Prognosis of transarterial chemoembolization-sorafenib compared to transarterial chemoembolization-alone in hepatocellular carcinoma stage C: a systematic review.

BACKGROUND: This systematic review aims to compare the prognosis of treatment transarterial chemoembolization (TACE) combined with sorafenib and TACE-alone in patients with hepatocellular carcinoma (HCC) with Barcelona clinic liver cancer-stage C (BCLC-C). MATERIALS AND METHODS: A systematic search was conducted on five electronic databases: PubMed, ScienceDirect, Cochrane, Embase, and Scopus. Studies were included if they compared overall survival (OS) of TACE-Sorafenib to TACE-alone in patients with HCC BCLC-C within the 2019-2023 timeframe. We excluded studies consisting of conference abstracts, letters, editorials, guidelines, case reports, animal studies, trial registries, and unpublished work. The selected articles were evaluated from August 2023 to September 2023. The journal's quality was assessed with NOS for a non-randomized controlled trial. RESULTS: This systematic review included four studies following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). All four studies compared the OS of 401 patients with TACE-sorafenib to TACE-alone. Two studies compared time-to-progression (TTP), one study compared progression-free survival (PFS), and two studies compared disease control rate (DCR). There were various population criteria, TACE techniques used, risk factors, follow-up time, and adverse events. The collected evidence generally suggested that the combination of TACE-sorafenib is superior compared to TACE-alone. Due to a lack of essential data for the included study, a meta-analysis couldn't be performed. CONCLUSION: The results of this systematic review suggested that TACE-sorafenib combination therapy in patients with HCC BCLC-C improves OS superior compared to TACE-alone, without a notable increase in adverse events.

Cost-effectiveness of albumin in the treatment of decompensated cirrhosis in resource-limited healthcare settings.

Background: Human albumin (HA) is an effective adjuvant treatment for patients with cirrhosis developing spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and ascites requiring large-volume paracentesis (LVP). However, cost remains a barrier to use, particularly in resource-limited settings. This study aims to assess the cost-effectiveness of HA in patients with cirrhosis with SBP, HRS or ascites requiring LVP in the Indonesian healthcare system as a representative of a resource-limited setting. Methods: Three decision-tree models were developed to assess the cost-effectiveness of (1) antibiotics and HA versus antibiotics alone in patients with SBP, (2) terlipressin and HA versus terlipressin alone in patients with HRS, and (3) LVP and HA versus LVP and gelatine for patients with ascites. Clinical utility and economic inputs were pooled from the available literature. Time horizon was 3 months. Outcomes were expressed as incremental cost-effectiveness ratios (ICER) reported as 2021 IDR per quality-adjusted life year (QALY) (exchange rate June 30, 2021: 1 EUR = 17,245 IDR). Willingness-to-pay thresholds considered were: three times the GDP per capita (199,355,561 IDR/QALY; 11,560 EUR/QALY) and one time the GDP per capita (66,451,854 IDR/QALY; 3853 EUR/QALY). Results: The ICER for antibiotics and HA (versus antibiotics alone) for SBP was 80,562,652 IDR per QALY gained (4672 EUR/QALY). The ICER for terlipressin and HA (versus terlipressin) for HRS was 23,085,004 IDR per QALY gained (1339 EUR/QALY). The ICER for LVP and HA versus LVP and gelatine was 24,569,827 IDR per QALY gained (1425 EUR/QALY). Conclusion: Adjunctive HA may be a cost-effective treatment for SBP, HRS and LVP in resource-limited settings.

Secondary Polycythemia and Non-Islet Cell Tumor-induced Hypoglycemia in Advanced Hepatocellular Carcinoma: A Case Report.

