-negative sepsis (at 9 months). CONCLUSIONS: LPE is feasible in a high-volume LDLT center and is a useful option to increase LDLT by overcoming ABO incompatibility. Nondirected donors can be utilized to initiate an LPE.
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Transplante de Fígado/estatística & dados numéricos , Doadores Vivos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/métodos , Sistema ABO de Grupos Sanguíneos , Adolescente , Adulto , Idoso , Incompatibilidade de Grupos Sanguíneos , COVID-19/mortalidade , Causas de Morte , Feminino , Humanos , Rim , Doadores Vivos/provisão & distribuição , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Transplantados/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Racial/ethnic minorities face known disparities in likelihood of kidney transplantation. These disparities may be exacerbated when coupled with ongoing substance use, a factor also reducing likelihood of transplantation. We examined whether race/ethnicity in combination with ongoing substance use predicted incidence of transplantation. METHODS: Patients were enrolled between March 2010 and October 2012 at the time of transplant evaluation. Substance use data were retrieved from transplant evaluations. Following descriptive analyses, the primary multivariable analyses evaluated whether, relative to the referent group (White patients with no substance use), racial/ethnic minority patients using any substances at the time of evaluation were less likely to receive transplants by the end of study follow-up (August 2020). RESULTS: Among 1152 patients, 69% were non-Hispanic White, 23% non-Hispanic Black, and 8% Other racial/ethnic minorities. White, Black, and Other patients differed in percentages of current tobacco smoking (15%, 26%, and 18%, respectively; P = 0.002) and illicit substance use (3%, 8%, and 9%; P < 0.001) but not heavy alcohol consumption (2%, 4%, and 1%; P = 0.346). Black and Other minority patients using substances were each less likely to receive transplants than the referent group (hazard ratios ≤0.45, P ≤ 0.021). Neither White patients using substances nor racial/ethnic minority nonusers differed from the referent group in transplant rates. Additional analyses indicated that these effects reflected differences in waitlisting rates; once waitlisted, study groups did not differ in transplant rates. CONCLUSIONS: The combination of minority race/ethnicity and substance use may lead to unique disparities in likelihood of transplantation. To facilitate equity, strategies should be considered to remove any barriers to referral for and receipt of substance use care in racial/ethnic minorities.
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Transplante de Rim , Transtornos Relacionados ao Uso de Substâncias , Minorias Étnicas e Raciais , Etnicidade , Disparidades em Assistência à Saúde , Humanos , Grupos Minoritários , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Ischemic injury during the agonal period of donation after circulatory death donors remains a significant barrier to increasing abdominal transplants. A major obstacle has been the inability to improve visceral perfusion, while at the same time respecting the ethics of the organ donor. A retrievable dual-chamber stentgraft could potentially isolate the organ perfusion from systemic hypotension and hypoxia, without increasing cardiac work or committing the donor. METHODS: Retrievable dumbbell-shaped stents were laser welded from nitinol wire and covered with polytetrafluoroethylene. Yorkshire pigs were assigned to either agonal control or dumbbell-shaped dual-chamber stentgraft. A central lumen maintained aortic flow, while an outer visceral chamber was perfused with oxygenated blood. A 1-hour agonal phase of hypoxia and hypotension was simulated. Stents were removed by simple sheath advancement. Cardiac monitoring, labs, and visceral flow were recorded followed by recovery of the animal to a goal of 48 hours. RESULTS: Cardiac stress did not increase during stent deployment. Visceral pO2 and flow were dramatically improved in stented animal relative to control animals. Five of 7 control animals were killed after renal failure complications, whereas all stent animals survived. Histology confirmed increased ischemic changes among control kidneys compared to stented animals. CONCLUSION: A dual-chamber stent improved outcomes after a simulated agonal phase. The stent did not increase cardiac work, thus respecting a key ethical consideration. The ability of a dual-chamber stent to prevent ischemia during organ recovery may become a powerful tool to address the critical donor organ shortage.
