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1.
Medicine (Baltimore) ; 100(26): e26436, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190166

RESUMO

ABSTRACT: Bariatric surgery has been reported to improve non-alcoholic steatohepatitis (NASH), which is a frequent comorbidity in morbidly obese patients. We performed a retrospective cohort study to estimate the therapeutic effect of sleeve gastrectomy (SG), the most common bariatric surgery in Japan, on obese patients with NASH by comparing the findings of paired liver biopsies.Eleven patients who underwent laparoscopic SG for the treatment of morbid obesity, defined as body mass index (BMI) > 35 kg/m2, from March 2015 to June 2019 at Hiroshima University Hospital, Japan, were enrolled. All patients were diagnosed with NASH by liver biopsy before or during SG and were re-examined with a second liver biopsy 1 year after SG. The clinical and histological characteristics were retrospectively analyzed.One year after SG, body weight and BMI were significantly reduced, with median reductions in body weight and BMI of-22 kg and -7.9 kg/m2, respectively. Body fat was also significantly reduced at a median of 13.7%. Liver-related enzymes were also significantly improved. On re-examination by paired liver biopsy, liver steatosis improved in 9 of the 11 patients (81.8%), ruling out of the pathological diagnosis of NASH. However, fibrosis stage did not significantly improve 1 year after SG. The non-alcoholic fatty liver disease activity score was significantly reduced in 10 of 11 patients (90.9%).Pathological improvement or remission of NASH could be achieved in most morbidly obese Japanese patients 1 year after SG.


Assuntos
Cirurgia Bariátrica/métodos , Gastrectomia/métodos , Testes de Função Hepática/métodos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Biópsia/métodos , Índice de Massa Corporal , Feminino , Humanos , Japão/epidemiologia , Laparoscopia/métodos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/complicações , Obesidade Mórbida/diagnóstico , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Indução de Remissão , Tempo
2.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072586

RESUMO

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports on the effects on mice of being fed a CDAHFD for long periods of 1 to 3 months. However, the effect of this diet over a short period is unknown. Therefore, we examined the effect of 1-week CDAHFD feeding on the mouse liver. Feeding a CDAHFD diet for only 1-week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis or cirrhosis. Additionally, it was demonstrated that CDAHFD significantly impaired mitochondrial respiration with severe oxidative stress to the liver, which is associated with a decreasing mitochondrial DNA copy number and complex proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that 1 week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of NASH in humans.


Assuntos
Deficiência de Colina/complicações , Dieta Hiperlipídica/efeitos adversos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo , Animais , Biomarcadores , Modelos Animais de Doenças , Suscetibilidade a Doenças , Gluconeogênese , Mediadores da Inflamação/metabolismo , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos , Lipogênese , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos , Hepatopatia Gordurosa não Alcoólica/patologia , Fenótipo
3.
Int J Mol Sci ; 22(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071064

RESUMO

More than 250 million people are living with chronic hepatitis B despite the availability of highly effective vaccines and oral antivirals. Although innate and adaptive immune cells play crucial roles in controlling hepatitis B virus (HBV) infection, they are also accountable for inflammation and subsequently cause liver pathologies. During the initial phase of HBV infection, innate immunity is triggered leading to antiviral cytokines production, followed by activation and intrahepatic recruitment of the adaptive immune system resulting in successful virus elimination. In chronic HBV infection, significant alterations in both innate and adaptive immunity including expansion of regulatory cells, overexpression of co-inhibitory receptors, presence of abundant inflammatory mediators, and modifications in immune cell derived exosome release and function occurs, which overpower antiviral response leading to persistent viral infection and subsequent immune pathologies associated with disease progression towards fibrosis, cirrhosis, and hepatocellular carcinoma. In this review, we discuss the current knowledge of innate and adaptive immune cells transformations that are associated with immunopathogenesis and disease outcome in CHB patients.