Continuously holding its position as the sixth most common cause of cancer and the third leading cause of cancer death, globally, Hepatocellular Carcinoma (HCC) remains as a healthcare priority. Production of various substances may result into systemic or metabolic complications, often known as paraneoplastic phenomena of HCC. A 56-year-old male with history of untreated chronic hepatitis B arrived with generalized weakness and intermittent headache in the last two days prior to admission. Laboratory findings demonstrated elevated hemoglobin (20.5 g/dl), alpha-fetoprotein (29,845 ng/dl), and d-Dimer (2,120 ng/ml) levels. Hypoglycemia (44 mg/dl) was documented with normal basal insulin level, confirming non-islet cell tumor hypoglycemia. Abdominal multiphasic CT-scan demonstrated a large solid lesion involving the whole right liver lobe, hyper-enhanced at arterial phase and wash-out pattern at venous and delayed phases, with portal vein thrombosis; thus, confirming HCC BCLC C. Further examinations revealed hypercellularity from bone marrow biopsy with the absence of JAK2 mutation. He underwent serial phlebotomy and received 80 mg acetylsalicylic acid orally, as well as cytoreductive agent to reduce the risk of thrombosis. Despite applications of different interventions, control of hypoglycemia could not be achieved without parenteral administration of high dextrose load. He was planned to receive oral multikinase inhibitor, however, he passed away due to severe hospital-acquired pneumonia. Paraneoplastic phenomena are common in HCC. Increased risk of blood hyper-viscosity and thrombosis attributed to polycythemia, as well as medical emergency resulting from hypoglycemia showed that both conditions should not be overlooked since they may worsen the patient's prognosis.

Scoring system for predicting 90-day mortality of in-hospital liver cirrhosis patients at Cipto Mangunkusumo Hospital.

BACKGROUND: Liver cirrhosis is the final stage of chronic liver disease. Complications due to progression of liver disease may deteriorate the liver function and worsen prognosis. Previous studies have shown that patients with liver cirrhosis are at increased risk of death within 90-day after hospitalization. It is necessary to identify patients who are at higher risk of early mortality. This study aims to develop a scoring system to predict the 90-day mortality among hospitalized patients with liver cirrhosis that could be used for modification of treatment plan according to the scores that have been obtained. By using this scoring system, crucial care of plans can be taken to reduce the risk of mortality. METHOD: This prospective cohort study was conducted on hospitalized cirrhotic patients at Cipto Mangunkusumo National General Hospital, Jakarta. Demographic, clinical, and laboratory data were recorded. Patients were monitored for up to 90-day after hospitalization to determine their condition. Cox regression analysis was performed to obtain predictor factors contributing to mortality in liver cirrhosis patients. The scoring system that resulted from this study categorized patients into low, moderate, and high-risk categories based on their predicted mortality rates. The sensitivity and specificity of the scoring system were evaluated using the AUC (area under the curve) metric. RESULT: The study revealed that liver cirrhosis patients who were hospitalized had a 90-day mortality rate of 42.2%, with contributing factors including Child-Pugh, MELD, and leukocyte levels. The combination of these variables had a good discriminative value with an AUC of 0.921 (95% CI: 0.876-0.967). The scoring system resulted in three risk categories: low risk (score of 0-3) with a 4.1-18.4% probability of death, moderate risk (score of 5-6) with a 40.5-54.2% probability of death, and high risk (score of 8-11) with a 78.1-94.9% probability of death. CONCLUSION: The scoring system has shown great accuracy in predicting 90-day mortality in hospitalized cirrhosis patients, making it a valuable tool for identifying the necessary care and interventions needed for these patients upon admission.

Effect of Roselle Flower Extract (Hibiscus sabdariffa Linn.) on Reducing Steatosis and Steatohepatitis in Vitamin B12 Deficiency Rat Model.