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Hipotensão , Isquemia Quente , Animais , Morte , Humanos , Hipotensão/complicações , Hipóxia/complicações , Isquemia , Preservação de Órgãos , Perfusão , Stents , Suínos , Doadores de TecidosRESUMO
Early acute kidney rejection remains an important clinical issue. METHODS: The current study included 552 recipients who had 1-2 surveillance or indication biopsy within the 1 y posttransplant. We evaluated the impact of type of allograft inflammation on allograft outcome. They were divided into 5 groups: no inflammation (NI: 95), subclinical inflammation (SCI: 244), subclinical T cell-mediated rejection (TCMR) (SC-TCMR: 110), clinical TCMR (C-TCMR: 83), and antibody-mediated rejection (AMR: 20). Estimated glomerular filtration rate (eGFR) over time using linear mixed model, cumulative chronic allograft scores/interstitial fibrosis and tubular atrophy (IFTA) ≥2 at 12 mo, and survival estimates were compared between groups. RESULTS: The common types of rejections were C-TCMR (15%), SC-TCMR (19.9%), and AMR (3.6%) of patients. Eighteen of 20 patients with AMR had mixed rejection with TCMR. Key findings were as follows: (i) posttransplant renal function: eGFR was lower for patients with C-TCMR and AMR (P < 0.0001) compared with NI, SCI, and SC-TCMR groups. There was an increase in delta-creatinine from 3 to 12 mo and cumulative allograft chronicity scores at 12 mo (P < 0.001) according to the type of allograft inflammation. (ii) Allograft histology: the odds of IFTA ≥2 was higher for SC-TCMR (3.7 [1.3-10.4]; P = 0.04) but was not significant for C-TCMR (3.1 [1.0-9.4]; P = 0.26), and AMR (2.5 [0.5-12.8]; P = 0.84) compared with NI group, and (iii) graft loss: C-TCMR accounted for the largest number of graft losses and impending graft losses on long-term follow-up. Graft loss among patient with AMR was numerically higher but was not statistically significant. CONCLUSIONS: The type of kidney allograft inflammation predicted posttransplant eGFR, cumulative chronic allograft score/IFTA ≥2 at 12 mo, and graft loss.
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Objective: To systematically review and compare the overall (OS) and disease-free (DFS) survival after hepatic resections for hepatocellular carcinoma (HCC) of patients with nonalcoholic fatty liver disease (NAFLD) versus other risk factors. Background: Different clinical and tumor characteristics are associated with HCC in the setting of NAFLD in comparison to other risk factors. It is still unclear whether these differences impact patient survival after radical hepatectomies. Methods: Randomized controlled trials and observational studies published in the English literature between July 1980 and June 2020 were searched using multiple databases. Patients' baseline characteristics and the hazard ratios (HRs) of the OS and DFS were extracted and meta-analyses were performed. Results: Fifteen retrospective cohort studies with a total of 7226 patients were included. Among them, 1412 patients (19.5%) had NAFLD and 5814 (80.4%) had other risk factors (eg, viral hepatitis B or C, alcoholic cirrhosis, or cryptogenic cirrhosis). Summary statistics showed that patients with NAFLD had better DFS (HR = 0.81; 95% CI: 0.70-0.94; P = 0.006) and OS (HR = 0.78; 95% CI: 0.67-0.90; P = 0.001) than the control group. Subgroups analyses also indicated that the OS favored NAFLD patients versus patients with viral hepatitis B or C (HR = 0.80; 95% CI: 0.67-0.96; P = 0.017) or alcoholic and cryptogenic cirrhosis (HR = 0.68; 95% CI: 0.47-1.0; P = 0.05). Conclusion: After hepatic resections for HCC, NAFLD patients have better DFS and OS than patients with other risk factors. Subgroup analysis and meta-regression suggested that the survival advantage of NAFLD patients was more pronounced in studies published after 2015 and from Asian centers.
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Renal transplantation is the treatment of choice for patients with end-stage renal disease. Because kidneys are the primary excretory organs for various drugs/drug metabolites, changes in renal graft function would significantly alter the clearance and exposure of renally secreted drugs. Renal allografts from living and deceased donors normally undergo numerous insults, including injuries associated with prolonged cold ischemic time, reperfusion, and nephrotoxicity due to calcineurin inhibitors. These physiologic and pharmacologic stresses can alter the expression and functional capacity of renal organic anionic transporters (OATs). METHODS: The objectives of this study were to assess the longitudinal changes in renal anionic secretion in kidney transplant patients, to study the effect of prolonged cold ischemic time on OAT secretion in kidney transplant patients (living- versus deceased-donor recipients), and to compare OAT secretory capacity of renal transplant recipients with healthy volunteers. Cefoxitin was used as a probe drug to assess OAT secretion. Cefoxitin pharmacokinetics was studied in 15 de novo renal transplant recipients following intravenous administration of 200 mg cefoxitin within 14 d and beyond 90 d posttransplantation. RESULTS: No longitudinal changes in real OAT secretion in early posttransplant period were observed, and there were no differences in renal OAT secretion between living- and deceased-donor renal transplant recipients. Overall, cefoxitin exposure was 2.6-fold higher and half-life increased by 2.2-fold in renal transplant recipients when compared with historical healthy controls. CONCLUSIONS: These results suggest that OAT system is functioning well, but renal transplant recipients would need significantly lower dosage of drugs that are primarily secreted via the OAT system compared with normal subjects.
