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1.
Metabolism ; 128: 154958, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34958817

RESUMO

BACKGROUND: With metabolic dysfunction-associated fatty liver disease (MAFLD) incidence and prevalence increasing, it is necessary to identify patients with advanced fibrosis (F3-F4 stages). We evaluated the performance of new biomarkers and algorithms for diagnosing advanced fibrosis in an Asian population. METHODS: Data from two Asian cohorts (including 851 biopsy-proven MAFLD [578 from Wenzhou, 273 from Hong Kong]) were studied. The association between N-terminal propeptide of type 3 collagen (PRO-C3) and the histologic stage of liver fibrosis was analyzed by multivariable linear regression. The area under the receiver operating characteristic curve (AUROC) was used to test the diagnostic performance of serum PRO-C3 and the ADAPT score for advanced fibrosis and compared them to other established non-invasive tests. RESULTS: Serum PRO-C3 levels increased progressively across liver fibrosis stages and correlated with advanced fibrosis (P < 0.001). The ADAPT score had an AUROC of 0.865 (95% confidence interval 0.829-0.901) for advanced fibrosis; the accuracy, sensitivity and negative predictive values were 81.4%, 82.2% and 96.1%, respectively. This result was better compared to that of PRO-C3 alone or other non-invasive fibrosis biomarkers (aspartate aminotransferase-to-platelet ratio index, Fibrosis-4, BARD, and NAFLD fibrosis score). In subgroup analyses (including sex, age, diabetes, NAFLD activity score, body mass index or serum alanine aminotransferase levels), the ADAPT score had good diagnostic performance. CONCLUSION: PRO-C3 and the ADAPT score reliably exclude advanced fibrosis in MAFLD patients and reduce the need for liver biopsy.

2.
Clin Mol Hepatol ; 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34839623

RESUMO

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. Methods: We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392 and vitamin D and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. Results: Carriage of the rs495392 A allele had a protective effect on steatosis severity (OR = 0.61, 95% CI: 0.42 - 0.89, P = 0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR = 0.66, 95% CI: 0.45 - 0.98, P = 0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. Conclusions: The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.

3.
Turk J Gastroenterol ; 32(9): 758-764, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34609305

RESUMO

BACKGROUND: Caspase-cleaved K18 (cK18) may accurately reflect hepatocyte apoptosis in patients with non-alcoholic steatohepatitis (NASH). However, NASH can also exist within the normal range of cK18. The aim of this study was to investigate the risk factors and characteristics of NASH within the normal serum levels of cK18. METHODS: In the study, 227 histopathologically confirmed non-alcoholic fatty liver disease (NAFLD) patients with normal cK18 levels (≤200 U/L), measured in serum using ELISA kits, were enrolled. The Rs738409 allele, coding patatin-like phospholipase domain-containing protein 3 (PNPLA3), was detected by MALDI-TOF mass spectrometry. Non-alcoholic steatohepatitis was defined as an NAFLD activity score (NAS) ≥5 with each part >0. RESULTS: The prevalence of NASH was 31.7% among NAFLD patients with normal serum cK18 levels. Compared with non-NASH, NASH had a higher possibility of occurrence with central obesity, insulin resistance, and the G allele of PNPLA3. The mean serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were higher in NASH patients. Moreover, ALT, AST, TC, LDL-C, central obesity, and the PNPLA3 G allele were risk factors for NASH in NAFLD patients with normal serum cK18 levels, with odds ratios of 1.01 (95% CI: 1.00, 1.02), 1.03 (95% CI: 1.01, 1.05), 1.33 (95% CI: 1.04, 1.68), 1.41 (95% CI: 1.03, 1.92), 2.19 (95% CI: 1.15, 4.18), and 2.48 (95% CI: 1.15, 5.36), respectively; all P < .05. CONCLUSIONS: The major risk factors for NASH were central obesity, AST, and the PNPLA3 G allele, in NAFLD with low hepatocyte apoptosis.

