Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease

Background/Aims

The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH.

Methods

One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea.

Results

According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH.

Conclusions

Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.     

Menopause and modifiable coronary heart disease risk factors: A population based study

Objectives

The aim of our study was to determine the effect of the menopause on various coronary heart disease (CHD) risk factors and on the global risk of CHD in a population based sample of women, making the difference between menopause and age related effects.

Study design

The Third French MONICA cross-sectional survey on cardiovascular risk included 1730 randomly selected women, aged 35–64 years, representative from the general population.

Main outcome measures

Women were defined as post-menopausal (postM; n = 696), peri-menopausal (periM; n = 183) or pre-menopausal (preM; n = 659) based on the date of last menses. Socio-demographic, clinical and biological data were collected. Analyses of variance were used to compare means.

Results

PostM women had significantly higher age-adjusted levels of total cholesterol (6.0 mmol/L in postM vs. 5.7 mmol/L in preM, p < 0.05) and LDL cholesterol (3.9 mmol/L vs. 3.6 mmol/L, p < 0.05). There was no difference in HDL cholesterol or triglyceride levels, glycemia or blood pressure. Further adjustment on body mass index and hormonal treatments did not modify the results. No risk factor was significantly different between periM and postM. However, the Framingham 10-year risk of CHD was higher in postM, as compared with periM (5.1% vs. 5.0%, p < 0.05). In postM women, lipids and the Framingham risk were not associated with elapsed time since menopause.

Conclusions

The CHD risk increases during the sixth decade could be explained not only by estrogen deprivation but also by an effect on lipid profile, which is likely to occur in the peri-menopause period.     

Apolipoprotein B is highly associated with the risk of coronary heart disease as estimated by the Framingham risk score in healthy Korean men

The aim of this study was to examine the association between serum apolipoprotein B (apoB) and the risk of coronary heart disease (CHD) using Framingham risk score (FRS) in healthy Korean men. A total of 13,523 men without medication history of diabetes and hypertension were enrolled in this study. The FRS is based on six coronary risk factors. FRS ≥ 10% was defined as more-than-a-moderate risk group and FRS ≥ 20% as high risk group, respectively. The logistic regression analyses were conducted. When quartile 1 (Q1) set as a reference, in unadjusted analyses, the Q2, Q3, Q4 of apoB level had increased odds ratio (OR) for the risk of CHD in both more-than-a-moderate risk and high risk group, respectively. After adjusting for confounding variables, multivariable-adjusted logistic regression analyses showed a strong relationship between the quartiles of apoB level and more-than-a-moderate risk and high risk group, respectively. These associations were attenuated, but still remained statistically significant. ApoB is found to be independently related to the risk of CHD using FRS in healthy Korean men, and the link between apoB and the risk of CHD is dose-dependent.     

Effect of vitamin E in nonalcoholic fatty liver disease with metabolic syndrome: A propensity score-matched cohort study

Background/Aims

Vitamin E improves the biochemical profiles and liver histology in nonalcoholic steatohepatitis, but the role of vitamin E is not clearly defined in the management of nonalcoholic fatty liver disease (NAFLD) which includes both simple steatosis and steatohepatitis. Co-morbid metabolic syndrome increases the probability of steatohepatitis in NAFLD. In this study, we aimed to determine the short-term effects of vitamin E and off-treatment durability of response in a propensity-score matched cohort of NAFLD patients with metabolic syndrome.

Methods

A retrospective cohort was constructed by retrieving 526 consecutive NAFLD patients from the electronic medical record data warehouse of a tertiary referral hospital in South Korea. Among them, 335 patients (63.7%) had metabolic syndrome and were eligible for vitamin E therapy. In order to assess the effect of vitamin E, propensity score matching was used by matching covariates between control patients (n=250) and patients who received vitamin E (n=85).

Results

The PS-matched vitamin E group (n=58) and control group (n=58) exhibited similar baseline metabolic profiles. After 6 months of vitamin E therapy, the mean ALT levels decreased significantly compared to PS-matched control (P<0.01). The changes in metabolic profiles (body weight, lipid and glucose levels) did not differ between control and vitamin E groups during the study period.

Conclusions

Short-term vitamin E treatment significantly reduces ALT levels in NAFLD patients with metabolic syndrome, but metabolic profiles are not affected by vitamin E.     