Background and Objectives: Non-alcoholic Fatty Liver Disease (NAFLD) can occur as a result of micronutrient deficiencies. Hibiscus sabdarifa, a plant used in traditional medicine, contains ingredients that can help prevent this process. This study looked at the potency of Hibiscus sabdariffa Ethanol Extract (HSE) to prevent homocysteine-induced liver damage in animals that were deficient in vitamin B12. Materials and Methods: A comparative study of the effects of roselle extract is presented in an experimental design. Thirty Sprague-Dawley rats were divided into six groups using randomization. To demonstrate the absence of liver damage in the experimental animals under normal conditions, a control group was fed a normal diet without HSE. For the induction of liver damage in the experimental animals, the vitamin B12-restricted group was administered a vitamin B12-restricted diet. To test the effect of HSE on liver damage, the treatment group was given HSE along with a vitamin B12-restricted diet. Each group was given two treatment periods of eight and sixteen weeks. These results were compared with the results of the parameter examination between the vitamin B12 restriction group, with and without HSE, using an ANOVA statistic. The data were analyzed with licensed SPSS 20.0 software. Results: HSE significantly increased the blood levels of vitamin B12 while lowering homocysteine levels. The administration of HSE reduced liver damage based on the activity of liver function enzymes in the plasma due to a limitation of vitamin B12. HSE decreased Sterol Regulatory Element-Binding Protein-1c (SREBP1c) and Nuclear Factor Kappa B (NFkB) protein expressions in the liver tissue, but did not decrease Glucose-Regulated Protein 78 (GRP78) protein expression. Significantly, the levels of Tumor Necrosis Factor alpha (TNF-a) and IL-6 in the liver tissue were lower, while the levels of IL-10 and Nuclear factor-erythroid-2 Related Factor 2 (NRF2) were higher with HSE administration. HSE produced a better histopathological profile of the Hematoxylin and Eosin (H&E)-Masson tricrome for inflammation, fat and fibrosis in the liver. Conclusions: In this study, HSE was found to slow the development of liver damage in experimental animals that were given a vitamin B12-deficient diet.

Factors Associated with Sarcopenia in Maintenance Hemodialysis Patients: A Cross-Sectional Study.

BACKGROUND: Sarcopenia is associated with worse outcomes in maintenance hemodialysis (MHD) patients. Differences in criteria and methods used to diagnose sarcopenia, results in a wide range of prevalence. Factors associated with sarcopenia in MHD have not been well-studied. This study aimed to investigate the prevalence and factors associated with sarcopenia in the MHD population. METHODS: Observational cross-sectional study was done with 96 MHD patients aged ≥18 years old, with dialysis vintage ≥120 days at Cipto Mangunkusumo Hospital March-May 2022. Descriptive, bivariate, and logistic regression analysis were done to find sarcopenia's prevalence and association with Simplify Creatinine Index (SCI), type 2 diabetes (DM), Interleukin-6 (IL-6), nutritional status, physical activity, and phosphate serum level. Asian Working Group for Sarcopenia (AWGS) 2019 criteria used to diagnose sarcopenia, Hand Grip Strength (HGS) to identify muscle strength, Bioimpedance Spectroscopy (BIS) to calculate muscle mass, and 6-meter walk test to evaluate physical performance. RESULTS: The prevalence of sarcopenia was 54.2%. Factors with a significant association in bivariate analysis were phosphate serum level (p=0.008), SCI (p=0.005) and low physical activity (International Physical Activity Questionnaire) (p-0.006). Logistic regression analysis found higher phosphate serum level and high physical activity protective of sarcopenia (OR 0.677;CI95% 0.493-0.93 and OR 0.313;CI95% 0.130-0.755 respectively). CONCLUSION: The prevalence of sarcopenia in the MHD population was 54.2%. Phosphate serum level, SCI, and physical activity were significantly correlated with sarcopenia. Both high phosphate level and high physical activity were protective against sarcopenia.

Diagnostic performance of Mac-2-binding protein glycosylation isomer (M2BPGi) as a liver fibrosis marker in chronic hepatitis C patients with chronic kidney disease on hemodialysis.

