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1.
Clin Transplant ; 38(2): e15259, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38375952

RESUMO

BACKGROUND: Guidelines recommend kidney transplant alone (KTA) in compensated cirrhosis based on a few small studies, but this is not widely performed despite its potential benefit to patients and the organ supply. Our aim was to determine the outcomes of KTA in patients with compensated cirrhosis. STUDY DESIGN: From 1/2012 to 12/2021, outcomes in KTA recipients with compensated cirrhosis were retrospectively compared to patients with chronic liver disease (CLD) but no cirrhosis. Patients with compensated cirrhosis were also compared to a matched cohort (based on age, time on hemodialysis, sex, and ethnicity) of KTA recipients without CLD. The outcomes included patient survival, allograft failure, allograft rejection, serious infection, liver decompensation, and length of stay (LOS). RESULTS: Over 9 years, 1562 KTAs were performed, with 150 (9.6%) patients having CLD mostly due to chronic hepatitis C, and a median follow-up of 3.5 years. 32/150 (21%) had compensated cirrhosis at the time of KTA with a mean MELD-Na of 22 (1.5). Matched controls (n = 189) were identified. We found no differences in patient survival (p = .07), allograft failure (p = .6), allograft rejection (p = .43), rates of serious infection (p = .31), as well as LOS (p = .61) among patients with compensated cirrhosis compared to patients with CLD but no cirrhosis, but with higher rates of liver decompensation (p = .004). Similarly, compared to patients without CLD, patients with cirrhosis had similar rates of patient survival (p = .20), allograft failure (p = .27), allograft rejection (p = .62) and LOS (p = .19) but with higher rates of serious infections (p = .001). CONCLUSIONS: Our study supports the safety and efficacy of KTA in patients with compensated cirrhosis.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Estudos de Casos e Controles , Estudos Retrospectivos , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Transplante Homólogo
2.
Clin Gastroenterol Hepatol ; 21(10): 2578-2587.e11, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36610497

RESUMO

BACKGROUND & AIMS: Genetic variants affecting liver disease risk vary among racial and ethnic groups. Hispanics/Latinos in the United States have a high prevalence of PNPLA3 I148M, which increases liver disease risk, and a low prevalence of HSD17B13 predicted loss-of-function (pLoF) variants, which reduce risk. Less is known about the prevalence of liver disease-associated variants among Hispanic/Latino subpopulations defined by country of origin and genetic ancestry. We evaluated the prevalence of HSD17B13 pLoF variants and PNPLA3 I148M, and their associations with quantitative liver phenotypes in Hispanic/Latino participants from an electronic health record-linked biobank in New York City. METHODS: This study included 8739 adult Hispanic/Latino participants of the BioMe biobank with genotyping and exome sequencing data. We estimated the prevalence of Hispanic/Latino individuals harboring HSD17B13 and PNPLA3 variants, stratified by genetic ancestry, and performed association analyses between variants and liver enzymes and Fibrosis-4 (FIB-4) scores. RESULTS: Individuals with ancestry from Ecuador and Mexico had the lowest frequency of HSD17B13 pLoF variants (10%/7%) and the highest frequency of PNPLA3 I148M (54%/65%). These ancestry groups had the highest outpatient alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and the largest proportion of individuals with a FIB-4 score greater than 2.67. HSD17B13 pLoF variants were associated with reduced ALT level (P = .002), AST level (P < .001), and FIB-4 score (P = .045). PNPLA3 I148M was associated with increased ALT level, AST level, and FIB-4 score (P < .001 for all). HSD17B13 pLoF variants mitigated the increase in ALT conferred by PNPLA3 I148M (P = .006). CONCLUSIONS: Variation in HSD17B13 and PNPLA3 variants across genetic ancestry groups may contribute to differential risk for liver fibrosis among Hispanic/Latino individuals.


