Use of hepatitis B viremic donors in kidney transplant recipients: A single center experience.

Utilization of Hepatitis B virus (HBV)-infected kidney allografts represents an opportunity to bridge the gap between organ supply and demand. Highly efficacious vaccines and antiviral therapies allow these allografts to be transplanted with negligible risk to the recipient. The purpose of this study was to describe the prophylactic strategies and related clinical outcomes of kidney transplant recipients who received a kidney from an HBV viremic donor. Eight patients received an allograft from an HBV viremic deceased kidney donor between January 1, 2017 and December 4, 2020. All recipients were immune to hepatitis B with a surface antibody titer greater than or equal to 10 mIU/ml (range: 12 - > 1000 mIU/ml). After transplant, 62.5% demonstrated HBV core antibody seroconversion at an average of 47.4 ± 28.5 days post-transplant. Anti-viral prophylaxis was initiated in 87.5% of patients; 62.5% preemptively during the transplant admission (range 1-3 days post-transplant) and 25% following HBcAb seroconversion (range 45-304 days post-transplant). Of the four patients who were started on entecavir preemptively, two subsequently core converted. These two patients had an HBV surface antibody less than 100 mIU/ml at the time of transplant. None of the recipients converted to HBV surface antigen positivity. The average estimated glomerular filtration rate was 41 ± 19 ml/min/1.73m2 , and there were no significant elevations in liver enzymes through one year post-transplant. The use of HBV viremic kidney allografts may represent an additional source of transplant organs; however, more studies are needed to better elucidate the optimal protective strategies for these recipients.

Evaluation of a multimodal analgesic regimen on outcomes following laparoscopic living donor nephrectomy.

Postoperative pain is a significant source of morbidity in patients undergoing living donor nephrectomy (LDN) and a deterrent for candidates. We implemented a standardized multimodal analgesic regimen, which consists of pharmacist-led pre-procedure pain management education, a combination transversus abdominis plane and rectus sheath block performed by the regional anesthesia team, scheduled acetaminophen and gabapentin, and as-needed opioids. This single-center retrospective study evaluated outcomes between patients undergoing LDN who received a multimodal analgesic regimen and a historical cohort. The multimodal cohort had a significantly shorter length of stay (LOS) (days, mean ± SD: 1.8 ± 0.7 vs. 2.6 ± 0.8; p < .001) and a greater proportion who were discharged on postoperative day (POD) 1 (38.6% vs. 1.5%; p < .001). The total morphine milligram equivalents (MME) that patients received during hospitalization were significantly less in the multimodal cohort on POD 0-2. The outpatient MME prescribed through POD 60 was also significantly less in the multimodal cohort (median [IQR]; 180 [150-188] vs. 225 [150-300]; p < .001). The mean patient-reported pain score (PRPS) was significantly lower in the multimodal cohort on POD 0-2. The maximum PRPS was significantly lower on POD 0 (mean ± SD: 7 ± 2 vs. 8 ± 1, respectively; p = .02). This study suggests that our multimodal regimen significantly reduces LOS, PRPS, and opioid requirements and has the potential to improve the donation experience.

Initial experience of bamlanivimab monotherapy use in solid organ transplant recipients.

The widespread transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to propagate the coronavirus disease 2019 (COVID-19) pandemic with solid organ transplant (SOT) recipients being an exceptionally vulnerable population for poor outcomes. Treatments for COVID-19 are limited; however, monoclonal antibodies are emerging as a potential therapeutic option to change the trajectory of high-risk patients. This retrospective single center cohort study evaluated the outcomes of SOT recipients with mild to moderate COVID-19 who received bamlanivimab monotherapy. Eighteen SOT recipients (15 kidney, 2 liver, and 1 heart) received the medication between November 9, 2020 and February 10, 2021 with no reported infusion reactions. One patient experienced headache and fatigue following the infusion that resolved within 3 days. Fourteen patients continued their recovery as an outpatient with no further escalation in care. Three patients required hospitalization: two for suspected bacterial pneumonia 9 and 32 days postinfusion, respectively, and one for acute kidney injury 7 days postinfusion. One patient had an emergency room visit for gastrointestinal symptoms 24 days postinfusion. In this small cohort of SOT recipients, bamlanivimab monotherapy appeared to be a well-tolerated option for treatment of mild to moderate COVID-19, but it was not completely effective in preventing hospitalization. One month following the end of this cohort, COVID-19 treatment guidance changed due to the rising prevalence of resistant variants. For this reason, bamlanivimab is now recommended to be used only in combination with etesevimab. Further studies are needed to fully elucidate the role of this therapy in SOT recipients.

