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Background/Aims@#A comprehensive analysis of trends in the incidence of hepatocellular carcinoma (HCC) is important for planning public health initiatives. We aimed to analyze the trends in HCC incidence in South Korea over 10 years and to predict the incidence for the year 2028. @*Methods@#Data from patients with newly diagnosed HCC between 2008 and 2018 were obtained from Korean National Health Insurance Service database. Age-standardized incidence rates (ASRs) were calculated to compare HCC incidence. A poisson regression model was used to predict the future incidence of HCC. @*Results@#The average crude incidence rate (CR) was 22.4 per 100,000 person-years, and the average ASR was 17.6 per 100,000 person-years between 2008 and 2018. The CR (from 23.9 to 21.2 per 100,000 person-years) and ASR (from 21.9 to 14.3 per 100,000 person-years) of HCC incidence decreased during the past ten years in all age groups, except in the elderly. The ASR of patients aged ≥80 years increased significantly (from 70.0 to 160.2/100,000 person-years; average annual percent change, +9.00%; P<0.001). The estimated CR (17.9 per 100,000 person-years) and ASR (9.7 per 100,000 person-years) of HCC incidence in 2028 was declined, but the number of HCC patients aged ≥80 years in 2028 will be quadruple greater than the number of HCC patients in 2008 (from 521 to 2,055), comprising 21.3% of all HCC patients in 2028. @*Conclusions@#The ASRs of HCC in Korea have gradually declined over the past 10 years, but the number, CR, and ASR are increasing in patients aged ≥80 years.
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Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, with a global prevalence estimated at approximately 25%. NAFLD is also the leading cause of liver cirrhosis, hepatocellular carcinoma, and death. Additionally, the risk of cardiovascular disease increases with greater NAFLD severity. The liver- and cardiovascular disease-related mortality incident rate ratios among the NAFLD population were 0.77 and 4.79 per 1,000 person-years, respectively. We intend to discuss the risk factors associated with NAFLD in terms of development and progression. Obesity or higher body mass index is closely associated with NAFLD in a dose-dependent manner, but growing evidence suggests that central obesity plays a more important role in the development of NAFLD. Saturated fat and fructose have been reported to be closely related to NAFLD. Fructose intake promotes lipogenesis and impairs mitochondria fat oxidation. The presence of type 2 diabetes is the most powerful predictive risk factor for hepatic fibrosis in patients with NAFLD. Single nucleotide polymorphism is not only associated with the prevalence of NAFLD but also associated with increased liver disease mortality. Obstructive sleep apnea, intestinal dysbiosis, and sarcopenia are associated with the development of NAFLD
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Background/Aims@#The 2030 hepatitis C virus (HCV) elimination targets of the World Health Organization are an 80% reduction in incidence and 65% reduction in mortality compared to the 2015 rates. However, information on the nationwide incidence and treatment rates of HCV infection are limited. We aimed to investigate the nationwide incidence and status of the care cascade for HCV infection in Korea. @*Methods@#This study used data from the Korea Disease Control and Prevention Agency linked with the data of the Korea National Health Insurance Service. Linkage to care was defined as visiting hospitals twice or more due to HCV infection within 1.5 years of the index date. The treatment rate was the number who had been prescribed antiviral medication within 1.5 years from the index date out of patients newly diagnosed with HCV. @*Results@#The new HCV infection rate was 17.2 per 100,000 person-years (n=8,810) in 2019. The number of new HCV infections was the highest in patients aged 50 to 59 years (n=2,480), and the new HCV infection rate significantly increased with age (p<0.001). Among newly infected patients with HCV, the linkage to care rate was 78.2% (78.2% men, 78.2% women) and the treatment rate was 58.1% (56.8% men, 59.3% women) within 1.5 years. @*Conclusions@#The new HCV infection rate was 17.2 per 100,000 person-years in Korea. It is necessary to continuously monitor the incidence and care cascade of HCV to establish proper strategies to reach the goal of HCV elimination by 2030.
