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During recent decades, the metabolic dysfunction-associated steatohepatitis (MASH) field has witnessed several paradigm shifts, including the recognition of liver fibrosis as the main predictor of major adverse liver outcomes. Throughout this evolution, liver histology has been recognised as one of the main hurdles in MASH drug development due to its invasive nature, associated cost, and high inter- and intra-reader variability. Collective experience demonstrates the importance of consistency in the central reading process, where consensus methods have emerged as appropriate ways to mitigate against well-known challenges. Using crystalized knowledge in the field, stakeholders should collectively work towards the next paradigm shift, where non-invasive biomarkers will be considered surrogate endpoints for accelerated approval. In this review, we provide an overview of the evolution of the regulatory histology endpoints and the liver biopsy reading process, within the MASH trial landscape, over recent decades; we then review the biggest challenges associated with liver biopsy endpoints. Finally, we discuss and provide recommendations on the best practices for liver biopsy evaluation in MASH drug development.
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BACKGROUND & AIMS: Non-invasive scores have been proposed to identify patients with fibrotic, metabolic dysfunction-associated steatohepatitis (MASH), who are at the highest risk of progression to complications of cirrhosis and may benefit from pharmacologic treatments. However, data in patients with type 2 diabetes (T2DM) are lacking. The aim of this multicenter prospective study was to perform a head-to-head comparison of FAST (FibroScan-aspartate aminotransferase [AST]), MAST (MRI-AST), MEFIB (magnetic resonance elastography [MRE] plus FIB-4), and FNI (fibrotic NASH index) for detecting fibrotic MASH in patients with T2DM. METHODS: A total of 330 outpatients with T2DM and biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) from the QUID-NASH study (NCT03634098), who underwent FibroScan, MRI-proton density fat fraction and MRE at the time of liver biopsy were studied. The main outcome was fibrotic MASH, defined as NAS ≥4 (with at least one point for each parameter) and fibrosis stage ≥2 (centrally reviewed). RESULTS: All data for score comparisons were available for 245 patients (median age 59 years, 65% male, median BMI 31 kg/m2; fibrotic MASH in 39%). FAST and MAST had similar accuracy (AUROCs 0.81 vs. 0.79, p = 0.41) but outperformed FNI (0.74; p = 0.01) and MEFIB (0.68; p <0.0001). When using original cut-offs, MAST outperformed FAST, MEFIB and FNI when comparing the percentage of correctly classified patients, in whom liver biopsy would be avoided (69% vs. 48%, 46%, 39%, respectively; p <0.001). When using cut-offs specific to our population, FAST outperformed FNI and MAST (56% vs. 40%, and 38%, respectively; p <0.001). CONCLUSION: Our findings show that FAST, MAST, MEFIB and FNI are accurate non-invasive tools to identify patients with T2DM and fibrotic MASH in secondary/tertiary diabetes clinics. Cut-offs adapted to the T2DM population should be considered. IMPACT AND IMPLICATIONS: Among patients with type 2 diabetes (T2DM), identifying those with metabolic dysfunction-associated steatohepatitis and significant fibrosis, who are the most at risk of developing clinical liver-related outcomes and who may benefit from pharmacologic treatments, is an unmet need. In this prospective multicenter study, we compared four non-invasive scores, three based on imaging (MRI or ultrasound technologies) and one on laboratory blood tests, for this purpose, using original and study-specific cut-offs. Our findings show that FAST, MAST, MEFIB and FNI are accurate non-invasive tools to identify patients with T2DM and fibrotic MASH in secondary/tertiary diabetes clinics. Cut-offs adapted to the T2DM population should be considered. TRIAL REGISTRATION NUMBER: NCT03634098.