Longterm Impact of Living Liver Donation: A Self-Report of the Donation Experience.

Outcomes for adult-to-adult living liver donors (LDs) are largely based on short-term data drawn from single-center studies. The aim of this study was to determine how living liver donation (LLD) impacts self-reported quality-of-life (QOL) up to 6 years after donation in a sample of residents from New York State. New York transplant programs are state-mandated to track LDs as part of a quality assurance and patient safety effort. Donor-reported QOL within 1 year of donation and longitudinal data over a 10-year period were analyzed. Self-reported surveys include the following domains: employment, finances, health/life insurance, activities of daily living, physical/emotional health, donor experience, relationships, and LD opinions. There were 220 LDs in New York (2004-2013) who completed a survey over the 10-year period with many donors completing surveys at several points in time. Overall, longterm LDs remain as comfortable about LLD as they were during the first year after donation (95%). The majority of LDs reported feeling as well as before LLD (72%). At 1 year after donation, 60% of subjects self-reported medical problems, and 30% reported emotional issues. However, the majority reported that they would willingly donate again. In conclusion, LDs remain satisfied with their decision to donate over time. A minority of LDs report longterm medical and emotional issues. The conclusions provide information for educational interventions to improve informed choice to those considering donation.

Disparities in Liver Transplantation for Nonalcoholic Steatohepatitis in Women.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is the fastest-growing indication for liver transplantation (LT). Sex disparities among patients with cirrhosis on the LT waitlist are well known. We wanted to understand these disparities further in women with end-stage liver disease patients listed for NASH cirrhosis in a contemporary cohort. METHODS: We used data from the Scientific Registry of Transplant Recipients to assess sex racial, and ethnic differences in NASH patients listed for LT. Adults transplanted from August 1997 to June 2021 were included. Inferential statistics were used to evaluate differences with univariate and multivariate comparisons, including competitive risk analysis. RESULTS: During the study time period, we evaluated 12 844 LT for NASH cirrhosis. Women were transplanted at a lower rate (46.5% versus 53.5%; P < 0.001) and higher model for end-stage liver disease (MELD) (23.8 versus 22.6; P < 0.001) than men. Non-White women were transplanted at a higher MELD (26.1 versus 23.1; P < 0.001) than White women and non-White male patients (26.1 versus 24.8; P < 0.001). Graft and patient survivals were significantly different (P < 0.001) between non-White women and White women and men (White and non-White). CONCLUSIONS: Evaluation of LT candidates in the United States demonstrates women with NASH cirrhosis have a higher MELD than men at LT. Additional disparities exist among non-White women with NASH as they have higher MELD and creatinine at LT compared with White women. After LT, non-White women have worse graft and patient survival compared with men or White women. These data indicate that non-White women with NASH are the most vulnerable on the LT waitlist.

Non-Lung Solid Organ Transplantation From SARS-CoV-2-Positive Donors to Uninfected Recipients.