Assuntos
Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Humanos , Predisposição Genética para Doença , Hispânico ou Latino/genética , Cirrose Hepática/enzimologia , Cirrose Hepática/genética , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo Único
3.
Am J Gastroenterol ; 117(12): 1990-1998, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35853462

RESUMO

INTRODUCTION: In the published studies of early liver transplantation (LT) for alcohol-associated hepatitis (AH), patients with a prior liver decompensation are excluded. The appropriateness of this criteria is unknown. METHODS: Among 6 American Consortium of Early Liver Transplantation for Alcohol-Associated Hepatitis sites, we included consecutive early LT for clinically diagnosed AH between 2007 and 2020. Patients were stratified as first vs prior history of liver decompensation, with the latter defined as a diagnosis of ascites, hepatic encephalopathy, variceal bleeding, or jaundice, and evidence of alcohol use after this event. Adjusted Cox regression assessed the association of first (vs prior) decompensation with post-LT mortality and harmful (i.e., any binge and/or frequent) alcohol use. RESULTS: A total of 241 LT recipients (210 first vs 31 prior decompensation) were included: median age 43 vs 38 years ( P = 0.23), Model for End-Stage Liver Disease Sodium score of 39 vs 39 ( P = 0.98), and follow-up after LT 2.3 vs 1.7 years ( P = 0.08). Unadjusted 1- and 3-year survival among first vs prior decompensation was 93% (95% confidence interval [CI] 89%-96%) vs 86% (95% CI 66%-94%) and 85% (95% CI 79%-90%) vs 78% (95% CI 57%-89%). Prior (vs first) decompensation was associated with higher adjusted post-LT mortality (adjusted hazard ratio 2.72, 95% CI 1.61-4.59) and harmful alcohol use (adjusted hazard ratio 1.77, 95% CI 1.07-2.94). DISCUSSION: Prior liver decompensation was associated with higher risk of post-LT mortality and harmful alcohol use. These results are a preliminary safety signal and validate first decompensation as a criterion for consideration in early LT for AH patients. However, the high 3-year survival suggests a survival benefit for early LT and the need for larger studies to refine this criterion. These results suggest that prior liver decompensation is a risk factor, but not an absolute contraindication to early LT.


Assuntos
Doença Hepática Terminal , Varizes Esofágicas e Gástricas , Hepatite Alcoólica , Transplante de Fígado , Humanos , Adulto , Doença Hepática Terminal/cirurgia , Hemorragia Gastrointestinal , Índice de Gravidade de Doença , Hepatite Alcoólica/cirurgia , Estudos Retrospectivos
5.
Hepatol Commun ; 8(9)2024 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-39167426

RESUMO

BACKGROUND: Severe alcohol-associated hepatitis (AH) that is nonresponsive to corticosteroids is associated with high mortality, particularly with concomitant acute-on-chronic liver failure (ACLF). Most patients will not be candidates for liver transplantation (LT) and their outcomes are largely unknown. Our aim was to determine the outcomes of these declined candidates and to derive practical prediction models for transplant-free survival applicable at the time of the waitlist decision. METHODS: We analyzed a database of patients with severe AH who were hospitalized at a LT center from January 2012 to July 2021, using the National Death Index for those lacking follow-up. Clinical variables were analyzed based on the endpoints of mortality at 30, 60, 90, and 180 days. Logistic and Cox regression analyses were used for model derivation. RESULTS: Over 9.5 years, 206 patients with severe AH were declined for LT, mostly for unfavorable psychosocial profiles, with a mean MELD of 33 (±8), and 61% with ACLF. Over a median follow-up of 521 (17.5-1368) days, 58% (119/206) died at a median of 21 (9-124) days. Of 32 variables, only age added prognostic value to MELD and ACLF grade. CLIF-C ACLF score and 2 new models, MELD-Age and ACLF-Age, had similar predictability (AUROC: 0.73, 0.73, 0.72, respectively), outperforming Lille and Maddrey's (AUROC: 0.63, 0.62). In internal cross-validation, the average AUROC was 0.74. ACLF grade ≥2, MELD score >35, and age >45 years were useful cutoffs for predicting increased 90-day mortality from waitlist decision. Only two patients initially declined for LT for AH subsequently underwent LT (1%). CONCLUSIONS: Patients with severe AH declined for LT have high short-term mortality and rare rates of subsequent LT. Age added to MELD or ACLF grade enhances survival prediction at the time of waitlist decision in patients with severe AH declined for LT.


