RESUMO
BACKGROUND: The diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) requires at least one of five cardiometabolic criteria. It is unclear whether these criteria can be used as predictors and treatment targets for complications including liver-related events and major adverse cardiovascular events (MACE). AIMS: To investigate the relationship between cardiometabolic criteria and complications. METHODS: We conducted a nationwide, population-based study of 979,352 patients with MASLD. We investigated relationships between a number of criteria at baseline and liver-related events or MACE risks. In a separate longitudinal analysis, we included patients with five criteria at baseline and investigated the relationship between improving the criteria and the incidence of complications after 1 year. RESULTS: The cumulative incidence of MACE, but not liver-related events, increased with increasing baseline cardiometabolic criteria. In the longitudinal study, multivariable analysis using patients with five criteria (no improvement) as the reference, adjusted hazard ratios (95% confidence interval) of MACE in patients with 4, 3, 2, and 0-1 criteria (1 to 4-5 criteria improvement) were 0.55 (0.52-0.58, p < 0.001), 0.20 (0.17-0.22, p < 0.001), 0.13 (0.11-0.16, p < 0.001), and 0.06 (0.02-0.3, p < 0.001), respectively. The risk of MACE decreased as the cardiometabolic criteria improved. There was no significant association between improvement of the criteria and liver-related events. CONCLUSIONS: Cardiometabolic criteria can be used as predictors and treatment targets for cardiovascular event risk in MASLD. Developing predictors and therapeutic targets for liver-related events is a future challenge.
RESUMO
Background and aims: The enhanced liver fibrosis (ELF) score is a blood test that combines three markers linked to liver fibrosis. The utility of the ELF score has been demonstrated primarily in Western countries, but whether it is useful in areas with a high number of elderly people suffering from chronic liver disease has yet to be determined. Methods: This is a prospective study that included 373 consecutive patients who underwent a liver biopsy and had their ELF score measured on the same day. The diagnostic accuracy of the ELF score for liver fibrosis and the effect of age on the ELF score were investigated. Results: The median (interquartile) ELF scores in F0, F1, F2, F3, and F4 are 8.7 (8.2-9.2), 9.3 (8.8-10.0), 10.1 (9.4-10.7), 10.7 (9.9-11.2), and 12.0 (11.2-12.7), respectively. ELF scores increased with increasing liver fibrosis stage (p < 0.001). The diagnostic accuracy of the ELF score and FIB-4 for significant fibrosis (F2-4) and advanced fibrosis (F3-4) was comparable, but the ELF score had a higher diagnostic accuracy for cirrhosis (F4) than FIB-4. When patients were stratified by age of 60 years, the median ELF score did not differ by age in F2, F3, and F4. However, the median FIB-4 increased in patients with ≥60 years compared to those with <60 years in all fibrosis stages. Conclusions: ELF score has high diagnostic accuracy for liver fibrosis, regardless of age, and it could be used as a primary screening method.
RESUMO
This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting. This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child-Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib. Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child-Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy. Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study.
RESUMO
Background and aim: In patients with chronic hepatitis C, 8 weeks of glecaprevir and pibrentasvir (GLE/PIB) treatment for chronic hepatitis (non-cirrhosis) and 12 weeks for cirrhosis have been approved in Japan. However, whether 8 weeks of treatment for cirrhosis may reduce treatment efficacy has not been adequately investigated. Methods: This prospective, nationwide, multicenter cohort study enrolled 1275 patients with chronic hepatitis C who received GLE/PIB therapy. The effect of liver fibrosis and treatment periods on the efficiency of GLE/PIB therapy was investigated. The primary endpoint was the sustained virological response (SVR) rate in patients with chronic hepatitis (non-cirrhosis) and cirrhosis. The association between treatment periods and liver fibrosis on the SVR after 12 weeks of treatment rate was investigated. Results: The SVR rates in patients with chronic hepatitis with 8 weeks of treatment, chronic hepatitis with 12 weeks of treatment, cirrhosis with 8 weeks of treatment, and cirrhosis with 12 weeks of treatment were 98.9% (800/809), 100% (87/87), 100% (166/166), and 99.1% (211/213), respectively, and were was not different among these groups (P = 0.4). Conclusion: GLE/PIB therapy for chronic hepatitis C had high efficacy regardless of liver fibrosis status and treatment periods. Periods of GLE/PIB therapy could be chosen with available modalities, and high SVR rates could be achieved regardless of the decision.