BACKGROUND: There is a paucity of evidence on the risk of donor-recipient transmission of the SARS-CoV-2 in solid organ transplant recipients. Initial impressions suggest non-lung solid organs may be safely transplanted from SARS-CoV-2-positive donors without risk of viral transmission. METHODS: We reviewed clinical results of transplants in which SARS-CoV-2-negative recipients received non-lung solid organs from SARS-CoV-2-positive donors at a single transplant center. No prisoners were used in this study, and participants were neither coerced nor paid. The manuscript was created in compliance with the Helsinki Congress and the Declaration of Istanbul. RESULTS: Between June 2021 and January 2023, we transplanted 26 solid organs, including 13 kidneys, 8 livers, 3 hearts, and 1 simultaneous heart and kidney, from 23 SARS-CoV-2-positive donors into 25 SARS-CoV-2 negative recipients. Two of the recipients had a positive SARS-CoV-2 real-time polymerase chain reaction after transplantation, but otherwise, patients had no SARS-CoV-2-related complications, and all patients to date are alive with excellent allograft function. CONCLUSION: Transplantation of non-lung solid organs from SARS-CoV-2-positive donors into uninfected recipients can be safely performed without adverse effects from SARS-CoV-2.

Short- and Long-Term Outcomes for Ethnic Minorities in the United States After Liver Transplantation: Parsing the Hispanic Paradox.

BACKGROUND: Racial and ethnic minorities are disproportionally affected by end-stage liver disease. Unfortunately, disparities in referrals to liver transplantation (LT), organ allocation, and posttransplant outcomes exist in this population. METHODS: We performed a retrospective analysis of patients over the age of 18 years undergoing LT in the United States using the Scientific Registry of Transplant Recipients from 2002 to 2016. We evaluated factors associated with patient and graft outcomes and explored the effect of race and ethnicity along with social variables. RESULTS: During the study time period, 78,999 patients received LT. Of these, 60,102 were non-Hispanic White (NHW), 7988 were African American (AA), and 10,909 were Hispanic. AA had significantly lower patient survival, graft survival, and death-censored graft survival at both 1 and 5 years when compared to NHW. Conversely, at 1 and 5 years, patient survival and graft survival were significantly higher for Hispanics compared to NWH. In addition, AA had significantly lower survival outcomes compared to Hispanics. On multivariate analysis after controlling for race/ethnicity, age, AA race, diagnosis, and deceased donor were independent risk factors for patient death and graft failure. CONCLUSIONS: Despite socioeconomic disadvantages seen among Hispanics, this population appears to have improved short- and long-term survival after LT compared to NHW and AA.

New ways: the pandemics of science fiction.

In unprecedented times, people have turned to fiction both for comfort and for distraction, but also to try and understand and anticipate what might come next. Sales and rental figures for works of fiction about pandemics and other disease outbreaks surged in 2020, but what can pandemic science fiction tell us about disease? This article surveys the long history of science fiction's engagement with disease and demonstrates the ways in which these narratives, whether in literature or film, have always had more to say about other contemporary cultural concerns than the disease themselves. Nonetheless, the ideas demonstrated in these texts can be seen perpetuating through the science fiction genre, and in our current crisis, we have seen striking similarities between the behaviours of key individuals, and the manner in which certain events have played out. Not because science fiction predicts these things, but because it anticipates the social structures which produce them (while at the same time permeating the culture to the extent that they become the touchstones with which the media choose to analyse current events). This paper demonstrates that science fiction can be a valuable tool to communicate widely around a pandemic, while also acting as a creative space in which to anticipate how we may handle similar events in the future.

Assessment of hepatocellular carcinoma using apparent diffusion coefficient and diffusion kurtosis indices: preliminary experience in fresh liver explants.