Assuntos
Insuficiência Hepática Crônica Agudizada , Hepatite Alcoólica , Transplante de Fígado , Índice de Gravidade de Doença , Listas de Espera , Humanos , Masculino , Transplante de Fígado/mortalidade , Hepatite Alcoólica/mortalidade , Hepatite Alcoólica/cirurgia , Hepatite Alcoólica/complicações , Feminino , Pessoa de Meia-Idade , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/cirurgia , Listas de Espera/mortalidade , Adulto , Fatores Etários , Estudos Retrospectivos , Seleção de Pacientes , Prognóstico
6.
Clin Liver Dis ; 25(3): 493-516, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34229836

RESUMO

Alcoholic hepatitis (AH) is a clinical syndrome of jaundice, abdominal pain, and anorexia due to prolonged heavy alcohol intake, and is associated with alterations in gene expression, cytokines, immune response, and the gut microbiome. Currently, we have limited biomarkers to diagnose and prognosticate in AH, but there are many novel noninvasive biomarkers under development. We evaluate the currently used algorithms to risk-stratify in AH (such as the Maddrey modified discriminant function), and discuss novel biomarkers in development, such as breath biomarkers, microRNAs, cytokeratin-18 fragments, and the AshTest. We also review the characteristics of an ideal biomarker in AH.


Assuntos
Microbioma Gastrointestinal , Hepatite Alcoólica , MicroRNAs , Biomarcadores , Hepatite Alcoólica/diagnóstico , Humanos , MicroRNAs/genética
7.
Hepatol Commun ; 5(7): 1151-1155, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34533000

RESUMO

Experts have forewarned about the coronavirus disease 2019 (COVID-19) pandemic environment fomenting the rising incidence of alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). We performed a cross-sectional study of ALD at our liver transplantation (LT) center, located in the initial U.S. epicenter, New York City. Centered around the "stay at home" order date in New York state, March 22, 2020, we defined three time periods: "pre-COVID" (January 1, 2020-March 21, 2020), "COVID-quarantine" (March 22, 2020-April 22, 2020), and "declining-COVID" (April 23, 2020-August 25, 2020). We found a 62% increase in interhospital patient transfers for ALD from pre-COVID (20 of 93, 21%) to the declining-COVID period (43 of 127, 34%). Our inpatient liver census with ALD also increased: 38% pre-COVID, 45% COVID-quarantine, and 49% declining-COVID. Among 30 patients with severe alcoholic hepatitis (AH) not responding to medical therapy since March 22, 2020, 9 underwent early LT for AH (16% of the total number of early LT during our 8-year program). Three of 9 early-LT recipients reported specific COVID-related stressors. All 25 previous LT recipients with established abstinence pre-COVID maintained abstinence at follow-up visits during the declining-COVID period. Of the 6 recipients with sustained alcohol use within 6 months before March 22, 2020, half regained abstinence during the declining-COVID period. Our findings help confirm the predictions of rising AUD and ALD as an immediate consequence of the COVID-19 pandemic. This aftershock particularly affected ethnically diverse patients with ALD with high inpatient mortality, reflecting the disproportionate impact of COVID-19 on underserved and minority populations. Alcohol relapse did not occur in long-term early LT for AH recipients during the time of COVID-19. This lends further support to AH being a viable indication for LT, with recipients able to demonstrate ongoing resilience in the face of this unprecedented universal stressor.

8.
Hepatol Commun ; 5(2): 177-188, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33230491

RESUMO

Liver injury is commonly seen in coronavirus disease 2019 (COVID-19); however, the mechanism behind liver injury, particularly in patients with severe and critical COVID-19, remains unclear, and the clinical course is poorly described. We conducted a single-center retrospective cohort study of consecutive patients hospitalized with severe and critical COVID-19 with or without liver injury and who underwent immunologic testing (interleukin [IL]-6, IL-8, tumor necrosis factor alpha [TNF-α], and IL-1ß). Liver injury was defined as peak aminotransferases ≥3 times the upper limit of normal (40 U/L) or ≥120 U/L. Patients with liver injury were compared to those who had normal aminotransferases throughout the hospital course. We studied 176 patients: 109 with liver injury and 67 controls. Patients with liver injury were more likely to be men (71.6% vs. 37.3%, P < 0.001). Peak inflammatory markers and IL-6 were higher in the liver injury group: C-reactive protein (CRP), 247 vs. 168 mg/L, P < 0.001; lactate dehydrogenase (LDH), 706 vs. 421 U/L; ferritin, 2,973 vs. 751 ng/mL, P < 0.001; IL-6, 121.0 vs. 71.8 pg/mL, P < 0.001. There was no difference in the levels of IL-8, TNF-α, and IL-1ß. The liver injury group had a longer length of stay in the hospital and more severe COVID-19 despite having less diabetes and chronic kidney disease. Conclusion: An exaggerated hyperinflammatory response (cytokine storm) characterized by significantly elevated CRP, LDH, ferritin, and IL-6 levels and increasing severity of COVID-19 appears to be associated with the occurrence of liver injury in patients with severe/critical COVID-19.