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Steatotic liver disease was suggested as an overarching term encompassing various etiologies of hepatic steatosis. Experts from multinational liver societies went through the Delphi process, including four rounds of surveys, and consented to adopt a new nomenclature and definition instead of the conventional nonalcoholic fatty liver disease (NAFLD). This was to improve the understanding of the patients and primary care physicians, with an explanation of the pathophysiology in the name of the disease. Also, it could minimize the stigmatization of patients by using the histological neutral term “steatosis” instead of “fatty”. Herein, we will discuss the changes and continuity between the two nomenclatures, metabolic dysfunction-associated steatotic liver disease (MASLD) and NAFLD, as well as the challenges to MASLD which need to be addressed in future.
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Background/Aims@#L-carnitine is potentially beneficial in patients with hepatic encephalopathy (HE). We aimed to evaluate the impact of L-carnitine on the quality of life and liver function in patients with liver cirrhosis and covert HE. @*Methods@#We conducted an investigator-initiated, prospective, multi-center, double- blind, randomized phase III trial in patients with covert HE. A total of 150 patients were randomized 1:1 to L-carnitine (2 g/day) or placebo for 24 weeks. Changes in quality of life and liver function were assessed at 6 months. The model for end-stage liver disease (MELD), the 36-Item Short Form Survey (SF-36), the psychometric hepatic encephalopathy score (PHES), and the Stroop Test were evaluated in all patients. @*Results@#The total SF-36 score significantly improved in the L-carnitine group after 24 weeks (difference: median, 2; interquartile range, 0 to 11; p < 0.001); however, these values were comparable between the two groups. Furthermore, there was a significant ordinal improvement in PHES scores among patients with minimal HE who were in the L-carnitine group (p = 0.007). Changes in the total carnitine level also positively correlated with improvements in the Stroop test in the L-carnitine group (color test, r = 0.3; word test, r = 0.4; inhibition test, r = 0.5; inhibition/switching test, r = 0.3; all p < 0.05). Nevertheless, the MELD scores at week 24 did not differ between the groups. @*Conclusions@#Twenty-four weeks of L-carnitine supplementation was safe but ineffective in improving quality of life and liver function.
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Background/Aims@#We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD). @*Methods@#An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to identify biomarkers that could predict the response to DPP-4 inhibitors. In the validation study (study II), the HFD-induced NAFLD model was divided into high and low hepatic insulin-like growth factor binding protein 1 (Igfbp-1) groups based on the pre-study liver biopsy. @*Results@#DPP-4 inhibitor attenuated the NAFLD activity score and fibrosis stage in the HFD model but not in the WD and MCD models. The overall response rate was 19% across the modified basket NAFLD trial and 42%, 25%, and 0% in the HFD, WD, and MCD models. Hepatic Igfbp-1 expression was higher in the responder group than in the non-responder group in pre-study biopsy samples. In contrast, hepatic Igfbp-1 expression was lower in the responder group than in the non-responder group in the end-study biopsy samples. DPP-4 inhibitor response rates were 83% and 17% in the baseline hepatic high Igfbp-1 and low Igfbp-1 groups, respectively. Hepatic messenger RNA Igfbp-1 expression was positively correlated with serum IGFBP-1 levels. @*Conclusions@#The DPP-4 inhibitor response was higher in the HFD phenotype and pre-treatment levels of hepatic or serum IGFBP-1 were high.
