BACKGROUND: There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension. METHODS: The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD. RESULTS: During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10-1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10-1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07-1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03-1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association. CONCLUSIONS NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.
Humans ; Non-alcoholic Fatty Liver Disease/complications* ; Prehypertension/diagnosis* ; Risk Factors ; Hypertension ; Incidence

Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with higher scores should be referred to a specialist. As the epidemic of diabetes mellitus, obesity and non-alcoholic fatty liver diseases is rising, CLD is becoming more prevalent. Easy-to-use fibrosis assessment composite scores can identify patients with minimal or advanced fibrosis, and should be an integral part of decision-making. Patients with cirrhosis, high composite scores, chronic hepatitis B with elevated alanine aminotransferase and aspartate aminotransferase, or deranged liver panel of uncertain aetiology should be referred to a specialist.
Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Decision Making ; End Stage Liver Disease ; complications ; diagnosis ; therapy ; Hepatitis B ; complications ; Humans ; Liver ; pathology ; Liver Cirrhosis ; complications ; diagnosis ; therapy ; Non-alcoholic Fatty Liver Disease ; complications ; diagnosis ; therapy ; Prognosis ; Referral and Consultation ; Treatment Outcome

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment.
Carcinoma, Hepatocellular ; pathology ; Diet ; Disease Progression ; Humans ; Life Style ; Liver ; pathology ; Liver Cirrhosis ; pathology ; Liver Neoplasms ; pathology ; Metabolic Syndrome ; complications ; Non-alcoholic Fatty Liver Disease ; diagnosis ; therapy ; Obesity ; complications ; Prevalence ; Risk Factors ; Treatment Outcome

OBJECTIVETo investigate the value of controlled attenuation parameter (CAP) in the diagnosis of fatty liver using FibroScan in patients with chronic liver disease (CLD).

METHODSA prospective cohort study was performed for the patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD) who underwent liver pathological examination followed by CAP measurement within 1 week in The Second People's Hospital of Tianjin from February 2013 to May 2014. According to related guidelines, hepatocyte steatosis was classified as S0: <5%, S1: 5%-33%, S2: 34%-66%, or S3: ≥67%. The receiver operating characteristic (ROC) curves were plotted with positive results as the diagnostic criteria, and the optimal cut-off values were determined at the maximum Youden index. Single linear regression and multiple stepwise regression were applied to analyze the influencing factors for CAP.

RESULTSA total of 427 patients were enrolled, consisting of 19 patients (4.4%) with NAFLD, 383 (89.7%) with CHB, and 25 (5.9%) with CHC. The optimal cut-off values for CAP in the diagnosis of steatosis ≥5%, ≥34%, and ≥67% were 230 dB/m, 252 dB/m, and 283 dB/m, respectively, and the areas under the ROC curve were 0.803, 0.942, and 0.938, respectively (Z = 14.194, 28.385, and 16.486, respectively, all P < 0.01). CAP differentiated S0 from S1, S1 from S2, S0 from S2, S0 from S3, and S1 from S3 (Z = 10.109, 10.224, 47.81, 29.917, and 10.999, all P < 0.01), but was not able to differentiate S2 from S3 (Z = 0.656, P = 0.5116). The single linear regression and multiple stepwise regression analyses showed that only body mass index (BMI; B = 4.001, P < 0.01) and hepatic steatosis (B = 33.015, P = 0.000) were correlated with CAP. The coincidence rates between CAP and liver pathological diagnosis were 77.4%, 81.0%, and 96.2% for S0, S3, and ≥S2, respectively.

CONCLUSIONCAP has a good value in the diagnosis of fatty liver in CLD patients, and can well differentiate between all stages of fatty liver except S2 and S3. CAP is influenced by BMI, but is not found to be associated with liver fibrosis, inflammation, liver stiffness measurement, and etiology.

Area Under Curve ; Biopsy ; Body Mass Index ; Cell Differentiation ; Elasticity Imaging Techniques ; Hepatitis B, Chronic ; complications ; Hepatitis C, Chronic ; complications ; Humans ; Inflammation ; complications ; Linear Models ; Liver Cirrhosis ; complications ; Multivariate Analysis ; Non-alcoholic Fatty Liver Disease ; complications ; diagnosis ; Prospective Studies ; ROC Curve

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.
Adult ; Aged ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Body Weight ; Cohort Studies ; Female ; Humans ; Lipoproteins, HDL/blood ; Lipoproteins, LDL/blood ; Liver/pathology ; Male ; Metabolic Syndrome X/*complications/diagnosis/drug therapy ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*complications/diagnosis/*drug therapy ; Propensity Score ; Republic of Korea ; Retrospective Studies ; Vitamin E/*therapeutic use