RESUMO
Background and Aim: Magnetic resonance elastography (MRE) is used for the evaluation of liver fibrosis; however, it remains unclear whether MRE-based liver stiffness is associated with hepatocellular carcinoma (HCC) development, particularly in patients with chronic hepatitis B. Methods: A total of 504 patients with chronic hepatitis B receiving MRE were enrolled. The primary endpoint was the association between MRE-based liver stiffness and HCC. Results: In a cross-sectional analysis at the time of MRE measurement, the median (interquartile range) liver stiffness values in patients with presence or history of HCC and those without HCC were 3.68 (2.89-4.96) and 2.60 (2.22-3.45) kPa, respectively, and liver stiffness was significantly higher in patients with presence or history of HCC than in those without HCC (P < 0.001). In a longitudinal analysis of patients without HCC, the 1-, 3-, and 5-year cumulative incidence of HCC in patients with liver stiffness ≥3.6 kPa and those with liver stiffness <3.6 kPa were 3.8%, 7.0%, and 22.9%, and 0%, 0.9%, and 1.5%, respectively (P < 0.001). In the multivariable analysis, MRE-based liver stiffness (per 1 kPa) or liver stiffness ≥3.6 kPa was an independent factor for HCC development with an adjusted hazard ratio (aHR) of 1.61 (95% confidence interval [CI], 1.3-2.0) or aHR of 8.22 (95% CI, 2.1-31). Conclusion: MRE-based liver stiffness is associated with HCC risk in patients with chronic hepatitis B and may be used for the early prediction of HCC development and determination of indications for treatment.
RESUMO
BACKGROUND: A multi-society consensus group proposed a new nomenclature for steatotic liver disease (SLD) including metabolic-dysfunction associated steatotic liver disease (MASLD), MASLD and increased alcohol intake (MetALD) and alcohol-associated liver disease (ALD). However, the risk of liver-related events, major adverse cardiovascular events (MACE) and all-cause mortality among various sub-groups is unknown. AIMS: To evaluate the risk of liver-related events, MACE and death among patients with SLD. METHODS: We conducted a nationwide, population-based study and enrolled 761,400 patients diagnosed with MASLD, MetALD or ALD. The primary endpoint was the occurrence of liver-related events, MACE and death in patients with MASLD, MetALD and ALD. RESULTS: The cumulative incidence of liver-related events and death were highest in ALD, followed by MetALD and MASLD (p < 0.001 for both liver-related events and death), while the incidence of MACE was highest in MASLD, followed by MetALD and ALD (p < 0.001). Using MASLD as the reference and adjusting for age, sex, smoking, diabetes mellitus, dyslipidaemia and hypertension, the adjusted hazard ratios (95% confidence intervals) for liver-related events, MACE and death in MetALD were 1.42 (1.1-1.8), 0.68 (0.63-0.73) and 1.13 (0.98-1.3), respectively. In ALD, they were 3.42 (2.6-4.6), 0.58 (0.49-0.67) and 1.60 (1.3-2.0), respectively, for liver-related events, MACE and death. CONCLUSIONS: The new consensus nomenclature can be used to stratify the risk of complications and prognosis. The nomenclature is beneficial for risk stratification and identifying new mechanisms for disease-specific therapeutic implications.