Pathologic features associated with fibrosis in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of clinicopatholologic conditions ranging from steatosis alone to nonalcoholic steatohepatitis (NASH), with varying risks for progression to cirrhosis. Although steatosis alone seems to be nonprogressive, some patients with NASH can progress. This study focuses on the clinical and pathological characteristics of patients with NAFLD associated with the development of histological fibrosis. Patients with an established diagnosis of nonalcoholic fatty liver were identified through our NAFLD database containing extensive clinical, demographic, and laboratory data. Liver biopsy specimens were read blindly by one hepatopathologist using a 19-item pathological protocol and by another hepatopathologist using a second pathological protocol. Clinical and pathological data were matched to the presence of different types of histological fibrosis. Univariate and multivariate analyses helped determine all of the variables independently associated with histological fibrosis. Of 132 NAFLD patients, 21.2% had advanced fibrosis (septal/bridging fibrosis or well-established cirrhosis). Sinusoidal fibrosis was present in 20.3% of patients, whereas perivenular fibrosis was seen in 17.2%. Ballooning degeneration and Mallory bodies were independently associated with both sinusoidal fibrosis and perivenular fibrosis. Aspartate aminotransferase/alanine aminotransferase ratio and ballooning degeneration were also independently associated with periportal-portal fibrosis. We conclude that the presence of hepatocyte injury in NAFLD is associated with fibrosis. These pathological features can be used to establish the pathological criteria for diagnosis of the progressive form of NAFLD or NASH.     

Development and validation of a simple index system to predict nonalcoholic fatty liver disease

Background/Aims

Abdominal ultrasonography is useful for the detection and diagnosis of nonalcoholic fatty liver disease (NAFLD). The aims of this study were to establish a predictive model for the selection of subjects for abdominal ultrasonography for the diagnosis of NAFLD and to assess validity of the model.

Methods

The subjects included 901 people who visited the health examination center of the Busan Medical Center. We conducted multiple logistic regression analyses of potential risk factors to identify independent risk factors for NAFLD, and developed an index system.

Results

Four independent risk factors were identified. The index system was developed by assigning 1 clinical scoring point to approximately 0.7 logistic regression coefficients to each factor as follows: alanine aminotransferase/aspartate aminotransferase ratio >1.5 (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.21-4.07; P=0.010), 1 point; γ-glutamyl transpeptidase >50 (OR, 2.15; 95% CI, 1.13-4.07; P=0.019), 1 point; triglyceride >150 mg/dL (OR, 1.92; 95% CI, 1.14-3.24; P=0.015), 1 point; 23 kg/m²≤BMI<25 kg/m² (OR, 3.68; 95% CI, 2.05-6.63; P<0.001), 2 points; and BMI 25 kg/m² (OR, 7.65; 95% CI, 4.29-13.62; P<0.001), 3 points. The area under the receiver operating characteristics curve was 0.797 (95% CI, 0.751-0.842), and when 3 points was used as a cut-off value, the sensitivity and specificity were 71.7% and 75.9%, respectively.

Conclusions

NAFLD can be predicted through the clinical application of the index system established herein. If abdominal ultrasonography is used for high-risk patients, NAFLD will be diagnosed and managed in its early stage.     

肝脏固有免疫在非酒精性脂肪性肝病中的作用

非酒精性脂肪性肝病发病机制尚未完全阐明,近年来研究表明肝脏固有免疫参与了非酒精性脂肪性肝病从单纯性脂肪肝进展至肝硬化的过程。肝脏通过固有免疫细胞的激活促进炎症介质的表达及肝细胞的凋亡参与非酒精性脂肪性肝病的病程进展。     

Prevalence trends of non-alcoholic fatty liver disease among young men in Korea: A Korean military population-based cross-sectional study

Background/AimsNon-alcoholic fatty liver disease (NAFLD) has become a major concern in Korea since its emergence as a dominant cause of chronic liver disease. However, no study has explored its prevalence in adults under 30 years of age. Therefore, we performed a cross-sectional study to investigate the prevalence of NAFLD in Korean men in their early 20s.MethodsWe collected data of 596,359 Korean soldiers who participated in a health examination between January 2015 and July 2021. A total of 571,872 individuals were analyzed after excluding those with missing data and hepatitis B antigen positivity. Hepatic steatosis was determined using the hepatic steatosis index (HSI). Participants with HSI >36 were considered to have NAFLD.ResultsAll participants were men, and the mean age was 20.9±1.3 years. Of the 571,872 participants screened, 77,020 (13.47%) were classified as having NAFLD. The prevalence of NAFLD consistently increased from 2015 to 2021 (10.66% vs. 16.44%, P<0.001). Increases from 2015 to 2021 were also noted in the prevalence of hypercholesterolemia, hyperglycemia, and hypertension (P<0.001 for all). The mean body mass index also increased from 23.3±3.0 kg/m² to 23.9±3.1 kg/m² between 2015 and 2021 (P<0.001).ConclusionsThe prevalence of NAFLD and of other metabolic dysfunctions in Korean men in their early 20s increased from 2015 to 2021.     

