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.

Achieving the Sustained Virologic Response With a Short-Course Treatment of Sofosbuvir/Velpatasvir.

Hepatitis C, a single-stranded RNA virus officially discovered in 1989, is one of the most known viruses of the Flaviviridae family. Direct-acting antiviral drugs helped revolutionize the management of hepatitis C infection by guaranteeing higher cure rates. The medical field has strived to optimize the management of this disease, with recent reports proposing a shorter treatment duration to achieve the sustained virologic response (SVR). We present a case of a patient diagnosed with hepatitis C decompensated liver cirrhosis who achieved the SVR after only two weeks of treatment with sofosbuvir/velpatasvir, suggesting that short-term therapy might be beneficial for these patients.

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.

Opioid Avoidance in Liver Transplant Recipients: Reduction in Postoperative Opioid Use Through a Multidisciplinary Multimodal Approach.

The prevalence of substance use disorder in the liver transplantation (LT) population makes postoperative pain management challenging. We report our initial experience with a novel, comprehensive, multidisciplinary opioid avoidance pathway in 13 LT recipients between January 2018 and September 2019. Patients received comprehensive pre-LT education on postoperative opioid avoidance by the surgeon, pharmacist, and psychologist at the time of listing. Immediately after LT, patients received a continuous incisional ropivacaine infusion, ketamine, acetaminophen, and gabapentin as standard nonopioid medications; rescue opioids were used as needed. We compared outcomes with a historical cohort of 27 LT recipients transplanted between August 2016 and January 2018 managed primarily with opioids. On average, opioid avoidance patients used 92% fewer median (interquartile range [IQR]) morphine milligram equivalents (MMEs) versus the historical cohort (7 [1-11] versus 87 [60-130] MME; P < 0.001) per postoperative day over a similar length of stay (8 [7-10] versus 6 [6-10] days; P = 0.14). Fewer outpatient MMEs were prescribed within the first 60 days after LT in the opioid avoidance group versus the historical cohort: 125 (25-150) versus 270 (0-463) MME (P = 0.05). This proof-of-concept study outlines the potential to profoundly reduce opioid utilization in the LT population using a comprehensive multidisciplinary approach.

Drug and herbal/dietary supplements-induced liver injury: A tertiary care center experience.

BACKGROUND: Drug-induced liver injury (DILI) and herbal/dietary supplements (HDS) related liver injury present unique diagnostic challenges. Collaboration between the clinician and the pathologist is required for an accurate diagnosis and management. AIM: To report our experience on the clinical-pathological findings of hepatic injury caused by drugs/HDS. METHODS: A retrospective review of clinically proven cases of DILI/HDS who presented to our institution from January 1, 2013 to December 31, 2017 was performed. Slides were reviewed for histopathological patterns of injury and correlated with the causative agent. Out of 600 patients presenting with unexplained rise in liver enzymes undergoing biopsy, 107 were suspected to have DILI/HDS. Of these, 53 had a directly linked exposure to drug/herbal supplements. Fifteen patients were excluded for concurrent known liver disease. Thirty-eight patients with clinically proven DILI/HDS were finally included. RESULTS: Thirty-eight cases of DILI/HDS with a male:female of 1:1.5 and mean age of 51 ± 3 years were identified. DILI was identified in 84.2% cases while HDS injury in 15.8%. Acute hepatitis (42.1%) was the most common pattern of injury while granulomatous hepatitis (2.6%) was the least common. We found one case of acute-cholestasis due to rivaroxaban and two cases of cholestatic-hepatitis due to rizatriptan and trimethobenzamide-hydrochloride that, to the best of our knowledge, have not been previously reported. One case of steatohepatitis due to trimethoprim-sulfamethoxazole and three unusual cases of cholestatic-hepatitis with bile duct injury and steatosis due to dronedarone, C4-Extreme and hydroxycut, were also seen. Of our cohort, 81.6% of the patients fared well with discontinuation of drug and 18.4% underwent transplant; of which 42.9% were deceased. CONCLUSION: We describe the clinical findings, histopathological patterns of injury and clinical outcomes caused by drugs. In particular, we report a few previously unreported/ rarely observed clinical and histopathological patterns of hepatic injury.

Mycophenolate mofetil monotherapy in liver transplant recipients.