OBJECTIVES: The objective was to perform ex vivo evaluation of non-Gaussian diffusion kurtosis imaging (DKI) for assessment of hepatocellular carcinoma (HCC), including presence of treatment-related necrosis, using fresh liver explants. METHODS: Twelve liver explants underwent 1.5-T magnetic resonance imaging using a DKI sequence with maximal b-value of 2000 s/mm(2). A standard monoexponential fit was used to calculate apparent diffusion coefficient (ADC), and a non-Gaussian kurtosis fit was used to calculate K, a measure of excess kurtosis of diffusion, and D, a corrected diffusion coefficient accounting for this non-Gaussian behavior. The mean value of these parameters was measured for 16 HCCs based upon histologic findings. For each metric, HCC-to-liver contrast was calculated, and coefficient of variation (CV) was computed for voxels within the lesion as an indicator of heterogeneity. A single hepatopathologist determined HCC necrosis and cellularity. RESULTS: The 16 HCCs demonstrated intermediate-to-substantial excess diffusional kurtosis, and mean corrected diffusion coefficient D was 23% greater than mean ADC (P=.002). HCC-to-liver contrast and CV of HCC were greater for K than ADC or D, although these differences were significant only for CV of HCCs (P≤.046). ADC, D and K all showed significant differences between non-, partially and completely necrotic HCCs (P≤.004). Among seven nonnecrotic HCCs, cellularity showed a strong inverse correlation with ADC (r=-0.80), a weaker inverse correlation with D (-0.24) and a direct correlation with K (r=0.48). CONCLUSIONS: We observed non-Gaussian diffusion behavior for HCCs ex vivo; this DKI model may have added value in HCC characterization in comparison with a standard monoexponential model of diffusion-weighted imaging.

Liver transplant for mixed capillary-cavernous hemangioma masquerading as hepatocellular carcinoma in a patient with hepatocellular carcinoma.

Hemangioma is the most common benign tumor of the liver. Unlike cavernous hemangioma, hepatic capillary or mixed capillary-cavernous hemangioma is a rare type of tumor in adults. Clinical presentation of hemangioma may mimic that of hepatocellular carcinoma. Furthermore, radiologic features on computed tomography and magnetic resonance imaging may not be typical for hemangioma and can be confused with hepatocellular carcinoma. Symptomatic hemangiomas require some form of treatment, such as corticosteroids, interferon, radiation, arterial embolization, surgical resection, or liver transplant. In the present case study, we present a patient treated with liver transplant for hemangioma mimicking hepatocellular carcinoma. This case report illustrates the atypical imaging appearance of hemangioma and possible confusion it can cause in diagnosing hepatocellular carcinoma, especially in a hepatitis C carrier.

Identification of hepatocytic and bile ductular cell lineages and candidate stem cells in bipolar ductular reactions in cirrhotic human liver.

Hepatocyte function and regeneration are severely compromised in severe liver disease, and a common sequela is cirrhosis. Structural changes caused by cirrhosis create a cellular environment conducive to the formation of ductular reactions (DRs). Ductular reactions are primarily composed of oval cells also known as "intermediate hepatobiliary cells". We have conducted single, double, and triple staining to study lineages of oval cells present in DRs. Staining with NCAM, CK19, and HepPar1 has revealed a distinctly bipolar structure to DRs that are embedded in cirrhotic tissue. Spatial analysis of cells that are singly HepPar1-positive, or CK19-positive, has revealed hepatocytic and biliary poles, respectively, in the DRs. Also, the location of singly NCAM-positive cells in DRs suggests that they may be bipotent liver stem/progenitor cells. The locations of other intermediate hepatobiliary cells, which have combinations of markers, suggest that CK19+/NCAM+ cells are transitional cells in the biliary lineage and that rare cells that are negative for all three markers are transitional cells in the hepatocytic lineage. A working cell lineage model for DRs is presented.

Dose- and time-dependent oval cell reaction in acetaminophen-induced murine liver injury.

We examined the response of murine oval cells, that is, the putative liver progenitor cells, to acetaminophen. Female C57BL/6J mice were injected intraperitoneally with varying doses of N-acetyl-paraaminophen (APAP) (250, 500, 750, and 1,000 mg/kg of weight) and sacrificed at 3, 6, 9, 24, and 48 hours. In preliminary studies, we showed that anticytokeratin antibodies detected A6-positive cells with a sensitivity and specificity of greater than 99%. The oval cell reaction was quantified, on immunostaining for biliary-type cytokeratins, as both number and density of oval cells per portal tract, analyzed by size of portal tract. Acetaminophen injury was followed by periportal oval cell accumulation displaying a moderate degree of morphological homogeneity. Oval cell response was biphasic, not temporally correlating with the single wave of injury seen histologically. Increases in oval cells were largely confined to the smallest portal tracts, in keeping with their primary derivation from the canals of Hering, and increased in a dose-dependent fashion. The timing of the two peaks of the oval cell reaction also changed with increasing dose, the first becoming earlier and the second later. In conclusion, our studies indicate a marked oval cell activation during the height of hepatic injury. Oval cells appear to be resistant to acetaminophen injury. The close fidelity of mechanism and histology of acetaminophen injury between mouse and human livers makes it a useful model for investigating liver regeneration and the participation of stem/progenitor cells in that process.