Assuntos
Imunidade Adaptativa , Hepatite B Crônica/imunologia , Imunidade Inata , Linfócitos B Reguladores/imunologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/imunologia , Células Dendríticas/imunologia , Progressão da Doença , Exossomos/imunologia , Anticorpos Anti-Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Humanos , Células Matadoras Naturais/imunologia , Cirrose Hepática/etiologia , Cirrose Hepática/imunologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Células Supressoras Mieloides/imunologia , Receptores Imunológicos/imunologia , Receptores de Células Matadoras Naturais/imunologia , Linfócitos T Reguladores/imunologia
4.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071962

RESUMO

Alcoholic liver disease (ALD) is a globally prevalent chronic liver disease caused by chronic or binge consumption of alcohol. The liver is the major organ that metabolizes alcohol; therefore, it is particularly sensitive to alcohol intake. Metabolites and byproducts generated during alcohol metabolism cause liver damage, leading to ALD via several mechanisms, such as impairing lipid metabolism, intensifying inflammatory reactions, and inducing fibrosis. Despite the severity of ALD, the development of novel treatments has been hampered by the lack of animal models that fully mimic human ALD. To overcome the current limitations of ALD studies and therapy development, it is necessary to understand the molecular mechanisms underlying alcohol-induced liver injury. Hence, to provide insights into the progression of ALD, this review examines previous studies conducted on alcohol metabolism in the liver. There is a particular focus on the occurrence of ALD caused by hepatotoxicity originating from alcohol metabolism.


Assuntos
Etanol/metabolismo , Inativação Metabólica , Fígado/metabolismo , Animais , Suscetibilidade a Doenças , Hepatócitos/metabolismo , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunomodulação , Metabolismo dos Lipídeos , Fígado/imunologia , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Redes e Vias Metabólicas , Oxirredução , Espécies Reativas de Oxigênio , Sensibilidade e Especificidade
5.
Nutrients ; 13(5)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065978

RESUMO

Non-alcoholic fatty liver disease impacts 15.2% of Hispanic adolescents and can progress to a build-up of scared tissue called liver fibrosis. If diagnosed early, liver fibrosis may be reversible, so it is necessary to understand risk factors. The aims of this study in 59 Hispanic adolescents with obesity were to: (1) identify potential biological predictors of liver fibrosis and dietary components that influence liver fibrosis, and (2) determine if the association between dietary components and liver fibrosis differs by PNPLA3 genotype, which is highly prevalent in Hispanic adolescents and associated with elevated liver fat. We examined liver fat and fibrosis, genotyped for PNPLA3 gene, and assessed diet via 24-h diet recalls. The prevalence of increased fibrosis was 20.9% greater in males, whereas participants with the GG genotype showed 23.7% greater prevalence. Arachidonic acid was associated with liver fibrosis after accounting for sex, genotype, and liver fat (ß = 0.072, p = 0.033). Intakes of several dietary types of unsaturated fat have different associations with liver fibrosis by PNPLA3 genotype after accounting for sex, caloric intake, and liver fat. These included monounsaturated fat (ßCC/CG = -0.0007, ßGG = 0.03, p-value = 0.004), polyunsaturated fat (ßCC/CG = -0.01, ßGG = 0.02, p-value = 0.01), and omega-6 (ßCC/CG = -0.0102, ßGG = 0.028, p-value = 0.01). Results from this study suggest that reduction of arachidonic acid and polyunsaturated fatty acid intake might be important for the prevention of non-alcoholic fatty liver disease progression, especially among those with PNPLA3 risk alleles.


