Access to hepatitis C direct-acting antiviral therapy in hepatitis C-positive donor to hepatitis C-negative recipient solid-organ transplantation in a real-world setting.

BACKGROUND: Emerging data supports expanding the solid organ donor pool with transplantation from hepatitis C virus (HCV)-positive donors into HCV-negative recipients. However, concerns exist regarding the ability to access direct-acting antivirals (DAAs) post-transplant in a real-world setting. METHODS: This single-center, retrospective study evaluated DAA access rates, time to first dose, and patient cost in donor-derived HCV solid-organ transplant recipients utilizing an integrated specialty pharmacy process. RESULTS: Among 91 patients, all accessed DAAs through prescription insurance (97%) or patient assistance programs (3%). Of those who received DAAs through insurance, only 65% received approval on initial insurance submission. Median time from transplant to first dose was 45d [IQR 34-66]. The on-site specialty pharmacy was used by 69% of patients. Copay assistance programs reduced the median monthly patient cost from $1914 [range $7-7536] to $0 [range $0-5]. CONCLUSION: Our findings indicate that access to DAAs in donor-derived HCV post-transplant is achievable and affordable; however, significant added administrative efforts may be required for insurance approval as well as obtaining copay assistance, which is a limited resource.

Monoclonal antibody treatment for COVID-19 in solid organ transplant recipients.

Solid organ transplant (SOT) recipients are at high risk for severe coronavirus disease 2019 (COVID-19). Studies suggest that early intervention with monoclonal antibody (MAB) treatment directed against the SARS-CoV-2 spike protein may reduce the risk of emergency department visits or hospitalization for COVID-19, especially in high-risk patients. Herein, we describe our single-center experience of 93 SOT (50 kidney, 17 liver, 11 lung, nine heart, and six dual-organ) recipients with mild to moderate COVID-19 who were treated with bamlanivimab or casirivimab-imdevimab per emergency use authorization guidelines. Median age of recipients was 55 [(Interquartile range) 44-63] years, and 41% were diabetic. Median time from transplant to MAB was 64 (IQR 24-122) months and median time from the onset of COVID-19 symptoms to the infusion was 6 (IQR 4-7) days. All patients had a minimum 30 days of study follow-up. The 30-day hospitalization rate for COVID-19-directed therapy was 8.7%. Infusion-related adverse events were rare and generally mild. Biopsy-proven organ rejection occurred in two patients, and there were no graft losses or deaths. A comparator group of 72 SOT recipients diagnosed with COVID-19 who were eligible but did not receive MAB treatment had a higher 30-day hospitalization rate for COVID-19-directed therapy (15.3%), although this difference was not statistically significant, after adjustment for age (Odds Ratio 0.49 [95% Confidence Interval 0.18-1.32], p = 0.16). Our experience suggests that MAB treatment, with respect to the available MAB formulations and circulating viral variants present during our study period, may provide favorable outcomes for mild to moderate COVID-19 in SOT recipients.

Kidney Transplantation From Hepatitis C Viremic Deceased Donors to Aviremic Recipients in a Real-world Setting.

Transplantation of hepatitis C viremic (HCV+) deceased donor kidney transplants (DDKT) into aviremic (HCV-) recipients is a strategy to increase organ utilization. However, there are concerns around inferior recipient outcomes due to delayed initiation of direct-acting antiviral (DAA) therapy and sustained HCV replication when implemented outside of a research setting. METHODS: This was a retrospective single-center matched cohort study of DDKT recipients of HCV+ donors (cases) who were matched 1:1 to recipients of HCV- donors (comparators) by age, gender, race, presence of diabetes, kidney donor profile index, and calculated panel-reactive antibody. Data were analyzed using summary statistics, t-tests, and chi-square tests for between-group comparisons, and linear mixed-effects models for longitudinal data. RESULTS: Each group consisted of 50 recipients with no significant differences in baseline characteristics. The 6-mo longitudinal trajectory of serum creatinine and estimated glomerular filtration rate did not differ between groups. All recipients had similar rates of acute rejection and readmissions (all P > 0.05). One case lost the allograft 151 d posttransplant because of acute rejection, and 1 comparator died on postoperative day 7 from cardiac arrest. HCV+ recipients initiated DAA on average 29 ± 11 d posttransplant. Ninety-eight percent achieved sustained virologic response at 4 and 12 wks with the first course of therapy; 1 patient had persistent HCV infection and was cured with a second course of DAA. CONCLUSIONS: Aviremic recipients of HCV+ DDKT with delayed DAA initiation posttransplant had similar short-term outcomes compared with matched recipient comparators of HCV- donors.

