A systematic review (SR) provides the best and most objective analysis of the existing evidence in a particular field. SRs and derived conclusions are essential for evidence-based strategies in medicine and evidence-based guidelines in clinical practice. The popularity of SRs has also increased markedly in the field of hepatology. However, although SRs are considered to provide a higher level of evidence with greater confidence than original articles, there have been no reports on the quality of SRs and meta-analyses (MAs) in the field of hepatology. Therefore, we performed a quality assessment of 225 SRs and MAs that were recently published in the field of hepatology (January 2011 to September 2014) using A MeaSurement Tool to Assess systematic Reviews (AMSTAR). Using AMSTAR, we revealed both a shortage of assessments of the scientific quality of individual studies and a publication bias in many SRs and MAs. This review addresses the concern that SRs and MAs need to be conducted in a stricter and more objective manner to minimize bias and random errors. Thus, SRs and MAs should be supported by a multi-disciplinary approach that includes clinical experts, methodologists, and statisticians.
*Gastroenterology ; Humans ; *Meta-Analysis as Topic ; *Publication Bias ; *Review Literature as Topic

BACKGROUND: This study aimed to investigate whether stimulated C-peptide is associated with microvascular complications in type 2 diabetes mellitus (DM). METHODS: A cross-sectional study was conducted in 192 type 2 diabetic patients. Plasma basal C-peptide and stimulated C-peptide were measured before and 6 minutes after intravenous injection of 1 mg glucagon. The relationship between C-peptide and microvascular complications was statistically analyzed. RESULTS: In patients with retinopathy, basal C-peptide was 1.9+/-1.2 ng/mL, and stimulated C-peptide was 2.7+/-1.6 ng/mL; values were significantly lower compared with patients without retinopathy (P=0.031 and P=0.002, respectively). In patients with nephropathy, basal C-peptide was 1.6+/-0.9 ng/mL, and stimulated C-peptide was 2.8+/-1.6 ng/mL; values were significantly lower than those recorded in patients without nephropathy (P=0.020 and P=0.026, respectively). Stimulated C-peptide level was associated with increased prevalence of microvascular complications. Age-, DM duration-, and hemoglobin A1c-adjusted odds ratios for retinopathy in stimulated C-peptide value were 4.18 (95% confidence interval [CI], 1.40 to 12.51) and 3.35 (95% CI, 1.09 to 10.25), respectively. The multiple regression analysis between nephropathy and C-peptide showed that stimulated C-peptide was statistically correlated with nephropathy (P=0.03). CONCLUSION: In patients with type 2 diabetes, the glucagon stimulation test was a relatively simple method of short duration for stimulating C-peptide response. Stimulated C-peptide values were associated with microvascular complications to a greater extent than basal C-peptides.
C-Peptide ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; Glucagon ; Hemoglobins ; Humans ; Injections, Intravenous ; Odds Ratio ; Plasma ; Prevalence

OBJECTIVE: To investigate the efficacy and safety of oral bovine type II collagen (C II) in the treatment of rheumatoid arthritis (RA). METHODS: Forty-five patients with active RA were enrolled and randomized to receive placebo or oral C II for 3 months. Efficacy parameters were assessed monthly. Cumulative response rates (percentages of patients meeting the criteria for response at anytime during the study) were analyzed utilizing 3 set of composite criteria : Paulus criteria, ACR criteria for improvement in RA, and a requirement for > or = 30% reduction in both swollen and tender joint counts. RESULTS: The C II-treated group (n=25) showed significant higher response rate by the Paulus criteria compared to placebo group (n=20, p=0.04), and MHAQ scores between baseline and 3 months of treatment were also significantly decreased in the C II-treated group (p<0.05). However, there were no significant differences in tender and swollen joint count, and physician and patient global scores between C II-treated and placebo groups. Only one patient treated with C II had a urticaria 1 week after administration, but no serious side effects were found in the two groups. Patients treated with C II (n=15) showed the decreased levels of circulating IgG antibodies to bovine C II 3 months after treatment (p=0.02), whereas significant changes of IgG antibodies to C II were not found in placebo group (n=12). CONCLUSION: Oral administration of C II was safe and effective for the treatment of rheumatoid arthritis. The finding that serum IgG antibodies to bovine C II was decreased in patients who treated with C II suggest that autoimmune response to C II could be decreased by repetitive administration of C II.
Administration, Oral ; Antibodies ; Arthritis, Rheumatoid* ; Autoimmunity ; Collagen Type II* ; Humans ; Immunoglobulin G ; Joints ; Urticaria

