Objective The therapeutic effect of pemafibrate on metabolic dysfunction-associated fatty liver disease (MAFLD) remains unknown. This retrospective, single-arm study investigated the efficacy and ...safety of pemafibrate in MAFLD patients with hypertriglyceridemia. Methods A total of 10 patients who received pemafibrate (oral, 0.1 mg, twice a day) at Gunma Saiseikai Maebashi Hospital between September 2018 and September 2019 were included. All patients underwent a liver biopsy, and the disease grade and stage were pathologically assessed based on the FLIP algorithm. Results The median age was 66.0 (53.8-74.8) years old, and 5 patients (50.0%) were men. All patients were diagnosed with non-alcoholic steatohepatitis (NASH). The fasting and non-fasting triglyceride (TG) levels were 175 (149-247) mg/dL and 228 (169-335) mg/dL, respectively. The AST and ALT values at 6 months were significantly lower than at baseline AST: 28.0 (22.0-33.8) U/L vs. 43.5 (24.0-55.0) U/L, p=0.008, ALT: 23.0 (14.8-26.5) U/L vs. 51.5 (23.0-65.3) U/L, p=0.005, respectively, especially in NASH patients with significant activity and advanced fibrosis (p=0.040 and 0.014, respectively). Fasting TG levels were significantly lower and HDL-C levels significantly higher at 6 months than at baseline (p=0.005 and 0.032, respectively). At six months, FIB-4, the aspartate aminotransferase-to-platelet ratio index, and the macrophage galactose-specific lectin-2 binding protein glycosylation isomer level were significantly improved compared with baseline (p=0.041, 0.005 and 0.005, respectively). Treatment-related adverse events were not observed. Conclusion Pemafibrate treatment may be safe and effective for MAFLD patients with hypertriglyceridemia.
A 70-year-old man with multicentric Castleman disease (MCD) was admitted to our hospital with jaundice and ascites. Elevations in his bilirubin and interleukin-6 levels were noted, and computed ...tomography revealed hepatic atrophy and portal vein and bile duct disorders. Steroid therapy was started for MCD, but he died of hepatic failure. An autopsy revealed that the MCD activity was mild, but advanced fibrosis and cholestasis were observed in the liver. Mild infiltration of interleukin-6-positive plasma cells was noted in the highly fibrotic area of the liver. Although rare, liver and biliary tract damage may be also considered organ disorders of MCD.
Aim
The aim of this study was to investigate the predictive factors of objective response rate (ORR) and progression‐free survival (PFS), and the correlation of albumin‐bilirubin (ALBI) grade with ...decreased appetite and fatigue in hepatocellular carcinoma patients treated with lenvatinib.
Methods
From March 2018 to December 2018, a total of 94 patients was included in this retrospective multicenter study.
Results
The median age of all patients was 73 years (interquartile range 66–79.3 years), and approximately 78% patients were men. The ALBI grade was 1, 2, and 3 in 27 (28.7%), 64 (68.1%), and three patients (3.2%), respectively. The Barcelona Clinic Liver Cancer stage was early, intermediate, and advanced in one (1.1%), 22 (23.4%), and 71 patients (75.5%), respectively. Best radiological response was determined to complete response, partial response, stable disease, and progressive disease in 0 (0.0%), 24 (30.4%), 38 (48.1%), and 17 patients (21.5%), respectively, giving the ORR of 30.4%. The 3‐, 6‐, and 12‐month PFS was calculated to be 78.7% (95% CI 70.3–87.1%), 46.7% (95% CI 36.1–57.3%), and 17.4% (95% CI 6.6–28.2%). Multivariate analysis showed that the Barcelona Clinic Liver Cancer intermediate stage was shown to be the only significant factor affecting the ORR (odds ratio 3.78, 95% CI 1.14–12.5, P = 0.030) and PFS (hazard ratio 0.49, 95% CI 0.26–0.94, P = 0.030). The incidence of all grades of decreased appetite and fatigue was significantly less in patients with ALBI grade 1 compared with ALBI grade 2 + 3.
