Hepatic Fat Content In Patients Research Articles

Empagliflozin add‐on therapy is superior to metformin monotherapy in diabetic patients with NAFLD: An open‐label, single‐center, pilot clinical trial

AbstractBackgroundThe prevalence of non‐alcoholic fatty liver disease (NAFLD), which is characterized by hepatic steatosis, inflammation, and advanced fibrosis, is high among type‐2 diabetes mellitus (T2DM) patients. Empagliflozin (EMPA), a sodium‐glucose cotransporter‐2 inhibitor, has been well established to improve glycemic status in T2DM. However, evidence of the desirable effects of EMPA, when added to the standard treatment in diabetics with coexisting NAFLD, has yet to be determined.ObjectiveThe main objective of the current study is to explore the benefits of EMPA on hepatic fat content in patients with T2DM and NAFLD, who received metformin (MET) monotherapy.MethodsIn this open‐label clinical trial study, 60 patients with T2DM and NAFLD were assigned to either the MET + EMPA or MET group in an up‐titrated manner for 24 weeks. Anthropometric characteristics, blood glucose indices, lipid profile, liver enzymes, and steatosis grades were measured at baseline and 24 weeks after the intervention.ResultsThe results showed that in patients with a mean age of 53.26 ± 7.64 who received MET+ EMPA, all the parameters had a greater decrease than the MET group. In addition, the reduction of FBS, BS, HbA1C, TG, and ALT had a statistically significant difference between the two groups after 24 weeks follow‐up (p < 0.05). Notably, in the MET+ EMPA group, there was a substantial improvement in steatosis grades based on the fibroscan and ultrasound modality results.ConclusionThe EMPA add‐on therapeutic schedule in uncontrolled T2DM patients with NAFLD significantly ameliorated steatosis stages, liver function, anthropometric features, and biochemical parameters.

Curcumin supplementation alleviates hepatic fat content associated with modulation of gut microbiota-dependent bile acid metabolism in patients with nonalcoholic simple fatty liver disease: a randomized controlled trial

BackgroundOur previous studies showed that curcumin prevented hepatic steatosis in animal models. ObjectivesThis study aimed to assess the effects of curcumin on hepatic fat content, body composition, and gut microbiota-dependent bile acid (BA) metabolism in patients with nonalcoholic simple fatty liver (NASFL). MethodsIn a 24-wk double-blind randomized trial, 80 patients with NASFL received 500 mg/d curcumin or placebo. Hepatic fat content was measured using FibroTouch-based controlled attenuation parameters (CAPs). Microbial composition and BA metabolites were analyzed using 16S rRNA sequencing and metabolomics. ResultsCurcumin consumption significantly reduced CAP value compared with placebo (−17.5 dB/m; 95% confidence interval [CI]: −27.1, −7.8 dB/m; P < 0.001). This corresponded to reduction in weight (−2.6 kg; 95% CI: −4.4, −0.8 kg; P < 0.001) and BMI (−1.0 kg/m2; 95% CI: −2.0, −0.1 kg/m2; P = 0.032) compared with placebo group. Additionally, free fatty acid (−0.12 mmol/L; 95% CI: −0.20, −0.04 mmol/L; P = 0.004), triglycerides (−0.29 mmol/L; 95% CI: −0.41, −0.14 mmol/L; P < 0.001), fasting blood glucose (−0.06 mmol/L; 95% CI: −0.12, −0.01 mmol/L; P = 0.038), hemoglobin A1c (−0.06%; 95% CI: −0.33, −0.01%; P = 0.019), and insulin (−4.94 μU/L; 95% CI: −9.73, −0.15 μU/L; P = 0.043) showed significant reductions in the curcumin group compared with placebo group. Gut microbiota analysis indicated that curcumin significantly decreased Firmicutes to Bacteroidetes ratio and significantly increased Bacteroides abundance. Serum levels of deoxycholic acid, the most potent activator of Takeda G protein-coupled receptor 5 (TGR5), were significantly elevated after curcumin intervention (37.5 ng/mL; 95% CI: 6.7, 68.4 ng/mL; P = 0.018). Curcumin treatment also increased TGR5 expression in peripheral blood mononuclear cells and serum glucagon-like peptide-1 levels (0.73 ng/mL; 95% CI: 0.16, 1.30 ng/mL; P = 0.012). ConclusionsImprovements in gut microbiota-dependent BA metabolism and TGR5 activation after 24-wk curcumin intervention were associated with a reduction in hepatic fat content in patients with NASFL, providing evidence that curcumin is a potential nutritional therapy for NASFL.The trial was registered at www.chictr.org.cn as ChiCTR2200058052.