BACKGROUND/AIMS: Levels of serum apelin (s-apelin), an endogenous ligand for angiotensin-like receptor 1, have been shown to be related to hepatic fibrosis and hemodynamic abnormalities in preclinical studies. We investigated the clinical implications of s-apelin as a noninvasive prognostic biomarker for chronic liver disease (CLD). METHODS: From January 2009 to December 2012, 215 CLD patients were enrolled and underwent clinical data collection, hepatic venous pressure gradient (HVPG) measurement, and liver biopsy. s-apelin was detected with a human total apelin enzyme-linked immunosorbent assay kit. All patients were prospectively observed during the median follow-up period of 23.0±12.9 months for decompensation and mortality. RESULTS: A total of 42 patients (19.5%) died during the follow-up period. s-apelin was significantly correlated with measurements of liver stiffness (R2=0.263, p<0.001) and collagen proportional area (R2=0.213, p<0.001) measured from liver biopsy tissue and HVPG (R2=0.356, p<0.001). In a multivariate analysis using a Cox regression hazard model, s-apelin was a weakly significant predictor of decompensation (hazard ratio [HR], 1.002; p<0.001) and mortality (HR, 1.003; p<0.001). CONCLUSIONS: s-apelin showed a significant relationship with CLD severity. However, its significance as a noninvasive biomarker for disease severity and prognosis was weak.
Adult ; Biomarkers/blood ; Biopsy ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Humans ; Hypertension, Portal/*blood/complications/mortality ; Intercellular Signaling Peptides and Proteins/*blood ; Liver/blood supply/pathology ; Liver Cirrhosis/*blood/etiology/mortality/pathology ; Male ; Middle Aged ; Portal Pressure ; Prognosis ; Proportional Hazards Models ; Prospective Studies

Teratoma is a congenital tumor containing tissues derived from all germ layers. Teratoma in the region of the adrenal gland is a very uncommon retroperitoneal tumor. Only 7 cases of adrenal teratoma have been reported worldwide, but in Korea, no similar cases have been reported until now. This case report describes an adrenal teratoma in a 38-year-old healthy woman who was incidentally diagnosed with a left adrenal mass on abdominal ultrasonography during a medical inspection. Computed tomographic scans revealed a 9-cm heterogeneous circumscribed round mass, containing primarily fat tissue, and a solid calcification component in the left adrenal gland. Adrenal hormonal assessment results and biochemical markers for gonadal neoplasia were negative. Result of serum laboratory tests were normal. The patient underwent laparoscopic adrenalectomy. Histologic analysis confirmed the diagnosis of a mature teratoma; the obtained specimen measured 5 x 7 x 7.5 cm and weighed 267 g. The surface of the mass was smooth, and sebaceous tissue and hair with hard material were observed on the incisional surface. The patient was discharged on postoperative day 4, without complications. In this case report, we describe the incidental finding of a teratoma occurring in the adrenal gland region in a healthy woman; the teratoma was laparoscopically excised.
Adrenal Glands ; Adrenalectomy ; Adult ; Female ; Germ Layers ; Gonads ; Hair ; Humans ; Incidental Findings ; Korea ; Teratoma ; Biomarkers