9.
Gastroenterol Hepatol (N Y) ; 16(12): 617-625, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34035697

RESUMO

Cigarette smoking is the leading cause of preventable disease and death in the United States, causing approximately 480,000 deaths per year, which is equivalent to 1 in 5 deaths being attributable to tobacco use. The adverse effects of cigarette smoking on the lungs and cardiovascular system are well described; however, the detrimental effects of smoking on the liver are not as well defined. Smoking affects the liver via 3 separate mechanisms: toxic (both direct and indirect), immunologic, and oncogenic. There is an emerging body of evidence of an association between cigarette smoking and progression of fibrosis in chronic liver diseases such as nonalcoholic fatty liver disease and primary biliary cholangitis. Smoking is associated with accelerated development of hepatocellular carcinoma in patients with chronic hepatitis B or C virus infection. Tobacco smoking adversely affects lung function, which increases physical limitations and may preclude liver transplantation. Following liver transplantation, smoking is associated with several adverse outcomes, including increased risk of de novo malignancy, vascular complications, and nongraft-associated mortality. The respiratory illness caused by the novel coronavirus disease 2019 serves as a good example of the complex interplay between the lungs and the liver. It is evident that cigarette smoking has important negative effects on a multitude of liver diseases and that patients' smoking cessation must be prioritized. The data are limited, and more research is needed to better understand how smoking affects the liver. This article summarizes what is known about the pathologic effects of cigarette smoking on common liver diseases.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31453368

RESUMO

AIM: Hepatitis C virus (HCV) is the leading cause of hepatocellular carcinoma (HCC) in the United States. Achieving sustained viral response with interferon (IFN) treatment reduces the risk from 3%-5% to 0.5%-1% annually. Several studies reported unexpectedly high rates of HCC after treatment with direct-acting antivirals (DAAs). The aim of our study was to compare HCC rates in DAA-, IFN-treated and untreated populations. METHODS: A literature search was conducted using ScienceDirect, Ovid®, Web of Science and MEDLINE through January 2019. Studies were included if they measured rates of de novo or recurrent HCC (following curative treatment) in HCV-infected persons. We included 138 studies (n = 177,512). Simple pooling of data and meta-analysis were performed, using the random effects method. RESULTS: Mean age was higher in the DAA-treated vs. IFN-treated group (58.4 years vs. 52.6 years; P = 0.0073), as were diabetes prevalence (34.5% vs. 11.7%; P ≤ 0.001) and incident cirrhosis (47.8% vs. 34.2%, P = 0.0017). The incidence rate of de novo HCC was 2.01/100 person-years (py) (95%CI: 1.38, 2.67) in the DAA group and 1.45/100py (95%CI: 0.98, 1.94) in the IFN-treated group. HCC recurred at 16.76/100py (95%CI: 10.75, 22.91) in the DAA-treated group vs. 20.04/100py (95%CI: 2.58, 45.21) after IFN. After adjusting for factors such as age and cirrhosis, the hazard ratio was 0.58 (95%CI: 0.20, 1.07) for HCC occurrence and 0.59 (95%CI: 0.24, 1.03) for HCC recurrence after DAA treatment compared to IFN-based treatment. CONCLUSION: We did not find evidence for increased rates of HCC in DAA-treated compared with IFN-treated patients. Compared to those treated with IFN, older patients with additional risk factors for HCC were treated with DAAs. This imbalance appears to explain the higher numerical incidence of HCC among DAA-treated patients.

11.
Rheum Dis Clin North Am ; 44(4): 675-698, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30274630

RESUMO

Autoimmune kidney diseases triggered by viruses are an important cause of kidney disease in patients affected by chronic viral infection. Hepatitis B virus (HBV) infection is associated with membranous nephropathy and polyarteritis nodosa. Hepatitis C virus (HCV) infection is a major cause of cryoglobulinemic glomerulonephritis. Patients with human immunodeficiency virus (HIV) may develop HIV-associated nephropathy, a form of collapsing focal segmental glomerulosclerosis, or various forms of immune-complex-mediated kidney diseases. This article summarizes what is known about the pathogenesis, diagnosis, and management of immune-mediated kidney diseases in adults with chronic HBV, HCV, and HIV infections.