Assuntos
Ácido Araquidônico/efeitos adversos , Gorduras Insaturadas na Dieta/efeitos adversos , Hispano-Americanos/genética , Lipase/genética , Cirrose Hepática/etiologia , Proteínas de Membrana/genética , Obesidade Pediátrica/genética , Adiposidade , Adolescente , Criança , Feminino , Genótipo , Hispano-Americanos/estatística & dados numéricos , Humanos , Cirrose Hepática/genética , Masculino , Obesidade Pediátrica/complicações , Obesidade Pediátrica/metabolismo , Obesidade Pediátrica/patologia
6.
Aliment Pharmacol Ther ; 54(1): 68-77, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33975381

RESUMO

BACKGROUND: Variants in multiple genetic loci modify the risk of non-alcoholic fatty liver disease (NAFLD) and cirrhosis but there are limited data on the quantitative impact of variant copies on liver fibrosis. AIM: To investigate the effect of PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13 genotype on liver fibrosis assessed by magnetic resonance elastography (MRE), a reproducible, accurate, continuous biomarker of liver fibrosis. METHODS: This is a cross-sectional analysis derived from a well-characterised cohort at risk for NAFLD who underwent genotyping and MRE assessment. Liver stiffness (LS) was estimated using MRE and advanced fibrosis was defined as liver stiffness ≥3.63 kilopascals (kPa). Univariable and multivariable linear and logistic regression analysis, were used to assess the association between genotype and MRE. RESULTS: Two hundred sixty-four patients (63% women) with a mean age 53 (±17) years, and 31% Hispanic ethnicity with genotyping and MRE were included. The odds of advanced fibrosis were 3.1 (95% CI: 1.1-8.9, P = 0.04) for CG and 6.5 (95% CI: 2.2-18.9, P < 0.01) for GG compared to CC PNPLA3 genotype. Each PNPLA3 risk variant copy was associated with 0.40 kPa (95% CI: 0.19-0.61, P < 0.01) increase in LS on MRE in analysis adjusted for age, sex and BMI and there was significant genotype-age interaction (P < 0.01). Conversely, the protective TA allele in HSD17B13 was associated with a -0.41 kPa (95% CI: -0.76 to -0.05, P = 0.03) decrease in liver stiffness on MRE multivariable analysis. CONCLUSION: Knowledge of PNPLA3 and HSD17B13 genotype may assist in the non-invasive risk stratification of NAFLD with closer monitoring recommended for those with high genetic risk.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Estudos Transversais , Feminino , Fibrose , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia
7.
Nihon Yakurigaku Zasshi ; 156(3): 152-156, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33952843

RESUMO

Non-alcoholic steatohepatitis (NASH) is a common risk factor for fibrosis, cirrhosis, and a predisposing factor for the development of hepatocellular carcinoma. Recently, incidence of NASH has increased due to an increase in metabolic syndrome. Connexin (Cx)32, a hepatocyte gap-junction protein, plays an important role in liver tissue homeostasis; Cx32 dominant-negative transgenic rat (Cx32ΔTg) has much decreased gap-junctional intercellular communication, and high susceptibility to carcinogens. We found for the first time that Cx32 has play suppressive roles in inflammation and fibrosis of NASH using Cx32ΔTg received methionine-choline deficient diet (MCDD). Elevation of reactive oxygen species (ROS) play important roles in progression of NASH and elimination of ROS by antioxidant luteolin inhibited NASH in the Cx32ΔTg-MCDD model. This model had histological changes similar to those of human NASH, but was not accompanied by the metabolic syndrome such as obesity and insulin resistance. Therefore, we further established an improved NASH model. Cx32ΔTg rats and wild-type rats were fed a high-fat diet (HFD) and dimethylnitrosamine to induce NASH with metabolic syndrome. The HFD and DMN increased body, liver, and visceral fat weights in both genotypes. Serum insulin level and HOMA-IR score in Cx32ΔTg rats were higher than those in wild-type rats. Elevation of serum hepatic enzymes (AST, ALT), inflammatory cytokine expressions, α-smooth muscle actin expression, progression of steatohepatitis and fibrosis were induced by HFD and dimethylnitrosamine especially in Cx32ΔTg rats. These results indicate Cx32 dysfunction promoted the development of NASH and fibrosis accompanied by metabolic syndrome through accumulation of oxidative stress.