Relationship between chronic kidney disease and risk of coronary heart disease in Korean men

There have been many epidemiological researches of chronic kidney disease (CKD), accompanied by an increase in the incidence of coronary heart disease (CHD). However, as far as we know, little research has been done to examine the extent of the relationship between CKD and CHD as estimated by Framingham risk score (FRS) in Korean men. CKD was defined as either proteinuria or an eGFR of < 60 mL/min per 1.73 m(2). The FRS has been used to predict the 10-yr risk of coronary events and usually divided into three levels of risk < 10% (low), 10%-19% (intermediate) and ≥ 20% (high). We defined FRS ≥ 10% as more-than-a-moderate CHD risk group and FRS ≥ 20% as a high CHD risk group, respectively. After adjusting for covariates, multivariable-adjusted logistic regression analyses showed a strong statistical significant relationship between CKD and high risk of CHD (adjusted OR, 1.95 [95% CI, 1.32-2.87]). Dipstick urinalysis and eGFR can be readily measured in most clinical settings. The measurement of kidney function may represent a relatively inexpensive and efficient way to identify individuals at higher risk for CHD.     

The influence of waist circumference on insulin resistance and nonalcoholic fatty liver disease in apparently healthy Korean adults

Background/Aims

Waist circumference (WC) is a risk factor for metabolic syndrome and is related to insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to determine the association between WC and IR and NAFLD in apparently healthy Korean adults.

Methods

The volunteers included in this cross-sectional study comprised 9,159 adults (5,052 men, 4,107 women) who participated in a comprehensive health checkup program. IR was evaluated by the homeostasis model assessment of IR (HOMA-IR) and was considered to be present when the HOMA-IR score was >2. NAFLD was evaluated by ultrasound examination. Elevated alanine aminotransferase (ALT) was defined as >40 IU/L in men and >35 IU/L in women. Logistic regression was performed to determine the odds ratios (ORs) and 95% confidence intervals (95% CIs) for NAFLD, IR, and ALT according to categorized levels of WC.

Results

NAFLD was found in 2,553 (27.9%) of the participants (82.6% men, 17.4% women), while IR and elevated ALT were found in 17.2% (68.1% men, 31.9% women) and 10% (83% men, 17% women), respectively. After adjusting for confounding factors, the prevalence of NAFLD, IR, and elevated ALT was significantly associated with increases in WC quartile: highest quartile for NAFLD in men, OR=15.539, 95% CI=12.687-19.033; highest quartile for NAFLD in women, OR=48.732, 95% CI=23.918-99.288 (P<0.001); and highest quartile for IR in men, OR=17.576, 95% CI=13.283-23.255; highest quartile for IR in women, OR=11.078, 95% CI=7.813-15.708 (P<0.001); highest quartile for elevated ALT in men, OR=7.952, 95% CI=6.046-10.459; and highest quartile for elevated ALT in women, OR=8.487, 95% CI=4.679-15.395 (P<0.001).

Conclusions

WC contributes to IR and NAFLD in apparently healthy Korean adults, and thus may be an important factor in the development of IR and NAFLD.     

Prehypertension among adults in Great Tunis region (Tunisia): A population-based study

Purpose

The present study aimed to determine the prevalence of prehypertension (preHTN) and its cardiometabolic profile in Tunisians, and to estimate the risk for coronary heart disease (CHD) according to blood pressure status.

Patients and method

This cross-sectional study was conducted in 2004–2005, and used a two-stage cluster sampling method to select a representative sample of the Great Tunis population. A total of 2712 individuals (1228 men and 1484 women), aged 35 to 69 years were included. Definition and classification of hypertension (HTN) was performed according to guidelines from the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure (JNC-7) report.

Results

The prevalence of preHTN and HTN was 56.8% and 25.0% in males, and 43.1% and 36.1% in females, respectively. Subjects with preHTN and those with HTN showed higher prevalence of diabetes, dyslipidemia, obesity and abdominal obesity than the normotensive (NT) group. The metabolic syndrome (MetS) was found in 8.0%, 17.8% and 53.8% of NT, preHT and HTN subjects, respectively. The risk of developing CHD within 10 years, as predicted by the Framingham-Anderson model, was above 15% for 3.9%, 31.1% and 65.0% among NT, preHTN and HTN subjects, respectively. In multivariate analysis, preHTN was associated with age (OR [95% CI], 1.02 [1.01–1.03]; P < 0.01), male gender (2.51 [1.89–3.23]; P < 0.001), obesity (2.36 [1.71–3.26]; P < 0.01), abdominal obesity (1.53 [1.14–2.06]; P < 0.01) and smoking (0.70 [0.53–0.92]; P < 0.01).