BACKGROUND/AIM: Liver fibrosis assessment is essential to determine the initiation, duration, and evaluation of chronic hepatitis C treatment. Therefore, the study aimed to assess the role of Mac-2-binding protein glycosylation isomer (M2BPGi) as a biomarker to measure liver fibrosis in chronic hepatitis C patients with chronic kidney disease on hemodialysis. METHODS: This study used a cross-sectional design. Serum M2BPGi level and transient elastography results were evaluated in 102 chronic hepatitis C patients with CKD on HD, 36 CKD on HD patients, and 48 healthy controls. ROC analysis was conducted to identify the optimal cutoff values to assess significant fibrosis and cirrhosis among chronic hepatitis C patients with CKD on HD. RESULTS: In chronic hepatitis C patients with CKD on HD, the level of serum M2BPGi had a moderately significant correlation with transient elastography (r = 0.447, p < 0.001). The median serum M2BPGi was higher among CKD on HD patients compared to healthy controls (1.260 COI vs. 0.590 COI, p < 0.001) and was even higher in chronic hepatitis C patients with CKD on HD compared to CKD on HD group (2.190 COI vs. 1.260 COI, p < 0.001). It is also increased according to the severity of liver fibrosis: 1.670 COI, 2.020 COI, and 5.065 COI for F0-F1, significant fibrosis, and cirrhosis, respectively. The optimal cutoff values for diagnosing significant fibrosis and cirrhosis were 2.080 and 2.475 COI, respectively. CONCLUSION: Serum M2BPGi could be a simple and reliable diagnostic tool for evaluating cirrhosis in chronic hepatitis C patients with CKD on HD.

Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region.

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

Comparison Between Neutrophil-Lymphocyte Ratio and Systemic Immune-Inflammation Index as Predictors of One-Year Survival in Patients with Untreated Advanced Hepatocellular Carcinoma.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) generally only come for treatment when cancer has reached an advanced stage, with very limited treatment options. There has not been an accurate predictor marker to be able to identify which group of patients may have better survival. This study wanted to analyze the role of the inflammatory status indices as predictors of 1-year survival in patients with advanced HCC who did not undergo therapy. METHODS: This study has a retrospective cohort design using secondary data on subjects with advanced HCC who did not undergo therapy at Cipto Mangunkusumo Hospital and Dharmais Hospital. The neutrophil-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) were evaluated for their role as predictors of 1-year survival based on the area under receiving operator curve (AUROC). The best optimal cut-off for NLR and SII was decided based on the Youden index, followed by survival analysis based on those cut-offs. Confounding factors were analyzed with multivariate cox regression analysis. RESULTS: A total of 196 subjects were included in the data analysis. One-year survival was 6.6%, with a median survival of 56 days (95% CI: 46-67). The NLR had a discriminatory ability based on AUROC of 0.667 (95% CI: 0.536-0.798; p = 0.044), with the optimal cut-off point to differentiate survival was 3.7513. The SII has a discriminatory ability based on AUROC of 0.766 (95% CI: 0.643-0.889; p = 0.001), with the optimal cut-off point to distinguish survival was 954.4782. SII had superiority in discriminatory ability (p = 0.0415). CONCLUSIONS: The discriminatory ability based on AUROC of SII was better than that of NLR in predicting 1-year survival in patients with advanced HCC who did not undergo therapy.

Indonesian consensus on systemic therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a deadly cancer with a rising incidence in the last 20 years. Most patients are diagnosed late when curative treatment is no longer feasible. With the background of chronic liver disease in most patients, the management of HCC becomes more complicated, in which well-preserved liver function is a prerequisite for locoregional or systemic therapies. In 2008, sorafenib became the first systemic agent proven to provide survival benefit for patients with advanced-stage HCC. For nearly a decade, no treatment has succeeded in providing better results than sorafenib. However, numerous advances in systemic therapies have emerged in the last 5 years to fulfill the unmet needs of effective therapeutic options. Several agents have been approved for clinical use after positive results in phase III clinical trials, including lenvatinib, regorafenib, cabozantinib, ramucirumab, and lastly immune checkpoint inhibitor atezolizumab in combination with bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor. With various options available, knowledge on the clinical evidence of each drug, their safety profile, as well as the patient characteristics and preferences become mandatory in clinical decision making. The objective of this consensus is to help clinicians, health-care workers, and policy makers in providing best clinical care for HCC patients.