Assuntos
Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Animais , Comunicação , Modelos Animais de Doenças , Fígado , Cirrose Hepática/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/patologia , Ratos
8.
Am J Gastroenterol ; 116(6): 1238-1247, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33852451

RESUMO

INTRODUCTION: We aimed to define the impact of the genetic background on overt hepatic encephalopathy (HE) in patients with liver cirrhosis by developing a combined clinical-genetic risk score. METHODS: Patients suffering from liver cirrhosis from the outpatient clinics of 4 hospitals (n = 600) were included and followed up for at least 5 years until HE bouts, liver transplant, or death. Patients were genotyped for 60 candidate single nucleotide polymorphisms together with the microsatellite in the promoter region of the gene GLS. RESULTS: Single nucleotide polymorphisms rs601338 (FUT2), rs5743836 (TRL9), rs2562582 (SLC1A3), rs313853 (SLC1A5), and GLS microsatellite did predict independently the incidence and severity of overt HE and were included as genetic score. Competing risk analysis revealed that bilirubin (subhazard ratio [sHR] 1.30 [1.15-1.48], P < 0.001), albumin (sHR 0.90 [0.86-0.93], P < 0.001), genetic score (sHR 1.90 [1.57-2.30], P < 0.001), and previous episodes of overt HE (sHR 2.60 [1.57-4.29], P < 0.001) were independently associated to HE bouts during the follow-up with an internal (C-index 0.83) and external validation (C-index 0.74). Patients in the low-risk group had 5% and 12% risk of HE at 1 (log-rank 92.1; P < 0.001) and 5 (log-rank 124.1; P < 0.001) years, respectively, whereas 36% and 48% in the high-risk group. DISCUSSION: The genetic background influenced overt HE risk and severity. The clinical-genetic HE Risk score, which combined genetic background together with albumin, bilirubin, and previous episodes of overt HE, could be a useful tool to predict overt HE in patients with cirrhosis.


Assuntos
Encefalopatia Hepática/genética , Cirrose Hepática/complicações , Medição de Risco/métodos , Idoso , Feminino , Genótipo , Encefalopatia Hepática/epidemiologia , Humanos , Incidência , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Espanha/epidemiologia
9.
J Food Sci ; 86(6): 2753-2765, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33928646

RESUMO

25-Hydroxylprotopanaxadiol-3ß, 12ß, 20-triol (25-OH-PPD or AD-2) belongs to dammarane ginsenoside, and is commonly obtained from the acidic hydrolysate of total ginsensides of Panax ginseng. This study investigated the potential mechanism of AD-2 toward improving thioacetamide (TAA)-induced hepatic fibrosis in mice. Mice were divided into seven groups: control group, TAA model group, TAA + AD-2 (5, 10, and 20 mg/kg) groups, TAA + silymarin (100 mg/kg) group, and TAA + Fu Fang Biejia (FFBj; 300 mg/kg) group. All mice were treated to intraperitoneal TAA injection to establish a hepatic fibrosis model, and drugs were administered orally. The mechanism and related pathways underlying the AD-2-mediated action against hepatic fibrosis were explored by Western blotting and immunohistochemical staining. After AD-2 treatment, the expression levels of Lipin-1, SREBP1, and F4/80 significantly decreased, meanwhile the protein expressions levels of IL1ß, IL1R1, IL18, Bax, Bid, Bcl-2, and cFlips also decreased. Furthermore, AD-2 inhibited RAF and MEK pathways. The results demonstrate that AD-2 can alleviate hepatic fibrosis. The mechanism is likely related to the regulation of lipid accumulation, inflammatory response, apoptosis pathway, and Raf-MEK signaling pathways, which provide a basis for clinical research for the treatment of hepatic fibrosis. PRACTICAL APPLICATION: Ginsenoside is one of the main active ingredients of ginseng, and can alleviate the symptoms of various diseases, for example, hepatic fibrosis. This paper mainly used Western blotting to explore its possible mechanism of action. The goal was to provide a reference for the development of traditional Chinese medicines for hepatic fibrosis.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Ginsenosídeos/farmacologia , Inflamação/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Tioacetamida/toxicidade , Quinases raf/metabolismo , Animais , Doença Hepática Crônica Induzida por Substâncias e Drogas/etiologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos , Panax/química , Transdução de Sinais/efeitos dos fármacos
10.
Lancet Gastroenterol Hepatol ; 6(6): 448-458, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33865507