Conclusion

PreHTN is very common in Tunisians. It is associated with a higher prevalence of cardiometabolic risk factors and confers a higher risk for subsequent CHD. These findings support the recommendations of lifestyle modification for preHTN patients.     

Prevalence of non-alcoholic fatty liver disease and its relation to hypoadiponectinaemia in the middle-aged and elderly Chinese population

Introduction

Hypoadiponectinaemia is an important risk factor for non-alcoholic fatty liver disease (NAFLD). However, little is known about its role in the Chinese population. This study sought to assess the prevalence of NAFLD and its association with hypoadiponectinaemia in middle-aged and elderly Chinese.

Material and methods

We conducted a population-based cross-sectional study in an urban Shanghai sample of 2201 participants age 50 years to 83 years (973 men, 1228 women). Hepatic ultrasonographic examination was performed for all participants. Serum adiponectin concentrations were measured by ELISA methods.

Results

The prevalence of NAFLD was 19.8% (16.0% in men, 22.8% in women). Serum adiponectin levels were significantly higher in female than in male subjects (p < 0.001). Serum adiponectin levels were significantly lower in NAFLD subjects than those in control subjects (p < 0.001). The prevalence of NAFLD progressively increased with declining adiponectin levels (p _{for trend} < 0.001). The participants in the lowest adiponectin quartile had a significantly increased risk for acquiring NAFLD (OR = 2.31, 95% CI 1.72-3.15) after adjustment for potential confounders.

Conclusions

Population-based screening suggests that NAFLD is highly prevalent in middle-aged and elderly people in Shanghai, particularly among women. Serum adiponectin level is negatively associated with NAFLD independently of potential cofounders, indicating that hypoadiponectinaemia may contribute to the development of NAFLD.     

Plasma brain natriuretic peptide levels in coronary heart disease with preserved systolic function

Abstract. We evaluated the circulating levels of brain natriuretic peptide (BNP) in stable angina, unstable angina, and myocardial infarction relating hormone levels to extension of coronary disease and number of vessels involved after angiographic examination. We studied 86 patients consecutively undergoing angiographic coronary examination and echocardiographic evaluation for coronary heart disease. These included 15 control subjects (group 0), 21 with stable angina (group I), 26 with unstable angina (group II), and 24 with non-Q myocardial infarction (group III). Patients with heart failure, a history of myocardial infarction, or recent myocardial damage with electrocardiographic S-T elevation were excluded. BNP levels in patients with unstable angina and myocardial infarction were significantly increased with respect to the group with stable angina (P<0.01). There were no differences between the groups with unstable angina and myocardial infarction. Analysis of peptide levels in relation to the number of involved vessels demonstrated a significant increase in patients with three-vessel disease compared with subjects with one or two vessels involved (P<0.03); among subjects with mono-vessel disease, patients with left descendent anterior stenosis had a moremarked BNP elevation than subjects with stenosis in other regions (P<0.01). Hence, BNP levels appear to be elevated in coronary disease, especially in acute coronary syndromes, even in the absence of systolic dysfunction. BNP levels also seem to be related to the severity of coronary atherosclerosis and number of vessels involved. BNP could prove a novel marker for risk stratification, not only in heart failure but also in coronary heart disease.     

Serum progranulin as an independent marker of liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease

Background: Elevated progranulin levels are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. Progranulin has not been previously investigated as a biomarker of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether serum progranulin levels are altered in patients with biopsy-proven NAFLD and if they are associated with their clinical, biochemical, and histological characteristics. Subjects and methods: We measured serum progranulin levels in 95 patients with biopsy-proven NAFLD and 80 age- and sex-matched controls. The potential associations between progranulin and the characteristics of NAFLD patients were examined by multiple linear regression analysis. Results: Serum progranulin levels were significantly higher in NAFLD patients (34 ± 13 ng/mL) than in controls (28 ± 7 ng/mL, P < 0.001). In NAFLD patients, serum progranulin levels were associated with lipid levels and the degree of hepatic fibrosis. After adjustment for potential confounders, serum progranulin remained an independent predictor of the degree of hepatic fibrosis in NAFLD patients (β = 0.392; t =2.226, P < 0.01). Conclusions: Compared with controls, NAFLD patients have higher serum progranulin concentrations, which are closely associated with lipid values and the extent of hepatic fibrosis.