The Clinical Role of Endoscopic Ultrasound for Management of Bleeding Esophageal Varices in Liver Cirrhosis.

Bleeding esophageal varices (BEV) is a serious clinical condition and can potentially be life-threatening. Esophageal varices are caused by abnormal dilated submucosal and collateral veins in the esophagus wall as a result of portal hypertension due to liver cirrhosis. Consequently, it is important to administer appropriate preventive treatment for the disease in order to decrease morbidity and mortality rates. The current gold standard to identify esophageal varices is the use of esophagogastroduodenoscopy (EGD). However, EGD has limitations due to its inability in observing detailed information of varices morphology and esophagogastric hemodynamics. This report shares the potential role of endoscopic ultrasound (EUS) to overcome the limitation of EGD in clinical practices. Two cases of BEV in hepatitis B liver cirrhosis patients were described in the report. In case 1, large esophageal varices were found through EGD, and large paraesophageal varices were found through EUS. In case 2, small esophageal varices were found through EGD, and submucosal varices with a large periesophageal collateral vein and perforating vein in the distal esophagus were found through EUS. Cyanoacrylate injection guided by EUS was performed in both cases, and no rebleeding occurred after the procedure. In these cases, we showed that EUS is proven to be a potential tool in diagnosis and management of BEV in liver cirrhosis. EUS provides more accurate diagnostic aspects to find varices, assess bleeding risk, and predict bleeding recurrence. EUS also provides more beneficial treatment aspects to guide the treatment procedure and to monitor post treatment response.

National Consensus on Portal Hypertension Management in Indonesia.

Portal hypertension is a clinical syndrome that consists of hypersplenism, ascites, gastroesophageal varices, and encephalopathy. This condition is marked by increased portal pressure gradient and may occur with or without liver cirrhosis. To date, portal hypertension remains as the leading cause of severe complications and death of a patient with chronic liver disease, especially liver cirrhosis. Therefore, thorough understanding about management of portal hypertension is strongly required, especially considering that many complications of portal hypertension require early diagnosis and treatment to improve the prognosis of the patients. Additionally, although hepatic venous pressure gradient (HVPG) measurement has become a gold standard procedure for measuring portal pressure in the last twenty years, utilization of this method in Indonesia has been hindered by reluctance of the patients due to its invasiveness, high cost, and limited availability. This consensus is developed with evidence-based medicine principles to provide a guideline for portal hypertension management for general practitioners, specialists, and consultants, to achieve better clinical outcomes of portal hypertension in Indonesia.  Keywords: portal hypertension, liver cirrhosis, chronic liver disease.

The Validity and Reliability of the Indonesian Version of the Chronic Liver Disease Questionnaire (CLDQ) in Measuring Quality of Life in Patients with Liver Cirrhosis.

BACKGROUND: Liver cirrhosis remains the major cause of liver-related morbidity and mortality around the world. Cirrhosis also negatively affects health-related quality of life. Quality of life evaluation in cirrhosis treatment is often overlooked, despite its importance compared to traditional outcome. One of the specific tools to measure quality of life in cirrhosis patient is the Chronic Liver Disease Questionnaire (CLDQ). Although this tool has been widely used in many countries, no studies have been conducted on its validity and reliability in the Indonesian language. This study aimed to assess the validity and reliability of the Indonesian version of CLDQ using appropriate methods. METHODS: This is a cross-sectional study conducted at Hepatobiliary outpatient clinic in Dr. Cipto Mangunkusumo National General Hospital (RSCM), from April-May 2021. The CLDQ was first translated into the Indonesian language and subsequent pretest was performed on 10 people, resulting in the final Indonesian version of the CLDQ. The final version was later tested in the main study with larger number of subjects (52 people). Validity was assessed using construct and external validity tests, while reliability was tested using internal consistency and test-retest methods. RESULTS: The Indonesian version of CLDQ had a good construct validity (r 0.613-0.917), moderate external validity (54.1%), strong correlations between CLDQ and SF-36, good internal consistency (Cronbach-Alpha ≥ 0.7), and good test-retest reliability (ICC > 0.7). CONCLUSION: The Indonesian version of CLDQ is valid and reliable in measuring the quality of life of liver cirrhosis patients in Indonesia.