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OBJECTIVE: The aim of this study was to compare outcomes between living donor liver transplant (LDLT) and deceased donor liver transplant (DDLT) at a single center to demonstrate the advantages of LDLT and provide justification for the increased utilization and application of this procedure. SUMMARY OF BACKGROUND DATA: LDLT comprises a very small percentage of all liver transplants performed in the United States, this despite its advantages and a shortage of the availability of deceased donor organs. METHODS: A retrospective review of all adult LDLT (n = 245) and DDLT (n = 592) performed at a single center over 10 years (2009-2019), comparing survival outcomes by Kaplan-Meier analysis and comparing other measures of outcome such as recovery times, complications, costs, and resource utilization. RESULTS: Patient survival outcomes were superior in LDLT recipients (3-year 86% vs 80%, P = 0.03). Other outcomes demonstrated shorter length of hospital stay (11 vs 13 days, P = 0.03), less likelihood of intraoperative blood transfusion (52% vs 78%, P < 0.01), and less likelihood of need for posttransplant dialysis (1.6% vs 7.4%, P < 0.01). Early reoperation and biliary/vascular complication rates were similar. Hospital costs related to the transplant were 29.5% lower for LDLT. Complications in living donors were acceptable with no early or late deaths, 3-month reoperation rate of 3.1%, and overall complication rate of 19.5%. Given its advantages, we have expanded LDLT-in 2018, LDLT comprised 53.6% of our transplants (national average 4.8%), and our transplant rate increased from 44.8 (rate per 100-person years) in 2015 to 87.5 in 2018. CONCLUSIONS: LDLT offers advantages over DDLT including superior outcomes and less resource utilization. The time has come to change the paradigm of how LDLT is utilized in this country.
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Causas de Morte , Seleção do Doador/métodos , Transplante de Fígado/mortalidade , Transplante de Fígado/métodos , Doadores Vivos/estatística & dados numéricos , Centros Médicos Acadêmicos , Adulto , Estudos de Coortes , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Falência Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: There are no instruments that can identify patients at an increased risk of poor outcomes after liver transplantation (LT) based only on their preoperative characteristics. The primary aim of this study was to develop such a scoring system. Secondary outcomes were to assess the discriminative performance of the predictive model for 90-day mortality, 1-year mortality, and 5-year patient survival. METHODS: The study population was represented by 30 458 adults who underwent LT in the United States between January 2002 and June 2013. Machine learning techniques identified recipient age, Model for End-Stage Liver Disease score, body mass index, diabetes, and dialysis before LT as the strongest predictors for 90-day postoperative mortality. A weighted scoring system (minimum of 0 to a maximum of 6 points) was subsequently developed. RESULTS: Recipients with 0, 1, 2, 3, 4, 5, and 6 points had an observed 90-day mortality of 6.0%, 8.7%, 10.4%, 11.9%, 15.7%, 16.0%, and 19.7%, respectively (P ≤ 0.001). One-year mortality was 9.8%, 13.4%, 15.8%, 17.2%, 23.0%, 25.2%, and 35.8% (P ≤ 0.001) and five-year survival was 78%, 73%, 72%, 71%, 65%, 59%, and 48%, respectively (P = 0.001). The mean 90-day mortality for the cohort was 9%. The area under the curve of the model was 0.952 for the discrimination of patients with 90-day mortality risk ≥10%. CONCLUSIONS: Short- and long-term outcomes of patients undergoing cadaveric LT can be predicted using a scoring system based on recipients' preoperative characteristics. This tool could assist clinicians and researchers in identifying patients at increased risks of postoperative death.
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Tomada de Decisão Clínica/métodos , Doença Hepática Terminal/mortalidade , Transplante de Fígado/estatística & dados numéricos , Modelos Estatísticos , Seleção de Pacientes , Adulto , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/cirurgia , Estudos de Viabilidade , Feminino , Sobrevivência de Enxerto , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Período Perioperatório , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença , Transplantados/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: We investigated the effect of clinical and subclinical T cell-mediated rejection (C-TCMR and SC-TCMR) on allograft histology, function, and progression. METHODS: Adult kidney recipients with 2 protocol biopsies were divided into No-TCMR on biopsies (n = 104), SC-TCMR (n = 56), and C-TCMR (n = 32) in at least 1 biopsy. Chronicity (ci + ct + cg + cv) scores, renal function, and the burden of renal disease measured by area under the curve (serum creatinine, mg mo/dL) were compared. RESULTS: Baseline characteristics were similar except for mean donor age and Kidney Donor Profile index scores. Patients with C-TCMR had higher mean serum creatinine, lower mean estimated glomerular filtration rate, and higher area under the curve with 95% confidence interval (75.2 [67.7-82.7]) as opposed to patients with SC-TCMR and No-TCMR (58.3 [53.6-62.9], 65.1 [58.8-71.5]), P = 0.0004. Chronicity scores were higher at 3 months in C-TCMR (2.30 ± 1.58) compared with SC-TCMR (2.02 ± 1.42) and No-TCMR (1.31 ± 1.18), P = 0.0001 and also at 12 months. At last follow-up, 18.8% patients with C-TCMR had ≥50% decline in estimated glomerular filtration rate from 3 months compared with 7% and 1% among No-TCMR and SC-TCMR groups (P = 0.038). Multivariate analyses revealed higher odds of Δ-creatinine ≥ 0.5 mg/dL from 3 months to last follow-up for C-TCMR (3.39 [95% confidence interval, 1.25-9.20]) versus No-TCMR (P = 0.016). CONCLUSIONS: Kidney transplant recipients with C-/SC-TCMR have heightened early allograft chronicity and worse renal function compared with those with No-TCMR. Progressive renal dysfunction was noted among patients with C-TCMR as opposed to SC-TCMR and No-TCMR.