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Diabetes Mellitus Tipo 2 , Técnicas de Imagem por Elasticidade , Cirrose Hepática , Imageamento por Ressonância Magnética , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Imageamento por Ressonância Magnética/métodos , Idoso , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Biópsia/métodos , Fígado/patologia , Fígado/diagnóstico por imagem , Aspartato Aminotransferases/sangueRESUMO
Limited data exist regarding the association between hepatitis B virus (HBV) DNA levels and liver histopathological changes in patients with chronic hepatitis B (CHB) during the immune tolerant (IT) phase. In this study, we retrospectively analysed liver biopsy results from 150 adult IT-CHB patients. The liver tissue necroinflammation and fibrosis were evaluated by the Scheuer scoring system. Multivariate logistic regression, smooth curve fitting, and segmented regression models were used to examine the association between HBV DNA levels and liver histopathological changes. A total of 26%, 30.67% and 42% of IT patients had significant necroinflammation (≥G2), significant fibrosis (≥S2) and significant histopathological changes (≥G2 and/or ≥S2), respectively. HBV DNA levels were independently and non-linear inversely associated with significant necroinflammation and histopathological changes in IT-CHB patients. Patients with HBV DNA levels <107 IU/mL had a higher risk of significant histopathological changes compared to those with levels >107 IU/mL. The findings were further confirmed by smooth curve fitting analyses, subgroup and sensitivity analyses. In segmented regression model analyses, the optimal DNA value for the lowest odds ratio of significant histopathological changes was 7.26 log10 IU/mL. A non-linear inverse association between HBV DNA levels and significant histopathological changes in IT-CHB patients. DNA 7.26 log10 IU/mL may serve as a potential cut-off point to define a 'true immune tolerant phase' with minimal liver histopathological changes.
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DNA Viral , Vírus da Hepatite B , Hepatite B Crônica , Fígado , Humanos , Hepatite B Crônica/patologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Masculino , Feminino , DNA Viral/sangue , Adulto , Fígado/patologia , Fígado/virologia , Estudos Retrospectivos , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/genética , Pessoa de Meia-Idade , Carga Viral , Biópsia , Tolerância Imunológica , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Cirrose Hepática/imunologia , Adulto JovemRESUMO
BACKGROUND AND AIMS: The use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR. METHODS: A randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety. RESULTS: Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed. CONCLUSIONS: Both the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146).
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Fígado , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Fígado/patologia , Fígado/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Crônica Induzida por Substâncias e Drogas/etiologia , Resultado do Tratamento , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Recidiva , Idoso , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Esquema de MedicaçãoRESUMO
BACKGROUND: The use of protocol liver biopsy to monitor liver allograft status remains controversial. There is limited data from modern transplantation populations that includes protocol biopsies to evaluate its value in predicting clinical outcomes. METHODS: All protocol liver biopsies were identified from 875 patients who underwent liver transplantation at Helsinki University Hospital between 2000 and 2019. Each histologic component was analyzed for its ability to predict long-term outcomes, especially graft survival. We determined the frequency of significant biopsy findings based on the Banff working group definition. Liver function tests (LFTs) and clinical markers were evaluated for their ability to predict significant biopsy findings. RESULTS: In total, 867 protocol liver biopsies were analyzed. Significant findings were identified in 20.1% of the biopsies. In the first protocol biopsy, steatohepatitis (hazard ratio [HR] 3.504, p = .03) and moderate or severe congestion (HR 3.338, p = .04) predicted graft loss. The presence of cholangitis (HR 2.563, p = .04), necrosis (HR 7.635, p < .001), mild congestion (HR 4.291, p = .009), and significant biopsy finding (HR 2.540, p = .02) predicted inferior death-censored graft survival. While the degree of elevation of LFTs was positively associated with significant biopsy findings, the discrimination was poor (AUC .572-.622). Combined LFTs and clinical risk factors remained suboptimal for discriminating significant biopsy findings (AUC .696). CONCLUSIONS: Our findings support the use of protocol liver biopsies after liver transplantation since they frequently revealed changes associated with long-term outcomes, even when LFTs were normal.
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Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Sobrevivência de Enxerto , Transplante Homólogo , Fígado/patologia , Biópsia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologiaRESUMO
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition worldwide. There is an urgent need to develop new biomarkers to assess disease severity and to define patients with a progressive phenotype. Activin A is a new promising biomarker with conflicting results about liver fibrosis. In this study we investigate levels of Activin A in patients with biopsy proven MASLD. We assess levels of Activin A in regard to fibrosis stage and genetic variant I148M in the patatin-like phospholipase domain-containing protein 3 (PNPLA3). METHODS: Activin A levels were assessed in plasma samples from patients with biopsy-proven MASLD in a cross-sectional study. All patients were clinically evaluated and the PNPLA3 I148M genotype of the cohort was assessed. FINDINGS: 41 patients were included and 27% of these had advanced fibrosis. In MASLD patients with advanced fibrosis, Activin A levels was higher (p < 0.001) and could classify advanced fibrosis with an AUROC for activin A of 0.836 (p < 0.001). Patients homozygous for PNPLA3 I148M G/G had higher levels of activin A than non-homozygotes (p = 0.027). CONCLUSIONS: Circulating activin A levels were associated with advanced fibrosis and could be a potential blood biomarker for identifying advanced fibrosis in MASLD. Patients with the risk genotype PNPLA3 I148M G/G had higher levels of activin A proposing activin A as a contributor of the transition from simple steatosis to a fibrotic phenotype.