Identification and Validation of Entrustable Professional Activities in Indonesian Internal Medicine Residency Programs.

BACKGROUND: Entrustable professional activities (EPAs) are tasks entrusted to students who assist supervisors in determining their competencies. However, the competencies required and the end-educational stage in which each EPA item is assigned have yet to be determined by the stakeholders of internal medicine residency programs in Indonesia. This study aimed to identify and determine the activities in internal medicine residency programs which could be defined as EPAs in the competency-based curriculum of Indonesian internal medicine residency programs. METHODS: A literature review was conducted to identify activities which could be examined as EPA items in Indonesian internal medicine residency programs, which were then validated by 10 educational experts. Two rounds of the Delphi method were conducted with participants consisting of the Indonesian Board of Internal Medicine professionals, residency program directors, internal medicine specialists, and internal medicine residents to evaluate the importance of the identified EPA items. The EPA items were rated on a Likert scale ranging from 1 to 5, and their variances were analyzed. The participants also rated the end-educational stage appropriate for each EPA item. The effect size was calculated between groups as (1) small, <0.3; (2) moderate, approximately 0.5; and (3) large, >0.8. RESULTS: The literature review identified 29 modified items from the Royal College of Physicians and Surgeons (RCPS) and three items from other academically developed EPA designs. The expert discussion resulted in the validation of 28 EPA items (out of the 32 items in the initial EPA draft). All 28 items were accepted after two rounds of the Delphi method, and a decrease in their variances was found. CONCLUSION: This study formulated 28 EPA items for Indonesian internal medicine residency programs. Further collaboration between the Board of Internal Medicine and residency program directors will be needed for the application of these EPA items at each residency year.

Diagnostic Value of Neutrophil to Lymphocyte Ratio in Non-Alcoholic Fatty Liver Disease Evaluated Using Transient Elastography (TE) with Controlled Attenuated Parameter (CAP).

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a chronic inflammatory disease with excessive fat accumulation in the liver. Transient elastography (TE) with controlled attenuation parameter (CAP) is a device and method to examine the degree of fibrosis and steatosis. However, this device is not widely available across Indonesia. Neutrophil and lymphocyte ratio (NLR) is a simple marker for inflammation, which has a potency to predict disease outcome. This study aims to know the diagnostic value of NLR as the indicator of steatosis and fibrosis severity. METHODS: This was a cross-sectional study with consecutive sample collection. We used secondary data from medical records, starting from 2016 to 2018. A descriptive and data analysis, including correlation test, multivariate linear regression, t-test, receiver operating curve (ROC) and area under the curve (AUC) were done to find out the outcome of the study. Statistical analyses were performed using Statistical Package for Social Sciences (SPSS) Version 20.0 (SPSS Inc, Chicago, Illinois). A P value <0.05 was considered as statistically significant. RESULTS: Out of 106 subjects, 62.3% patients were women with the mean of age 57.29 years old and 77.4% had metabolic syndrome. Most patients had moderate to severe steatosis degree (66%) with the mean of TE mean 6.14 (2.8-18.2) kPa. There was a positive correlation between CAP and TE compared with NLR with r = 0.648 (p < 0.001) and r = 0.621 (p < 0.001), respectively. The use of RNL to assess moderate-severe steatosis has a cutoff point of 1.775 with sensitivity, specificity, PPV and NPV, respectively, at 81.5%, 80.6%, 89.1%, and 69.1%; cutoff point 2.150 to assess significant fibrosis with sensitivity, specificity, PPV and NPV of 92.3%, 87.5%, 70.6%, and 97.2%, respectively. CONCLUSION: NLR has a positive and significant correlation with the degree of steatosis and fibrosis with high sensitivity and specificity as evaluated by TE/CAP.