801-P: Short-Acting Exenatide Added Three Times Daily to Insulin Therapy Improves Fatty Liver Index in Type 1 Diabetes

Fatty liver index (FLI), a marker of hepatic fat content, has been reported as an independent risk factor for all-cause mortality and major cardiovascular events in type 1 diabetes. How short-acting glucagon-like peptide 1 receptor agonists (GLP-1RA) influence FLI in type 1 diabetes remains unknown. We analyzed FLI post-hoc in a phase 2, double-blind, randomized (1:1), clinical trial (NCT03017352) that assessed the efficacy of short-acting GLP-1RA exenatide 10 μg added three times daily to insulin therapy as compared with placebo over 26 weeks of treatment in 108 individuals with type 1 diabetes (76/32 men/women, age 50 (14) years (mean (standard deviation)), diabetes duration 21 (12) years, BMI 28 (4) kg/m2, glycated hemoglobin A1c 8.2 (0.7) % / 66 (7) mmol/mol). Exenatide significantly reduced FLI by 23 % (95 % confidence interval -44; -10, P = 0.001) (Table 1) as compared with placebo after 26 weeks’ treatment. In conclusion, short-acting exenatide reduced FLI-assessed hepatic fat content in patients with long-standing type 1 diabetes and inadequate glycemic control, alluding to potential beneficial effects of this GLP-1RA on both morbidity and mortality in type 1 diabetes. Disclosure N.Johansen: Other Relationship; AstraZeneca, Novo Nordisk, Research Support; JDRF. T.F.Dejgaard: Advisory Panel; Novo Nordisk, Research Support; Novo Nordisk, Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk, AstraZeneca. A.Lund: Speaker's Bureau; Novo Nordisk. C.K.Nielsen: None. T.Vilsbøll: Consultant; AstraZeneca, Boehringer Ingelheim Inc., Gilead Sciences, Inc., Eli Lilly and Company, Mundipharma, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi, Sun Pharmaceutical Industries Ltd., Bristol-Myers Squibb Company. F.K.Knop: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Lundbeck. Funding AstraZeneca

A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ALS-L1023 in Non-Alcoholic Fatty Liver Disease.

Preclinical data have shown that the herbal extract, ALS-L1023, from Melissa officinalis reduces visceral fat and hepatic steatosis. We aimed to assess the safety and efficacy of ALS-L1023 as the treatment of non-alcoholic fatty liver disease (NAFLD). We conducted a 24-week randomized, double-blind, placebo-controlled 2a study in patients with NAFLD (MRI-proton density fat fraction [MRI-PDFF] ≥ 8% and liver fibrosis ≥ 2.5 kPa on MR elastography [MRE]) in Korea. Patients were randomly assigned to 1800 mg ALS-L1023 (n = 19), 1200 mg ALS-L1023 (n = 21), or placebo (n = 17) groups. Efficacy endpoints included changes in liver fat on MRI-PDFF, liver stiffness on MRE, and liver enzymes. For the full analysis set, a relative hepatic fat reduction from baseline was significant in the 1800 mg ALS-L1023 group (-15.0%, p = 0.03). There was a significant reduction in liver stiffness from baseline in the 1200 mg ALS-L1023 group (-10.7%, p = 0.03). Serum alanine aminotransferase decreased by -12.4% in the 1800 mg ALS-L1023 group, -29.8% in the 1200 mg ALS-L1023 group, and -4.9% in the placebo group. ALS-L1023 was well tolerated and there were no differences in the incidence of adverse events among the study groups. ALS-L1023 could reduce hepatic fat content in patients with NAFLD.

