Citations

Abstract Objective . Ultrasound attenuation coefficient estimation (ACE) has diagnostic potential for clinical applications such as quantifying fat content in the liver. Previously, we have proposed a system-independent ACE technique based on spectral normalization of different frequencies, called the reference frequency method (RFM). This technique does not require a well-calibrated reference phantom for normalization. However, this method may be vulnerable to severe reverberation clutter introduced by the body wall. The clutter superimposed on liver echoes may bias the estimation. Approach . We proposed to use robust principal component analysis, combined with wavelet-based sparsity promotion, to suppress the severe reverberation clutters. The capability to mitigate the reverberation clutters was validated through phantom and in vivo studies. Main Results . In the phantom studies with added reverberation clutters, higher normalized cross-correlation and smaller mean absolute errors were attained as compared to RFM results without the proposed method, demonstrating the capability to reconstruct tissue signals from reverberations. In a pilot patient study, the correlation between ACE and proton density fat fraction (PDFF), a measurement of liver fat by MRI as a reference standard, was investigated. The proposed method showed an improvement of the correlation (coefficient of determination, R = 0.82) as compared with the counterpart without the proposed method ( R = 0.69). Significance : The proposed method showed the feasibility of suppressing the reverberation clutters, providing an important basis for the development of a robust ACE with large reverberation clutters.

Abstract Liver transplantation (LT) is the definitive treatment for end‐stage liver disease. Unfortunately, women are disadvantaged at every stage of the LT process. We conducted a literature review to increase the understanding of this disparity. Hormonal differences, psychological factors, and Model for End‐Stage Liver Disease (MELD) score inequalities are some pretransplantation factors that contribute to this disparity. In the posttransplantation setting, women have differing risk than men in most major outcomes (perioperative complications, rejection, long‐term renal dysfunction, and malignancy) and assessing the two groups together is disadvantageous. Herein, we propose interventions including standardized criteria for LT referral, using an alternate MELD, education for support of women, and motivating women to seek living donors. Understanding sex‐based differences will allow us to improve access, tailor management, and improve overall outcomes for all patients, particularly women.

Post‐transplant diabetes mellitus (PTDM) is a significant contributor to morbidity and mortality in liver transplant recipients (LTRs). With concurrent comorbidities and use of various immunosuppression medications, identifying a safe and personalized regimen for management of PTDM is needed. There are many comorbidities associated with the post‐transplant course including chronic kidney disease, cardiovascular disease, allograft steatosis, obesity, and de novo malignancy. Emerging data suggest that available diabetes medications may carry beneficial or, in some cases, harmful effects in the setting of these co‐existing conditions. Sodium‐glucose co‐transporter 2 inhibitors and glucagon‐like peptide 1 receptor agonists have shown the most promising beneficial results. Although there is a deficiency of LTR‐specific data, they appear to be generally safe. Effects of other medications are varied. Metformin may reduce the risk of malignancy. Pioglitazone may be harmful in patients combatting obesity or heart failure. Insulin may exacerbate obesity and increase the risk of developing malignancy. This review thoroughly discusses the roles of these extra‐glycemic effects and safety considerations in LTRs. Through weighing the risks and benefits, we conclude that alternatives to insulin should be strongly considered, when feasible, for personalized long‐term management based on risk factors and co‐morbidities.

De novo malignancies (DNMs) following liver transplantation (LT) have been reported as 1 of the major causes of late mortality, being the most common cause of death in the second decade after LT. The overall incidence of DNMs is reported to be in the range of 3.1% to 14.4%, and the incidence is 2- to 3-fold higher in transplant recipients than in age- and sex-matched healthy controls. Long-term immunosuppressive therapy, which is the key in maintaining host tolerance and achieving good long-term outcomes, is known to contribute to a higher risk of DNMs. However, the incidence and type of DNM also depends on different risk factors, including patient demographics, cause of the underlying chronic liver disease, behavior (smoking and alcohol abuse), and pre-existing premalignant conditions. The estimated standardized incidence ratio for different DNMs is also variable. The International Liver Transplantation Society–Spanish Society of Liver Transplantation Consensus Conference working group on DNM has summarized and discussed the current available literature on epidemiology, risk factors, management, and survival after DNMs. Recommendations for screening and surveillance for specific tumors, as well as immunosuppression and cancer-specific management in patients with DNM, are summarized.

The International Liver Transplantation Society and the Spanish Society of Liver Transplantation consensus conference on extrahepatic cancer and liver transplantation (LT) was held on January 28–30, 2021. Working groups were organized to focus on one topic and develop evidence-based recommendations specifically addressing (a) nonhepatic cancer in LT candidates, (b) de novo malignancies after LT, (c) prevention and management of donor-derived malignancies after LT, and (d) nonhepatic cancer in the pediatric population. All consensus conference attendees voted on the recommendations proposed as well as the quality of evidence according to the Grading of Recommendations, Assessment, Development and Evaluation system.