Overall Survival of Hepatocellular Carcinoma Patients Underwent Radiofrequency Ablation (RFA) Treatment: a Retrospective Cohort Study from Two Referral Hospitals in Indonesia.

BACKGROUND: Radiofrequency ablation (RFA) is one of the curative modality therapies commonly used for the early stage of HCC management. Although numerous studies have reported the outcome of RFA around the world, the data regarding the usage of RFA for the early and intermediate stage of HCC remains limited. Hence, the study aimed to report the survival rate of the early and intermediate stage HCC patients who underwent RFA in two tertiary referral hospitals in Jakarta, Indonesia. METHODS: A retrospective cohort study was conducted in Cipto Mangunkusumo and Medistra multicenter hospital in Jakarta, Indonesia. The patients with HCC BCLC A and B who underwent RFA treatments between January 2015 to December 2017 were recruited for the study. Baseline characteristics of patients were collected from the medical record. Survival analysis was calculated using the Kaplan Meier. p value result was obtained from the log-rank test. Sub-analysis of factors associated with the survival was also included in this study. RESULTS: There were 62 patients enrolled in this study (32.3% were BCLC A and 67.7% were BCLC B). Forty-six out of 62 patients (74.2%) were reported to have RFA as their first line of treatment, while 12 (25.8%) were reported to have a combination of RFA and other therapy modalities. All these patients were follow-up with an average duration of 27 months. The survival rate of liver cancer due to HCC for 12 and 36 months in patients who received RFA was 82.3% and 57.8%, respectively. Moreover, BCLC staging of liver cancer and response after RFA was significantly associated with survival. CONCLUSION: RFA still can be used as initial modality therapy nor combination with another therapy for the early and intermediate stage of HCC. BCLC staging and response after RFA had shown to be the independent factors related to survival.

Diagnostic Performance of Mac-2-Binding Protein Glycosylation Isomer (M2BPGi), compared to Transient Elastography to Assess Liver Stiffness in Treatment Naïve Chronic Hepatitis C Patients.

BACKGROUND: Liver fibrosis is an essential factor in the management of Hepatitis C virus infection. Its assessment is crucial in decision-making regarding the therapeutic decisions, and the patients' follow up. However, the established liver measurement methods have several limitations. Therefore, this study aims to assess the role of Mac-2-Binding Protein Glycosylation Isomer (M2BPGi) as a novel biomarker to measure liver stiffness in treatment naïve Chronic Hepatitis C Indonesian patients. METHODS: This study used a cross-sectional design to determine the correlation between serum M2BPGi and the degree of liver stiffness, Transient Elastrography, and differences in serum M2BPGi levels in chronic hepatitis C patients. Serum M2BPGi level and Transient Elastography results were evaluated in 56 Chronic Hepatitis C patients and 48 healthy controls. Pearson correlation analysis was conducted to find the correlation between the level of M2BPGi and Transient Elastography result. ROC analysis was conducted to find the optimum cut-off to assess fibrosis's degree among Chronic Hepatitis C Patients. RESULTS: The level of serum M2BPGi and Transient Elastography result was strongly correlated with the median level of serum M2BPGi. It was also significantly higher among Chronic Hepatitis C Patients than among healthy controls (r: 0.708, p<0.001; 0.590 COI vs. 4.130 COI, p<0.001). Among the Chronic Hepatitis C patients, the median serum of M2BPGi increased according to the degree of liver fibrosis: 1.500 COI (F0-F1), 2.985 COI (F2-F3) and 8.785 COI (≥F4). The optimum cut-off value for diagnosing significant fibrosis (F2-F3) was 1.820 COI (AUC: 90.8%) and for diagnosing cirrhosis (≥F4) was 3.770 COI (AUC: 89.3%). CONCLUSION: Serum M2BPGi was a reliable diagnostic tool for identifying liver fibrosis in Indonesian patients with Chronic Hepatitis C.

