Epidemiology and Management of Infections in Liver Transplant Recipients.

Background: Improvements in liver transplant (LT) outcomes are attributed to advances in surgical techniques, use of potent immunosuppressants, and rigorous pre-LT testing. Despite these improvements, post-LT infections remain the most common complication in this population. Bacteria constitute the most common infectious agents, while fungal and viral infections are also frequently encountered. Multi-drug-resistant bacterial infections develop because of polymicrobial overuse and prolonged hospital stays. Immediate post-LT infections are commonly caused by viruses. Conclusions: Appropriate vaccination, screening of both donor and recipients before LT and antiviral prophylaxis in high-risk individuals are recommended. Antimicrobial drug resistance is common in high-risk LT and associated with poor outcomes; epidemiology and management of these cases is discussed. Additionally, we also discuss the effect of coronavirus disease 2019 (COVID-19) infection and monkeypox in the LT population.

Banff 2022 Liver Group Meeting report: Monitoring long-term allograft health.

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participants included hepatologists, surgeons, pathologists, immunologists, and histocompatibility specialists. Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimization, and long-term structural changes. Potential revision of the rejection classification scheme to better accommodate and communicate late T cell-mediated rejection patterns and related structural changes, such as nodular regenerative hyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression to match the heterogeneity of patient settings will be central to improving long-term patient survival. Such personalized therapeutics are in turn contingent on a better understanding and monitoring of allograft status within a rational decision-making approach, likely to be facilitated in implementation with emerging decision-support tools. Proposed revisions to rejection classification emerging from the meeting include the incorporation of interface hepatitis and fibrosis staging. These will be opened to online testing, modified accordingly, and subject to consensus discussion leading up to the next Banff conference.

Radiological and pathological assessment with EOB-MRI after Y90 radiation lobectomy prior to liver resection for hepatocellular carcinoma.

BACKGROUND: Radiation lobectomy (RL) utilizes Yttrium-90 (Y90) radioembolization for achieving tumor control and inducing contralateral lobe hypertrophy. Our objective was to evaluate the chronological changes occurring radiologically and histopathologically after Y90 RL. METHODS: We retrospectively reviewed 22 patients with chronic liver disease who underwent Y90 RL prior to planned liver resection for hepatocellular carcinoma. Gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (EOB-MRI) was performed every 3 months. RESULTS: Future liver remnant volume (FLRV) significantly increased up to 9 months after Y90 RL. Gd-EOB-DTPA uptake in the treated lobe experienced a 40% reduction in enhancement ratio (ER) during ensuing first 3 months, and never recovered. The reduced ER in the non-tumoral parenchyma was significantly correlated with increased FLRV and FLR (r = 0.41 and r = 0.35, respectively; both p < 0.01). Histopathological evaluation of non-tumor liver tissue found features of sinusoidal obstruction syndrome as an early change after Y90 RL (median 5.7 months) and parenchymal collapse as a late change (mean 11 months). DISCUSSION: The reduced uptake of Gd-EOB-DTPA at 3 months post Y90 RL correlates with a significant increase in FLRV prior to liver resection. EOB-MRI evaluation at 3 months can guide future plan of action after Y90 RL.

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.

Noninvasive imaging assessment of portal hypertension.

Portal hypertension (PH) is a spectrum of complications of chronic liver disease (CLD) and cirrhosis, with manifestations including ascites, gastroesophageal varices, splenomegaly, hypersplenism, hepatic hydrothorax, hepatorenal syndrome, hepatopulmonary syndrome and portopulmonary hypertension. PH can vary in severity and is diagnosed via invasive hepatic venous pressure gradient measurement (HVPG), which is considered the reference standard. Accurate diagnosis of PH and assessment of severity are highly relevant as patients with clinically significant portal hypertension (CSPH) are at higher risk for developing acute variceal bleeding and mortality. In this review, we discuss current and upcoming noninvasive imaging methods for diagnosis and assessment of severity of PH.

A review of the use of transient elastography in the assessment of fibrosis and steatosis in the post-liver transplant patient.

Liver biopsy is considered the gold standard method for diagnosing and staging liver disease, particularly in the post-liver transplant setting. Given the invasive nature of biopsy, alternate means for accurately assessing liver fibrosis and steatosis are preferred especially as the number of patients with fatty liver disease is increasing. Transient elastography has been validated as a useful tool for evaluation of liver fibrosis, as has controlled attenuation parameter index as a tool for assessing steatosis. It is a non-invasive, rapid, and highly reproducible approach to demonstrate the presence of fibrosis among non-transplant patients with chronic liver disease of various etiologies. However, it has not yet found wide acceptance in liver transplant recipients. There are few published studies evaluating the merits and applicability of transient elastography to assess allografts after liver transplantation. We review the published data on the use of transient elastography with concurrent controlled attenuation parameter in liver transplant recipients and recommend its greater use to follow allograft function over time.

