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Background/aims: The metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity are frequent comorbidities with a high prevalence worldwide. Their pathogenesis are multifactorial, including intestinal dysbiosis. The role of small intestinal bacterial overgrowth (SIBO) in MASLD progression in obese patients remains unknown. We aimed to determine the association between SIBO and the severity of MASLD in obese patients. Methods: An observational and cross-sectional study was conducted in obese patients, diagnosed with or without MASLD by liver biopsy. Metabolic dysfunction-associated steatotic liver (MASL), metabolic dysfunction-associated steatohepatitis without fibrosis (MASH-NF), MASH with fibrosis (MASH-F), or without MASLD (control subjects, CS) were identified by presence of steatosis, portal and lobular inflammation, and fibrosis. SIBO was determined by standardized lactulose breath tests. Results: A total of 59 patients with MASLD, 16 with MASL, 20 with MASH-NF, 23 with MASH-F, and 14 CS were recruited. Higher percentages of SIBO were observed in MASLD patients (44.2%) compared to CS (14.2%; p = 0.0363). Interestingly, MASH-F showed higher percentages of SIBO (65.2%) in comparison to non-fibrotic MASLD (33.3%; p = 0.0165). The presence of SIBO was not correlated with the level of hepatic steatosis in MASLD patients. Conclusions: A positive correlation between MASLD and SIBO in obese patients was principally explained by the presence of liver fibrosis. Our findings suggest a pathogenic role of intestinal dysbiosis in the progression of MASLD. Future research will elucidate the underlying mechanisms of SIBO in MASLD advancement.
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INTRODUCTION AND OBJECTIVES: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at an increased cardiovascular risk. On the contrary, non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with coronary heart disease (CHD). However, it is not known whether patients with significant CHD show a higher frequency of liver fibrosis. This study aimed to determine the frequency of MASLD and liver fibrosis in patients with CHD and to assess whether coronary stenosis is significantly associated with MASLD and fibrosis. PATIENTS AND METHODS: This observational and analytical study included adult patients without any known liver disease who underwent coronary angiography for suspected coronary artery disease (Jul 2021-Jul 2022). The presence of significant CHD (> 50% stenosis of at least one coronary artery) was determined. Liver elastography (FibroScan®) was performed up to 6 months after the coronary angiographic study to determine liver fibrosis, a measurement of liver stiffness (> 6.5 Kpa). Fisher's test, Mann-Whitney U test, and logistic regression models were used (p < 0.05). RESULTS: The study included 113 patients (76% men, average age: 63 years [standard deviation: 9.9]), of which 72% presented with significant CHD. The prevalence rate of MASLD was 52%. Liver fibrosis was present in 12% of the patients and all patients in the significant CHD group (p = 0.007). An increase in the number of vessels with significant CHD increased the probability of liver fibrosis (odds ratio, 1.79; 95% confidence interval, 1.06-3.04; p = 0.029). CONCLUSIONS: MASLD is highly prevalent in patients with significant CHD but without known liver damage. These data suggest that MASLD and liver fibrosis should be investigated in patients with CHD. The presence of confounding variables, especially the presence of type 2 diabetes mellitus, should be evaluated in further studies.