Assuntos
Doenças Cardiovasculares , Fígado Gorduroso , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Incidência , Fígado Gorduroso/mortalidade , Fígado Gorduroso/complicações , Fígado Gorduroso/epidemiologia , Idoso , Adulto , Fatores de Risco , Causas de MorteRESUMO
BACKGROUND: Conflicting evidence regarding the prognosis of lean metabolic dysfunction-associated steatotic liver disease (MASLD) has raised substantial questions. AIM: This study aimed to elucidate the prognosis of lean MASLD by conducting a comprehensive analysis of a vast Asian cohort. METHODS: This study used a nationwide, population-based database and analyzed 2.9 million patients. The primary endpoints were liver-related events (LREs) and cardiovascular events (CVEs) in patients with lean MASLD, non-lean MASLD, and normal liver control groups. RESULTS: The median observation period was 4.2 years. The 5-year incidence values of LREs in the lean MASLD, non-lean MASLD, and normal liver control groups were 0.065%, 0.039%, and 0.006%, respectively. The LRE risk of lean MASLD was significantly higher than that of normal liver control (adjusted hazard ratio [aHR]: 5.94, 95% confidence interval [CI]: 3.95-8.92) but comparable to that of non-lean MASLD (aHR: 1.35, 95% CI: 0.87-2.08). By contrast, for CVEs, the non-lean MASLD group exhibited a higher 5-year cumulative incidence rate (0.779%) than the lean MASLD (0.600%) and normal liver control (0.254%) groups. The lean MASLD group had a reduced risk of CVEs compared with the non-lean MASLD group (aHR, 0.73; 95% CI: 0.64-0.84), and comparable risk of CVEs to the normal liver control group (aHR, 0.99; 95% CI: 0.88-1.12). CONCLUSION: Lean MASLD exhibits a similar LRE risk and a lower CVE risk to non-lean MASLD. Therefore, follow-up and treatment strategies should be tailored to the specific MASLD condition.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Incidência , Prognóstico , Adulto , Idoso , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Bases de Dados Factuais , Magreza/epidemiologia , Fígado Gorduroso/epidemiologiaRESUMO
BACKGROUND & AIMS: The natural progression of hepatic decompensation in metabolic dysfunction-associated steatotic liver disease (MASLD) is not well-characterised. We aimed to describe it by conducting a retrospective analysis. METHODS: This longitudinal, retrospective analysis of well-characterised MASLD cohorts followed for hepatic decompensation and death. The sequence of liver-related events was evaluated, and the median time between hepatic decompensation episodes and death versus. transplantation was measured. RESULTS: Of the 2016 patients identified, 220 (11%) developed at least one episode of hepatic decompensation during a median follow-up of 3.2 years. Ascites was the most common first liver-related event [153 (69.5%)], followed by hepatic encephalopathy (HE) [55 (25%)] and variceal haemorrhage (VH) [30 (13.6%)]. Eighteen out of the 220 (8.1%) patients had more than one liver-related event as their first hepatic decompensation. Among the patients who had the first episode, 87 (39.5%) had a second episode [44 (50.5%) HE, 31 (35.6%) ascites, and 12 (13.7%) VH]. Eighteen out of 220 (8.1%) had a third episode [10 (55.5%) HE, 6 (33.3%) VH, and 2 (11.1%) ascites]. Seventy-three out of 220 (33.1%) died, and 31 (14%) received liver transplantation. The median time from the first episode to the second was 0.7 years and 1.3 years from the second episode to the third. The median survival time from the first episode to death or transplantation was 2.0 years. CONCLUSION: The most common first liver-related event in MASLD patients is ascites. The median survival from the first hepatic decompensation to either death or transplantation is 2 years.