Do Ultrasound Based Quantitative Hepatic Fat Content Measurements Have Differences Between Respiratory Phases?

The recently developed ultrasound based tools using attenuation coefficient (AC) and scatter distribution coefficient (SDC) values can be used to quantify hepatic fat content in patients with non-alcoholic fatty liver disease (NAFLD). However, currently the impact of respiratory phase on these measurements is not known. The purpose of this study is to compare AC and SDC measurements acquired at peak inspiration and end expiration phases. AC and SDC measurements were obtained in 50 patients with NAFLD. Tissue Attenuation Imaging (TAI) and Tissue Scatter Distribution Imaging (TSI) tools were utilized to measure AC and SDC values, respectively. Five measurements were performed at respiratory phases using TAI and TSI tools and the median values were noted. Subgroup analyses were performed and Wilcoxon signed rank test was used for comparison of the measurements. The median values of the AC measurements at peak inspiration and end expiration phases were 0.87 dB/cm/MHz and 0.89 dB/cm/MHz, respectively. The median values of the SDC measurements at peak inspiration and end expiration phases were 97.91 and 96.62, respectively. There were no statistically significant differences in AC and SDC measurements between the respiratory phases except for AC measurements in BMI <30 kg/m2 subgroup. Our results revealed that respiratory phases have no impact on SDC measurements. However, while the AC measurements in BMI ≥30 kg/m2 subgroup showed no significant difference, there was a significant difference in AC measurements in BMI <30 kg/m2 subgroup between the respiratory phases.

Increased Hepatic Fat Content in Patients with Resistance to Thyroid Hormone Beta.

Background: Thyroid hormone (TH) has important functions in controlling hepatic lipid metabolism. Individuals with resistance to thyroid hormone beta (RTHβ) who harbor mutations in the THRB gene experience loss-of-function of thyroid hormone receptor beta (TRβ), which is the predominant TR isoform expressed in the liver. We hypothesized that individuals with RTHβ may have increased hepatic steatosis. Methods: Controlled attenuation parameter (CAP) was assessed in individuals harboring the R243Q mutation of the THRB gene (n = 21) and in their wild-type (WT) first-degree relatives (n = 22) using the ultrasound-based transient elastography (TE) device (FibroScan). All participants belonged to the same family, lived on the same small island, and were therefore exposed to similar environmental conditions. CAP measurements and blood samples were obtained after an overnight fast. The observers were blinded to the status of the patients. Results: The hepatic fat content was increased in RTHβ individuals compared with their WT relatives (CAP values of 263 ± 21 and 218.7 ± 43 dB/m, respectively, p = 0.007). The CAP values correlated with age and body mass index (BMI) (age: r = 0.55, p = 0.011; BMI: r = 0.51, p = 0.022) in the WT first-degree relatives but not in RTHβ individuals, suggesting that the defect in TRβ signaling was predominant over the effects of age and obesity. Circulating free fatty acid levels were significantly higher in RTHβ individuals (0.29 ± 0.033 vs. 0.17 ± 0.025 mmol/L, p = 0.02). There was no evidence of insulin resistance evaluated by the homeostatic model assessment of insulin resistance in both groups studied. Conclusions: Our findings provide evidence that impairments in intrahepatic TRβ signaling due to mutations of the THRB gene can lead to hepatic steatosis, which emphasizes the influence of TH in the liver metabolism of lipids and provides a rationale for the development TRβ-selective thyromimetics. Consequently, new molecules with a very high TRβ affinity and hepatic selectivity have been developed for the treatment of lipid-associated hepatic disorders, particularly nonalcoholic fatty liver disease.