Liver and Biliary Disease of Pregnancy and Anesthetic Implications: A Review.

Liver and biliary disease complicates pregnancy in varying degrees of severity to the mother and fetus, and anesthesiologists may be asked to assist in caring for these patients before, during, and after birth of the fetus. Therefore, it is important to be familiar with how different liver diseases impact the pregnancy state. In addition, knowing symptoms, signs, and laboratory markers in the context of a pregnant patient will lead to faster diagnosis and treatment of such patients. This review article discusses changes in physiology of parturients, patients with liver disease, and parturients with liver disease. Next, general treatment of parturients with acute and chronic liver dysfunction is presented. The article progresses to specific liver diseases with treatments as they relate to pregnancy. And finally, important aspects to consider when anesthetizing parturients with liver disease are discussed.

Key histopathologic features in idiopathic noncirrhotic portal hypertension: an interobserver agreement study and proposal for diagnostic criteria.

Histologic features of idiopathic noncirrhotic portal hypertension (INCPH), loosely termed as obliterative portal venopathy (OPV), are heterogenous, often subtle, and overlap with other entities. To this date, no consensus histopathologic diagnostic criteria have been established for INCPH. For these reasons, rendering a reproducible consensus histologic diagnosis of OPV on a liver biopsy may often be challenging even for experienced hepatopathologists. We report herein a two-phase interobserver agreement study on the diagnosis of OPV and assessed the relative value of histologic features in 104 liver biopsies in distinguishing between INCPH and non-INCPH with the goal to obtain a consensus on specific practical diagnostic criteria. Six hepatopathologists blinded to clinical information and original pathologic diagnosis reviewed internet-based case study sets with high-resolution whole-slide images. The initial interobserver agreement on OPV was expectedly low, but significantly improved (moderate agreement in most categories) upon adopting a consensus view recognizing portal vein sclerosis as the only strong independent histologic predictor for INCPH, and that contrary to the conventional view, aberrant portal/periportal vessels does not significantly contribute to the positive assignment of OPV status. We propose a three-tiered classification with diagnostic criteria to facilitate the histologic assignment of OPV status for the evaluation of INCPH. Furthermore, we have validated the performance of the proposed criteria either based on histology alone or coupled with clinicopathologic correlation. This classification may aid in practical histologic assessment of liver biopsies with or without portal hypertension and help to improve diagnostic consistency and accuracy.

Adult Combined Heart-Liver Transplantation: The United States Experience.

Background: We aimed to review the indications and outcomes of adults undergoing combined heart-liver transplantation (CHLT) in the US using national registry data. Methods: Adult (≥18 years) CHLT recipients in the United Network for Organ Sharing database were included (09/1987-09/2020; era 1 = 1989-2000, era 2 = 2001-2010, era 3 = 2011-2020). Survival analysis was conducted by means of Kaplan-Meier method, log-rank test, and Cox regression. Results: We identified 369 adults receiving CHLT between 12/1989-08/2020. The number of adult CHLT recipients (R2 = 0.75, p < 0.001) and centers performing CHLT (R2 = 0.80, p < 0.001) have increased over the study period. The most common cardiac diagnosis in the first two eras was restrictive/infiltrative cardiomyopathy, while the most common in era 3 was congenital heart disease (p = 0.03). The 1-, 3-, and 5-years patient survival was 86.8, 80.1, and 77.9%, respectively. In multivariable analysis, recipient diabetes [adjusted hazard ratio (aHR) = 2.35, 95% CI: 1.23-4.48], CHLT between 1989-2000 compared with 2011-2020 (aHR = 5.00, 95% CI: 1.13-22.26), and sequential-liver first CHLT compared with sequential-heart first CHLT (aHR = 2.44, 95% CI: 1.15-5.18) were associated with increased risk of mortality. Higher left ventricular ejection fraction was associated with decreased risk of mortality (aHR = 0.96, 95% CI: 0.92-0.99). Conclusion: CHLT is being increasingly performed with evolving indications. Excellent outcomes can be achieved with multidisciplinary patient and donor selection and surgical planning.

Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient?

Nivolumab is an immune checkpoint inhibitor (ICI) currently in phase 3 clinical trials for hepatocellular carcinoma. The safety of ICIs in recipients of organ allotransplant is unclear, and several reports of fatal alloimmune injury after posttransplant ICI use have been published. We present the first published case of nivolumab used in the pretransplant setting for HCC resulting in fatal acute hepatic necrosis in the immediate postoperative period from a profound immune reaction likely propagated by nivolumab. Further investigation and significant caution are needed in the evaluation of patients awaiting transplant who are receiving ICI therapy.

Trends in Renal Function Among Heart Transplant Recipients of Donor-Derived Hepatitis C Virus.

Donor-derived hepatitis C (dd-HCV) infection may increase the risk of renal impairment (RI) among heart transplantation (HT) recipients. Sofosbuvir, an integral component of HCV direct-acting antivirals (DAAs) has also been linked to RI. To date, no study has examined the trends in renal function for HT recipients of dd-HCV infection and assessed safety and efficacy of Sofosbuvir-based DAAs. Between September 2016 and June 2018, 46 HCV-naive patients and one patient with a history of HCV treated pretransplant, underwent HT from HCV-positive donors (follow-up available through October 10, 2018). Patients were treated with Ledipasvir-Sofosbuvir (genotype 1) or Sofosbuvir-Velpatasvir (genotype 3) for 12 or 24 weeks; no dose adjustments were made for renal function. Data on renal function were available for 23 patients who achieved a sustained virologic response at 12 weeks after the treatment (SVR12; cohort A) and 18 patients who completed 1 year of follow-up (cohort B). Treatment of dd-HCV infection was initiated at a median of 6 weeks post-HT. In both cohorts, a nonsignificant reduction in median estimated glomerular filtration rate (eGFR; ml/min/1.73 m) was noted (cohort A: pretransplant eGFR: 62 [interquartile range {IQR}: 1-84] to SVR12 eGFR: 49 [IQR: 37-82]; p = 0.43; cohort B: pretransplant eGFR: 65 [IQR: 54-84] to 1 year post-HT eGFR: 56 [IQR: 39-75]; p = 0.29). Pretreatment renal function had no significant impact on changes in renal function during treatment. All patients tolerated DAAs well with 100% completion rate to the assigned therapy and duration and 100% success at achieving SVR12. In this first and largest reported case series to date of HT recipients with dd-HCV infection, we observed that neither the dd-HCV infection nor its treatment with Sofosbuvir-based DAAs increased the risk of RI. Sofosbuvir-based DAAs appear safe, tolerable, and effective for HCV treatment even in presence of severe RI.

Expanding Heart Transplant in the Era of Direct-Acting Antiviral Therapy for Hepatitis C.

Importance: For patients awaiting heart transplant, hepatitis C-positive donors offer an opportunity to expand the donor pool, shorten wait times, and decrease wait-list mortality. While early reported outcomes among few heart transplant recipients have been promising, knowledge of 1-year outcomes in larger cohorts of patients is critical to shared decision-making with patients about this option. Objective: To better define the association of hepatitis C-positive donors with heart transplant volumes, wait-list duration, the transmission and cure of donor-derived hepatitis C, and morbidity and mortality at 1 year. Design, Setting, and Participants: This was a prospective, single-center observational study of 80 adult (age 18 years or older) patients who underwent heart transplant using hearts from hepatitis C-positive donors between September 2016 and April 2019 at a large academic medical center. Among donors, who were considered hepatitis C-positive if results from hepatitis C antibody and/or nucleic acid testing were positive, 70 had viremia and 10 were seropositive but did not have viremia. Follow-up was available through May 15, 2019. Comparisons were drawn with patients who underwent transplant with hearts from hepatitis C-negative donors during the same period. Exposures: In addition to standard posttransplant management, transplant recipients who developed donor-derived hepatitis C infection were treated with direct-acting antivirals. Main Outcomes and Measures: The main outcomes included wait-list duration and 1-year survival in all patients, and for those who developed donor-derived hepatitis C, the response to direct-acting antiviral treatment. Results: Of 80 patients, 57 (71.3%) were men, 55 (68.7%) were white, and 17 (26.3%) were black; the median age at transplant was 54.5 years (interquartile range, 46-62 years). Following consent to accept hearts from hepatitis C-exposed donors, the median days to heart transplant was 4 (interquartile range, 1-18). No recipients of donors with negative nucleic acid testing results (10 [12.5%]) developed donor-derived hepatitis C. Of 70 patients who were recipients of donors with positive nucleic acid testing results, 67 (95.7%) developed donor-derived hepatitis C over a median follow-up of 301 days (interquartile range, 142-617). Treatment with direct-acting antivirals was well tolerated and yielded sustained virologic responses in all treated patients. Within the cohort with infection, 1-year patient survival was 90.4%, which was not significantly different compared with the cohort without infection or with patients who received transplants from hepatitis C-negative donors during the same period. Conclusions and Relevance: In the era of direct-acting antivirals, hepatitis C-positive donors are a viable option to expand the donor pool, potentially reducing wait-list duration and mortality. In heart transplant recipients with donor-derived hepatitis C, infection is well-tolerated and curable, and 1-year survival is equivalent to that in recipients of hepatitis C-negative donors.