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Background/Aims@#Subepithelial tumors (SETs) are small, mostly asymptomatic lesions with normal overlying mucosa, usually identified incidentally on endoscopy. The aim of this study was to evaluate the pathologic diagnosis of SETs, and to assess the diagnostic yield and impact of endoscopic submucosal dissection (ESD) biopsy on the management of patients with SETs. @*Materials and Methods@#We included 52 subepithelial lesions in this study during the study period. Inclusion criteria included size of the SET >2 cm, and a gastrointestinal stromal tumor (GIST) that cannot be excluded using EUS. We performed an endoscopic biopsy of each SET using the ESD technique. @*Results@#The mean diameter of the lesions was 24.15±6.0 mm. The diagnostic yield of this method was 96.15%. Among the 52 participants, 45 were located in the stomach, four in the esophagus, and three in the duodenum. The pathologic diagnoses included: 17 leiomyomas, 13 GISTs, 11 ectopic pancreases, two carcinomas, two inflammatory fibroid polyps, two Brunner’s gland hyperplasia, two lipomas, one glomus tumor, and two remained undiagnosed. The mean duration of the procedure was 13.44±2.41 minutes. Three complications were associated with the procedure. @*Conclusions@#Deep biopsy via ESD is useful in determining the histopathologic nature of SETs. This method minimizes the need for unnecessary surgery in benign SETs.
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Background and Objectives@#Hypoxia is frequently used to enhance stem cell function. However, the optimal level of hypoxia for growth and function of human embryonic stem cell-derived mesenchymal stem cells (hES-MSCs) is yet to be determined. The purpose of this study was to find the optimal level of hypoxia for hES-MSCs and characteristics of hES-MSCs cultured under these optimal hypoxic conditions. @*Methods@#and Results: Cell viability and changes in the morphology of hES-MSCs were determined through cell proliferation and CCK-8 assay. The hES-MSCs were preconditioned under various hypoxic conditions (0.5∼5% O2 and 24∼72 h). The expression of cytokines in each culture condition was compared using cytokine array analysis. The morphology of hES-MSCs did not change under various hypoxic culture conditions. hES-MSCs viability after 48 h incubation in 2% O2condition was higher than that in normoxic condition. HIF1α expression was increased up to six folds after 48 h of hypoxic preconditioning. HIF1α expression in hES-MSCs peaked after 48 h of incubation in 1% O2 condition. The expressions of PDGF-BB, IGFBP-6, VEGF-A, and angiogenin were increased after hES-MSCs were incubated for 48 h in 2% O2 condition. @*Conclusions@#The hES-MSCs viability and expressions of PDGF-BB, IGFBP-6, VEGF-A, and angiogenin increased after 48 h incubation in 2% O2 condition.
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Background/Aims@#Subepithelial tumors (SETs) are small, mostly asymptomatic lesions with normal overlying mucosa, usually identified incidentally on endoscopy. The aim of this study was to evaluate the pathologic diagnosis of SETs, and to assess the diagnostic yield and impact of endoscopic submucosal dissection (ESD) biopsy on the management of patients with SETs. @*Materials and Methods@#We included 52 subepithelial lesions in this study during the study period. Inclusion criteria included size of the SET >2 cm, and a gastrointestinal stromal tumor (GIST) that cannot be excluded using EUS. We performed an endoscopic biopsy of each SET using the ESD technique. @*Results@#The mean diameter of the lesions was 24.15±6.0 mm. The diagnostic yield of this method was 96.15%. Among the 52 participants, 45 were located in the stomach, four in the esophagus, and three in the duodenum. The pathologic diagnoses included: 17 leiomyomas, 13 GISTs, 11 ectopic pancreases, two carcinomas, two inflammatory fibroid polyps, two Brunner’s gland hyperplasia, two lipomas, one glomus tumor, and two remained undiagnosed. The mean duration of the procedure was 13.44±2.41 minutes. Three complications were associated with the procedure. @*Conclusions@#Deep biopsy via ESD is useful in determining the histopathologic nature of SETs. This method minimizes the need for unnecessary surgery in benign SETs.