716-P: Reduced Carbohydrate and Increased Protein and Fat in the Diet Augment the Positive Effect of Weight Loss on Glucose Control in Type 2 Diabetes Patients

Background: We hypothesized that dietary carbohydrate reduction will add to the effect of a diet-induced 6% body-weight loss on glycemic control and hepatic fat content in patients with type 2 diabetes (T2D). Methods: Forty-four persons of mean HbA1c 56.4 mmol/mol and 9 years of T2D were randomized 1:1 for 6-weeks full food provision, a hypo-caloric carbohydrate-reduced high-protein (CRHP) or a conventional diabetes (CD) diet (carbohydrate 30E%/50E%, protein 30E%/17E% and fat 40E%/33E%). Body-weight loss was aimed at 6% and reinforced bi-weekly by adjustment of hypo-caloric diets. Hepatic fat content was estimated by Magnetic Resonance (MR) spectroscopy and analyzed by a MR research technician, blinded to the protocol. Results: Six weeks of a hypo-caloric CRHP diet compared with a CD diet improved HbA1c (mean±SD) by further 2 mmol/mol (-8.7±4.6 mmol/mol vs. -6.7±3.9 mmol/mol, p=0.04) with comparable weight losses, 5.5±1.7 kg (5.6 %) and 5.6±2.2 kg (5.9 %) of body-weight, respectively. Hepatic fat content (median (IQR) was reduced significantly while consuming the CRHP diet (5.2% (1.3-6.9)) and CD diet (2.6% (1.6-6.5)), but with no difference between diets (p=0.40). Conclusion: Reducing carbohydrate and increasing protein and fat adds clinical relevance to the positive effects of body-weight loss on glucose control in T2D patients. Disclosure M.N. Thomsen: None. M.J. Skytte: None. A. Samkani: None. M.H. Carl: None. P. Weber: None. A. Astrup: Advisory Panel; Self; Gelesis, Novo Nordisk A/S, Saniona, Weight Watchers International, Inc. Research Support; Self; Arla Food for Health, Gelesis, Novo Nordisk A/S. Speaker’s Bureau; Self; Arla Food for Health. Stock/Shareholder; Self; Gelesis. T.M. Larsen: Advisory Panel; Self; Advisor for Sense diet programme. J. Frystyk: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. B. Hartmann: None. H. Thomsen: None. E. Chabanova: None. S. Madsbad: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. S.B. Haugaard: None. T. Krarup: None.

Lomitapide and Mipomersen-Inhibiting Microsomal Triglyceride Transfer Protein (MTP) and apoB100 Synthesis.

The goal of this review is to evaluate the role of inhibiting the synthesis of lipoproteins when there is no or little residual LDL-receptor function as in patients with homozygous familial hypercholesterolaemia. Lomitapide is administered orally once a day while mipomersen is given by subcutaneous injection once a week. Lomitapide inhibits microsomal triglyceride transfer protein while mipomersen is an antisense oligonucleotide directed against apoB100. The pivotal registration trials for lomitapide and mipomersen were published in 2013 and 2010, respectively. More recently published data from extension trials and cohort studies provides additional information on long-term safety and efficacy. The mean LDL cholesterol reduction was 50% with lomitapide in its single-arm open-label registration trial. Mipomersen reduced LDL cholesterol by approximately 25% in its double-blind, placebo-controlled registration study. Both lomitapide and mipomersen therapy are associated with variable increases in hepatic fat content. The long-term safety of increased hepatic fat content in patients receiving these therapies is uncertain and requires further study. Both drugs may cause elevated transaminase in some patients, but no cases of severe liver injury have been reported. Lomitapide may also cause gastrointestinal discomfort and diarrhoea, especially if patients consume high-fat meals and patients are advised to follow a low-fat diet supplemented with essential fatty acids and fat-soluble vitamins. Mipomersen may cause injection-site and influenza-like reactions. The effect of lomitapide and mipomersen on cardiovascular outcomes has not been studied, but circumstantial evidence suggests that the LDL cholesterol lowering achieved with these two agents may reduce cardiovascular event rates.