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Angiografia Coronária , Doença da Artéria Coronariana , Cirrose Hepática , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Cirrose Hepática/epidemiologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Fatores de Risco , Idoso , Prevalência , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Técnicas de Imagem por Elasticidade , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/complicações , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/epidemiologiaRESUMO
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex disorder whose prevalence is rapidly growing in South America. The disturbances in the microbiota-gut-liver axis impact the liver damaging processes toward fibrosis. Gut microbiota status is shaped by dietary and lifestyle factors, depending on geographic location. We aimed to identify microbial signatures in a group of Chilean MASLD patients. Forty subjects were recruited, including healthy controls (HCs), overweight/obese subjects (Ow/Ob), patients with MASLD without fibrosis (MASLD/F-), and MASLD with fibrosis (MASLD/F+). Both MASLD and fibrosis were detected through elastography and/or biopsy, and fecal microbiota were analyzed through deep sequencing. Despite no differences in α- and ß-diversity among all groups, a higher abundance of Bilophila and a lower presence of Defluviitaleaceae, Lachnospiraceae ND3007, and Coprobacter was found in MASLD/F- and MASLD/F+, compared to HC. Ruminococcaceae UCG-013 and Sellimonas were more abundant in MASLD/F+ than in Ow/Ob; both significantly differed between MASLD/F- and MASLD/F+, compared to HC. Significant positive correlations were observed between liver stiffness and Bifidobacterium, Prevotella, Sarcina, and Acidaminococcus abundance. Our results show that MASLD is associated with changes in bacterial taxa that are known to be involved in bile acid metabolism and SCFA production, with some of them being more specifically linked to fibrosis.
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Microbioma Gastrointestinal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Cirrose Hepática/microbiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Fezes/microbiologia , Fígado/metabolismo , Fígado/patologia , Fígado Gorduroso/microbiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Progressão da Doença , Obesidade/microbiologia , Obesidade/complicações , Obesidade/metabolismo , Chile , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/metabolismo , IdosoRESUMO
INTRODUCTION AND OBJECTIVES: Acute-on-chronic liver failure (ACLF) is associated with reduced short-term survival, and liver transplantation is frequently the only therapeutic option. Nonetheless, the post-transplantation prognosis seems to be worse in ACLF patients. MATERIALS AND METHODS: The databases of two university centers were retrospectively evaluated, and adult patients with cirrhosis who underwent transplantation between 2013 and 2020 were included. One-year survival of patients with ACLF was compared to that of patients without ACLF. Variables associated with mortality were identified. RESULTS: A total of 428 patients were evaluated, and 303 met the inclusion criteria; 57.1% were male, the mean age was 57.1 ± 10.2 years, 75 patients had ACLF, and 228 did not. The main etiologies of ACLF were NASH (36.6%), alcoholic liver disease (13.9%), primary biliary cholangitis (8.6%) and autoimmune hepatitis (7.9%). Mechanical ventilation, renal replacement therapy, the use of vasopressors and the requirement of blood product transfusion during liver transplantation were significantly more frequent in ACLF patients. Among those recipients without and with ACLF, survival at 1, 3 and 5 years was 91.2% vs. 74.7%, 89.1% vs. 72.6% and 88.3% vs. 72.6%, respectively (p=0.001). Among pre-transplantation variables, only the presence of ACLF was independently associated with survival (HR 3.2, 95% CI: 1.46-7.11). Post-transplantation variables independently associated with survival were renal replacement therapy (HR 2.8, 95% CI: 1.1-6.8) and fungal infections (HR 3.26, 95% CI: 1.07-9.9). CONCLUSIONS: ACLF is an independent predictor of one-year post-transplantation survival. Importantly, transplant recipients with ACLF require the use of more resources than patients without ACLF.