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Background and Objectives@#Hypoxia is frequently used to enhance stem cell function. However, the optimal level of hypoxia for growth and function of human embryonic stem cell-derived mesenchymal stem cells (hES-MSCs) is yet to be determined. The purpose of this study was to find the optimal level of hypoxia for hES-MSCs and characteristics of hES-MSCs cultured under these optimal hypoxic conditions. @*Methods@#and Results: Cell viability and changes in the morphology of hES-MSCs were determined through cell proliferation and CCK-8 assay. The hES-MSCs were preconditioned under various hypoxic conditions (0.5∼5% O2 and 24∼72 h). The expression of cytokines in each culture condition was compared using cytokine array analysis. The morphology of hES-MSCs did not change under various hypoxic culture conditions. hES-MSCs viability after 48 h incubation in 2% O2condition was higher than that in normoxic condition. HIF1α expression was increased up to six folds after 48 h of hypoxic preconditioning. HIF1α expression in hES-MSCs peaked after 48 h of incubation in 1% O2 condition. The expressions of PDGF-BB, IGFBP-6, VEGF-A, and angiogenin were increased after hES-MSCs were incubated for 48 h in 2% O2 condition. @*Conclusions@#The hES-MSCs viability and expressions of PDGF-BB, IGFBP-6, VEGF-A, and angiogenin increased after 48 h incubation in 2% O2 condition.
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Background/Aims@#To date, studies on various noninvasive techniques have been suggested to evaluate the degree of liver fibrosis. We aimed to investigate the diagnostic performance of se-rum asialo α1-acid glycoprotein (AsAGP) in the diagnosis of liver cirrhosis compared with chronic hepatitis for clinically useful result. @*Methods@#We conducted a case-control study of 96 patients with chronic liver disease. Chronic hepatitis was defined as the presence of chronic liver disease on ultrasonography, with a liver stiffness of less than 5.0 kPa as shown on magnetic resonance elastography (MRE). Liver cirrho-sis was defined as liver stiffness of more than 5.0 kPa on MRE. The serum AsAGP concentration was compared between the two groups. @*Results@#Serum AsAGP levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis (1.83 μg/mL vs 1.42 μg/mL, p<0.001). Additionally, when comparing pa-tients in each cirrhotic group (Child-Pugh grades A, B, and C) to those with chronic hepatitis, AsAGP levels were significantly higher in all the cirrhotic groups (p<0.05, p<0.01, p<0.001, respectively). The sensitivity and specificity of AsAGP for detecting cirrhosis were 79.2% and 64.6%, respectively, and the area under the curve value was 0.733. The best diagnostic cutoff to predict cirrhosis was 1.4 μg/mL. AsAGP and bilirubin were found to be independent risk factors for the prediction of cirrhosis in the logistic regression analysis. @*Conclusions@#Serum AsAGP showed an acceptable diagnostic performance in predicting liver cirrhosis.
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Tyrosine kinase inhibitors are widely used as targeted treatments for various malignancies. Sorafenib is an orally active tyrosine kinase inhibitor that blocks the signaling pathways of several growth factors. Its use is approved for various malignancies such as unresectable hepatocellular carcinoma, renal cell carcinoma, and gastrointestinal stromal tumors. Several adverse effects have been reported in the literature; however, cardiotoxicity is rare. We present a case of recurrent coronary vasospasm caused by short-term administration (5 days) of sorafenib. Since it caused refractory ischemia after re-administration, we had no choice but to stop the treatment.
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Background/Aims@#We aimed to assess the role of vitamin D supplementation in the response to pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment in patients with chronic hepatitis C (CHC). @*Methods@#Our study was a multi-center, randomized controlled trial in 11 hospitals. CHC patients were randomly assigned (1:1) to two groups namely, PEGIFN-α plus RBV (control group) or PEG-IFN-α plus RBV + vitamin D (800 IU daily) (vitamin D group). The primary end-point was the rate of sustained virologic response (SVR). @*Results@#One hundred forty eight CHC patients were randomly assigned to two groups. Seventy-one patients received the PEG-IFN-α plus RBV and 77 patients received the PEG-IFN-α plus RBV + vitamin D. A total of 105 patients completed the study (control group, 47 vs. vitamin D group, 58). Baseline characteristics were mostly similar in both the groups. There was a modest but non-significant increase in SVR in the vitamin D group compared to the control group with the intention to treat analysis (64.0% vs. 49.3 %, p = 0.071) as well as in the per protocol analysis (control group vs. vitamin D group: 74.5% vs. 84.5%, p = 0.202). Fifty-two patients (73.2%) in the control group and 63 patients (81.8%) in the vitamin D group experienced at least one adverse event. The drop-out rate due to adverseeffects was not different between both groups (control group vs. vitamin D group: 19.7% vs. 10.4%, p = 0.111). @*Conclusions@#Vitamin D supplement did not increase SVR in treatment naïve patients with CHC irrespective of genotype.