MRI Assessment of Treatment Response in HIV-associated NAFLD: A Randomized Trial of a Stearoyl-Coenzyme-A-Desaturase-1 Inhibitor (ARRIVE Trial).

Aramchol, an oral stearoyl-coenzyme-A-desaturase-1 inhibitor, has been shown to reduce hepatic fat content in patients with primary nonalcoholic fatty liver disease (NAFLD); however, its effect in patients with human immunodeficiency virus (HIV)-associated NAFLD is unknown. The aramchol for HIV-associated NAFLD and lipodystrophy (ARRIVE) trial was a double-blind, randomized, investigator-initiated, placebo-controlled trial to test the efficacy of 12 weeks of treatment with aramchol versus placebo in HIV-associated NAFLD. Fifty patients with HIV-associated NAFLD, defined by magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) ≥5%, were randomized to receive either aramchol 600 mg daily (n=25) or placebo (n=25) for 12 weeks. The primary endpoint was a change in hepatic fat as measured by MRI-PDFF in colocalized regions of interest. Secondary endpoints included changes in liver stiffness using magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE), and exploratory endpoints included changes in total-body fat and muscle depots on dual-energy X-ray absorptiometry (DXA), whole-body MRI, and cardiac MRI. The mean (± standard deviation) of age and body mass index were 48.2±10.3 years and 30.7±4.6 kg/m2 , respectively. There was no difference in the reduction in mean MRI-PDFF between the aramchol group at -1.3% (baseline MRI-PDFF 15.6% versus end-of-treatment MRI-PDFF 14.4%, P=0.24) and the placebo group at -1.4% (baseline MRI-PDFF 13.3% versus end-of-treatment MRI-PDFF 11.9%, P=0.26). There was no difference in the relative decline in mean MRI-PDFF between the aramchol and placebo groups (6.8% versus 1.1%, P=0.68). There were no differences in MRE-derived and VCTE-derived liver stiffness and whole-body (fat and muscle) composition analysis by MRI or DXA. Compared to baseline, end-of-treatment aminotransferases were lower in the aramchol group but not in the placebo arm. There were no significant adverse events. Conclusion: Aramchol, over a 12-week period, did not reduce hepatic fat or change body fat and muscle composition by using MRI-based assessment in patients with HIV-associated NAFLD (clinicaltrials.gov ID:NCT02684591).

Controlled attenuation parameter is correlated with actual hepatic fat content in patients with non-alcoholic fatty liver disease with none-to-mild obesity and liver fibrosis.

Non-invasive steatosis-quantifying methods are required for non-alcoholic fatty liver disease (NAFLD) patients in order to monitor disease severity and assess therapeutic efficacy. Controlled attenuation parameter (CAP) evaluated with vibration-controlled transient elastography can predict the presence of steatosis, but its application to absolute hepatic fat quantitation remains unclear. The aim of this st\udy was to examine whether CAP is correlated with real hepatic fat content in NAFLD patients. Eighty-two NAFLD patients who had undergone percutaneous liver biopsy were enrolled. CAP was measured using FibroScan(®) just before liver biopsy. The percentage of fat droplet area to hepatocyte area in biopsied specimen was determined morphometrically using computerized optical image analyzing system. The correlation between CAP and liver histology was examined. CAP showed an excellent correlation with actual liver fat percentage in the NAFLD patients with body mass index (BMI) of less than 28kg/m(2) (r = 0.579, P <0.0001), especially less than 25kg/m(2) (r = 0.708, P <0.01), but the meaningful correlation disappeared in the patients with BMI of 28kg/m(2) or more. In the patients with BMI of less than 28kg/m(2) , CAP quantitativeness was affected by the presence of stage 2-4 fibrosis, but not the presence of hepatocyte ballooning and severity of lobular inflammation. CAP may be a promising tool for quantifying hepatic fat content in NAFLD patients with none-to-mild obesity and liver fibrosis. Further improvement of CAP performance is needed for the NAFLD patients with BMI of more than 28kg/m(2) or significant hepatic fibrosis.