Conclusions
The Barcelona Clinic Liver Cancer intermediate stage was the predictive factor affecting the ORR and PFS, and ALBI grade was a good predictive factor affecting the incidence of fatigue and decreased appetite.
Background
Patients with morbid obesity selected for bariatric surgery have a high prevalence of nonalcoholic steatohepatitis (NASH); however, the incidence is varied and depends on race. The ...prevalence of NASH in obese Japanese patients is unknown. We evaluated the prevalence of NASH in a prospective cohort of Japanese patients with morbid obesity.
Methods
From October 2009 to July 2011, consecutive patients requiring bariatric surgery underwent a liver biopsy during the operation. The indications for bariatric surgery followed the guidelines of the Asia–Pacific Metabolic and Bariatric Surgery Society.
Results
One hundred two patients (55 males and 47 females, age 42.7 ± 10.7 years) were analyzed. The mean body mass index was 42.1 ± 8.2 kg/m
2
. Among the 102 patients, 84 patients (82.4 %) had nonalcoholic fatty liver disease and 79 patients (77.5 %) had NASH. The grading and staging of NASH by Brunt’s classification were as follows: grade 0 steatosis, one patient; grade 1 steatosis, 35 patients; grade 2 steatosis, 32 patients; grade 3 steatosis, 11 patients; stage 1 fibrosis, 25 patients; stage 2 fibrosis, 38 patients; stage 3 fibrosis, 16 patients, stage 4 fibrosis, no patients. The body weight, waist–hip ratio, visceral fat area, and aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, fasting plasma glucose, fasting plasma insulin, C peptide, hemoglobin A
1c
, and homeostasis model assessment insulin resistance levels were significantly elevated in the NASH group in comparison with the non-NASH group. The platelet count was significantly decreased in the NASH group. The waist–hip ratio and the alanine aminotransferase, fasting plasma glucose, and homeostasis model assessment insulin resistance levels were found to be independent predictors of NASH in a multivariate analysis.
Conclusion
The prevalence of NASH was 77.5 % in this prospective Japanese cohort. The prevalence of NASH in Japanese morbidly obese patients was extremely high, and early intervention should be undertaken.
Background
Patients with morbid obesity are complicated with metabolic diseases and have a high incidence of non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH).
...Methods
We report on a follow-up study of a cohort included 102 obese patients (55 males and 47 females, mean age 42.9 ± 10.6 years) undergoing bariatric surgery for the management of morbid obesity. Abdominal computed tomography was performed before and 1 year after surgery. Anthropometric and biochemical measurements were performed at 1, 3, and 5 years after surgery.
Results
The mean body mass index (BMI) of the NAFLD patients improved from 42.5 ± 8.3 kg/m
2
to 28.5 ± 6.9, and 29.1 ± 5.7, 29.7 ± 5.5 kg/m
2
at 1, 3, and 5 years, respectively. The liver fat accumulation and visceral fat areas were significantly improved at 1 year after surgery. The decrease in the BMI, waist-hip ratio, body fat percentage, and basal metabolic rate remained decreased for at least 5 years after surgery. Blood test findings including AST, ALT, γ-GTP, uric acid, albumin, CRP, HDL cholesterol, LDL cholesterol, triglycerides, and homeostasis model assessment insulin resistance (HOMA-IR) were also still improved at least 5 years after surgery.
Conclusion
Bariatric surgery is useful for ensuring the long-term treatment of NAFLD/NASH in morbidly obese Japanese patients. Bariatric surgery is a therapeutic option for patients resistant to conventional treatment.