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BACKGROUND: The heterogeneity of histological findings in preclinical diet-induced nonalcoholic fatty liver disease (NAFLD) animal models is highly challenging. Here, we aimed to evaluate the feasibility and stability of repeated liver biopsy in NAFLD animal models. METHODS: Heterogeneity of diet-induced NAFLD was evaluated at different time points in 52 high-fat diet (HFD), 35 methionine choline-deficiency diet (MCD), and 166 western diet (WD) induced NAFLD mice. Serial liver biopsies (left lateral, right medial, and left medial lobes) were performed monthly for up to 3 months. Mortality rates and changes in food intake, body weight, and liver enzymes were assessed. RESULTS: At 12 weeks, of the HFD animals, 14% and 30% did not develop steatosis and lobular inflammation, respectively; of the MCD animals, 7% did not develop lobular inflammation; and of the WD animals, 14% and 51% did not develop steatosis and lobular inflammation, respectively. The mortality rate of repeated liver biopsy was 1.62% (2/123 mice died). Repeated liver biopsy can be used to trace disease progression. Although body weight, food intake, and liver enzymes slightly changed after biopsy, all recovered within a week. Repeated liver biopsy did not affect the degrees of inflammation and steatosis of the other liver lobes. CONCLUSION: The diet-induced NAFLD models were quite heterogeneous. Our results suggest that the repeated liver biopsy before treatment was applicable and stable in this NAFLD animal study.
Subject(s)
Animals , Mice , Biopsy , Body Weight , Diet , Diet, High-Fat , Diet, Western , Disease Progression , Eating , Inflammation , Liver , Methionine , Models, Animal , Mortality , Non-alcoholic Fatty Liver Disease , Population CharacteristicsABSTRACT
BACKGROUND/AIMS: For the clinical application of stem cell therapy, functional enhancement is needed to increase the survival rate and the engraftment rate. The purpose of this study was to investigate functional enhancement of the paracrine effect using stem cells and hepatocyte-like cells and to minimize stem cell homing by using a scaffold system in a liver disease model. METHODS: A microporator was used to overexpress Foxa2 in adipose tissue-derived stem cells (ADSCs), which were cultured in a poly(lactic-co-glycolic acid) (PLGA) scaffold. Later, the ADSCs were cultured in hepatic differentiation medium for 2 weeks by a 3-step method. For in vivo experiments, Foxa2-overexpressing ADSCs were loaded in the scaffold, cultured in hepatic differentiation medium and later were implanted in the dorsa of nude mice subjected to acute liver injury (thioacetamide intraperitoneal injection). RESULTS: Foxa2-overexpressing ADSCs showed greater increases in hepatocyte-specific gene markers (alpha fetoprotein [AFP], cytokeratin 18 [CK18], and albumin), cytoplasmic glycogen storage, and cytochrome P450 expression than cells that underwent the conventional differentiation method. In vivo experiments using the nude mouse model showed that 2 weeks after scaffold implantation, the mRNA expression of AFP, CK18, dipeptidyl peptidase 4 (CD26), and connexin 32 (CX32) was higher in the Foxa2-overexpressing ADSCs group than in the ADSCs group. The Foxa2-overexpressing ADSCs scaffold treatment group showed attenuated liver injury without stem cell homing in the thioacetamide-induced acute liver injury model. CONCLUSIONS: Foxa2-overexpressing ADSCs applied in a scaffold system enhanced hepatocyte-like differentiation and attenuated acute liver damage in an acute liver injury model without homing effects.