Scirrhous changes in dysplastic nodules do not indicate high-grade status.

BACKGROUND AND AIMS: Dysplastic nodules (DN) may be divided into high-grade and low-grade, and the former has been known as a precancerous or borderline lesion. Recently many morphological characteristics concerning these types of DN have been reported. In the present study we attempted to evaluate the scirrhous change in DN as an indicative feature of high-grade DN, based on the morphological and cell-kinetic analyses using immunohistochemical stains for Ki-67. METHODS: We reviewed 35 livers with DN and selected 15 DN with scirrhous change. We stained DN-bearing sections of each case with hematoxylin and eosin, trichrome, reticulin and Perls' stain. We tried to subclassify and characterize the scirrhous change according to the fibrosis pattern. We also stained with Ki-67 immunohistochemically to assess the proliferative activity of DN with scirrhous change. RESULTS: We found two types of scirrhous change, that is, pericellular and stellate. The pericellular type was related to the Mallory body-forming cholestatic degeneration, whereas the stellate type was associated with extensive portal fibrosis probably induced by ischemic damage. Among DN with scirrhous change, high-grade DN comprised five nodules (33%) and there were 10 (67%) low-grade nodules. There was no significant relationship between the presence or the types of scirrhous change and the grade of DN. The significant differences of Ki-67 labeling indices between types of scirrhous change were not shown in this study. We also could not find the differences between Ki-67 labeling indices of scirrhous DN (high and low grades) and those of surrounding regenerative nodules. CONCLUSIONS: This evidence indicated that the scirrhous change in DN was not a specific feature of high-grade DN. We also found that scirrhous DN have two morphological varieties that may represent biologically different processes, that is, pericellular scirrhous type and stellate scirrhous type.

Defining intrahepatic biliary anatomy in living liver transplant donor candidates at mangafodipir trisodium-enhanced MR cholangiography versus conventional T2-weighted MR cholangiography.

PURPOSE: To compare three-dimensional (3D) mangafodipir trisodium-enhanced T1-weighted magnetic resonance (MR) cholangiography with conventional T2-weighted MR cholangiography for depiction and definition of intrahepatic biliary anatomy in liver transplant donor candidates. MATERIALS AND METHODS: One hundred eight healthy liver transplant donor candidates were examined with two MR cholangiographic methods. All candidates gave written informed consent, and the study was approved by the institutional review board. First, breath-hold transverse and coronal half-Fourier single-shot turbo spin-echo and breath-hold oblique coronal heavily T2-weighted turbo spin-echo sequences were performed. Second, mangafodipir trisodium-enhanced breath-hold fat-suppressed 3D gradient-echo sequences were performed through the ducts (oblique coronal plane) and through the entire liver (transverse plane). Interpretation of biliary anatomy findings, particularly variants affecting right liver lobe biliary drainage, and degree of interpretation confidence at both 3D mangafodipir trisodium-enhanced MR cholangiography and T2-weighted MR cholangiography were recorded and compared by using the Wilcoxon signed rank test. Then, consensus interpretations of both MR image sets together were performed. Intraoperative cholangiography was the reference-standard examination for 51 subjects who underwent right lobe hepatectomy. The McNemar test was used to compare the accuracies of the individual MR techniques with that of the consensus interpretation of both image sets together and to compare each technique with intraoperative cholangiography. RESULTS: Biliary anatomy was visualized with mangafodipir trisodium enhancement in all patients. Mangafodipir trisodium-enhanced image findings agreed with findings seen at combined interpretations significantly more often than did T2-weighted image findings (in 107 [99%] vs 88 [82%] of 108 donor candidates, P < .001). Confidence was significantly higher with the mangafodipir trisodium-enhanced images than with the T2-weighted images (mean confidence score, 4.5 vs 3.4; P < .001). In the 51 candidates who underwent intraoperative cholangiography, mangafodipir trisodium-enhanced imaging correctly depicted the biliary anatomy more often than did T2-weighted imaging (in 47 [92%] vs 43 [84%] donor candidates, P = .14), whereas the two MR imaging techniques combined correctly depicted the anatomy in 48 (94%) candidates. CONCLUSION: Mangafodipir trisodium-enhanced 3D MR cholangiography depicts intrahepatic biliary anatomy, especially right duct variants, more accurately than does conventional T2-weighted MR cholangiography.