RESUMO

BACKGROUND: In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV. METHODS: STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183. FINDINGS: Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment. INTERPRETATION: In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality. FUNDING: National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.


Assuntos
Benzimidazóis/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Sofosbuvir/uso terapêutico , Valina/análogos & derivados , Proteínas não Estruturais Virais/antagonistas & inibidores , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Coinfecção/epidemiologia , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , RNA Viral/efeitos dos fármacos , Segurança , Sofosbuvir/administração & dosagem , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Tailândia/epidemiologia , Resultado do Tratamento , Valina/administração & dosagem , Valina/efeitos adversos , Valina/uso terapêutico
11.
J Card Surg ; 36(7): 2329-2335, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33834526

RESUMO

OBJECTIVE: We investigated a relationship between a composite index comprised of Fontan-circuit anatomical features and hepatic fibrosis scores from biopsy. METHODS: We identified living extracardiac Fontan patients, ≥7 years old and ≥5 but <20 years postoperative, that underwent cardiac catheterization and transvenous liver biopsy between March 2012 and September 2020. We divided patients into anatomical groups and applied a risk score to each patient. We compared average anatomical risk scores with average hepatic total fibrosis scores by group. RESULTS: We identified 111 patients that met inclusion criteria. After excluding four patients, we assigned 107 to one of 12 anatomical variant groups (n ≥ 3). For the 107, the average age at liver biopsy was 14 ± 6 years old. Of the 107, 105 (98%) were New York Heart Association Class 1. We found average anatomical risk scores by group correlated with average total fibrosis scores by group (R = 0.8; p = .005). An average Fontan duration to biopsy of 10 ± 1 years was similar for all 12 anatomical groups. We found no other clinical variables, laboratory, or hemodynamic values that trended with anatomical risk scores or hepatic total fibrosis scores. CONCLUSIONS: In a cohort of relatively young, stable extracardiac Fontan patients, average composite anatomical risk scores strongly correlated with average hepatic total fibrosis scores by anatomical group. These findings suggest that some anatomical variants in extracardiac Fontan patients are associated with higher Fontan-associated liver disease (FALD)-related hepatic total fibrosis scores than others, despite similar Fontan durations.


Assuntos
Técnica de Fontan , Cardiopatias Congênitas , Hepatopatias , Adolescente , Adulto , Biópsia , Cateterismo Cardíaco , Criança , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/cirurgia , Humanos , Fígado , Cirrose Hepática/etiologia , Adulto Jovem
12.
Ugeskr Laeger ; 183(14)2021 04 05.
Artigo em Dinamarquês | MEDLINE | ID: mdl-33832558

RESUMO

Alcohol-related liver disease is the most common cause of cirrhosis, and patients are diagnosed at late stages of disease, with high mortality and limited treatment options. However, we have plenty of opportunities to detect alcohol-related liver disease earlier, as most patients have prior contacts with the healthcare system, as discussed in this review. Growing evidence supports algorithms of routine liver blood tests as first-line risk stratification tools, to select which patients could be referred to secondary care for accurate diagnostic testing with liver stiffness measurements or the enhanced liver fibrosis test.