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Ativinas , Biomarcadores , Fígado Gorduroso , Lipase , Cirrose Hepática , Proteínas de Membrana , Humanos , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/sangue , Feminino , Pessoa de Meia-Idade , Lipase/genética , Lipase/sangue , Cirrose Hepática/genética , Cirrose Hepática/sangue , Estudos Transversais , Ativinas/sangue , Ativinas/genética , Biomarcadores/sangue , Adulto , Fígado Gorduroso/genética , Fígado Gorduroso/sangue , Fígado Gorduroso/patologia , Idoso , Genótipo , Fígado/patologia , Índice de Gravidade de Doença , Aciltransferases , Fosfolipases A2 Independentes de CálcioRESUMO
OBJECTIVES: In patients evaluated for hepatocellular carcinoma (HCC), magnetic resonance imaging (MRI) is often used secondarily when multiphase contrast-enhanced computed tomography (ceCT) is inconclusive. We investigated the clinical impact of adding MRI. MATERIALS AND METHODS: This single-institution retrospective study included 48 MRI scans (44 patients) conducted from May 2016 to July 2023 due to suspicion of HCC on a multiphase ceCT scan. Data included medical history, preceding and subsequent imaging, histology when available, and decisions made at multidisciplinary team meetings. RESULTS: In case of possible HCC recurrence, 63% of the MRI scans were diagnostic of HCC. For 80% of the negative MRI scans, the patients were diagnosed with HCC within a median of 165 days in the suspicious area of the liver. In case of possible de-novo HCC in patients with cirrhosis, 22% of the scans were diagnostic of HCC and 33% of the negative MRI scans were of patients diagnosed with HCC within a median of 109 days. None of the non-cirrhotic patients with possible de-novo HCC and negative MRI scans (64%) were later diagnosed with HCC, but 3/5 of the indeterminate scans were of patients diagnosed with HCC in a biopsy. CONCLUSIONS: Secondary MRI to a multiphase ceCT scan suspicious of HCC is highly valuable in ruling out HCC in non-cirrhotic patients and in diagnosing HCC non-invasively in cirrhotic patients and patients with prior HCC. Patients with cirrhosis or prior HCC are still at high risk of having HCC if MRI results are inconclusive or negative.
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BACKGROUND: Histopathological characterization obtained by transjugular liver biopsy (TJLB) may theoretically contribute to clarification of the exact aetiology of acute liver failure (ALF). It's unclear whether the histopathological information from TJLB, due to the small specimen size, significantly contributes to diagnosing ALF causes, guiding therapy decisions, or predicting overall prognosis. This retrospective study aimed to analyse safety and clinical significance of TJLB in patients with ALF. METHODS: This retrospective, monocentric study investigated safety and efficacy of TJLB in patients with ALF over a ten-year period at a tertiary care transplant-center. The predictive value of various clinical and laboratory characteristics as well as histopathological findings obtained by TJLB on 28-day liver-transplant-free survival were evaluated by calculating uni- and multivariate Cox-proportional hazard regression models. Additional univariate logistic regression analyses were performed to explore the influence of degree of intrahepatic necrosis on the secondary endpoints intensive-care-unit (ICU) admission, need for endotracheal intubation, renal replacement therapy and high-urgency listing for LTX. RESULTS: A total of 43 patients with ALF receiving TJLB were included into the study. In most cases (n = 39/43 cases) TJLB confirmed the initially already clinically presumed ALF aetiology and the therapeutic approach was unchanged by additional histological examination in the majority of patients (36/43 cases). However, in patients with a high suspicion for aetiologies potentially treatable by medical immunosuppression (e.g. AIH, GvHD), TJLB significantly influenced further treatment planning and/or adjustment. While the degree of intrahepatic necrosis showed significance in the univariate analysis (p = 0.04), it did not demonstrate a significant predictive effect on liver transplant-free survival in the multivariate analysis (p = 0.1). Only consecutive ICU admission was more likely with higher extent of intrahepatic necrosis (Odds ratio (OR) 1.04 (95% CI 1-1.08), p = 0.046). CONCLUSIONS: Performance of TJLB in ALF led to a change in suspected diagnosis and to a significant change in therapeutic measures only in those patients with a presumed high risk for aetiologies potentially responsive to immunosuppressive therapy. Clinical assessment alone was accurate enough, with additional histopathological examination adding no significant value, to predict overall prognosis of patients with ALF.