Subject(s)
Animals , Mice , Cytochrome P-450 Enzyme System , Cytoplasm , Dipeptidyl Peptidase 4 , Fetal Proteins , Glycogen , Keratin-18 , Liver Diseases , Liver Failure, Acute , Liver , Mesenchymal Stem Cells , Methods , Mice, Nude , RNA, Messenger , Stem Cells , Survival RateABSTRACT
Whether moderate alcohol intake is beneficial remains an unsolved issue. Recent studies have suggested that moderate alcohol consumption is associated with beneficial effects related to the prevention of cardiovascular diseases. Moderate alcohol consumption leads to a higher risk of hepatocellular carcinoma in patients with chronic viral liver diseases. However, the effects of moderate alcohol intake in patients with nonalcoholic fatty liver disease are unclear. In this review, we analyzed, from various perspectives, the effect of moderate alcohol consumption in patients with nonalcoholic fatty liver disease. We reviewed four cohort studies and seven cross-sectional studies. The results showed that moderate alcohol consumption was negatively related to the incidence of nonalcoholic steatohepatitis and liver fibrosis. However, moderate alcohol consumption was positively associated with the incidence of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease. The results of the analysis of the relationship between moderate alcohol consumption and the levels of triglycerides, total cholesterol, high-density lipoprotein, and hypertension were diverse. More clinical data are needed to draw a conclusion about the effects of moderate alcohol consumption in patients with nonalcoholic fatty liver disease.
Subject(s)
Humans , Alcohol Drinking , Carcinoma, Hepatocellular , Cardiovascular Diseases , Cholesterol , Cohort Studies , Cross-Sectional Studies , Hypertension , Incidence , Lipoproteins , Liver Cirrhosis , Liver Diseases , Non-alcoholic Fatty Liver Disease , TriglyceridesABSTRACT
Nonalcoholic fatty liver disease (NAFLD), together with metabolic syndrome and obesity, has shown a rapid increase in prevalence worldwide and is emerging as a major cause of chronic liver disease and liver transplantation. Among the various phenotypes of NAFLD, nonalcoholic steatohepatitis (NASH) is highly likely to progress to development of end-stage liver disease and cardiometabolic disease, resulting in liver-related and non-liver–related mortality. Nonetheless, there is no standardized pharmacotherapy against NASH and many drugs are under development in ongoing clinical trials. To develop a successful anti-NASH drug, it is necessary to select an appropriate target population and treatment outcomes depending on whether the mode of action is anti-metabolic, anti-inflammatory or anti-fibrotic. Recently, innovative surrogate markers have been investigated to replace hard outcomes such as liver histology and mortality and reduce the clinical trial duration. Currently, several drugs with fast track designation are being tested in phase III clinical trials, and many other drugs have moved into phase II clinical trials. Both lean NAFLD and typical obese NAFLD have been extensively studied and genetic variants such as PNPLA3 and TM6SF2 have been identified as significant risk factors for lean NAFLD. In the near future, noninvasive biomarkers and effective targeted therapies for NASH and associated fibrosis are required to develop precision medicine and tailored therapy according to various phenotypes of NAFLD.