Assuntos
Ascite , Progressão da Doença , Fígado Gorduroso , Encefalopatia Hepática , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Encefalopatia Hepática/etiologia , Ascite/etiologia , Estudos Longitudinais , Fígado Gorduroso/complicações , Adulto , Idoso , Transplante de Fígado , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/mortalidade , Doenças Metabólicas/complicaçõesRESUMO
BACKGROUND AND AIM: Immune checkpoint inhibitors pose the risk of immune-related adverse events (irAEs). Recent data suggest that irAEs may be associated with a favorable prognosis. This study aimed to investigate and analyze the association between these adverse events and the clinical benefits in patients with unresectable hepatocellular carcinoma. METHODS: The study enrolled 130 patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab between November 2020 and January 2023 at a single center. The relationship between irAEs and both response rate and post-treatment outcomes was investigated. RESULTS: Out of the 130 patients, irAEs developed in 36 (27.7%) patients. The irAE group exhibited a significantly longer progression-free survival (PFS) than the non-irAE group, with a median PFS of 8.9 compared with 4.6 months (P < 0.01). No difference was found in the overall survival between the irAE and non-irAE groups. The irAE group demonstrated significantly higher disease control rate (DCR) than the non-irAE group (97.0% vs 65.5%, P < 0.01). The analysis by irAE severity revealed that the grade 1/2 group exhibited significantly longer PFS (7.9 vs 4.6 months, P = 0.007) and higher DCR (100% vs 65.5%, P < 0.01) than the non-irAE group. Furthermore, hypothyroidism correlated with a favorable PFS (8.9 vs 5.4 months, P = 0.02), DCR (100% vs 71.3%, P = 0.03), and overall response rate (58.3% vs 18.5%, P = 0.005). CONCLUSION: The presence of irAEs is associated with prolonged PFS and higher DCR. Specifically, mild irAEs (grade 1/2) and hypothyroidism displayed prolonged PFS and higher DCR.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/imunologia , Bevacizumab/efeitos adversos , Bevacizumab/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Adulto , Resultado do Tratamento , Intervalo Livre de Progressão , Idoso de 80 Anos ou maisRESUMO
PURPOSE: The effect of hepatic fibrosis stage on quantitative ultrasound based on the attenuation coefficient (AC) for liver lipid quantification is controversial. The objective of this study was to determine how the degree of fibrosis assessed by magnetic resonance (MR) elastography affects AC based on the ultrasound-guided attenuation parameter according to the grade of hepatic steatosis, using magnetic resonance imaging (MRI)-derived proton density fat fraction (MRIderived PDFF) as the reference standard. METHODS: Between February 2020 and April 2021, 982 patients with chronic liver disease who underwent AC and MRI-derived PDFF measurement as well as MR elastography were enrolled. Multiple regression was used to investigate whether AC was affected by the degree of liver stiffness. RESULTS: AC increased as liver stiffness progressed in 344 patients without hepatic steatosis (P=0.009). In multivariable analysis, AC was positively correlated with skin-capsule distance (P<0.001), MR elastography value (P=0.037), and MRI-derived PDFF (P<0.001) in patients without hepatic steatosis. In 52 of 982 patients (5%), the correlation between AC and MRIderived PDFF fell outside the 95% confidence interval for the regression line slope. Patients with MRI-derived PDFF lower than their AC (n=36) had higher fibrosis-4 scores, albumin-bilirubin scores, and MR elastography values than patients with MRI-derived PDFF greater than their AC (n=16; P=0.018, P=0.001, and P=0.011, respectively). CONCLUSION: AC is affected by liver fibrosis (MR elastography value ≥6.7 kPa) only in patients without hepatic steatosis (MRI-derived PDFF <5.2%). These values should be interpreted with caution in patients with advanced liver fibrosis.
RESUMO
AIMS: Optimizing glycemic control may prevent liver-related events and major adverse cardiovascular events (MACE) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the optimal hemoglobin A1c (HbA1c) threshold associated with a lower risk of complications, particularly liver-related events as well as MACE is unknown. METHODS: We investigated a nationwide population-based cohort and identified 633 279 patients with MASLD, with a mean follow-up of 4.2 years. Hemoglobin A1c levels were measured annually. The primary endpoint was the risk of liver-related events and MACE and to determine the optimal HbA1c level associated with the risk of complications. RESULTS: Mean HbA1c (per 1%) was associated with liver-related events (subdistribution hazard ratio [sHR] 1.26; 95% confidence interval [CI], 1.12-1.42) as well as MACE (sHR 1.36; 95% CI, 1.32-1.41) after adjustment for confounders. Multivariable sHR (95% CI) for HbA1c of <5.0%, 6.0%-6.9%, 7.0%-7.9%, 8.0%-8.9%, and ≥9.0% (reference, 5.0%-5.9%) were 14 (9.1-22), 1.70 (1.2-2.3), 3.32 (2.3-4.8), 3.81 (2.1-6.8), and 4.83 (2.4-9.6) for liver-related events, and 1.24 (0.8-1.8), 1.27 (1.2-1.4), 1.70 (1.5-2.0), 2.36 (1.9-2.9), and 4.17 (3.5-5.0) for MACE. An HbA1c level of 7% was selected as the optimal threshold for predicting complications (sHR 2.40 [1.8-3.2] for liver-related events and 1.98 [1.8-2.2] for MACE). CONCLUSION: The risk of liver-related events as well as MACE increased in a dose-dependent fashion with an increase in HbA1c levels, except for patients with HbA1c <5.0% for liver-related events. An HbA1c level of 7% was the optimal threshold associated with a lower risk of complications and may be utilized as a target for glycemic control in patients with MASLD.