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Falência Hepática Aguda , Transplante de Fígado , Fígado , Humanos , Estudos Retrospectivos , Feminino , Masculino , Falência Hepática Aguda/patologia , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/diagnóstico , Pessoa de Meia-Idade , Fígado/patologia , Adulto , Biópsia , Veias Jugulares/patologia , Prognóstico , Modelos de Riscos Proporcionais , Valor Preditivo dos Testes , Relevância ClínicaRESUMO
BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is defined as the occurrence of hepatic fat accumulation in patients with negligible alcohol consumption or any other cause of hepatic steatosis. This study aimed to correlate the ultrasound-based diagnosis of MAFLD with the histological diagnosis of nonalcoholic steatohepatitis (NASH) and alanine aminotransferase (ALT) levels in patients with MAFLD. METHODS: This was a hospital-based cross-sectional study of 71 patients with MAFLD diagnosed by ultrasound. Percutaneous liver biopsy was performed for histological evidence of NASH in all patients, regardless of liver function test (LFT) values, provided that they had no contraindications. Liver histology was graded using the NASH Clinical Research Network MAFLD Activity Score. The data obtained were entered into SPSS version 21 and analysed using descriptive and inferential statistics. The significance level was set at < 0.05. RESULTS: A total of 71 patients (26 males and 45 females) with MAFLD were included. Thirty-nine (76.5%) patients with MAFLD and normal ALT levels had NASH, while 14 (82.4%) had elevated ALT levels. There was no statistically significant difference in the histological grade of NASH between patients with normal and elevated ALT levels. A weak correlation was found between the severity of steatosis on ultrasound scan and NASH incidence (p = 0.026). The sensitivity and specificity of ALT levels for predicting NASH according to the area under the receiver operating characteristics (AUROC 0.590) at an ALT cut-off value of 27.5 IU/L were 55.8% and 64.7%, respectively. CONCLUSION: NASH can occur in patients with MAFLD, irrespective of alanine transaminase (ALT) levels, and ultrasound grading of the severity of steatosis cannot accurately predict NASH. Liver biopsy remains the investigation of choice.
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Alanina Transaminase , Fígado , Hepatopatia Gordurosa não Alcoólica , Ultrassonografia , Humanos , Masculino , Feminino , Alanina Transaminase/sangue , Estudos Transversais , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/sangue , Pessoa de Meia-Idade , Adulto , Fígado/patologia , Fígado/diagnóstico por imagem , Nigéria , Biópsia , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/patologia , Fígado Gorduroso/sangue , Idoso , Índice de Gravidade de Doença , Curva ROCRESUMO
BACKGROUND: This study aimed to evaluate the diagnostic abilities of the non-invasive serum biomarkers to predict liver fibrosis staging and evaluate the progress of hepatitis B. METHODS: We enrolled 433 patients with chronic HBV infection had complete medical data available for the study, who underwent percutaneous liver biopsy. The extent of fibrosis was assessed using the modified METAVIR score. The predictive values of the non-invasive serum biomarkers were evaluated by the areas under the receiving operator characteristics curves (AUROCs) with 95% confidence intervals. RESULTS: The proportion of males with progressive stages of liver fibrosis was relatively larger, and the average age of patients with cirrhosis stages is older than the non-cirrhotic stages. We found PLT, GGT, ALP, TB, FIB4 and GPR to be significantly associated with liver fibrosis in our cohort. GGT showed a sensitivity of 71.4% and specificity of 76.7% in distinguishing cirrhosis (F4) from non-cirrhotic stages (F1-3), with an AUROC of 0.775 (95%CI 0.711-0.840).The AUROCs of the GPR in distinguishing cirrhosis (F4) from non-cirrhotic stages (F1-3) was 0.794 (95%CI 0.734-0.853), but it had a lower sensitivity of 59.2%. Additionally, GGT, FIB4, and GPR could differentiate advanced fibrosis (F3-4) from non-advanced fibrosis (F1-2) among individuals with chronic hepatitis B, with AUROCs of 0.723 (95%CI 0.668-0.777), 0.729 (95%CI 0.675-0.782), and 0.760 (95%CI: 0.709-0.811) respectively. CONCLUSIONS: GGT was a better biomarker to distinguish cirrhosis (F4) from non-cirrhotic stages (F1-3), while GPR was a better biomarker to identify advanced fibrosis (F3-4) and non-advanced fibrosis (F1-2) in patients with chronic hepatitis B.