AbstractBackgroundHypertrophic cardiomyopathy (HCM) presents with a hypertrophied left ventricle (LV). It is often associated with LV outflow tract obstruction (LVOTO) and a risk for sudden death. This study aimed to describe outcomes of patients with HCM who underwent liver transplant (LT).MethodsA retrospective review was conducted for patients diagnosed with HCM undergoing LT. Patient characteristics, preoperative echocardiography results, HCM risk of sudden cardiac death prediction model score, and 5‐year mortality were examined. A univariable Cox proportional hazards model was used to evaluate the association between risk factors and 5‐year mortality. All tests were two‐sided with the alpha level set at .05.ResultsTwenty‐nine patients were included in the analysis. Six patients (21%) had a perioperative cardiopulmonary complication. The 5‐year survival rate was 61% (95% CI, 45–82). The analyzed risk factors showed that 5‐year post‐LT survival was significantly predicted by maximal LV outflow tract gradient at rest > 60 mmHg (hazard ratio, 1.04 [95% CI, 1.01‐1.06]).ConclusionsPreoperative LV outflow tract resting gradient > 60 mmHg was associated with 5‐year post‐LT mortality. The results suggest the severity of LVOTO identified by echocardiography is a prognostic tool for patients with HCM after LT.

Prostate‐specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with 68Ga‐PSMA‐11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored. In a subset (n = 30), messenger RNA (mRNA) data from the Cancer Genome Atlas HCC RNA sequencing were correlated with PSMA expression. In phase 2, 68Ga‐PSMA‐11 PET was prospectively performed in patients with treatment‐naïve HCC on a digital PET scanner using cyclotron‐produced 68Ga. Uptake was graded qualitatively and semi‐quantitatively using standard metrics. On IHC, PSMA expression was significantly higher in HCC compared with CCA and HCA (P < 0.0001); 91% of HCCs (n = 134) expressed PSMA, which principally localized to tumor‐associated neovasculature. Higher tumor grade was associated with PSMA expression (P = 0.012) but there was no association with tumor size (P = 0.14), fibrosis (P = 0.35), cirrhosis (P = 0.74), hepatitis B virus (P = 0.31), or hepatitis C virus (P = 0.15). Overall survival tended to be longer in patients without versus with PSMA expression (median overall survival: 4.2 vs. 1.9 years; P = 0.273). FGF14 (fibroblast growth factor 14) mRNA expression correlated positively (rho = 0.70; P = 1.70 × 10‐5) and MAD1L1 (Mitotic spindle assembly checkpoint protein MAD1) correlated negatively with PSMA expression (rho = −0.753; P = 1.58 × 10‐6). Of the 190 patients who met the eligibility criteria, 31 patients with 39 HCC lesions completed PET; 64% (n = 25) lesions had pronounced 68Ga‐PSMA‐11 standardized uptake value: SUVmax (median [range] 9.2 [4.9‐28.4]), SUVmean 4.7 (2.4‐12.7), and tumor‐to‐liver background ratio 2 (1.1‐11). Conclusion: Ex vivo expression of PSMA in neovasculature of HCC translates to marked tumor avidity on 68Ga‐PSMA‐11 PET, which suggests that PSMA has the potential as a theranostic target in patients with HCC.

The World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (WHO 2017) included updated criteria for diagnosis and classification of post-transplant lymphoproliferative disorders (PTLDs). This study evaluated the clinicopathologic spectrum using WHO 2017 criteria and adult PTLD patients’ outcomes over 30 years between 1987 and 2017 at Mayo Clinic (Rochester, MN). Patients were retrospectively reviewed for clinical features, outcomes, and diagnostic pathology material and classified based on WHO 2017 criteria. A total of 227 patients were diagnosed with PTLD, with a median time from transplant to PTLD of 45 months. PTLD occurred >1 year after transplant in 149 (66%) patients. Monomorphic PTLD was the most common subtype (173, 76%), with diffuse large B cell lymphoma as the commonest morphology (n = 137). Epstein-Barr virus was positive in 61% of total cases and 90% of PTLD that developed within 1 year from transplant. The median event-free survival (EFS) and overall survival for the entire cohort were 21 months (95% confidence interval [CI]: 9–35) and 82 months (95% CI: 39–115), respectively. The EFS or overall survival was not impacted by Epstein-Barr virus status but differed based on WHO subtypes and year of diagnosis. Management changed over time with increased use of rituximab or chemotherapy + immunosuppression reduction as initial therapy. When compared to the matched general population and de novo diffuse large B cell lymphoma, patients not achieving EFS 24 status (no progression/treatment or death within 24 mo of diagnosis) had a worse standardized mortality ratio 16.75 (95% CI: 13.91–20) versus SMR 1.72 (95% CI: 1.26–2.28) in those who achieved EFS24. Cause of death was mostly attributed to non-lymphoma–related causes in those achieving EFS 24.