More than the heart: Hepatic, renal, and cardiac dysfunction in adult Fontan patients.

SETTING: Fontan-associated liver disease universally affects adults with single ventricle heart disease. Chronic kidney disease is also highly prevalent in adult Fontan patients. In this study, we evaluate the relationship of Fontan hemodynamics invasively and noninvasively with extra-cardiac dysfunction as measured by MELD and MELD-XI. OBJECTIVE: We hypothesize that invasive and noninvasive measures of Fontan circuit congestion and ventricular dysfunction are associated with increased MELD and MELD-XI scores. DESIGN: Single-center data from adults with Fontan palliation who had ongoing care, including cardiac catheterization, were retrospectively collected. Hemodynamic data from cardiac catheterization and echocardiographic assessment of ventricular and atrioventricular valve function were tested for association with serum creatinine, MELD, and MELD-XI. Linear regression was used to perform multivariable analysis in the echocardiogram cohort. RESULTS: Fifty-seven patients had congruent lab and catheterization data for analysis. Sixty-three and sixty-nine patients had congruent lab and echocardiogram data for MELD and MELD-XI, respectively. Of the hemodynamic variables analyzed, only decreased systemic oxygen saturation had significant correlation with elevated MELD and MELD-XI (P = .045). Patients with moderately or severely reduced ejection fraction by echocardiogram had significantly higher MELD and MELD-XI scores compared to those with normal or mildly depressed systolic ventricular function (P = .008 and P < .001 for MELD and MELD-XI, respectively). Significant differences in creatinine were also found among the ventricular dysfunction groups (P = .02). CONCLUSIONS: In adults following Fontan palliation, systolic ventricular dysfunction and decreased oxygen saturation were associated with hepatic and renal dysfunction as assessed by elevated serum creatinine, MELD, and MELD-XI scores.

The Changing Face of Liver Transplantation in the United States: The Effect of HCV Antiviral Eras on Transplantation Trends and Outcomes.

BACKGROUND: Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States, although nonalcoholic steatohepatitis (NASH) is on the rise. Increasingly effective HCV antivirals are available, but their association with diagnosis-specific liver transplantation rates and early graft survival is not known. METHODS: The Scientific Registry of Transplant Recipients database records were retrospectively stratified by HCV antiviral era: interferon (2003-2010), protease inhibitors (2011-2013), and direct-acting antivirals (2014 to present). Kaplan-Meier, χ2, and multivariable Cox proportional hazards regression models evaluated the effects of antiviral era and etiology of liver disease on transplantation rates and graft survival over 3 years. RESULTS: Liver transplants for HCV decreased (35.3% to 23.6%), whereas those for NASH and alcoholic liver disease increased (5.8% to 16.5% and 15.6% to 24.0%) with each advancing era (all P < 0.05). Early graft survival improved with each advancing era for HCV but not for hepatitis B virus, NASH, or alcoholic liver disease (multivariable model era by diagnosis interaction P < 0.001). Era-specific multivariable models demonstrated that the risk of early graft loss for NASH was 22% lower than for HCV in the interferon era (hazard ratio, 0.78; 95% confidence interval, 0.64-0.96; P = 0.02) but risks associated with these diagnoses did not differ significantly in the protease inhibitor (P = 0.06) or direct-acting antiviral eras (P = 0.08). CONCLUSIONS: Increasing effectiveness of HCV antivirals corresponds with decreased rates of liver transplantation for HCV and improved early graft survival. As the rates of liver transplant for NASH continue to increase, focus will be needed on the prevention and effective therapies for this disease.