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Biomarcadores , Hepatite B Crônica , Cirrose Hepática , Humanos , Masculino , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Hepatite B Crônica/complicações , Biomarcadores/sangue , Feminino , Pessoa de Meia-Idade , Adulto , Curva ROC , Progressão da Doença , Fígado/patologia , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Biópsia , gama-Glutamiltransferase/sangueRESUMO
OBJECTIVES: Neighborhood contextual factors are associated with liver transplant outcomes. We analyzed associations between neighborhood-level socioeconomic status and healthcare utilization for pediatric liver transplant recipients. METHODS: We merged the Pediatric Health Information System and Scientific Registry of Transplant Recipients databases and included liver transplant recipients ≤21 years hospitalized between January 2004 and May 2022. Outcomes were annual inpatient bed-days, risk of hospitalizations, and risk of liver biopsies. The primary exposure was zip code-based neighborhood income at transplant. We applied causal inference for variable selection in multivariable analysis. We modeled annual inpatient bed-days with mixed-effect zero-inflated Poisson regression, and rates of hospitalization and liver biopsy with a Cox-type proportional rate model. RESULTS: We included 1006 participants from 29 institutions. Children from low-income neighborhoods were more likely to be publicly insured (67% vs. 46%), Black (20% vs. 12%), Hispanic (30% vs. 17%), and have higher model for end-stage liver disease/pediatric end-stage liver disease model scores at transplant (17 vs. 13) than the remaining cohort. We found no differences in inpatient bed-days or rates of hospitalization across neighborhood groups. In univariable analysis, low-income neighborhoods were associated with increased rates of liver biopsy (rate ratio [RR]: 1.57, 95% confidence interval [CI]: 1.04-2.34, p = 0.03). These findings persisted after adjusting for insurance, race, and ethnicity (RR: 1.86, 95% CI: 1.23-2.83, p < 0.01). CONCLUSIONS: Children from low-income neighborhoods undergo more liver biopsies than other children. These procedures are invasive and potentially preventable. In addition to improving outcomes, interventions to mitigate health inequities among liver transplant recipients may reduce resource utilization.
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Renda , Transplante de Fígado , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , Transplante de Fígado/estatística & dados numéricos , Criança , Masculino , Feminino , Adolescente , Renda/estatística & dados numéricos , Pré-Escolar , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Lactente , Estados Unidos , Características da Vizinhança/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Adulto Jovem , Estudos Retrospectivos , Disparidades em Assistência à Saúde/estatística & dados numéricosRESUMO
OBJECTIVES: We performed a single-centre retrospective study comparing the accuracy of non-invasive elastography with liver biopsy in accurate assessment of Fontan-associated liver disease. METHODS: Fontan patients who underwent combined assessment with a percutaneous liver biopsy and non-invasive elastography between January 2015 and December 2023 at our Children's hospital were included. Liver biopsies were classified using the Congestive Hepatic Fibrosis Score as early Fontan-associated liver disease (scores 1, 2) and advanced Fontan-associated liver disease (score 3/bridging fibrosis and score 4/cirrhosis). Elastography values were categorised as advanced Fontan-associated liver disease for liver elasticity >2.1 m/s by ultrasound and liver stiffness >5 KPa on magnetic resonance elastography. RESULTS: We included 130 patients (116 children, 89%, mean age at biopsy: 14.6 years ± 3.6) who underwent liver biopsy at a mean duration of 11.1 years (±0.3) following Fontan surgery. Advanced Fontan-associated liver disease was noted in 41 (31.5%) patients with 13 (10%) showing frank cirrhosis. Pre-biopsy ultrasound showed advanced liver fibrosis in 18/125 (14%), with low sensitivity (23%), high specificity (90%), and low accuracy (68%, k = 0.1) in diagnosing advanced Fontan-associated liver disease. Similarly, pre-biopsy magnetic resonance elastography showed advanced fibrosis in 23/86 (27%) of patients, with low sensitivity (30%), fair specificity (75%), and low accuracy (63%, k = 0.1). Interestingly, advanced Fontan-associated liver disease was missed by ultrasound in 29% and by magnetic resonance elastography in 25% of patients. Advanced Fontan-associated liver disease was associated with lower platelet count (p = 0.02) and higher Gamma-glutamyl Transferase levels (p = 0.02). CONCLUSION: Advanced hepatic fibrosis is common among paediatric Fontan patients. Non-invasive elastography may overestimate and underestimate the degree of liver fibrosis, and therefore, liver biopsy may be required for confirming disease severity.