RESUMO
The number of cancer cases diagnosed during the coronavirus disease 2019 (COVID-19) pandemic has decreased. This study investigated the impact of the pandemic on the clinical practice of hepatocellular carcinoma (HCC) using a novel nationwide REgistry for Advanced Liver diseases (REAL) in Japan. We retrieved data of patients initially diagnosed with HCC between January 2018 and December 2021. We adopted tumor size as the primary outcome measure and compared it between the pre-COVID-19 (2018 and 2019) and COVID-19 eras (2020 and 2021). We analyzed 13,777 patients initially diagnosed with HCC (8074 in the pre-COVID-19 era and 5703 in the COVID-19 era). The size of the maximal intrahepatic tumor did not change between the two periods (mean [SD] = 4.3 [3.6] cm and 4.4 [3.6] cm), whereas the proportion of patients with a single tumor increased slightly from 72.0 to 74.3%. HCC was diagnosed at a similar Barcelona Clinic Liver Cancer stage. However, the proportion of patients treated with systemic therapy has increased from 5.4 to 8.9%. The proportion of patients with a non-viral etiology significantly increased from 55.3 to 60.4%. Although the tumor size was significantly different among the etiologies, the subgroup analysis showed that the tumor size did not change after stratification by etiology. In conclusion, the characteristics of initially diagnosed HCC remained unchanged during the COVID-19 pandemic in Japan, regardless of differences in etiology. A robust surveillance system should be established particularly for non-B, non-C etiology to detect HCC in earlier stages.
Assuntos
COVID-19 , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Pandemias , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/complicações , Sistema de Registros , Teste para COVID-19RESUMO
AIM: A multisociety consensus group proposed a new nomenclature for metabolic dysfunction-associated steatotic liver disease (MASLD). Although patients with nonalcoholic fatty liver disease (NAFLD) are expected to be reclassified as patients with MASLD under the new nomenclature, the concordance between MASLD and NAFLD remains unclear. Moreover, waist circumference could be adjusted by ethnicity for diagnosing MASLD; however, there are limited data on the optimal waist circumference in the Japanese population. METHODS: This cross-sectional study was conducted on 3709 Japanese patients with NAFLD. The primary endpoint was the prevalence of MASLD in patients with NAFLD. The difference between the original waist circumference criteria (>94 cm for men and >80 cm for women) and the Japanese metabolic syndrome criteria (≥85 cm for men and ≥90 cm for women) for concordance between NAFLD and MASLD was also investigated. RESULTS: According to the original criteria, the prevalence of MASLD in patients with NAFLD was 96.7%. Similarly, according to the Japanese waist circumference criteria, 96.2% of patients with NAFLD could be reclassified as those with MASLD. The concordance rate was significantly higher in the original criteria than in the Japanese criteria (p = 0.02). CONCLUSIONS: NAFLD could be considered MASLD using the original MASLD criteria in the Japanese population, and insights from NAFLD research could be applied to MASLD.