BACKGROUND/AIMS: Hypothyroidism is reported to contribute to the development of nonalcoholic fatty liver disease (NAFLD). We compared the risk of the development of NAFLD among three groups with different thyroid hormonal statuses (control, subclinical hypothyroidism, and overt hypothyroidism) in a 4-year retrospective cohort of Korean subjects. METHODS: Apparently healthy Korean subjects without NAFLD and aged 20-65 years were recruited (n=18,544) at health checkups performed in 2008. Annual health checkups were applied to the cohort for 4 consecutive years until December 2012. Based on their initial serum-free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels, they were classified into control, subclinical hypothyroidism (TSH >4.2 mIU/L, normal fT4), and overt hypothyroidism (TSH >4.2 mIU/L, fT4 <0.97 ng/dL) groups. NAFLD was diagnosed on the basis of ultrasonography findings. RESULTS: NAFLD developed in 2,348 of the 18,544 subjects, representing an overall incidence of 12.7%: 12.8%, 11.0%, 12.7% in the control, subclinical hypothyroidism, and overt hypothyroidism groups, respectively. The incidence of NAFLD did not differ significantly with the baseline thyroid hormonal status, even after multivariate adjustment (subclinical hypothyroidism group: hazard ratio [HR]=0.965, 95% confidence interval [CI]=0.814-1.143, P=0.67; overt hypothyroidism group: HR=1.255, 95% CI=0.830-1.899, P=0.28). CONCLUSIONS: Our results suggest that the subclinical and overt types of hypothyroidism are not related to an increased incidence of NAFLD.
Adult ; Aged ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Hypothyroidism/*complications/*diagnosis ; Incidence ; Kaplan-Meier Estimate ; Liver/ultrasonography ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*complications/*diagnosis/epidemiology ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Thyrotropin/analysis ; Thyroxine/analysis

Radiological imaging plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC) as the noninvasive diagnosis of HCC in high-risk patients by typical imaging findings alone is widely adopted in major practice guidelines for HCC. While imaging techniques have markedly improved in detecting small liver lesions, they often detect incidental benign liver lesions and non-hepatocellular malignancy that can be misdiagnosed as HCC. The most common mimicker of HCC in cirrhotic liver is nontumorous arterioportal shunts that are seen as focal hypervascular liver lesions on dynamic contrast-enhanced cross-sectional imaging. Rapidly enhancing hemangiomas can be easily misdiagnosed as HCC especially on MR imaging with liver-specific contrast agent. Focal inflammatory liver lesions mimic HCC by demonstrating arterial-phase hypervascularity and subsequent washout on dynamic contrast-enhanced imaging. It is important to recognize the suggestive imaging findings for intrahepatic cholangiocarcinoma (CC) as the management of CC is largely different from that of HCC. There are other benign mimickers of HCC such as angiomyolipomas and focal nodular hyperplasia-like nodules. Recognition of their typical imaging findings can reduce false-positive HCC diagnosis.
Carcinoma, Hepatocellular/*diagnosis/radiography ; Diagnosis, Differential ; Hemangioma/complications/radiography/ultrasonography ; Hepatitis B/complications ; Humans ; Inflammation/radiography/ultrasonography ; Liver/radiography/ultrasonography ; Liver Cirrhosis/complications/radiography ; Liver Neoplasms/*diagnosis/radiography ; Magnetic Resonance Imaging ; Non-alcoholic Fatty Liver Disease/radiography/ultrasonography

BACKGROUND/AIMS: A close relationship has been established between nonalcoholic fatty liver disease (NAFLD) and an elevated risk of coronary heart disease (CHD), but little is known about the association between alcoholic fatty liver disease (AFLD) and CHD risk. The aim of this study was to determine whether AFLD is associated with elevated CHD risk. METHODS: We retrospectively enrolled 10,710 subjects out of 11,469 individuals who visited the Konkuk University Health Care Center for a routine health checkup in 2010. AFLD was diagnosed made when the usual amount of alcohol consumption exceeded 210 g/week in males and 140 g/week in females for the previous 2 years and when hepatic steatosis was detected by liver ultrasonography. The 10-year risk for CHD was estimated using the Framingham Risk Score. RESULTS: Hepatic steatosis was diagnosed in 4,142 of the 10,710 individuals (38.7%); the remainder (i.e., n=6,568) became the control group. The 4,142 individuals with hepatic steatosis were divided into two groups: NAFLD (n=2,953) and AFLD (n=1,189). The risk of CHD was higher in AFLD (6.72+/-0.12) than in the control group (5.50+/-0.04, P<0.001), and comparable to that in NAFLD (7.32+/-0.07, P=0.02). CONCLUSIONS: Individuals with AFLD have an elevated 10-year risk of CHD that is comparable to those with NAFLD. Therefore, AFLD should be considered a significant risk for future CHD, and preventive measures should be considered earlier.
Adult ; Age Factors ; Alcohol Drinking ; Body Mass Index ; Coronary Disease/*diagnosis/etiology ; Cross-Sectional Studies ; Fatty Liver, Alcoholic/complications/*diagnosis/ultrasonography ; Female ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/complications/*diagnosis/*epidemiology/ultrasonography ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Sex Factors