Accuracy of Ultrasonography and Different CT Techniques in Diagnosis and Grading of Hepatic Steatosis in Chronic Hepatitis C Virus Patients

Objective: This study aims to assess the diagnostic utility of ultrasonography and which methods of measuring attenuation on computed tomography scans is best for detection and grading of hepatic fat content in patients with chronic hepatitis C virus (HCV) infection. Materials and Methods: This study included 65 patients, withchronic hepatitis C virus infection, who had liver biopsies as a part of pre-requirement for interferon therapy. All patients submitted to ultrasound; non enhanced and enhanced CT. Attenuation measurements were obtained from 3 regions of interest in the liver and three in the spleen on both unenhanced and portal phase contrast-enhanced CT images. Hepatic attenuation measurements were analyzed both with and without normalization with the spleen. Normalization included both differences and ratios between hepatic and splenic attenuation values. Average attenuation values of the liver were compared with pathologic fat content, as were the differences and ratios between hepatic and splenic attenuation values. Results: Ultrasound had a sensitivity of 76% and specificity 73.3% in the diagnosis of hepatic steatosis. Also ultrasound accurately graded 41 out of the 65 (63.1%) patients included in the study. The simple measurement of hepatic attenuation on non enhanced CT (CTL) had the best parameters for diagnosis of hepatic steatosis with sensitivity 83%, specificity 93.3% and positive predictive value (PPV) 97.6%. All series of R2 values for the unenhanced CT scans were higher than those for the contrast-enhanced images. The R2 values for simple liver attenuation measurement without comparison with splenic attenuation were higher than the values in which splenic measurements were considered. Conclusion: Ultrasound and non enhanced CT can be used as screening tools for detection of hepatic steatosis in patients with chronic hepatitis C virus patients. Simple measurement of hepatic attenuation on unenhanced CT is more accurate than differential liver spleen values. Also, unenhanced CT can differentiate between mild-moderate and severe steatosis.

Imaging of non alcoholic fatty liver disease: A road less travelled

Non alcoholic fatty liver disease (NAFLD) is a spectrum that includes simple steatosis, nonalcoholic steatohepatitis and cirrhosis. It is increasingly emerging as a cause of elevated liver enzymes, cryptogenic cirrhosis and hepatocellular carcinoma. The morbidity and mortality related to NAFLD is expected to rise with the upsurge of obesity and type 2 diabetes mellitus. The need of the hour is to devise techniques to estimate and then accurately follow-up hepatic fat content in patients with NAFLD. There are lots of imaging modalities in the radiological armamentarium, namely, ultrasonography with the extra edge of elastography, computed tomography, and magnetic resonance imaging with chemical shift imaging and spectroscopy to provide an estimation of hepatic fat content.