Assuntos
Técnicas de Imagem por Elasticidade , Diagnóstico Precoce , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Atenção Secundária à Saúde
13.
Isr Med Assoc J ; 23(4): 223-228, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33899354

RESUMO

BACKGROUND: Point shear-wave elastography (pSWE) is a new method to assess the degree of liver fibrosis. It has been shown to be effective in detecting stiffness in viral hepatitis. OBJECTIVES: To determine the feasibility of pSWE for assessing liver stiffness and fibrosis in liver diseases of different etiologies. METHODS: This prospective single-center study included a population of adult patients with chronic liver diseases from different etiologies, who were scheduled for liver biopsy, and a control group of healthy adults who prospectively underwent pSWE. Ten consecutive pSWE measurements of the liver were performed using a Philips iU22 ultrasound system. Stiffness degree was compared to liver biopsy results. Fibrosis degree was staged according to METAVIR scoring system. RESULTS: The study group was comprised of 202 patients who underwent liver biopsy and pSWE test and a control group consisting of 14 healthy adults who underwent pSWE for validation. In the study group, the median stiffness was 5.35 ± 3.37 kilopascal (kPa). The median stiffness for F0-1, F2, F3, and F4 as determined by liver biopsy results were 4.9 kPa, 5.4 kPa, 5.7 kPa, and 8 kPa, respectively. The median stiffness in the control group was 3.7 ± 0.6 kPa. Subgroup analyses were conducted for viral hepatitis vs. non-viral hepatitis and steatohepatitis vs. non-steatohepatitis groups. CONCLUSIONS: pSWE is a reproducible method for assessing liver stiffness and is in a linear relationship with fibrosis degree as seen in pathology. Compared with patients with non-significant fibrosis, healthy controls showed significantly lower values.


Assuntos
Técnicas de Imagem por Elasticidade , Cirrose Hepática , Hepatopatias/diagnóstico , Fígado , Biópsia/métodos , Doença Crônica , Técnicas de Imagem por Elasticidade/instrumentação , Técnicas de Imagem por Elasticidade/métodos , Estudos de Viabilidade , Feminino , Humanos , Israel/epidemiologia , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Hepatopatias/classificação , Hepatopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
14.
Obes Surg ; 31(8): 3548-3556, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33844174

RESUMO

BACKGROUND: Bariatric surgery is among the therapeutic options for non-alcoholic fatty liver disease (NAFLD), affecting 90% of patients with obesity. The aim of this study was to evaluate the evolution of NAFLD lesions 1 year after surgery using noninvasive markers. METHODS: From November 2011 to November 2012, 253 patients with obesity undergoing bariatric surgery in three French University Hospitals were included. Histological data regarding intraoperative liver biopsy were collected at baseline, clinical, and biological data, including FibroTest®, SteatoTest®, and NASHTest®, before and after surgery. RESULTS: Fibrosis' prevalence was 74.2% with a positive predictive value (PPV) for FibroTest® of 78.6% and 43.4% for significant fibrosis (Kleiner ≥ F2) with a negative predictive value (NPV) of 56.1%. NAFLD's prevalence was 84% with a PPV for SteatoTest® of 85.9% and 7.7% for NASH with an NPV for NASHTest® of 93.8%. One year after bariatric surgery, mean BMI had significantly decreased from 46.5 to 31.7 kg/m2 (p < 0.001). Fibrosis assessed by the FibroTest® showed that 82.5% of patients were F0 after surgery compared to 90.9% before. Using SteatoTest®, the percent of patient without steatosis (S0) increased from 1.6 to 49.6% after surgery, and rate of severe steatosis (S3) improved from 43.3 to 3.9%. NASHTest® revealed that the percent of patients without NASH increased from 12.8 to 73.6% and rates of NASH improved from 12 to 0.8%. CONCLUSIONS: Validated noninvasive biomarkers SteatoTest® and NASHTest® suggested NAFLD and steatohepatitis improvement after bariatric surgery and might be useful tools for patient follow-up. Regarding fibrosis, FibroTest® was not accurate in patients with extreme obesity.