Histological assessment of the liver explant in transplanted hepatitis C virus patients achieving sustained virological response with direct-acting antiviral agents.

AIMS: The use of direct-acting anti-viral agents (DAAs) has resulted in extremely high sustained virological response (SVR) rates in patients being treated while on liver transplantation (LT) waiting lists. The aim of this study was to evaluate the histological findings of hepatitis C virus (HCV) patients who achieved SVR after receiving DAA treatment [SVR(+)] prior to LT, and compare them with HCV patients who had not achieved SVR [SVR(-)]. METHODS AND RESULTS: Fifty-eight adult HCV patients who underwent LT at our institution from 2014 to 2016 were included in the study. Two pathologists, blinded to SVR status, simultaneously evaluated the histological sections. Assessment included the Histology Activity Index (HAI/modified Knodell score), fibrosis stage (Ishak score), and Laennec cirrhosis stage. The study group comprised 25 SVR(+) patients (56% male; mean age, 63.8 years), and the control group comprised 33 SVR(-) patients (69% male; mean age, 61.7 years). There was no significant difference in HAI between the groups (P = 0.414). Patients who achieved SVR also did not show less portal inflammation (P = 0.787), interface hepatitis (P = 0.999), confluent necrosis (P = 0.627) or spotty necrosis (P = 0.093) than the control group. There was a trend towards a higher degree of inflammation in patients who achieved SVR in <24 weeks (P = 0.07). The degree of focal lytic necrosis/apoptosis and portal inflammation was more prominent in SVR(+) patients with shorter SVR-LT intervals. CONCLUSIONS: Our study is the first to report persistent inflammation in HCV patients who received DAAs prior to LT. This supports the notion that inflammation is immunologically driven and that inflammation persists despite the absence of virus.

Primary sclerosing cholangitis: detailed histologic assessment and integration using bioinformatics highlights arterial fibrointimal hyperplasia as a novel feature.

OBJECTIVES: Liver biopsy diagnosis of primary sclerosing cholangitis (PSC) is difficult. We performed a detailed histologic analysis of PSC cases using novel bioinformatics analysis to identify histologic features that may be useful in its diagnosis. METHODS: PSC liver explants were examined and compared with primary biliary cirrhosis and hepatitis C explants to act as controls. Demographic, macroscopic, and histologic variables were analyzed using both conventional statistics and an integrative bioinformatics approach, significance analysis of microarrays (SAM), and hierarchical clustering analysis (HCA). RESULTS: The PSC group was younger and had distinctive PSC features, including bile duct scars, onion-skin fibrosis, and arterial fibrointimal hyperplasia. SAM allowed the integration of variables by comparing PSC and control groups, whereas HCA was able to correctly categorize each group. CONCLUSIONS: This study demonstrates characteristic PSC histology as well as arterial hyperplasia to be distinctive features that may aid in PSC diagnosis and be confirmed by bioinformatics.

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.

Costs of telaprevir-based triple therapy for hepatitis C: $189,000 per sustained virological response.

UNLABELLED: In registration trials, triple therapy with telaprevir (TVR), pegylated interferon (Peg-IFN), and ribavirin (RBV) achieved sustained virological response (SVR) rates between 64% and 75%, but the clinical effectiveness and economic burdens of this treatment in real-world practice remain to be determined. Records of 147 patients who initiated TVR-based triple therapy at the Mount Sinai Medical Center (May-December 2011) were reviewed. Direct medical costs for pretreatment, on-treatment, and posttreatment care were calculated using data from Medicare reimbursement databases, RED Book, and the Healthcare Cost and Utilization Project database. Costs are presented in 2012 U.S. dollars. SVR (undetectable hepatitis C virus [HCV] RNA 24 weeks after the end of treatment) was determined on an intention-to-treat basis. Cost per SVR was calculated by dividing the median cost by the SVR rate. Median age of the 147 patients was 56 years (interquartile range [IQR] = 51-61), 68% were male, 19% were black, 11% had human immunodeficiency virus/HCV coinfection, 36% had advanced fibrosis/cirrhosis (FIB-4 scores ≥3.25), and 44% achieved an SVR. The total cost of care was $11.56 million. Median cost of care was $83,721 per patient (IQR = $66,652-$98,102). The median cost per SVR was $189,338 (IQR = $150,735-$221,860). Total costs were TVR (61%), IFN (24%), RBV (4%), adverse event management (8%), professional fees (2%), and laboratory tests (1%). CONCLUSIONS: TVR and Peg-IFN accounted for 85% of costs. Pharmaceutical prices and the low (44%) SVR rate, in this real-world study, were major contributors to the high cost per SVR.