BACKGROUND/AIMS: The therapeutic effect of transarterial chemoembolization (TACE) against hepatocellular carcinoma (HCC) is usually assessed using multidetector computed tomography (MDCT). However, dense lipiodol depositions can mask the enhancement of viable HCC tissue in MDCT. Contrast-enhanced ultrasonography (CEUS) could be effective in detecting small areas of viability and patency in vessels. We investigated whether arterial enhancement in CEUS after treatment with TACE can be used to detect HCC viability earlier than when using MDCT. METHODS: Twelve patients received CEUS, MDCT, and gadoxetic-acid-enhanced dynamic magnetic resonance imaging (MRI) at baseline and 4 and 12 weeks after TACE. The definition of viable HCC was defined as MRI positivity after 4 or 12 weeks. RESULTS: Eight of the 12 patients showed MRI positivity at 4 or 12 weeks. All patients with positive CEUS findings at 4 weeks (n=8) showed MRI positivity and residual viable HCC at 4 or 12 weeks. Five of the eight patients with positive CEUS findings at 4 weeks had negative results on the 4-week MDCT scan. Four (50%) of these eight patients did not have MRI positivity at 4 weeks and were ultimately confirmed as having residual HCC tissue at the 12-week MRI. Kappa statistics revealed near-perfect agreement between CEUS and MRI (kappa=1.00) and substantial agreement between MDCT and MRI (kappa=0.67). CONCLUSIONS: In the assessment of the response to TACE, CEUS at 4 weeks showed excellent results for detecting residual viable HCC, which suggests that CEUS can be used as an early additive diagnosis tool when deciding early additional treatment with TACE.
Aged ; Aged, 80 and over ; Antineoplastic Agents/administration & dosage ; Carcinoma, Hepatocellular/pathology/therapy/*ultrasonography ; Chemoembolization, Therapeutic ; Contrast Media/*chemistry ; Female ; Gadolinium DTPA/chemistry ; Humans ; Liver Neoplasms/pathology/therapy/*ultrasonography ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pilot Projects ; Tomography, X-Ray Computed ; Treatment Outcome

OBJECTIVE: Studies have presented conflicting results regarding the accuracy of ultrasonography (US) for diagnosing portal hypertension (PH). We sought to identify evidence in the literature regarding the accuracy of US for assessing PH in patients with liver cirrhosis. MATERIALS AND METHODS: We conducted a systematic review by searching databases, including MEDLINE, EMBASE, and the Cochrane Library, for relevant studies. RESULTS: A total of 14 studies met our inclusion criteria. The US indices were obtained in the portal vein (n = 9), hepatic artery (n = 6), hepatic vein (HV) (n = 4) and other vessels. Using hepatic venous pressure gradient (HVPG) as the reference, the sensitivity (Se) and specificity (Sp) of the portal venous indices were 69-88% and 67-75%, respectively. The correlation coefficients between HVPG and the portal venous indices were approximately 0.296-0.8. No studies assess the Se and Sp of the hepatic arterial indices. The correlation between HVPG and the hepatic arterial indices ranged from 0.01 to 0.83. The Se and Sp of the hepatic venous indices were 75.9-77.8% and 81.8-100%, respectively. In particular, the Se and Sp of HV arrival time for clinically significant PH were 92.7% and 86.7%, respectively. A statistically significant correlation between HVPG and the hepatic venous indices was observed (0.545-0.649). CONCLUSION: Some US indices, such as HV, exhibited an increased accuracy for diagnosing PH. These indices may be useful in clinical practice for the detection of significant PH.
Hepatic Veins/ultrasonography ; Humans ; Hypertension, Portal/*diagnosis/*ultrasonography ; Liver Cirrhosis/*ultrasonography ; Middle Aged ; Portal Pressure ; Portal Vein/ultrasonography ; Prospective Studies ; Sensitivity and Specificity ; Vascular Resistance

Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.
Adult ; Aged ; Biopterin/*analogs & derivatives/analysis ; *Chromatography, High Pressure Liquid ; Chronic Disease ; Elasticity Imaging Techniques ; Female ; Hepatic Veins/physiology ; Humans ; Hypertension, Portal/complications/*diagnosis/metabolism ; Liver/pathology ; Liver Cirrhosis/ultrasonography ; Liver Diseases/complications/*diagnosis/metabolism ; Male ; Middle Aged ; Nitric Oxide/metabolism ; Portal Pressure ; Regression Analysis ; Severity of Illness Index