Assuntos
Cirurgia Bariátrica , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Biomarcadores , Biópsia , Humanos , Fígado/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/cirurgia , Estudos Prospectivos , Perda de Peso
15.
World J Pediatr Congenit Heart Surg ; 12(2): 168-172, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33684008

RESUMO

OBJECTIVE: We hypothesized that a relationship between post-Fontan hepatic fibrosis and anatomical variants might exist. METHODS: Attempting to limit confounding variables, we analyzed data from living, stable, post-extracardiac Fontan patients who underwent cardiac catheterization and transvenous hepatic biopsy procedures between March 2012 and June 2020. RESULTS: We identified 120 patients who met the inclusion criteria. Of the 120, 35 (29%) had pulmonary artery stents. For the 35 with pulmonary artery stents, the average total fibrosis score was 3.2 ± 1.9 and the fibrosis progression rate was 0.36 ± 0.33, and for those with no pulmonary artery stents, the total fibrosis score was 2.6 ± 1.8 and the fibrosis progression rate was 0.27 ± 0.33 (P = .13 and P = .11, respectively). Of the 120, 65 had functional univentricles of right ventricular type. Of these 65, 27 had pulmonary artery stents. For the 27 with pulmonary artery stents, the average total fibrosis score was 3.4 ± 1.8 and the average fibrosis progression rate was 0.39 ± 0.30, and for the 38 without pulmonary artery stents, the average fibrosis score was 2.3 ± 1.5 and the average fibrosis progression rate was 0.23 ± 0.21 (P = .01 for comparison of both values). CONCLUSIONS: This study's findings suggest that a post-extracardiac Fontan with a functional univentricle of right ventricular type plus a pulmonary artery stent may have more advanced liver pathology than those without a pulmonary artery stent at similar Fontan duration years and ages at liver biopsy.


Assuntos
Técnica de Fontan/efeitos adversos , Cardiopatias Congênitas/cirurgia , Cirrose Hepática/etiologia , Fígado/diagnóstico por imagem , Adolescente , Adulto , Biópsia , Criança , Feminino , Humanos , Cirrose Hepática/diagnóstico , Masculino , Adulto Jovem
17.
Transplant Proc ; 53(4): 1333-1336, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33750588

RESUMO

Liver allografts are unique in solid organ transplantation as they are less susceptible to both acute and chronic rejection. Operational tolerance, defined as prolonged graft survival in the absence of immunosuppression, is also achieved more frequently with liver allografts. It is unknown if the presence of multiple allografts in the same individual, levels of immunosuppression, or the presence of cystic fibrosis (CF) impacts the livers ability to ward off rejection or achieve operational tolerance. We describe an unsensitized, ABO-compatible patient with CF who underwent double lung transplantation and several years later a combined liver-kidney transplant. He developed isolated late acute T-cell mediated rejection of his liver allograft despite a high level of immunosuppression (IS) required for his lung and kidney allografts. To our knowledge, this is the first case of isolated liver rejection in a patient with 3 separate organ allografts, or in a patient with CF, to be reported in the literature. This isolated liver rejection is out of keeping with typically accepted ideas about orthotopic liver tolerance.


Assuntos
Rejeição de Enxerto/diagnóstico , Transplante de Rim , Transplante de Fígado , Fígado/patologia , Transplante de Pulmão , Adulto , Inibidores de Calcineurina/efeitos adversos , Fibrose Cística/complicações , Fibrose Cística/patologia , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/induzido quimicamente , Falência Renal Crônica/cirurgia , Cirrose Hepática/etiologia , Cirrose Hepática/cirurgia , Masculino , Linfócitos T/imunologia , Transplante Homólogo
18.
Front Immunol ; 12: 608498, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33708204