Transplant tourism.

PURPOSE OF REVIEW: Because of the ongoing organ donor shortage, transplant tourism is occurring at an increasing rate both in the USA and abroad. To date, there have been little published data to help guide the programmatic philosophy of the USA transplant centers regarding transplant tourism. RECENT FINDINGS: We summarize position statements from several transplant societies regarding transplant tourism and specifically transplantation occurring in China (because of the use of executed prisoners as organ donors). Transplant tourism is ever increasing and patients may be at risk for greater post-transplant morbidity as well as inadequate follow up care. Transplant centers require some guidance with regard of how to deal with these patients. SUMMARY: Transplant tourism is an increasing reality facing the USA transplant centers. Most professional societies do not condone it yet cannot abrogate a physician's right to care for such patients. Ethical principles mandate transplant physicians provide adequate care for returning transplant tourists. Better ways of assessing the scope of the problem are necessary. Transplant tourism may exist because of the disparity between the need for organ donors and their availability and is thus is likely to continue into the future.

Transplant tourism in China: a tale of two transplants.

The use of organs obtained from executed prisoners in China has recently been condemned by every major transplant organization. The government of the People's Republic of China has also recently made it illegal to provide transplant organs from executed prisoners to foreigners transplant tourists. Nevertheless, the extreme shortage of transplant organs in the U.S. continues to make organ transplantation in China an appealing option for some patients with end-stage disease. Their choice of traveling to China for an organ leaves U.S. transplant programs with decisions about how to respond to the needs of patients who return after transplantation. By discussing two cases that raised this dilemma, we argue for upholding medicine's commitments to traditional principles of beneficence and nonjudgmental regard in sorting out the policies that a transplant program should adopt. We also explain how position statements that aim for the high ground of moral purity fail to give appropriate weight to the needs and suffering of present and future patients in the U.S. and in China.

Adult live donor liver transplantation.

The increasing awareness of liver diseases and their early detection have led to an increase in the number of transplant waiting list candidates over the past decade. This need has not been matched by the actual number of orthotopic liver transplantations performed. Live donor liver transplantation (LDLT) is an innovative surgical technique intended to expand the available organ donor pool. Although LDLT offers definite advantages to the recipient, it offers none to the donor except for the possibility of psychological well-being. Clinical research studies aimed at the prospective collection of data for donors and recipients need to be conducted.

Treating chronic hepatitis C in the primary care setting.

The National Institutes of Health and other institutions have emphasized the need to expand access to treatment of chronic hepatitis C virus infection to a larger and more diverse patient population. To begin to address this need, the divisions of General Internal Medicine and Liver Diseases of the Mount Sinai Medical Center created a program to identify patients who might benefit from hepatitis C treatment, to treat uncomplicated patients in the primary care setting, and to refer appropriate patients to liver disease specialists. Preliminary data from this program suggest that primary care-based treatment of chronic hepatitis C may offer unique advantages. The primary care setting allows special needs to be addressed and allows comprehensive services to be provided. Patients are guided through the complex pretreatment evaluation process, and non-liver-related comorbidities are managed. Our program may provide a useful model for increasing hepatitis C literacy among primary care providers and for extending treatment to a broader population of patients with hepatitis C.

Quality of life after lobectomy for adult liver transplantation.

INTRODUCTION: Adult-to-adult living donor liver transplants are being increasingly performed. Although considerable data are available on the quality of life after kidney donation, there is little comparable information on liver donors. METHODS: Between August 1998 and July 2000, 48 adults received liver grafts from living donors. At least 2 months after donation, donors were mailed a structured questionnaire and the standardized Medical Outcomes Study Short-Form Health Survey (SF-36), a generic measure assessing health-related quality of life outcomes using eight scales: mental health, emotional limits, vitality, social function, physical function, physical limits, pain, general health. RESULTS: Thirty donors (62.5%) responded at a mean of 280+/-157 days after donation. Fifteen (50%) of their recipients had major complications (two deaths, four retransplants, nine biliary complications). Regarding overall satisfaction, all said they would donate again. Compared to published U.S. norms (n=2474), our group of donors scored higher than the general population in seven of eight domains on the SF-36. Donors whose recipients had no complications scored significantly higher in mental health (P<0.007) and general health (P<0.008) compared with U.S. norms. Donors whose recipients had major complications scored significantly lower on the mental health scale than those with recipients without major complications. CONCLUSIONS: Donors did not regret their decision to donate; several felt the experience had changed their lives for the better. Donors scored as well as or better than U.S. norms in general health. Quality of life after donation must remain a primary outcome measure when we consider the utility of living-donor liver transplants.