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Twenty-nine patients with HCV infection (HCV+) and mixed cryoglobulinemia (MC+) were retrospectively selected and matched for age and sex with 31 HCV+ MC- patients. Biomarkers of cholestasis (direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase), HCV-RNA and genotype, and plasma cryoprecipitates were measured before and after virus eradication; liver histology and plasma cells (aggregation and distribution), observed blinded by two pathologists, were analyzed. Sixty participants (mean age: 56.5; range: 35-77, males: 50%) with HCV infection were enrolled. Cholestasis (≥2 pathologically increased cholestasis biomarkers) was significantly higher in the MC group (p = 0.02) and correlated with cryoglobulinemia (OR 6.52; p = 0.02). At liver histological assessment, plasma cells were significantly increased in the MC+ group (p = 0.004) and tended to form aggregates more than the control group (p = 0.05). At multivariate analysis with MC, age, HCV-RNA, HBV diabetes, and cirrhosis, cholestasis was only significantly correlated to MC (OR 8.30; p < 0.05). In 25% patients, MC persisted after virus eradication with new antiviral treatment. Our study identified for the first time an association between MC, cholestasis, and an increased number of intrahepatic plasma cells in chronic hepatitis C (CHC) patients before virus eradication. Future studies are required to understand how MC contributes to liver damage and how its persistence affects the patients' follow-up after antiviral therapies.
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Colestase , Crioglobulinemia , Hepatite C Crônica , Hepatite C , Masculino , Humanos , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Estudos de Casos e Controles , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Crioglobulinemia/tratamento farmacológico , Crioglobulinemia/etiologia , Estudos Retrospectivos , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Colestase/complicações , Colestase/tratamento farmacológico , Biomarcadores , RNARESUMO
Purpose: To evaluate if implementation of the 2019 Society of Interventional Radiology (SIR) guidelines for periprocedural management of bleeding risk in patients undergoing percutaneous ultrasound guided liver biopsy is associated with increased haemorrhagic adverse events, change in pre-procedural blood product utilization, and evaluation of guideline compliance rate at a single academic institution. Methods: Ultrasound guided percutaneous liver biopsies from (January 2019-January 2023) were retrospectively reviewed (n = 504), comparing biopsies performed using the 2012 SIR pre-procedural coagulation guidelines (n = 266) to those after implementation of the 2019 SIR pre-procedural guidelines (n = 238). Demographic, preprocedural transfusion, laboratory, and clinical data were reviewed. Chart review was conducted to evaluate the incidence of major bleeding adverse events defined as those resulting in transfusion, embolization, surgery, or death. Results: Implementation of the 2019 SIR periprocedural guidelines resulted in reduced guideline non-compliance related to the administration of blood products, from 5.3% to 1.7% (P = .01). The rate of pre-procedural transfusion remained the same pre and post guidelines at 0.8%. There was no statistically significant change in the incidence of bleeding adverse events, 0.8% pre guidelines versus 0.4% post (P = 1.0). Conclusion: Implementation of the 2019 SIR guidelines for periprocedural management of bleeding risk in patients undergoing percutaneous ultrasound guided liver biopsy did not result in an increase in bleeding adverse events or pre-procedural transfusion rates. The guidelines can be safely implemented in clinical practice with no increase in major adverse events.
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Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. Materials and Methods: We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild (n = 7), moderate (n = 19), or severe (n = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Results: The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group (p = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.008 and p = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.005 and p < 0.0001, respectively). Conclusions: In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.