RESUMO

Liver cirrhosis is one major cause of mortality in the clinic, and treatment of this disease is an arduous task. The scenario will be even getting worse with increasing alcohol consumption and obesity in the current lifestyle. To date, we have no medicines to cure cirrhosis. Although many etiologies are associated with cirrhosis, abnormal intestinal microbe flora (termed dysbiosis) is a common feature in cirrhosis regardless of the causes. Toll-like receptors (TLRs), one evolutional conserved family of pattern recognition receptors in the innate immune systems, play a central role in maintaining the homeostasis of intestinal microbiota and inducing immune responses by recognizing both commensal and pathogenic microbes. Remarkably, recent studies found that correction of intestinal flora imbalance could change the progress of liver cirrhosis. Therefore, correction of intestinal dysbiosis and targeting TLRs can provide novel and promising strategies in the treatment of liver cirrhosis. Here we summarize the recent advances in the related topics. Investigating the relationship among innate immunity TLRs, intestinal flora disorders, and liver cirrhosis and exploring the underlying regulatory mechanisms will assuredly have a bright future for both basic and clinical research.


Assuntos
Suscetibilidade a Doenças , Microbioma Gastrointestinal , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Receptores Toll-Like/metabolismo , Animais , Translocação Bacteriana , Biomarcadores , Suscetibilidade a Doenças/imunologia , Disbiose , Humanos , Imunidade Inata , Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Transdução de Sinais
19.
CMAJ Open ; 9(1): E167-E174, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688024

RESUMO

BACKGROUND: High-quality estimates of health care costs are required to understand the burden of illness and to inform economic models. We estimated the costs associated with hepatitis C virus (HCV) infection from the public payer perspective in Ontario, Canada. METHODS: In this population-based retrospective cohort study, we identified patients aged 18-105 years diagnosed with chronic HCV infection in Ontario from 2003 to 2014 using linked administrative data. We allocated the time from diagnosis until death or the end of follow-up (Dec. 31, 2016) to 9 mutually exclusive health states using validated algorithms: no cirrhosis, no cirrhosis (RNA negative) (i.e., cured HCV infection), compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, both decompensated cirrhosis and hepatocellular carcinoma, liver transplantation, terminal (liver-related) and terminal (non-liver-related). We estimated direct medical costs (in 2018 Canadian dollars) per 30 days per health state and used regression models to identify predictors of the costs. RESULTS: We identified 48 239 patients with chronic hepatitis C, of whom 30 763 (63.8%) were men and 35 891 (74.4%) were aged 30-59 years at diagnosis. The mean 30-day costs were $798 (95% confidence interval [CI] $780-$816) (n = 43 568) for no cirrhosis, $661 (95% CI $630-$692) (n = 6422) for no cirrhosis (RNA negative), $1487 (95% CI $1375-$1599) (n = 4970) for compensated cirrhosis, $3659 (95% CI $3279-$4039) (n = 3151) for decompensated cirrhosis, $4238 (95% CI $3480-$4996) (n = 550) for hepatocellular carcinoma, $8753 (95% CI $7130-$10 377) (n = 485) for both decompensated cirrhosis and hepatocellular carcinoma, $4539 (95% CI $3746-$5333) (n = 372) for liver transplantation, $11 202 (95% CI $10 645-$11 760) (n = 3201) for terminal (liver-related) and $8801 (95% CI $8331-$9271) (n = 5278) for terminal (non-liver-related) health states. Comorbidity was the most significant predictor of total costs for all health states. INTERPRETATION: Our findings suggest that the financial burden of HCV infection is substantially higher than previously estimated in Canada. Our comprehensive, up-to-date cost estimates for clinically defined health states of HCV infection should be useful for future economic evaluations related to this disorder.


Assuntos
Carcinoma Hepatocelular/economia , Custos de Cuidados de Saúde , Hepatite C Crônica/economia , Cirrose Hepática/economia , Neoplasias Hepáticas/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/economia , Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/terapia , Estudos de Coortes , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/terapia , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/terapia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/terapia , Transplante de Fígado/economia , Masculino , Pessoa de Meia-Idade , Ontário , Estudos Retrospectivos , Adulto Jovem
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