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Rejeição de Enxerto/imunologia , Imunidade Celular , Nefropatias/imunologia , Transplante de Rim/efeitos adversos , Rim/imunologia , Linfócitos T/imunologia , Adulto , Biópsia , Creatinina/sangue , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/fisiopatologia , Humanos , Rim/patologia , Rim/fisiopatologia , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Transdução de Sinais , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Improvements in renal allograft outcomes have permitted kidney transplantation after prior kidney allograft failure as well as after nonrenal solid organ transplantation. This study compares renal allograft outcomes in the 3 groups, that is, primary, repeat, and kidney after nonrenal solid organ transplantation, where transplant group was coded as a time-dependent variable. METHODS: We retrospectively reviewed registry data for kidney transplant recipients at University of Pittsburgh Medical Center from January 2000 to December 2011. We compared overall graft survival between the 3 groups using Cox regression modeling. We calculated 1-, 3-, and 5-year graft survival and half-lives for each group where feasible. RESULTS: The study cohort (N = 2014) consisted of group A (primary kidney transplant, n = 1578, with 7923.2 years of follow-up time), group B (repeat kidney transplant, n = 314, with 1566.7 years of follow-up time) and group C (kidney post-nonrenal solid organ transplant, n = 176, with 844.8 years of follow-up time). Of the 1578 patients in the primary kidney transplant group, 74 later received a repeat transplant and thus also have follow-up counted in the repeat kidney transplant group. The median follow-up was 56, 53, and 55 months, respectively. The 5-year actuarial and death-censored graft survival was 68.69%, 68.79%, and 66.48% and 65.53%, 67.68%, and 62.92%, respectively (P = 0.70). There was no difference in overall graft survival in the Cox-adjusted analysis (group B: odds ratio, 1.02; 95% confidence interval, 0.84-1.26; P = 0.79; group C: odds ratio, 0.96; 95% confidence interval, 0.75-1.23; P = 0.76). CONCLUSIONS: The adjusted kidney graft survivals in the 3 groups were similar.
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Frailty with sarcopenia in cirrhosis causes liver transplant wait-list attrition and deaths. Regular physical activity is needed to protect patients with cirrhosis from frailty. We subjectively assess physical performance in selecting patients for transplant listing, but we do not know whether clinical assessments reflect the extent of activity patients actually perform. To investigate this question, 53 wait-listed patients self-assessed their performance of ordinary physical tasks using the Rosow-Breslau survey, and clinicians assessed their physical performance status with the Karnofsky index. We compared these assessments with actual activity measured using an accelerometer/thermal sensing armband worn from 4 to 7 days. We found that their measured activity was among the lowest reported in chronic disease, similar to that of patients with advanced chronic pulmonary disease or renal failure. Their percentages of waking hours spent in sedentary, light, and moderate-vigorous activity were 75.9% ± 18.9%, 18.9% ± 14.3%, and 4.9% ± 6.9%, respectively. Higher mean sedentary and lower mean moderate-vigorous activity was significantly associated with 9 wait-list deaths (P = 0.004). Compared with a range of 7000-13,000 steps/day in healthy adults, patients' mean steps/day were 3164 ± 2842. Both their activity percentage and step data were typical of other severely inactive populations. Neither their Rosow-Breslau scores (mean 2.3 ± 0.8, maximum 3.0) nor their Karnofsky scores (mean 79 ± 12, maximum 100) suggested major impairment or showed a correlation with patients' actual physical performance. In conclusion, physical activity in patients with cirrhosis wait-listed for transplantation is highly sedentary. Self-assessments and provider assessments of physical activity do not reliably indicate actual performance. Whether the gap between assessed and actual performance may be favorably modified by interventions to improve activity and ameliorate frailty merits further study. Liver Transplantation 22 1324-1332 2016 AASLD.