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) may be one of the important causes of cryptogenic hepatocellular carcinoma (HCC). The aim of this study was to evaluate whether patients with cryptogenic HCC share clinical features similar to that of NAFLD. METHODS: Cryptogenic HCC was defined as HCC that occurs in patients with the following conditions: HBsAg(-), anti-HCV(-), and alcohol ingestion of less than 20 g/day. All patients diagnosed with cryptogenic HCC from 2005 to 2012 (cryptogenic HCC group), and all patients diagnosed with HBV associated HCC between 2008 and 2012 (HBV-HCC group) were enrolled in the present study. Clinical features, BMI, lipid profiles, presence of diabetes mellitus, hypertension, and metabolic syndrome were compared between the two groups. RESULTS: Cryptogenic HCC group was composed of 35 patients (19 males and 16 females) with a mean age of 70+/-11 years. HBV-HCC group was composed of 406 patients (318 males and 88 females) with a mean age of 56+/-7 years. Patients in the cryptogenic HCC group were older (p=0.001) and female dominant (p=0.042) than those in the HBV-HCC group. There were no differences in the laboratory test results including lipid profiles and Child-Turcotte-Pugh class between the two groups. Patients in the cryptogenic HCC group had higher prevalence of diabetes (37% vs. 17%, p=0.015), hypertension (49% vs. 27%, p=0.051), metabolic syndrome (37% vs. 16%, p=0.001), and higher BMI (25.3 kg/m2 vs. 24.1 kg/m2, p=0.042) than those in the HBV-HCC group. The tumor stage was more advanced (stage III and IV) at diagnosis in the cryptogenic HCC group than in the HBV-HCC group (60% vs. 37%, p=0.007). CONCLUSIONS: Cryptogenic HCC has clinical features similar to that of NAFLD and is diagnosed at a more advanced tumor stage.
Age Factors ; Aged ; Body Mass Index ; Carcinoma, Hepatocellular/*diagnosis/etiology/pathology ; Diabetes Complications ; Diabetes Mellitus/pathology ; Female ; Hepatitis B/complications ; Humans ; Hypertension/complications ; Lipids/blood ; Liver Neoplasms/*diagnosis/etiology/pathology ; Male ; Metabolic Syndrome X/complications ; Middle Aged ; Neoplasm Staging ; Non-alcoholic Fatty Liver Disease/*diagnosis/pathology ; Risk Factors ; Severity of Illness Index ; Sex Factors

Previous epidemiologic studies have shown the clinical association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). However, there is only limited information about the effect of NAFLD on the development of hypertension. Accordingly, we investigated the clinical association between NAFLD and prehypertension. A prospective cohort study was conducted on the 11,350 Korean men without prehypertension for 5 yr. The incidences of prehypertension were evaluated, and Cox proportional hazard model was used to measure the hazard ratios (HRs) for the development of prehypertension according to the degree of NAFLD (normal, mild, moderate to severe). The incidence of prehypertension increased according to NAFLD states (normal: 55.5%, mild: 63.7%, moderate to severe: 70.3%, P<0.001). Even after adjusting for multiple covariates, the HRs (95% confidence interval) for prehypertension were higher in the mild group (1.18; 1.07-1.31) and moderate to severe group (1.62; 1.21-2.17), compared to normal group, respectively (P for trend <0.001). The development of prehypertension is more potentially associated with the more progressive NAFLD than normal and milder state. These findings suggest the clinical significance of NAFLD as one of risk factors for prehypertension.
Adult ; Blood Glucose ; Blood Pressure ; Cohort Studies ; Diabetes Mellitus, Type 2/complications/diagnosis ; Humans ; Incidence ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/complications/*diagnosis ; Prehypertension/diagnosis/*epidemiology/etiology ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Smoking