RESUMO
BACKGROUND: Progression to cirrhosis in non-alcoholic steatohepatitis (NASH) is associated with a decrease in liver fat. However, the prognostic significance of liver fat content in NASH-related significant fibrosis and cirrhosis is unclear. AIM: To investigate the risk of decompensation, hepatocellular carcinoma (HCC) and mortality stratified by liver fat content in NASH-related significant fibrosis and cirrhosis. METHODS: In this meta-analysis of individual participant data, 456 patients with both magnetic resonance elastography (MRE) and MRI-derived protein density fat fraction (MRI-PDFF) were enrolled, and 296 patients with longitudinal follow-up were analysed. MRE combined with fibrosis-4 (MEFIB-index), and MRI-PDFF were used to measure liver fibrosis and fat, respectively. MEFIB-negative, MEFIB-positive+ MRI-PDFF ≥5% and MEFIB-positive+ MRI-PDFF <5% were defined as no significant liver fibrosis, NASH with significant fibrosis and higher liver fat content, and NASH with significant fibrosis and low liver fat content groups, respectively. The primary outcome was hepatic decompensation, HCC and death. RESULTS: The rates of decompensation, HCC and mortality were highest in the NASH with significant fibrosis and low liver fat group (33%, 17% and 17%, respectively), followed by the NASH with significant fibrosis and higher liver fat group (18%, 13% and 13% respectively), and lowest in the no significant fibrosis (MEFIB-negative) group (0%, 1% and 2% respectively). In multivariable-adjusted analysis, low liver fat content was strongly associated (HR = 42.2 [95% CI: 7.5-235.5, p < 0.0001]) with HCC, decompensation and death. Sensitivity analyses for patients with cirrhosis (MRE ≥5 kPa) determined consistent findings. CONCLUSIONS: Low liver fat content in patients with burnt-out NASH-related significant fibrosis and cirrhosis is associated with an increase in hepatic decompensation, HCC and mortality.
Assuntos
Carcinoma Hepatocelular , Técnicas de Imagem por Elasticidade , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Fibrose , Imageamento por Ressonância MagnéticaRESUMO
Introduction: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or superselective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, superselective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone. Results: Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and 3 patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status. Conclusion: The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug-free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread.
RESUMO
Objective Pemafibrate is a recently developed selective peroxisome proliferator-activated receptor alpha modulator that can improve alanine aminotransferase (ALT) levels in patients with nonalcoholic fatty liver disease (NAFLD). However, the effectiveness of ALT normalization with pemafibrate and bezafibrate, a traditional fibrate, has not been compared. Methods In this retrospective study, we compared the effects of pemafibrate and bezafibrate on ALT normalization in patients with NAFLD. The primary endpoint was the ALT normalization rate at 12 months after administration. Patients Twenty and 14 patients with NAFLD receiving pemafibrate and bezafibrate, respectively, were included in this retrospective analysis. All patients had elevated ALT levels and dyslipidemia at entry. Results The ALT normalization rates at 3, 6, and 12 months were 40%, 55%, and 60% for pemafibrate and 14.3%, 28.6%, and 14.3% for bezafibrate, respectively. The ALT normalization rate at 12 months was significantly higher in patients treated with pemafibrate than in those treated with bezafibrate (p=0.01). Pemafibrate, when compared with bezafibrate, was shown to be a significant factor for ALT normalization in a multivariable analysis with an adjusted odds ratio (95% confidence interval) of 13.8 (1.6-115, p=0.01). Conclusion Pemafibrate is effective in ALT normalization in patients with NAFLD and may be used as a treatment for NAFLD.
