Gaeun Kim

Therapeutic Effects of Mesenchymal Stem Cells for Patients with Chronic Liver Diseases: Systematic Review and Meta-analysis

Based on their ability to differentiate into multiple cell types including hepatocytes, the transplantation of mesenchymal stem cells (MSCs) has been suggested as an effective therapy for chronic liver diseases. The aim of this study was to evaluate the safety, efficacy and therapeutic effects of MSCs in patients with chronic liver disease through a literature-based examination. We performed a systematic review (SR) and meta-analysis (MA) of the literature using the Ovid-MEDLINE, EMBASE and Cochrane Library databases (up to November 2014) to identify clinical studies in which patients with liver diseases were treated with MSC therapy. Of the 568 studies identified by the initial literature search, we analyzed 14 studies and 448 patients based on our selection criteria. None of the studies reported the occurrence of statistically significant adverse events, side effects or complications. The majority of the analyzed studies showed improvements in liver function, ascites and encephalopathy. In particular, an MA showed that MSC therapy improved the total bilirubin level, the serum albumin level and the Model for End-stage Liver Disease (MELD) score after MSC treatment. Based on these results, MSC transplantation is considered to be safe for the treatment of chronic liver disease. However, although MSCs are potential therapeutic agents that may improve liver function, in order to obtain meaningful insights into their clinical efficacy, further robust clinical studies must be conducted to evaluate the clinical outcomes, such as histological improvement, increased survival and reduced liver-related complications, in patients with chronic liver disease.

Ultrasonographic scoring system score versus liver stiffness measurement in prediction of cirrhosis.

Background/Aims We compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system (USSS) combining six representative sonographic indices with that of liver stiffness measurement (LSM) by transient elastography, and prospectively investigated the correlation between the USSS score and LSM in predicting cirrhosis. Methods Two hundred and thirty patients with chronic liver diseases (187 men, 43 women; age, 50.4±9.5 y, mean±SD) were enrolled in this prospective study. The USSS produces a combined score for nodularity of the liver surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen size, splenic vein diameter, and abnormality of the hepatic vein waveform. The correlations of the USSS score and LSM with that of a pathological liver biopsy (METAVIR scoring system: F0-F4) were evaluated. Results The mean USSS score and LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729, respectively. On the basis of ROC curves, criteria of USSS ≥6: LSM ≥17.4 had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%, 74.6%:51.9% and 0.83:0.73, respectively, in predicting F4. Conclusions The results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis.

Mesenchymal stem cell therapy for cirrhosis: Present and future perspectives

Cirrhosis occurs as a result of various chronic liver injuries, which may be caused by viral infections, alcohol abuse and the administration of drugs and chemicals. Recently, bone marrow cells (BMCs), hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) have been used for developing treatments for cirrhosis. Clinical trials have investigated the therapeutic potential of BMCs, HSCs and MSCs for the treatment of cirrhosis based on their potential to differentiate into hepatocytes. Although the therapeutic mechanisms of BMC, HSC and MSC treatments are still not fully characterized, the evidence thus far has indicated that the potential therapeutic mechanisms of MSCs are clearer than those of BMCs or HSCs with respect to liver regenerative medicine. MSCs suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, reverse liver fibrosis and enhance liver functionality. This paper summarizes the clinical studies that have used BMCs, HSCs and MSCs in patients with liver failure or cirrhosis. We also present the potential therapeutic mechanisms of BMCs, HSCs and MSCs for the improvement of liver function.

Transient elastography versus hepatic venous pressure gradient for diagnosing portal hypertension: a systematic review and meta-analysis

Background/Aims Transient elastography (TE) has been proposed as a promising noninvasive alternative to hepatic venous pressure gradient (HVPG) for detecting portal hypertension (PH). However, previous studies have yielded conflicting results. We gathered evidence from literature on the clinical usefulness of TE versus HVPG for assessing PH. Methods We conducted a systematic review by searching databases for relevant literature evaluating the clinical usefulness of non-invasive TE for assessing PH in patients with cirrhosis. A literature search in Ovid Medline, EMBASE and the Cochrane Library was performed for all studies published prior to December 30, 2015. Results Eight studies (1,356 patients) met our inclusion criteria. For the detection of PH (HVPG ≥6 mmHg), the summary sensitivity and specificity were 0.88 (95% confidence interval [CI] 0.86-0.90) and 0.74 (95% CI 0.67-0.81), respectively. Regarding clinically significant PH (HVPG ≥10 mmHg), the summary sensitivity and specificity were 0.85 (95% CI 0.63-0.97) and 0.71 (95% CI 0.50-0.93), respectively. The overall correlation estimate of TE and HVPG was large (0.75, 95% CI: 0.65; 0.82, P<0.0001). Conclusions TE showed high accuracy and correlation for detecting the severity of PH. Therefore, TE shows promise as a reliable and non-invasive procedure for the evaluation of PH that should be integrated into clinical practice.