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Insuficiência Hepática Crônica Agudizada , Transplante de Fígado , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/cirurgia , Estudos Retrospectivos , Cirrose Hepática/complicações , Transplante de Fígado/efeitos adversos , PrognósticoRESUMO
INTRODUCTION: For the diagnosis of liver diseases, clinical criteria, biochemical, immunological and histological parameters are included. The autoimmune panel is an immunoblot that contemplates the detection of antibodies against 9 different hepatic antigens, which could guide the diagnosis of these pathologies. OBJECTIVE: To describe the usefulness of the autoimmune panel in the diagnosis of liver diseases. Methods: Observational, descriptive study. All autoimmune panels performed between January 2020 and August 2021 (n = 279) were reviewed, and the ones with positive result selected (n = 101). Clinical records were reviewed, including: clinical, biochemical, immunological and histological characteristics. Diagnosis was determined by clinical suspicion (clinical, biochemical and immunological parameters), only through autoimmune panel, and according to liver biopsy in available cases. RESULTS: 45 patients with complete clinical history were included in the analysis; 82% women, median age 58 years (16-79). Clinical suspicions included autoimmune hepatitis (AIH) in 12 patients (27%), primary biliary cholangitis (PBC) in 10 patients (22%), overlap syndrome (AIH/PBC) in 17 (38%), and others in 6 (13%). The diagnosis of PBC was confirmed by autoimmune panel in 9/10 and 11/17 patients with clinical suspicion of PBC and HAI/PBC, respectively. Of the 27 patients with initial clinical suspicion of PBC, 14 had negative AMA and AMA-M2 (6 had Sp100 and 5 gp210 as the only markers and 3 had positive Sp100 and PML). In 10/14 patients, the diagnosis was confirmed by panel and/or compatible liver biopsy. CONCLUSION: The autoimmune panel turns out to be a useful diagnostic tool for liver diseases, especially PBC in isolation or in overlap syndrome.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Autoanticorpos/sangue , Immunoblotting/métodos , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/imunologia , Hepatite Autoimune/sangue , Hepatopatias/diagnóstico , Hepatopatias/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/sangue , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/sangueRESUMO
Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model's original thresholds. Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell's adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model's original thresholds. Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p <0.0001). At last tumor reassessment before LT, c-statistics did not significantly differ between the two composite models, either as original or threshold versions, for recurrence (0.72 vs. 0.68; p = 0.06), HCC survival, and overall survival after LT. We observed predictive gaps and overlaps between the model's thresholds, and no significant gain on reclassification. Patients meeting both models ("within-ALL") at last tumor reassessment presented the lowest 5-year cumulative incidence of HCC recurrence (7.7%; 95% CI 5.1-11.5) and higher 5-year post-LT survival (70.0%; 95% CI 64.9-74.6). Conclusions: In this multicenter cohort, Metroticket 2.0 and the AFP score demonstrated a similar ability to predict HCC recurrence post-LT. The combination of these composite models might be a promising clinical approach. Impact and implications: Composite models were recently proposed for the selection of liver transplant (LT) candidates among individuals with hepatocellular carcinoma (HCC). We found that both the AFP score and Metroticket 2.0 predicted post-LT HCC recurrence and survival better than Milan criteria; the Metroticket 2.0 did not result in better reclassification for transplant selection compared to the AFP score, with predictive gaps and overlaps between the two models; patients who met low-risk thresholds for both models had the lowest 5-year recurrence rate. We propose prospectively testing the combination of both models, to further optimize the LT selection process for candidates with HCC.
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To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.
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Hepatite C Crônica , Hepatite C , Humanos , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , América Latina/epidemiologia , Perda de Seguimento , Hepacivirus/genética , Organização Mundial da SaúdeRESUMO
INTRODUCTION: For the diagnosis of liver diseases, clinical criteria, biochemical, immunological and histological parameters are included. The autoimmune panel is an immunoblot that contemplates the detection of antibodies against 9 different hepatic antigens, which could guide the diagnosis of these pathologies. OBJECTIVE: To describe the usefulness of the autoimmune panel in the diagnosis of liver diseases. METHODS: Observational, descriptive study. All autoimmune panels performed between January 2020 and August 2021 (n = 279) were reviewed, and the ones with positive result selected (n = 101). Clinical records were reviewed, including: clinical, biochemical, immunological and histological characteristics. Diagnosis was determined by clinical suspicion (clinical, biochemical and immunological parameters), only through autoimmune panel, and according to liver biopsy in available cases. RESULTS: 45 patients with complete clinical history were included in the analysis; 82% women, median age 58 years (16-79). Clinical suspicions included autoimmune hepatitis (AIH) in 12 patients (27%), primary biliary cholangitis (PBC) in 10 patients (22%), overlap syndrome (AIH/PBC) in 17 (38%), and others in 6 (13%). The diagnosis of PBC was confirmed by autoimmune panel in 9/10 and 11/17 patients with clinical suspicion of PBC and HAI/PBC, respectively. Of the 27 patients with initial clinical suspicion of PBC, 14 had negative AMA and AMA-M2 (6 had Sp100 and 5 gp210 as the only markers and 3 had positive Sp100 and PML). In 10/14 patients, the diagnosis was confirmed by panel and/or compatible liver biopsy. CONCLUSION: The autoimmune panel turns out to be a useful diagnostic tool for liver diseases, especially PBC in isolation or in overlap syndrome.