Objective Chronic hepatitis C virus (HCV) infection carries a residual risk of hepatocarcinogenesis even after viral elimination, so appropriate follow-up is necessary. The present study investigated ...the current hospital visits and hepatocarcinogenesis status of patients who received daclatasvir plus asunaprevir treatment (DCV+ASV) to determine whether or not appropriate follow-up was being performed. Methods We retrospectively analyzed hepatocarcinogenesis, the overall survival, and the length of hospital visits in 442 patients who applied for the medical expense subsidy system for viral hepatitis and received DCV+ASV treatment in Gunma Prefecture between October 2014 and December 2015. This also included 61 patients who had a history of hepatocellular carcinoma (HCC). Results Among 442 patients, 388 achieved a sustained viral response (SVR) by DCV+ASV therapy (87.8%), and 95.9% achieved an SVR if additional treatment was included. HCC was found in 75 cases (17.0%). A history of HCC, the FIB-4 index and the treatment effect SVR were determined to be factors affecting the incidence of HCC. Regarding the follow-up rate, 89.9% of patients continued to regularly visit the hospital after 5 years of treatment. However, patients ≤60 years old had significantly lower persistence rates than older patients. The persistence rate of hospital visits to the same institution was 67.7% over a 5-year period, which was significantly better in small and medium-sized institutions than in large, specialized institutions (71.7% vs. 63.9%, p=0.039). Conclusion Patients with direct-acting antiviral treatment generally received adequate follow-up, but younger patients had a slightly higher rate of follow-up interruption and were considered to need support.
Aim
This study aimed to investigate the factors predicting overall response and overall survival in hepatocellular carcinoma patients undergoing balloon‐occluded transcatheter arterial ...chemoembolization (B‐TACE).
Methods
Sixty‐six patients treated with B‐TACE at a Japanese tertiary referral hospital between January 2011 and August 2015 were included in this retrospective cohort study.
Results
The overall response was classified as complete response, partial response, stable disease, and progressive disease in 35 (53.0%), 7 (10.6%), 13 (19.7%), and 11 (16.7%) patients, respectively. The response rate was 63.6%, and the disease control rate was 83.3%. The number of tumors (hazard ratio HR, 4.44; 95% confidence interval CI, 1.26–15.7; P = 0.021) and α‐fetoprotein level (HR, 11.40; 95% CI, 2.75–46.9; P < 0.001) were significantly associated with the tumor response in a multivariate analysis. The 1‐, 2‐, and 3‐year survival rates were 76.8% (95% CI, 64.5–85.3%), 57.3% (95% CI, 42.3–69.7%), and 46.7% (95% CI, 30.7–61.2%), respectively. The median survival time was 902 days. Albumin (≥3.4 g/dL) (HR, 0.28; 95% CI, 0.12–0.63; P = 0.002) and overall response (complete response and partial response) (HR, 0.33; 95% CI, 0.16–0.71; P = 0.004) were factors significantly associated with overall survival in a multivariate analysis. No mortalities were observed, but biloma requiring percutaneous transhepatic biliary drainage occurred in one patient (1.5%).
Conclusion
Balloon‐occluded transcatheter arterial chemoembolization may exert a good antitumor effect and result in good overall survival in select hepatocellular carcinoma patients.
Aim
Amino acid transporters play an important role in tumor progression and survival of cancer cells. However, the prognostic significance of L‐type amino acid transporter 1 (LAT1), system ASC amino ...acid transporter‐2 (ASCT2) and xCT expression in patients with hepatocellular carcinoma (HCC) remains unclear. The aim of this study is to investigate the clinicopathological significance of these amino acid transporters in patients with HCC.
Methods
We examined 84 patients with surgically resected HCC. Tumor sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki‐67 and microvessel density (MVD) determined by CD34.
Results
LAT1, 4F2hc, ASCT2 and xCT were positively expressed in 61% (50/84), 77% (65/84), 63% (53/84) and 65% (55/84), respectively. Positive LAT1 expression was significantly associated with 4F2hc expression, Ki‐67 and the serum albumin. By univariate analysis, LAT1 expression, disease stage and albumin had a significant relationship with overall survival. Tumor size, disease stage, portal vein invasion, albumin and α‐fetoprotein had a significant relationship with progression‐free survival. Multivariate analysis confirmed that LAT1 expression is an independent and significant prognostic factor for predicting worse outcome after surgery.