INTRODUCTION: Complete conversion of calcineurin inhibitor (CNI) immunosuppressant therapy to non-nephrotoxic agents such as mycophenolate mofetil (MMF) is controversial, but may be safe in selected patients, although appropriate protocols and long-term benefits of conversion are not well reported. METHODS: We analyzed all liver transplant (LT) recipients at our institution who were converted from CNI-based therapy to MMF monotherapy because of renal dysfunction (n = 23) and compared them with patients remaining on CNI-based therapy (n = 23). Renal function, rejection episodes, and markers of CNI-related comorbidities (lipid profile, blood pressure, and glycosylated hemoglobin) were noted. RESULTS: Overall, serum creatinine (SCr) and calculated glomerular filtration rate improved on MMF monotherapy. This improvement was significant when compared with patients who remained on CNI-based therapy. Improvement was most pronounced in patients with milder renal dysfunction (SCr <2.2 mg/dL prior to conversion) (n = 14) with decrease in SCr from 1.63 ± 0.29 to 1.34 ± 0.26 mg/dL (p = 0.02) at last follow-up. Five patients on MMF monotherapy (21.7%) progressed to end-stage renal disease (ESRD), while only two (8.7%) had rejection episodes following conversion. Clinical markers of CNI-related comorbidities also improved. MMF monotherapy was well tolerated. CONCLUSION: In summary, our data support the safety and efficacy of CNI to MMF monotherapy conversion.

Cerebral magnetic resonance imaging reveals marked abnormalities of brain tissue density in patients with cirrhosis without overt hepatic encephalopathy.

BACKGROUND & AIMS: We applied advanced magnetic resonance imaging and Voxed based Morphometry analysis to assess brain tissue density in patients with cirrhosis. METHODS: Forty eight patients with cirrhosis without overt hepatic encephalopathy (17 Child A, 13 Child B, and 18 Child C) and 51 healthy subjects were matched for age and sex. Seventeen patients had history of overt hepatic encephalopathy, eight of them had minimal hepatic encephalopathy at inclusion, 10 other patients had minimal hepatic encephalopathy at inclusion but without history of previous overt hepatic encephalopathy, and 21 patients had none of these features. RESULTS: Patients with cirrhosis presented decreased brain density in many areas of the grey and white matter. The extension and size of the affected areas were greater in patients with alcoholic cirrhosis than in those with post-hepatitic cirrhosis and correlated directly with the degree of liver failure and cerebral dysfunction (as estimated by neuropsychological tests and the antecedent of overt hepatic encephalopathy). Twelve additional patients with cirrhosis who underwent liver transplantation were explored after a median time of 11months (7-50months) after liver transplant. At the time of liver transplantation, three patients belonged to class A of the Child-Pugh classification, five to class B and four to class C. Compared to healthy subjects, liver transplant patients showed areas of reduced brain density in both grey and white matter. CONCLUSIONS: These results indicate that loss of brain tissue density is common in cirrhosis, progresses during the course of the disease, is greater in patients with history of hepatic encephalopathy, and persists after liver transplantation. The significance, physiopathology, and clinical relevance of this abnormality cannot be ascertained from the current study.

Impact of preoperative overt hepatic encephalopathy on neurocognitive function after liver transplantation.

In the current Model for End-Stage Liver Disease allocation system, patients are at risk of suffering repeated episodes of hepatic encephalopathy (HE) while waiting for an orthotopic liver transplantation (OLT); the posttransplantation impact of these episodes has not been well explored. We evaluated the cognitive function and quality of life in a group of OLT recipients (n = 25) who had suffered from overt HE prior to their procedure (HE-PreLT group) and compared their performance to that of a similar group of patients (n = 14) without overt HE (No HE-PreLT group) as well as to controls. Patients were selected from a cohort of 280 patients who underwent OLT during this period; the presence of clinical confounders excluded many of the remaining subjects. Demographic and clinical characteristics were balanced among groups. At an average of 18 months after OLT, we administered 2 neuropsychological batteries [Psychometric Hepatic Encephalopathy Score (PHES) test battery and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)]; a pyschophysiological test (critical flicker frequency); and the SF-36 quality of life score. The HE-PreLT group scored below controls in 5 of 6 cognitive domains tested by RBANS, 3 of 6 PHES subtests, as well as the critical flicker frequency test. The No HE-PreLT group scored below the controls in 1 of the 6 cognitive domains tested by RBANS. The more severe neurocognitive abnormalities seen in the HE-PreLT group did not appear to affect quality of life, as lower values than normative data were only found in 1 of the 8 SF-36 scales. In conclusion, neurocognitive abnormalities were more severe in liver transplant recipients that had suffered from overt HE prior to OLT. Prospective studies of neurocognitive function pre-OLT and post-OLT are needed to fully determine the impact of such abnormalities.

Serum enzymes associated with cholestasis.

Alkaline phosphatase, gamma-glutamyl transferase, and 5' nucleotidase are the most common enzymes used in the evaluation of cholestasis. The present knowledge of these enzymes including their function, activity measurement, biologic variables of enzyme activity in healthy persons and disease states, and clinical significance are reviewed. Usefulness of enzymes patterns for diagnosis of specific cholestatic disorders and future directions in evaluation of cholestasis are also discussed.