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Autoanticorpos , Hepatite Autoimune , Immunoblotting , Hepatopatias , Humanos , Feminino , Autoanticorpos/sangue , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Adolescente , Adulto Jovem , Immunoblotting/métodos , Hepatite Autoimune/imunologia , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/sangue , Hepatopatias/imunologia , Hepatopatias/diagnóstico , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/sangue , Doenças Autoimunes/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/sangueRESUMO
Background: Cholangiocarcinoma (CCA) is a primary hepatic tumor, frequently found in patients with liver cirrhosis and biliary tract diseases. Its varieties include isolated CCA or "combined hepatocellular-cholangiocarcinoma" (cHCC-CCA). The latter is uncommon, with poorly defined diagnostic criteria and natural history. Aim: To characterize patients with cirrhosis with a pathological diagnosis of CCA and cHCC-CCA. Material and Methods: Forty-nine liver biopsies with a pathological diagnosis of CCA were reviewed. The clinical records of patients were reviewed to fetch demographic variables, etiology of cirrhosis and clinical presentation. Results: Eight of the 49 patients had cirrhosis (16% of CCA biopsies reviewed). Their median age was 64 (27-71) years and five were females. Four patients had CCA, three patients cHCC-CCA and one had a bifocal tumor. Patients in the CCA group were more commonly symptomatic. Alpha-fetoprotein and CA 19-9 levels were elevated in one of eight and four of six patients, respectively. Within 12 months from diagnosis, five of eight patients died. Conclusions: In most of these cases, the diagnosis of cHCC-CCA and CCA was made in the liver explant study without previous imaging diagnosis. This reinforces the usefulness of the histological study, in specific cases, prior to liver transplantation and emphasizes the importance of systematic explant exploration in these cases.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/complicações , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patologia , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/diagnóstico , Ductos Biliares Intra-Hepáticos/patologia , Estudos Retrospectivos , Cirrose Hepática/complicaçõesRESUMO
Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease with a relevant inflammatory component and an unknown etiology. Evidence for clinical characteristics and risk factors in large cohorts of patients with acute AIH (AAIH) is lacking. We clinically characterized patients with AAIH, the prevalence of a combined adverse outcome (death or liver transplantation (LT)), and its risk factors. Methods: A retrospective study of adult patients diagnosed with AAIH at three centers (Santiago, Chile; 2000-2018) was conducted. Clinical and laboratory characteristics were obtained. A liver biopsy was performed for all patients. Descriptive statistics and logistic regression models were used. Results: A total of 126 patients were admitted; 77% were female, 33 (26.2%) had a severe presentation, and 14 (11.1%) had a fulminant presentation. Overall, 24 patients (19.0%) lacked typical autoantibodies, and 26.2% had immunoglobulin G levels in the normal range. The most frequent histological findings were plasma cells (86.5%), interface hepatitis (81.7%), and chronic hepatitis (81.0%). Rosettes were uncommon (35.6%). Advanced fibrosis was present in 27% of patients. Combined adverse outcomes occurred in 7.9% of cases, all fulminant with histological cholestasis. Alkaline phosphatase, bilirubin, and prothrombin less than 50% were independent risk factors for in-hospital death or LT (p value <0.05). Although corticosteroid treatment was associated with better outcomes (OR 0.095, p value = 0.013), more severe patients were less likely to receive this therapy. Discussion. In this large cohort of patients with AAIH, clinical characteristics differ from those reported in patients with chronic AIH. Fulminant hepatitis, histological cholestasis, alkaline phosphatase, bilirubin, and prothrombin were associated with death/LT.