4.
J Clin Transl Hepatol ; 9(2): 194-202, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-34007801

RESUMO

Background and Aims: In Europeans, variants in the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene impact liver histology in metabolic-associated fatty liver disease (MAFLD). The impact of these variants in ethnic Chinese is unknown. The aim of this study was to investigate the potential associations in Chinese patients. Methods: In total, 427 Han Chinese with biopsy-confirmed MAFLD were enrolled. Two single nucleotide polymorphisms in HSD17B13 were genotyped: rs72613567 and rs6531975. Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology. Results: In our cohort, the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis [odds ratio (OR): 2.93 (1.20-7.17), p=0.019 for the additive model; OR: 3.32 (1.39-7.91), p=0.007 for the recessive model], representing an inverse association as compared to the results from European cohorts. In contrast, we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant [OR: 0.48 (0.24-0.98), p=0.043 for the additive model; OR: 0.62 (0.40-0.94), p=0.025 for the dominant model]. HSD17B13 variants were only associated with fibrosis but no other histological features. Furthermore, HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis. Conclusions: HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans. These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.

5.
J Hepatobiliary Pancreat Sci ; 28(7): 593-603, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33908180

RESUMO

BACKGROUND: The presence of significant liver fibrosis is a key determinant of long-term prognosis in non-alcoholic fatty liver disease (NAFLD). We aimed to develop a novel machine learning algorithm (MLA) to predict fibrosis severity in NAFLD and compared it with the most widely used non-invasive fibrosis biomarkers. METHODS: We used a cohort of 553 adults with biopsy-proven NAFLD, who were randomly divided into a training cohort (n = 278) for the development of both logistic regression model (LRM) and MLA, and a validation cohort (n = 275). Significant fibrosis was defined as fibrosis stage F ≥ 2. MLA and LRM were derived from variables that were selected using a least absolute shrinkage and selection operator (LASSO) logistic regression algorithm. RESULTS: In the training cohort, the variables selected by LASSO algorithm were body mass index, pro-collagen type III, collagen type IV, aspartate aminotransferase and albumin-to-globulin ratio. The diagnostic accuracy of MLA showed the highest values of area under the receiver operator characteristic curve (AUROC: 0.902, 95% CI 0.869-0.904) for identifying fibrosis F ≥ 2. The LRM AUROC was 0.764, 95% CI 0.710-0.816 and significantly better than the AST-to-Platelet ratio (AUROC 0.684, 95% CI 0.605-0.762), FIB-4 score (AUROC 0.594, 95% CI 0.503-0.685) and NAFLD Fibrosis Score (AUROC 0.557, 95% CI 0.470-0.644). In the validation cohort, MLA also showed the highest AUROC (0.893, 95% CI 0.864-0.901). The diagnostic accuracy of MLA outperformed that of LRM in all subgroups considered. CONCLUSIONS: Our newly developed MLA algorithm has excellent diagnostic performance for predicting fibrosis F ≥ 2 in patients with biopsy-confirmed NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Algoritmos , Biomarcadores , Biópsia , Fibrose , Humanos , Cirrose Hepática/diagnóstico , Aprendizado de Máquina , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Valor Preditivo dos Testes , Curva ROC , Índice de Gravidade de Doença
7.
Nutr Metab Cardiovasc Dis ; 31(2): 552-560, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33250371

RESUMO

BACKGROUND AND AIMS: Some previous studies reported serum autoantibody positivity in patients with nonalcoholic fatty liver disease (NAFLD). The clinical significance of these findings remains uncertain. We aimed to investigate the association between the presence of serum autoantibodies and liver disease severity in NAFLD. METHODS AND RESULTS: A total of 388 consecutive patients with biopsy-proven NAFLD were included in the study. Various serum autoantibodies (including also anti-nuclear antibodies [ANA]) were detected by indirect immunofluorescent or immunoblotting assays. Overall, 84 (21.6%) patients with biopsy-confirmed NAFLD had positivity for at least one of the measured serum autoantibodies. ANA positivity was present in 50 (12.9%) patients, whereas anti-U1RNP or pANCA antibodies were detectable in 9 (2.3%) and 6 (1.5%) patients, respectively. Multivariate logistic regression analysis showed that ANA positivity (adjusted-odds ratio: 4.51, 95%CI: 1.77-11.5; P = 0.002) or positivity of any serum autoantibodies (adjusted-odds ratio: 3.14, 95%CI: 1.30-7.62; P = 0.01) were independently associated with advanced liver fibrosis (stages F3-F4). In serum autoantibody/ANA-positive patients, the proportion of those with advanced fibrosis was also greater among carriers of PNPLA3 rs738409 GG or CG than among those carrying PNPLA3 rs738409 CC genotype. CONCLUSIONS: Serum autoantibody positivity was independently associated with advanced liver fibrosis in patients with biopsy-proven NAFLD. The presence of serum autoantibodies in patients with advanced fibrosis occurred more frequently amongst those carrying PNPLA3 rs738409 GG or CG genotypes.