Assuntos
Nefropatias , Viroses , Autoimunidade , Gerenciamento Clínico , Humanos , Nefropatias/diagnóstico , Nefropatias/etiologia , Nefropatias/imunologia , Nefropatias/prevenção & controle , Viroses/classificação , Viroses/complicações , Viroses/imunologia
12.
Hemodial Int ; 22 Suppl 1: S81-S96, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29694729

RESUMO

Cryoglobulinemia is a common extrahepatic manifestation of infection with hepatitis C virus (HCV). When signs and symptoms of systemic vasculitis or glomerulonephritis occur in the presence of circulating cryoglobulins, this syndrome is called "mixed cryoglobulinemia syndrome" (MCS). Historically, interferon-based therapies in HCV have been associated with lower rates of viral cure in patients with MCS than in the general HCV-infected population. The advent of direct-acting antiviral therapies have revolutionized the treatment of HCV, dramatically increasing rates of cure. Early studies of first-generation protease inhibitors (telaprevir and boceprevir) in combination with interferon and ribavirin demonstrated HCV cure rates of 67% and complete clinical response rates of vasculitis symptoms in 60% of patients with MCS; however, regimens were poorly tolerated by patients, 22% discontinued treatment early. More recently, all-oral, interferon-free regimens have become available and combination therapies are now being approved for patients with and without renal impairment. Patients with HCV-MCS achieved sustained virologic response in 297 out of 313 patients (95%) treated with direct-acting antiviral therapy, and 85% had a complete or partial clinical response of MCS symptoms. Current direct-acting antiviral therapies are well tolerated in patients with HCV-MCS and only 1.6% discontinued treatment early. Patients with cryoglobulinemic glomerulonephritis also had an excellent cure rate (94%). The majority improved; 17/52 (33%) experienced full remission and 15/52 (29%) experienced partial remission. There were no reports of worsening kidney function in patients treated with direct-acting antiviral therapies. Less than 5% of patients with HCV-MCS treated with IFN-free direct-acting antiviral therapy required immunosuppression. However, patients with severe vasculitis appear to still require concomitant immunosuppression.


Assuntos
Antivirais/uso terapêutico , Crioglobulinemia/etiologia , Glomerulonefrite/etiologia , Hepacivirus/patogenicidade , Hepatite C/terapia , Antivirais/farmacologia , Crioglobulinemia/patologia , Crioglobulinemia/terapia , Glomerulonefrite/patologia , Glomerulonefrite/terapia , Hepatite C/patologia , Humanos
13.
Hepatol Commun ; 2(5): 529-545, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29761169

RESUMO

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease projected to become the leading cause of cirrhosis and liver transplantation in the next decade. Cenicriviroc (CVC), a dual chemokine receptor 2 and 5 antagonist, prevents macrophage trafficking and is under clinical investigation for the treatment of human NASH fibrosis. We assessed the efficacy and durability of short and prolonged CVC therapy in a diet-induced mouse model of NASH, the choline deficient, L-amino acid-defined, high-fat diet (CDAHFD) model. C57BL/6 mice received 4 or 14 weeks of standard chow or the CDAHFD. CVC (10 mg/kg/day and 30 mg/kg/day for 4 weeks and 20 mg/kg/day and 30 mg/kg/day for 14 weeks) was initiated simultaneously with the CDAHFD. At 4 and 14 weeks, livers were harvested for histology and flow cytometric analyses of intrahepatic immune cells. High-dose CVC (30 mg/kg/day) therapy in CDAHFD mice for 4 or 14 weeks inhibited intrahepatic accumulation of Ly6Chigh bone marrow-derived macrophages. Prolonged CVC therapy (14 weeks) yielded no significant differences in the total intrahepatic macrophage populations among treatment groups but increased the frequency of intrahepatic anti-inflammatory macrophages in the high-dose CVC group. Despite ongoing steatohepatitis, there was significantly less fibrosis in CDAHFD mice receiving high-dose CVC for 14 weeks based on histologic and molecular markers, mirroring observations in human NASH CVC trials. CVC also directly inhibited the profibrotic gene signature of transforming growth factor-ß-stimulated primary mouse hepatic stellate cells in vitro. Conclusion: CVC is a novel therapeutic agent that is associated with reduced fibrosis despite ongoing steatohepatitis. Its ability to alter intrahepatic macrophage populations and inhibit profibrogenic genes in hepatic stellate cells in NASH livers may contribute to its observed antifibrotic effect. (Hepatology Communications 2018;2:529-545).

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