Conclusion
LAT1 can serve as a significant prognostic marker for predicting negative prognosis after surgery.
Nuclear receptor pregnane X receptor (PXR) was shown to be protective in case of dextran sulfate sodium (DSS)-induced colitis. Constitutive androstane receptor (CAR) belongs to the same nuclear ...receptor subfamily with PXR. The roles of both receptors in DSS-induced colitis were evaluated.
Wild-type, Car-null, Pxr-null, and Car/Pxr-null mice were treated with a CAR/PXR agonist or vehicle and administered 2.5% DSS in the drinking water. The typical clinical symptoms, histological scoring, proinflammatory cytokine, and apoptosis were analyzed.
Mice treated with the PXR agonist pregnenolone-16α-carbonitrile (PCN) were protected from DSS-induced colitis, as in a previous study. Mice treated with the CAR agonist, 4-bis2-(3,5-dichloropyridyloxy)benzene (TCPOBOP) were also protected from DSS-induced colitis. Interestingly, the protective effects of PCN in the Car-null mice and those of TCPOBOP in the Pxr-null mice both decreased. PCN or TCPOBOP pretreatment significantly decreased the macrophage and monocyte infiltration in DSS-induced colitis. PXR and CAR agonists reduced the mRNA expression of several proinflammatory cytokines in a PXR- and CAR-dependent manner, respectively. CAR inhibited apoptosis by inducing Gadd45b. PXR inhibited TNF-α and IL-1b and CAR induced Gadd45b in in vitro cell analyses.
We showed that CAR and PXR cooperatively ameliorate DSS-induced colitis. PXR and CAR protected against DSS-induced colitis by inhibiting proinflammatory cytokines and apoptosis, respectively.
Background and Aim
This retrospective study investigated the effect of 48‐week pemafibrate therapy in non‐alcoholic fatty liver disease (NAFLD) with hypertriglyceridemia, as evaluated by the ...FibroScan‐aspartate aminotransferase (FAST) score.
Methods
A total of 31 NAFLD patients who were treated with pemafibrate in Gunma Saiseikai Maebashi Hospital and Kusunoki Hospital from September 2018 to April 2020 were included in the current study. We used the FAST score, which is a novel index of steatohepatitis that can be calculated based on the AST value, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM), to evaluate the effect of pemafibrate treatment.
Results
The median age was 64.0 (interquartile range IQR 55.0–75.0) years and 14 patients (45.2%) were male. Median body mass index was 26.8 (IQR 23.8–28.8). Hypertension and diabetes mellitus were detected in 14 (45.2%) and five (16.1%) patients, respectively. Fasting triglyceride and high‐density lipoprotein cholesterol were significantly improved (P < 0.001 and 0.013, respectively) and the AST, alanine aminotransferase (ALT), alkaline phosphatase, and γ‐glutamyl transpeptidase values were significantly decreased during pemafibrate treatment (P = 0.041, <0.001, <0.001, and <0.001, respectively). While the LSM value and CAP value did not differ to a statistically significant extent (P = 0.19 and 0.140, respectively), the FAST score was significantly improved during pemafibrate treatment (P = 0.029). The delta FAST score was found to be correlated with the variations of ALT (r = 0.504, P = 0.005), which represents the effect of pemafibrate.
Conclusions
Pemafibrate improved the FAST score due to the hepatic anti‐inflammatory effect, indicating that pemafibrate may prevent disease progression in NAFLD patients with hypertriglyceridemia.
The FibroScan‐aspartate aminotransferase (FAST) score, which stratifies patients with risk of progressive non‐alcoholic steatohepatitis effectively, was significantly improved during pemafibrate treatment. The delta FAST score was correlated with the variations of alanine aminotransferase, which represents the effect of pemafibrate. Pemafibrate may prevent disease progression in non‐alcoholic fatty liver disease patients with hypertriglyceridemia.
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