Assuntos
Autoanticorpos/sangue , Cirrose Hepática/sangue , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , Biomarcadores/sangue , Biópsia , Estudos Transversais , Feminino , Humanos , Lipase/genética , Cirrose Hepática/genética , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/patologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Índice de Gravidade de Doença
8.
Br J Nutr ; 126(6): 813-824, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-33198849

RESUMO

The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.

9.
Zhonghua Nan Ke Xue ; 26(7): 605-610, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-33377715

RESUMO

Objective: To analyze the whole genome sequences of Staphylococcus aureus strains from the sperm of infertile males and identify the gene which may induce the inhibition of sperm motility (ISM). METHODS: Twenty-two Staphylococcus aureus strains were isolated from the sperm of infertile males in the First Hospital Affiliated to Wenzhou Medical University and, according to the ability of ISM, divided into an ISM and a non-ISM group. Two strains most representative of the biological function of each group were selected, namely MJ015 from the ISM and MJ163 from the non-ISM group, and DNA extracted from them for whole genome sequencing. The data obtained were subjected to whole-genome sequence assembly and submitted to NCBI for annotation, with the accession number of CP038183 for MJ015 and CP038229 for MJ163. The whole genome sequences of MJ015 and MJ163 were compared in full detail using BRIG and Artemis software suite to identify the target gene. RESULTS: The whole genome sequence of MJ015 was 2 784 836 bp in length, containing 2 plasmids, and that of MJ163 was 2 746 673, containing 1 plasmid, each with a 32.13%, 32.08% content of guanine-cytosine (GC), and annotated with 2 921 and 2 844 genes respectively. Comparison between the whole genome sequences of MJ015 and MJ163 revealed an almost 130 kb gap, in which a gene named sak was found to express a potential serum inhibition factor, whose transcription product was proved to be a differentially expressed protein in the two strains. CONCLUSIONS: The gene sak in MJ015 may play a key role in the inhibition of sperm mobility, but the inhibition intensity of its transcription product staphylococcus kinase has to be further studied.


Assuntos
Genes Bacterianos , Infertilidade Masculina/microbiologia , Motilidade Espermática , Infecções Estafilocócicas/complicações , Staphylococcus aureus/genética , DNA Bacteriano/genética , Humanos , Masculino , Espermatozoides
10.
Nutr Metab Cardiovasc Dis ; 30(10): 1820-1825, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32636124

RESUMO

BACKGROUND AND AIMS: Emerging evidence suggests that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are decreased in patients with imaging-defined nonalcoholic fatty liver disease (NAFLD), but no data are currently available on the association between plasma NT-proBNP levels and the histological severity of NAFLD. METHODS AND RESULTS: We enrolled 351 (73.5% men) consecutive adult patients with biopsy-proven NAFLD without a prior history of cardiovascular disease (CVD). Plasma NT-proBNP levels were measured using a commercially available immunochemical system (VITROS® 5600, Johnson, New Jersey). Fifty-three percent of these subjects had nonalcoholic steatohepatitis (NASH). After stratification of patients by plasma NT-proBNP tertiles; compared to those in the 1st tertile (NT-proBNP ≤16 pg/ml), the odds ratio for NASH was 0.52 (95% CI 0.29-0.95) in patients in the 2nd tertile (NT-proBNP of 17-33 pg/ml) and 0.49 (95% CI 0.26-0.93) in those in the 3rd tertile (NT-proBNP ≥34 pg/ml) of plasma NT-proBNP levels, even after adjustment for age, sex, body mass index, homeostasis model assessment (HOMA)-estimated insulin resistance, pre-existing diabetes, hypertension, and dyslipidemia. CONCLUSION: In subjects with biopsy-proven NAFLD without known CVD, this cross-sectional study shows for the first time, that lower plasma NT-proBNP levels are strongly associated with a higher prevalence of NASH.