Liver transplant donor candidates: associations between vascular and biliary anatomic variants.

Our objective was to investigate the coexistence of vascular and biliary anatomic variants, the latter of which are known to increase the risk of biliary complications in living liver donor transplantation. A total of 108 consecutive liver donor candidates were examined by magnetic resonance (MR) imaging that included 2 MR cholangiography methods, T2-weighted MR cholangiography and mangofodipir-enhanced T1-weighted three-dimensional (3D) MR cholangiography, as well as gadolinium-enhanced MR angiography and venography of the liver. Images were interpreted by at least 2 investigators in consensus for definition of hepatic arterial, portal venous, and biliary anatomy. A subset of 51 subjects underwent laparotomy for right hepatectomy. Of the 108 subjects examined, 50 (46%) demonstrated normal hepatic artery, portal vein, and biliary anatomy. Variants of the hepatic artery were found in 27 of 108 (25%) subjects, of the portal vein in 12 of 108 (11%) subjects, and of the bile ducts in 30 of 108 (28%) subjects. Of the 27 subjects with hepatic arterial variants, 8 (30%) also had variant biliary anatomy. The association between hepatic arterial variants and biliary variants was not statistically significant (P >.5). However, of the 12 subjects with portal vein variants, 7 (58%) had biliary variants, and in 6 of 7 cases, the right posterior hepatic duct was anomalous. By chi-square analysis, the association between portal venous and biliary variants was significant (P =.012). In conclusion, over half of subjects with portal vein variants were found to have anomalous biliary anatomy, which always involved the hepatic ducts of the right lobe. The association between portal venous and biliary variants is statistically significant, while there is no significant association between hepatic arterial and biliary variants.

Transplantation for hepatocellular carcinoma and cirrhosis: sensitivity of magnetic resonance imaging.

The sensitivity of magnetic resonance imaging (MRI) in patients who undergo transplantation for hepatocellular carcinoma (HCC) and cirrhosis is not known. We prospectively evaluated 24 patients with known HCC who underwent MRI and subsequent transplantation within 60 days (mean, 20 days). Using a phased-array coil at 1.5T, breath-hold turbo STIR and T2-weighted MR images were performed. Dynamic gadolinium-enhanced MRI was performed using a two- or three-dimensional gradient echo pulse sequence with images obtained in the hepatic arterial, portal venous, and equilibrium phases. The prospective interpretation of the MR study was directly compared with thin-section pathology evaluation of the explanted livers. All 24 patients had at least one HCC, and MR diagnosed tumor in 21 (88%) of these patients. On a lesion-by-lesion basis, MRI depicted 39 of 118 HCC for an overall sensitivity of 33%. MRI detected five (100%) of five lesions >5 cm, 20 (100%) of 20 lesions >2 cm but not exceeding 5 cm, 11 (52%) of 21 lesions between 1 and 2 cm, and three (4%) of 72 lesions <1 cm. Of the nine patients with carcinomatosis (innumerable lesions less than 1 cm), MR detected three lesions in one patient. Of the 15 dysplastic nodules found at pathology, MRI depicted a single 1.8-cm high-grade lesion, for a sensitivity of 7%. In conclusion, MRI is sensitive for the detection of HCC measuring at least 2 cm in diameter but is insensitive for the diagnosis of small HCC (<2 cm) and carcinomatosis.