Early outcomes using hepatitis C-positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies.

BACKGROUND: Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors. METHODS: Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent. Patients who acquired HCV were referred to hepatology and treated with direct-acting anti-viral therapies (DAAs). Data collection and analysis were performed with institutional review board approval. RESULTS: At the time of HT, mean age of recipients was 53 ± 10 years, and 8 patients (61.5%) were on left ventricular assist device support. After consent to consider an HCV-positive heart, mean time to HT was 11 ± 12 days. Nine of 13 patients (69%) developed HCV viremia after transplant, including 8 who completed DAA treatment and demonstrated cure, as defined by a sustained virologic response 12 weeks after treatment. One patient died during Week 7 of his treatment due to pulmonary embolism. DAAs were well tolerated in all treated patients. CONCLUSIONS: In the era of highly effective DAAs, the use of HCV-positive donors represents a potential approach to safely expand the donor pool. Additional follow-up is needed to elucidate long-term outcomes.

Perioperative risk assessment for patients with cirrhosis and liver disease.

Patients with cirrhosis are at an increased risk of complications of operative procedures. There is a growing understanding of the nature of the risks that cirrhotic patients experience, as well as more precise and objective tools to gauge the patients at risk for surgical complications. Surgical procedures that are common and high risk for patients with cirrhosis are cardiac surgery, cholecystectomy and hepatic resections, as well as other abdominal surgeries and orthopedic surgeries. The physicians who care for patients with cirrhosis who require a surgical procedure can apply an understanding of the type of surgery anticipated with knowledge of the severity of the patient's liver disease to predict those patients at risk for operative morbidity and mortality. A sound knowledge of the specific operative risks faced by patients with cirrhosis should prompt the clinician to take steps to prevent these complications.

A prospective evaluation of computerized tomographic (CT) scanning as a screening modality for esophageal varices.

UNLABELLED: Patients with cirrhosis require endoscopic screening for large esophageal varices. The aims of this study were to determine the cost-effectiveness and patient preferences of a strategy employing abdominal computerized tomography (CT) as the initial screening test for identifying large esophageal varices. In a prospective evaluation,102 patients underwent both CT and endoscopic screening for gastroesophageal varices. Two radiologists read each CT independently; standard upper gastrointestinal endoscopy was the reference standard. Agreement between radiologists, and between endoscopists regarding size of varices was determined using kappa statistic. Cost-effectiveness analysis was performed to determine the optimal screening strategy for varices. Patient preference was assessed by questionnaire. CT was found to have approximately 90% sensitivity in the identification of esophageal varices determined to be large on endoscopy, but only about 50% specificity. The sensitivity of CT in detecting gastric varices was 87%. In addition, a significant number of gastric varices, peri-esophageal varices, and extraluminal pathology were identified by CT that were not identified by endoscopy. Patients overwhelmingly preferred CT over endoscopy. Agreement between radiologists was good regarding the size of varices (Kappa = 0.56), and exceeded agreement between endoscopists (Kappa = 0.36). Use of CT as the initial screening modality for the detection of varices was significantly more cost-effective compared to endoscopy irrespective of the prevalence of large varices. CONCLUSION: Abdominal CT as the initial screening test for varices could be cost-effective. CT also permits evaluation of extra-luminal pathology that impacts management.

Graft vs. host disease after liver transplantation: a new approach is needed.

Graft-vs.-host disease (GVHD) is a rare, serious complication of orthotopic liver transplantation (OLT). We have treated 5 patients to date with GVHD after OLT. A total of 78 patients worldwide have been reported to have experienced this complication. The means by which GVHD after OLT has been managed is guided by experience with the more common GVHD that occurs after stem cell transplantation. However, despite the use of various treatment modalities, the mortality of GVHD after OLT remains high. This case series and review of the literature demonstrates that successful resolution of GVHD after OLT cannot be expected with the use of those modalities that have been tried to date. It is imperative that new treatments be applied to GVHD after OLT in order to improve the prognosis of patients with this diagnosis.