Assuntos
Inflamação , Interleucina-10 , Fígado , Obesidade Mórbida , Humanos , Interleucina-10/sangue , Interleucina-10/análise , Obesidade Mórbida/complicações , Obesidade Mórbida/sangue , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Fígado/metabolismo , Fígado/patologia , Estudos Prospectivos , Inflamação/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicaçõesRESUMO
Liver biopsy is an important means of clinical diagnosis and treatment of liver diseases, but it is not easily accepted by patients because of its invasiveness. The most commonly employed liver biopsy approaches are percutaneous or transjugular. Endoscopic ultrasound-guided liver biopsy (EUS-LB), a newly emerging transjugular technique, has been widely studied and applied in recent years, but its application in China is less common. The EUS-LB has the advantages of high safety and comfort, simultaneous sampling of both liver lobes, and adequate sampling volume; however, it also has the disadvantages of high requirements for hardware, operators, and cost. This article reviews the clinical application of EUS-LB in accordance with pertinent research findings from recent years and discusses its advantages, disadvantages, and implementation feasibility.
Assuntos
Endossonografia , Fígado , Humanos , Fígado/patologia , Fígado/diagnóstico por imagem , Endossonografia/métodos , Hepatopatias/patologia , Hepatopatias/diagnóstico por imagem , Hepatopatias/diagnósticoRESUMO
BACKGROUND: Liver biopsy is a procedure that is carried out for making the diagnosis of abnormal liver conditions. OBJECTIVES: This study assessed the factors that influence patients' acceptance of liver biopsy. METHODS: A hospital based prospective study among patients scheduled for outpatient liver biopsy. They completed an interviewer administered questionnaire that captured their expectations, the degree of pain, areas they think need improvement during the biopsy process and whether they would consent to a second liver biopsy. A qualitative aspect involved an in-depth interview of participants purposively selected for their experience of liver biopsy. Data from the quantitative group were entered into SPSS version 20 and analyzed using simple and inferential statistics while content analysis was done for the qualitative aspect. RESULTS: There were 100 participants in the quantitative group, 61 males and 39 females, and 16 in the qualitative group. Participants in the quantitative group expected a painful procedure (92%) that was likely to restrict their movement (64%). After biopsy, 44%, 40%, 28%, 26%, 18% and 17% of participants were unhappy with the long monitoring hours, biopsy needle pain, number of biopsy passes, lying on the biopsy site, shoulder tip pain and pain of local anaesthetic injection respectively. The qualitative aspect identified five thematic areas and showed that liver biopsy pain was influenced by preoperative anxiety occasioned by ill-advice and was exaggerated among females. CONCLUSION: Consenting for liver biopsy may be influenced by advice from others, while factors relating to the procedure and long monitoring period remain as deterrent factors.
CONTEXTE: La biopsie hépatique est une procédure qui est effectuée pour établir le diagnostic d'affections hépatiques anormales. OBJECTIFS: Cette étude a évalué les facteurs qui influencent l'acceptation de la biopsie hépatique par les patients. MÉTHODES: Une étude prospective en milieu hospitalier parmi les patients devant subir une biopsie hépatique en ambulatoire. Ils ont rempli un questionnaire administré par un intervieweur qui capturait leurs attentes, le degré de douleur, les domaines qu'ils pensaient devoir améliorer au cours du processus de biopsie et s'ils consentiraient à une deuxième biopsie du foie. Un aspect qualitatif impliquait un entretien approfondi avec des participants sélectionnés à dessein pour leur expérience de la biopsie hépatique. Les données du groupe quantitatif ont été saisies dans SPSS version 20 et analysées à l'aide de statistiques simples et inférentielles tandis que l'analyse de contenu a été effectuée pour l'aspect qualitatif. RÉSULTATS: Il y avait 100 participants dans le groupe quantitatif, 61 hommes et 39 femmes, et 16 dans le groupe qualitatif. Les participants du groupe quantitatif s'attendaient à une intervention douloureuse (92 %) susceptible de restreindre leurs mouvements (64 %). Après la biopsie, 44 %, 40 %, 28 %, 26 %, 18 % et 17 % des participants étaient mécontents des longues heures de surveillance, de la douleur à l'aiguille de biopsie, du nombre de passages de biopsie, de la position allongée sur le site de la biopsie, de la douleur et de la pointe de l'épaule d'injection d'anesthésique local respectivement. L'aspect qualitatif a identifié cinq domaines thématiques et a montré que la douleur de la biopsie hépatique était influencée par l'anxiété préopératoire occasionnée par un mauvais conseil et était exagérée chez les femmes. CONCLUSION: Le consentement à une biopsie hépatique peut être influencé par les conseils d'autrui, tandis que les facteurs liés à la procédure et à la longue période de surveillance restent des facteurs dissuasifs. MOTS CLÉS: Facteurs, influence, acceptation, biopsie hépatique. Nigérians.