A moderate weight reduction through dietary intervention decreases hepatic fat content in patients with non-alcoholic fatty liver disease (NAFLD): a pilot study

As a diet rich in fructose and an impaired intestinal barrier function have been proposed to be risk factors for the development of non-alcoholic fatty liver disease (NAFLD), the aim of the present pilot study was to determine whether a dietary intervention focusing on a reduction of fructose intake (-50 % in comparison with baseline) has a beneficial effect on liver status. A total of 15 patients with NAFLD were enrolled in the study of which 10 finished the study. Fructose and total nutrient intake were assessed using a diet history. At baseline and after 6 months liver status and markers of intestinal barrier function as well as plasminogen activator inhibitor (PAI-) 1 concentration were determined in plasma. Hepatic lipid content and transaminases in plasma as well as body mass index and some parameters of glucose metabolism (e.g., fasting plasma insulin) were significantly lower at the end of the intervention when compared to baseline. Whereas the dietary intervention had no effect on the prevalence of bacterial overgrowth, orocecal transit time and the intestinal permeability or blood ethanol levels endotoxin and PAI-1 concentration in plasma were significantly lower at the end of 6 months intervention period than at baseline. Taken together, our results indicate that a dietary intervention focusing only on one dietary parameter like fructose may help to decrease intrahepatic fat content of NAFLD patients.

Circulating Fibroblast Growth Factor 21 Levels Are Closely Associated with Hepatic Fat Content: A Cross-Sectional Study

Background and AimsFibroblasts growth factor 21 (FGF21), a liver-secreted endocrine factor involved in regulating glucose and lipid metabolism, has been shown to be elevated in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the quantitative correlation between serum FGF21 level and hepatic fat content.MethodsA total of 138 subjects (72 male and 66 female) aged from 18 to 65 years with abnormal glucose metabolism and B-ultrasonography diagnosed fatty liver were enrolled in the study. Serum FGF21 levels were determined by an in-house chemiluminescence immunoassay and hepatic fat contents were measured by proton magnetic resonance spectroscopy.ResultsSerum FGF21 increased progressively with the increase of hepatic fat content, but when hepatic fat content increased to the fourth quartile, FGF21 tended to decline. Serum FGF21 concentrations were positively correlated with hepatic fat content especially in subjects with mild/moderate hepatic steatosis (r = 0.276, p = 0.009). Within the range of hepatic steatosis from the first to third quartile, FGF21 was superior to any other traditional clinical markers including ALT to reflect hepatic fat content. When the patients with severe hepatic steatosis (the fourth quartile) were included, the quantitative correlation between FGF21 and hepatic fat content was weakened.ConclusionsSerum FGF21 was a potential biomarker to reflect the hepatic fat content in patients with mild or moderate NAFLD. In severe NAFLD patients, FGF21 concentration might decrease due to liver inflammation or injury.

Effects of Oral 5-Fluorouracil Drugs on Hepatic Fat Content in Patients With Colon Cancer 1

The association between hepatic steatosis and oral 5-fluorouracil (5-FU) agents is clinically recognized but has not been systematically studied. The aim of this study was to determine the effects of 5-FU on hepatic fat content in patients undergoing oral 5-FU therapy and to compare the effects in three subgroups of 5-FU drugs. Fifty-one patients with postoperative colon cancer (mean 61.1 years) were retrospectively studied. Forty-three patients were given adjuvant oral 5-FU therapy for a mean 3.3 years (5-FU group), and eight patients were not (control group). All patients underwent preoperative and postoperative abdominal computed tomography (CT) studies. The liver/spleen ratio was calculated from the CT attenuation values for the liver and spleen. We also compared the effects on hepatic appearance under CT of three 5-FU drugs: fluorouracil (n = 13), doxifluridine (n = 14), or UFT (a mixture of tegafur and uracil; n = 9). In the 5-FU group, the mean CT values for the liver were significantly reduced relative to values before therapy (P < .01) and to those of the control group (P < .0001). Fifteen of 43 patients (34.9%) developed steatosis. Of the three 5-FU drugs, fluorouracil and doxifluridine caused a significant decrease in hepatic CT values. 5-FU caused a significant decrease in CT attenuation, indicating an increase in hepatic fat content, and was associated with very frequent hepatic steatosis. UFT seemed less likely to cause hepatic fatty infiltration. CT examination was useful for early detection of drug-induced side effects on liver even before lab abnormality or clinical manifestation is observed.