Defects in cGMP-PKG pathway contribute to impaired NO-dependent responses in hepatic stellate cells upon activation.

NO antagonizes hepatic stellate cell (HSC) contraction, although activated HSC in cirrhosis demonstrate impaired responses to NO. Decreased NO responses in activated HSC and mechanisms by which NO affects activated HSC remain incompletely understood. In normal rat HSC, the NO donor diethylamine NONOate (DEAN) significantly increased cGMP production and reduced serum-induced contraction by 25%. The guanylate cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) abolished 50% of DEAN effects, whereas the cGMP analog 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) reiterated half the observed DEAN response, suggesting both cGMP-dependent protein kinase G (PKG)-dependent and -independent mechanisms of NO-mediated antagonism of normal HSC contraction. However, NO donors did not increase cGMP production from in vivo activated HSC from bile duct-ligated rats and showed alterations in intracellular Ca(2+) accumulation suggesting defective cGMP-dependent effector pathways. The LX-2 cell line also demonstrated lack of cGMP generation in response to NO and a lack of effect of ODQ and 8-BrcGMP in modulating the NO response. However, cGMP-independent effects in response to NO were maintained in LX-2 and were associated with S-nitrosylation of proteins, an effect reiterated in primary HSC. Adenovirus-based overexpression of PKG significantly attenuated contraction of LX-2 by 25% in response to 8-BrcGMP. In summary, these studies demonstrate that NO affects HSC through cGMP-dependent and -independent pathways. The HSC activation process is associated with maintenance of cGMP-independent actions of NO but defects in cGMP-PKG-dependent NO signaling that are improved by PKG gene delivery in LX-2 cells. Activating targets downstream from NO-cGMP in activated HSC may represent a novel therapeutic target for portal hypertension.

Outcome of liver transplantation for familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant disorder caused by mutation in the transthyretin gene. The most common mutation is substitution of valine for methionine at position 30 (MET30). Liver transplantation (LT) is the preferred treatment. After LT, although many patients show stabilization or improvement in the disease, adverse outcomes have been reported in those who have malnutrition, long-standing disease, and non-MET (NMET) mutations at position 30. Our aim is to compare survival and outcome of symptoms associated with FAP after LT in patients with MET30 and NMET30 mutations. Medical records of all patients who underwent LT for amyloidosis at our institution were reviewed to obtain demographic information and clinical features, such as severity of neuropathy, diarrhea, orthostatic hypotension, and posterior wall or ventricle septal thickness before and after LT. Fifteen patients underwent LT for amyloidosis at our institution between 1990 and 2000 (MET30, n = 5; NMET30, n = 7; hereditary amyloidosis, n = 2; primary amyloidosis, AL type, n = 1). Patients with hereditary and primary amyloidosis were excluded from analysis. One- and 3-year survival rates after LT in MET30 patients were 100%. Before LT, five of five patients had sensorimotor neuropathy; five of five patients had diarrhea, and four of five patients had orthostatic hypotension. After LT, improvement or stabilization of neuropathy was seen in two of five patients; of diarrheal symptoms, in three of five patients; and of orthostatic hypotension, in three of four patients. One- and 3-year survival rates after LT in NMET30 patients were 100% and 85.7%, respectively. Before LT, six of seven patients had sensorimotor neuropathy, six of seven patients had diarrhea, and five of seven patients had orthostatic hypotension. After LT in this group, improvement or stabilization of neuropathy was seen in two of six patients; of diarrhea, in six of six patients; and of orthostatic hypotension, in five of five patients. Before LT, posterior wall and/or ventricle septal thickness was increased in two of five MET patients and seven of seven NMET patients. Five of seven NMET30 patients (71.4%) who received a combined liver and heart transplant had stabilization, and two patients in the NMET group and one patient in the MET group had progression of heart disease. Outcomes for LT for patients with FAP with MET or NMET mutations were similar. Earlier LT for patients with FAP with MET30 or NMET30 mutation would improve outcomes after LT.