Assuntos
Fígado/patologia , Peptídeo Natriurético Encefálico/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Fragmentos de Peptídeos/sangue , Adulto , Biomarcadores/sangue , China/epidemiologia , Estudos Transversais , Regulação para Baixo , Feminino , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Valor Preditivo dos Testes , Prevalência , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
11.
Artigo em Inglês | MEDLINE | ID: mdl-32139603

RESUMO

BACKGROUND AND AIM: Imaging-confirmed non-alcoholic fatty liver disease (NAFLD) with normal alanine aminotransferase (nALT) levels is infrequently the subject for further evaluation. Early diagnosis of non-alcoholic steatohepatitis (NASH) is needed to prevent disease progression. Thus, we tested the clinical utility of serum Golgi protein 73 (GP73) levels and developed a new non-invasive score to diagnose NASH in patients with biopsy-confirmed NAFLD and persistent nALT levels. METHODS: Serum GP73 and cytokeratin-18 M30 fragments (CK18-M30) levels were measured in 345 patients with biopsy-proven NAFLD. We developed a new score, named G-NASH model (by incorporating serum GP73), and combined it with serum CK18-M30 measurement in a sequential non-invasive approach to accurately identify NASH among patients with NAFLD and persistent nALT levels. RESULTS: 105 (30.4%) patients had persistent nALT, 53 of whom had histologically confirmed NASH. Both serum GP73 and CK18-M30 levels alone had poor diagnostic accuracy in identifying NASH (55.2% and 51.6%, respectively) in these patients. Conversely, G-NASH model performed better than other established non-invasive scoring systems, and by using our proposed sequential non-invasive approach 82.9% of patients with NASH were correctly identified. CONCLUSIONS: NASH is highly prevalent in patients with NAFLD with persistent nALT levels. The G-NASH model accurately identifies NASH in this patient group.


Assuntos
Alanina Transaminase/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto , Biomarcadores/sangue , Feminino , Humanos , Queratina-18/sangue , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Sensibilidade e Especificidade
12.
J Gastroenterol Hepatol ; 35(6): 1057-1064, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31677195

RESUMO

BACKGROUND AND AIM: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) genotype influences clinical/biochemical characteristics in patients with nonalcoholic fatty liver disease (NAFLD), but whether PNPLA3-I148M (rs738409) genotype also influences the diagnostic performance of noninvasive diagnostic tests for NAFLD is uncertain. Our aim was to investigate the differences in diagnostic performance of noninvasive diagnostic tests for NAFLD according to PNPLA3-I148M (rs738409) genotype. METHODS: Fifty-eight healthy controls and 349 patients with biopsy-proven NAFLD were included. Areas under the receiver operating characteristic curve (AUROCs) were calculated to predict hepatic steatosis (fatty liver index and hepatic steatosis index), nonalcoholic steatohepatitis (cytokeratin-18 M30 and M65), and significant fibrosis (≥F2 fibrosis) (fibrosis-4 and BARD), stratifying by rs738409 genotypes (CC and CG + GG groups). RESULTS: Fatty liver index and hepatic steatosis index showed good diagnostic performance for diagnosing steatosis only in the CG + GG group with AUROCs ranging from 0.819 to 0.832. Cytokeratin-18 M30 (AUROC = 0.688) and M65 (AUROC = 0.678) had suboptimal performance for diagnosing nonalcoholic steatohepatitis in the CG + GG group, whereas both had good performance (AUROC = 0.814 and 0.813, respectively) in the CC group. BARD score showed good performance in the CG + GG group compared with the CC group (AUROC = 0.805 and 0.532, respectively). Fibrosis-4 had suboptimal performance in the CG + GG group and good performance in the CC group (AUROC = 0.662 and 0.801, respectively). CONCLUSIONS: Diagnostic performance of noninvasive tests for NAFLD varied markedly according to PNPLA3 genotypes. Clinicians should be aware that PNPLA3 genotype limits the clinical utility of noninvasive diagnostic tests for diagnosing NAFLD.