Subject(s)
Biomarkers , Drug Therapy , Fibrosis , Health Services Needs and Demand , Liver , Liver Diseases , Liver Transplantation , Mortality , Non-alcoholic Fatty Liver Disease , Obesity , Phenotype , Precision Medicine , Prevalence , Risk FactorsABSTRACT
BACKGROUND/AIMS@#A number of clinical trials reported varying effects of cholesterol lowering agents in nonalcoholic fatty liver disease (NAFLD) patients. We, therefore, assessed the changes in hepatic steatosis and NAFLD activity score (NAS) after treatment with cholesterol lowering agents in NAFLD patients by metaanalysis.@*METHODS@#The Cochrane Library, the MEDLINE, and the Embase databases were searched until May 2015, without any language restrictions, for randomized controlled trials (RCTs) and nonrandomized studies (NRSs). Additional references were obtained from review of bibliography of relevant articles. The quality of evidence was assessed using the grading of recommendations assessment, development and evaluation guidelines.@*RESULTS@#Three RCTs (n = 98) and two NRSs (n = 101) met our study inclusion criteria (adult, NAFLD, liver biopsy). Liver biopsy was performed in all five studies, but only the three studies reported NAS. Ezetimibe significantly decreased NAS (standardized mean difference [SMD], –0.30; 95% confidence interval [CI], –0.57 to –0.03) but not hepatic steatosis in RCT (SMD, –0.1; 95% CI, –0.53 to 0.32), while the effect was significant for both NAS and intrahepatic content in NRSs (SMD, –3.0; 95% CI, –6.9 to 0.91).@*CONCLUSIONS@#Ezetimibe decreased NAS without improving hepatic steatosis.
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BACKGROUND/AIMS@#Intestinal cholesterol absorption includes intestinal Niemann-Pick C1-like 1 (NPC1L1) and is an important target pathway in nonalcoholic fatty liver disease (NAFLD). We investigated the expression of NPC1L1 and its correlation with liver X receptor (LXR) expression in peripheral mononuclear (PMN) cells in patients with NAFLD.@*METHODS@#We evaluated intestinal expression of NPC1L1 in 25 NAFLD patients and 28 healthy controls. We calculated the mRNA expression levels of LXR and farnesoid X receptor (FXR), which are master players of cholesterol metabolism in PMN cells. The protein expression of ABCA1, ABCG5/8, NPC1L1, SREBP, LXR, FXR, and CD36 was measured on tissue samples from the duodenum and ileum.@*RESULTS@#The expression of LXR (p = 0.01) and FXR (p = 0.03) in PMN cells was increased in the NAFLD group compared to the control group. Duodenal NPC1L1 decreased in the NAFLD group compared to the healthy controls (3.38 ± 1.4 vs. 2.42 ± 1.2, p = 0.05). NPC1L1 expression in the duodenum was negatively correlated with LXR expression in PMN cells. Expression of LXR and FXR in the ileum was also negatively correlated with the expression of LXR in PMN cells.@*CONCLUSIONS@#Duodenal NPC1L1 expression was decreased in NAFLD and was negatively correlated with LXR expression in PMN cells.
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BACKGROUND: Sarcopenia is associated with a poor prognosis in patients with liver cirrhosis. However, it is not known whether the rate of skeletal muscle depletion is also associated with a poor prognosis. We investigated the prognostic impact of the rate of skeletal muscle depletion in patients with liver cirrhosis. METHODS: We included retrospectively all patients with liver cirrhosis who underwent both multiple computed tomography scans and hepatic venous pressure gradient (HVPG) measurements. RESULTS: A total of 131 patients with liver cirrhosis were enrolled. The mean age of the patients was 53.7 years and alcoholic liver disease was the most common cause (61.8%). Sixty-four patients (48.9%) were diagnosed with sarcopenia. The median changes in skeletal muscle area per year (ΔSMA/y) were −0.89%. During a median follow-up period of 46.2 months (range, 3.4–87.6), 45 patients (34.4%) died. In multivariate analyses, age, Child-Pugh score, HVPG, presence of sarcopenia and ΔSMA/y were independently associated with mortality. Cumulative mortality was significantly higher in patients with ΔSMA/y <−2.4% than those with ΔSMA/y ≥−2.4% (log-rank test, P < 0.001). CONCLUSION: Both the presence and rate of change of sarcopenia are independently associated with long-term mortality in patients with liver cirrhosis.