Social values and healthcare priority setting in Korea

PURPOSE The purpose of this paper is to present the role of social values in setting healthcare priorities in Korea. DESIGN/METHODOLOGY/APPROACH Using Clark and Weales draft framework, Korean healthcare priority setting was analysed. The process values used were transparency, accountability, and participation, and the content values used were clinical effectiveness, cost effectiveness, justice/equity, solidarity and autonomy. FINDINGS In the Korean health priority setting, it was found that multiple factors influence the decision-making process. Effectiveness and safety are the two most important values mentioned in the process. Cost-effectiveness is also considered in reimbursement decisions for new drugs since 2007. Recently, health technology assessment (HTA) has begun to change the social value system traditionally used in the Korean healthcare priority setting. ORIGINALITY/VALUE The paper extends understanding of health priority setting in Korea, and how the interpretation and use of social values has changed over recent years.

Overview and recent trends of systematic reviews and meta-analyses in hepatology

A systematic review (SR) is a research methodology that involves a comprehensive search for and analysis of relevant studies on a specific topic. A strict and objective research process is conducted that comprises a systematic and comprehensive literature search in accordance with predetermined inclusion/exclusion criteria, and an assessment of the risk of bias of the selected literature. SRs require a multidisciplinary approach that necessitates cooperation with clinical experts, methodologists, other experts, and statisticians. A meta-analysis (MA) is a statistical method of quantitatively synthesizing data, where possible, from the primary literature selected for the SR. Review articles differ from SRs in that they lack a systematic methodology such as a literature search, selection of studies according to strict criteria, assessment of risk bias, and synthesis of the study results. The importance of evidence-based medicine (EBM) in the decision-making for public policy has recently been increasing thanks to the realization that it should be based on scientific research data. SRs and MAs are essential for EBM strategy and evidence-based clinical practice guidelines. This review addresses the current trends in SRs and MAs in the field of hepatology via a search of recently published articles in the Cochrane Library and Ovid-MEDLINE.

The need for histological subclassification of cirrhosis: a systematic review and meta‐analysis

The need for further histological subclassification of cirrhosis has been increasingly recognized because of the heterogeneity of severity within cirrhosis. We sought to identify evidence in the literature regarding the histological subclassification of cirrhosis using the Laennec stage.

Assessment for Risk of Bias in Systematic Reviews and Meta-Analyses in the Field of Hepatology.

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.

Factors associated with organized and opportunistic cancer screening: Results of the Korea National Health and Nutrition Examination Survey (KNHANES) 2007-2011

BACKGROUND Cancer is one of the leading causes of death in Korea. To reduce cancer incidence, the Korean National Cancer Center (KNCC) has been expanding its organized cancer screening program. In addition, there are opportunistic screening programs that can be chosen by individuals or their healthcare providers. The purpose of this study was to investigate factors associated with participation in organized and opportunistic cancer screening programs, with a particular focus on socioeconomic factors. MATERIALS AND METHODS We used data from the Korea National Health and Nutrition Examination Survey (KNHANES), a cross-sectional nationwide study conducted by the Korean Ministry of Health and Welfare from 2007 to 2011. The study included information from 9,708 men and 12,739 women aged 19 years or over. Multinomial logistic regression analysis was conducted, adjusting for age, year of data collection, residential region, current smoking status, current alcohol consumption status, exercise, marriage status, job status, perceived health status, stress level, BMI, limitation of activities, cancer history, health insurance type, and private insurance status, to investigate the association between education level, economic status, and cancer screening participation. RESULTS In terms of education level, disparities in attendance were observed only for the opportunistic screening program. In contrast, there was no association between education level and participation in organized screening. In terms of economic status, disparities in opportunistic screening participation were observed at all income levels, but disparities in organized screening participation were observed only at the highest income level. CONCLUSIONS Our findings reveal that socioeconomic factors, including educational level and economic status, were not significantly associated with participation in organized cancer screening, except at the highest level of income.

Diagnostic Accuracy of Hepatic Vein Arrival Time Performed with Contrast-Enhanced Ultrasonography for Cirrhosis: A Systematic Review and Meta-Analysis

Background/Aims We identified reports in the literature regarding the diagnostic accuracy of hepatic vein arrival time (HVAT) measured by contrast-enhanced ultrasonography (CEUS) to assess hepatic fibrosis in cirrhosis. Methods The Ovid MEDLINE, Embase, and Cochrane databases were searched for all studies published up to 23 July 2015 that evaluated liver status using CEUS and liver biopsy (LB). The QUADAS-II (quality assessment of diagnostic accuracy studies-II) was applied to assess the internal validity of the diagnostic studies. Selected studies were subjected to a meta-analysis with MetaDisc 1.4 and RevMan 5.3. Results A total of 12 studies including 844 patients with chronic liver disease met our inclusion criteria. The overall summary sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of the HVAT measured by CEUS for the detection of cirrhosis compared to LB were 0.83 (95% confidence interval [CI], 0.77 to 0.89), 0.75 (95% CI, 0.69 to 0.79), 3.45 (95% CI, 1.60 to 7.43), and 0.28 (95% CI, 0.10 to 0.74), respectively. The summary diagnostic odds ratio (random effects model) was 15.23 (95% CI, 3.07 to 75.47), the summary receiver operator characteristics area under the curve was 0.74 (standard error [SE]=0.14), and the index Q was 0.69 (SE=0.11). Conclusions Based on a systematic review, the measurement of HVAT by CEUS exhibited an increased accuracy and correlation for the detection of cirrhosis.