RESUMO
Background Because of the global increase in the incidence of nonalcoholic fatty liver disease, the development of noninvasive, widely available, and highly accurate methods for assessing hepatic steatosis is necessary. Purpose To evaluate the performance of models with different combinations of quantitative US parameters for their ability to predict at least 5% steatosis in patients with chronic liver disease (CLD) as defined using MRI proton density fat fraction (PDFF). Materials and Methods Patients with CLD were enrolled in this prospective multicenter study between February 2020 and April 2021. Integrated backscatter coefficient (IBSC), signal-to-noise ratio (SNR), and US-guided attenuation parameter (UGAP) were measured in all participants. Participant MRI PDFF value was used to define at least 5% steatosis. Four models based on different combinations of US parameters were created: model 1 (UGAP alone), model 2 (UGAP with IBSC), model 3 (UGAP with SNR), and model 4 (UGAP with IBSC and SNR). Diagnostic performance of all models was assessed using area under the receiver operating characteristic curve (AUC). The model was internally validated using 1000 bootstrap samples. Results A total of 582 participants were included in this study (median age, 64 years; IQR, 52-72 years; 274 female participants). There were 364 participants in the steatosis group and 218 in the nonsteatosis group. The AUC values for steatosis diagnosis in models 1-4 were 0.92, 0.93, 0.95, and 0.96, respectively. The C-indexes of models adjusted by the bootstrap method were 0.92, 0.93, 0.95, and 0.96, respectively. Compared with other models, models 3 and 4 demonstrated improved discrimination of at least 5% steatosis (P < .01). Conclusion A model built using the quantitative US parameters UGAP, IBSC, and SNR could accurately discriminate at least 5% steatosis in patients with CLD. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Han in this issue.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Curva ROC , Razão Sinal-Ruído , Imageamento por Ressonância Magnética/métodos , Prótons , FígadoRESUMO
Background: Advanced fibrosis detection in the general population is an unmet need. Additionally, screening method for advanced fibrosis in the general population is not established. Thus, this study aimed to examine the use of shear wave measurement (SWM), which measures liver stiffness by ultrasound elastography as a screening tool for advanced fibrosis in health checkups that represents the general population. Methods: SWM was performed in all subjects. Magnetic resonance elastography (MRE) was performed in those with SWM shear wave velocity (Vs) ≥1.3 m/s to determinate advanced fibrosis. The diagnostic accuracy of SWM Vs for advanced fibrosis (determined by MRE of ≥3.62 kPa) was examined. This prospective study was registered with the University Hospital Medical Information Network clinical trial registry (UMIN000041609). Results: A total of 2,233 subjects were included. SWM Vs of 1.64 m/s was selected as the best threshold for advanced fibrosis. Using the threshold of SWM Vs at ≥1.64 m/s, subjects were narrowed down to 1.7%, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for advanced fibrosis were 53.3%, 92.4%, 47.1%, and 94.0%, respectively, among these subjects. The multivariable analysis, after adjusting the age, sex, body mass index (BMI), hypertension, diabetes mellitus (DM), dyslipidemia, and alcohol use, revealed an SWM Vs of ≥1.64 m/s as the significant factor for advanced fibrosis with an odds ratio (95% confidence interval) of 14.5 (3.4-62; P<0.001). Conclusions: SWM has high diagnostic accuracy for advanced fibrosis (PPV 47.1%) and may be used as a screening tool for liver fibrosis in the general population.
RESUMO
BACKGROUND: There are limited data regarding the longitudinal association between MEFIB-Index (MRE combined with FIB-4) versus MAST-Score (MRI-aspartate aminotransferase) and hepatic decompensation. AIM: To examine the longitudinal association between MEFIB-Index versus MAST-Score in predicting hepatic decompensation in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This was a longitudinal, retrospective analysis of subjects from United States, Japan, and Turkey who underwent a baseline MRE and MRI-PDFF and were followed for hepatic decompensation. Cox-proportional hazard analyses were used to assess the association between MEFIB-Index versus MAST-Score with a composite primary outcome (hepatic decompensation) defined as ascites, hepatic encephalopathy, and varices needing treatment. RESULTS: This meta-analysis of individual participants (IPDMA) included 454 patients (58% women) with a mean (±SD) age of 56.0 (±13.5) years. The MEFIB-Index (MRE ≥3.3 kPa + FIB 4 ≥1.6) and MAST-Score (>0.242) were positive for 34% and 9% of the sample, respectively. At baseline, 23 patients met criteria for hepatic decompensation. Among 297 patients with available longitudinal data with a median (IQR) of 4.2 (5.0) years of follow-up, 25 incident cases met criteria for hepatic decompensation. A positive MEFIB-Index [HR = 49.22 (95% CI: 6.23-388.64, p < 0.001)] and a positive MAST-Score [HR = 3.86 (95% CI: 1.46-10.17, p < 0.001)] were statistically significant predictors of the incident hepatic decompensation. MEFIB-Index (c-statistic: 0.89, standard error (SE) = 0.02) was statistically superior to the MAST-Score (c-statistic: 0.81, SE = 0.03) (p < 0.0001) in predicting hepatic decompensation. CONCLUSION: A combination of MRI-based biomarker and blood tests, MEFIB-Index and MAST-Score can predict the risk of hepatic decompensation in patients with MASLD.