Assuntos
Técnicas de Diagnóstico do Sistema Digestório , Genótipo , Lipase/genética , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Liver Int ; 40(1): 107-119, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31519069

RESUMO

BACKGROUND & AIMS: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism is associated with NAFLD severity and the PNPLA3 gene is expressed in the kidneys, but whether PNPLA3 rs738409 polymorphism is also associated with renal tubular injury (RTI) is uncertain. We assessed the effect of PNPLA3 genotypes on biomarkers of RTI and glomerular function in subjects with NAFLD who had either normal (nALT) or abnormal (abnALT) alanine aminotransaminase levels. METHODS: Two hundred and seventeen patients with histologically proven NAFLD of which 75 had persistently nALT (below upper limit of normal for 3 months) were included. Multivariable regression analyses were undertaken to test associations between PNPLA3 genotype and biomarkers of kidney dysfunction. RESULTS: The nALT patient group had higher urinary neutrophil gelatinase-associated lipocalin levels (u-NGAL, a biomarker of RTI) (P < .001), higher albuminuria (P = .039) and greater prevalence of chronic kidney disease (CKD; P = .046) than the abnALT group. The association between PNPLA3 GG genotype and risk of CKD and abnormal albuminuria remained significant after adjustment for kidney risk factors and severity of NAFLD histology, mostly in the nALT group. Similarly, PNPLA3 GG genotype was associated with higher u-NGAL levels in the nALT group, even after adjustment for the aforementioned risk factors and glomerular filtration-based markers (ß-coefficient: 22.29, 95% CI: 0.99-43.60, P = .041). CONCLUSION: Patients with NAFLD and persistently nALT, who carry the PNPLA3 rs738409 G allele, are at higher risk of early glomerular and tubular damage. We suggest PNPLA3 genotyping may help identify patients with NAFLD at higher risk of RTI.


Assuntos
Rim/fisiopatologia , Lipase/genética , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Adulto , Alanina Transaminase/sangue , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Taxa de Filtração Glomerular , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
14.
Expert Rev Gastroenterol Hepatol ; 12(3): 295-302, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29300103

RESUMO

BACKGROUND: Alpha-fetoprotein (AFP) has been shown to predict the prognosis of liver disease in several studies. This study aimed to evaluate the prognostic value of stratified AFP in patients with acute-on-chronic hepatitis B liver failure (ACHBLF). METHODS: A total of 192 patients were included and AFP were categorized into quartiles. The prognostic value was determined for overall survival (OS) and assessed by Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazard regression analyses studied the association of all independent parameters with disease prognosis. RESULTS: The optimal cut-off points of AFP were: (Q1) 252.3-4800.0 ng/ml, (Q2) 76.0-252.2 ng/ml, (Q3) 18.6-75.9 ng/ml, and (Q4) 0.7-18.5 ng/ml. Based on the Kaplan-Meier analysis of the OS, each AFP quartile revealed a progressively worse OS and apparent separation (log-rank P = 0.006). The second-highest quartiles of AFP (Q2) always demonstrated an extremely favorable short-term survival. Combining the lowest AFP quartiles with a serum sodium < 131mmol/L or an INR ≥ 3.3 showed a poor outcome (90-days survival of 25.0% and 11.9% respectively). CONCLUSIONS: Stratified AFP could strengthen the predictive power for short-term survival of patients with ACHBLF. Combining AFP quartiles with low serum sodium and high INR may better predict poor outcome in ACHBLF patients.


Assuntos
Insuficiência Hepática Crônica Agudizada/sangue , Insuficiência Hepática Crônica Agudizada/virologia , Hepatite B Crônica/complicações , alfa-Fetoproteínas/metabolismo , Adulto , Feminino , Humanos , Coeficiente Internacional Normatizado , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Sódio/sangue , Taxa de Sobrevida
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