BACKGROUND/AIMS: Liver stiffness measurement (LSM) has been proposed as a non-invasive method for estimating the severity of fibrosis and the complications of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence of portal hypertension, but its invasiveness limits its clinical application. In this study we evaluated the relationship between LSM and HVPG, and the predictive value of LSM for clinically significant portal hypertension (CSPH) and severe portal hypertension in cirrhosis. METHODS: LSM was performed with transient elastography in 59 consecutive cirrhotic patients who underwent hemodynamic HVPG investigations. CSPH and severe portal hypertension were defined as HVPG > or =10 and > or =12 mmHg, respectively. Linear regression analysis was performed to evaluate the relationship between LSM and HVPG. Diagnostic values were analyzed based on receiver operating characteristic (ROC) curves. RESULTS: A strong positive correlation between LSM and HVPG was observed in the overall population (r2=0.496, P<0.0001). The area under the ROC curve (AUROC) for the prediction of CSPH (HVPG > or =10 mmHg) was 0.851, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for an LSM cutoff value of 21.95 kPa were 82.5%, 73.7%, 86.8%, and 66.7%, respectively. The AUROC at prediction of severe portal hypertension (HVPG > or =12 mmHg) was 0.877, and the sensitivity, specificity, PPV, and NPV at LSM cutoff value of 24.25 kPa were 82.9%, 70.8%, 80.6%, and 73.9%, respectively. CONCLUSIONS: LSM exhibited a significant correlation with HVPG in patients with cirrhosis. LSM could be a non-invasive method for predicting CSPH and severe portal hypertension in Korean patients with liver cirrhosis.
Adult ; Aged ; Alcohol-Related Disorders/complications ; Area Under Curve ; *Elasticity Imaging Techniques ; Female ; Hepatitis B/complications ; Hepatitis C/complications ; Humans ; Hypertension, Portal/*complications/*diagnosis ; Linear Models ; Liver Cirrhosis/*complications/*diagnosis/pathology ; Male ; Middle Aged ; ROC Curve ; Republic of Korea ; Sensitivity and Specificity

BACKGROUND/AIMS: In 2010, the American Diabetes Association (ADA) adopted glycated hemoglobin (HbA1c) as a new diagnostic criterion for diabetes mellitus. However, HbA1c values may differ among races. We determined whether this criterion could be applied to Korean diabetics. METHODS: Between January 2000 and January 2010, 1,862 patients among Konyang University Hospital visitors in which the 75 g oral glucose tolerance test (OGTT) and HbA1c were checked at the same time were enrolled. We excluded patients with acute disease, an Hb < or = 10 g/dL, a Cr > or = 2 mg/dL, those prescribed oral hypoglycemic agents or insulin, and those who were pregnant. RESULTS: After applying the exclusion criteria, 1,474 Korean patients were enrolled. All had common features of Korean diabetics for body mass index and homeostatic model assessment of insulin resistance values. Using the 0 and 120 minute glucose levels of the OGTT from the receiver operating characteristic curve, the HbA1c cutoff value was 6.25%. The cutoff value to diagnose diabetes with the presence of diabetic retinopathy was 6.75%. CONCLUSIONS: Our study showed a difference between the HbA1c values for diagnosing diabetes and the new diagnostic criterion from the ADA. Considering that the HbA1c characteristics may be influenced by race or culture, larger studies on diabetes complications are needed to identify the appropriate HbA1c value for Korean diabetics.
Acute Disease ; Body Mass Index ; Continental Population Groups ; Diabetes Complications ; Diabetes Mellitus ; Diabetic Retinopathy ; Glucose ; Glucose Tolerance Test ; Hemoglobins ; Humans ; Hypoglycemic Agents ; Insulin ; Insulin Resistance ; Korea ; ROC Curve