Correlation of gut Firmicutes/Bacteroidetes ratio with fibrosis and steatosis stratified by body mass index in patients with non-alcoholic fatty liver disease.

We investigated the gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD) and its correlation with fibrosis and steatosis stratified by body mass index, as reflected in the controlled attenuation parameter and transient elastography values. A cross-sectional study was performed on 37 patients with NAFLD at Cipto Mangunkusumo National General Hospital from December 2018 to March 2019. The gut microbiota was investigated in fecal samples with 16S RNA sequencing using the MiSeq next-generation sequencing platform (Illumina). NAFLD was more common in patients with metabolic syndrome. Firmicutes, Bacteroidetes, and Proteobacteria were the predominant phyla. Bacteroides was more dominant than Prevotella, contrary to the results of previous studies on healthy populations in Indonesia. Microbiota dysbiosis was observed in most samples. The gastrointestinal microbiota diversity was significantly decreased in patients with NAFLD, high triglyceride levels, and central obesity. The Firmicutes/Bacteroidetes ratio correlated with steatosis and obesity, whereas some of the other species in lower taxonomy levels were mostly associated with steatosis and obesity without fibrosis. Proteobacteria was the only phylum strongly correlated with fibrosis in patients with an average body mass index. The gut microbiota diversity was decreased in patients with NAFLD, high triglyceride levels, and central obesity, and certain gut microbes were correlated with fibrosis and steatosis.

The Association between Peripheral Th17, Th1, IL-17, and IFN-γ Levels and TACE Response in Patients with Unresectable Hepatocellular Carcinoma with or without Cirrhosis.

BACKGROUND: Th17 cells, a subset of CD4+ T cells with the capacity to produce IL-17, were reported to have pro-tumor and anti-tumor effects. Th1 cells are known for their capacity to eliminate tumor cells by producing IFN-γ. Transarterial chemoembolization (TACE) is a treatment of choice for patients with unresectable hepatocellular carcinoma (HCC). Therefore, this study aimed to determine the association between peripheral Th17, Th1, IL-17, and IFN-γ levels and TACE response in patients with unresectable HCC with or without cirrhosis. METHODS: a prospective cohort study was conducted in Cipto Mangunkusumo Hospital and several affiliated hospitals from June 2015 to January 2019. HCC patients with or without cirrhosis who met the inclusion criteria were included in this study. Blood samples were obtained immediately before TACE and 30 days after TACE. Th1 and Th17 cells were analyzed by flowcytometry, while IL-17 and IFN-γ were examined with ELISA method. TACE response was assessed with mRECIST. RESULTS: forty-one HCC patients were enrolled in this study. According to mRECIST, 12 patients were assessed as response group (complete and partial response) and 29 patients were assessed as nonresponse group (stable and progressive disease). Levels of Th1 and Th17 increased significantly after TACE in the response group. On the other hand, IL-17 and IFN-γ decreased after TACE in both groups, although not statistically significant. Interestingly, in the response group, a significant increase was found in the number of T cells subset showing both IFN-γ and IL-17 markers on their surfaces, i.e. CD4+/IFN-γ+/IL-17+ T cells. CONCLUSION: increased circulating Th1, Th17, and CD4+/IFN-γ+/IL-17+ T cells were observed in HCC patients with complete or partial response to TACE.

Successful Treatment of Hepatitis C Virus Infection Using Direct-Acting Antiviral Agents (DAAs) in Adolescents with Kidney Transplantation: A Case Series.

INTRODUCTION: Hepatitis C virus (HCV) infection is common among end-stage renal disease patients undergoing hemodialysis. The standard treatment for HCV infection has been interferon-ribavirin combination prior to renal transplantation. However, compared to direct-acting antiviral agents (DAAs), the risk of graft rejection is higher with interferon therapy. Many recent studies have investigated the efficacy and safety of DAAs for treating HCV infection in kidney disease in adults; however, it has not been established in pediatric patients. To the best of our knowledge, this is the first report describing successful treatment using the DAAs sofosbuvir/daclatasvir in two pediatric kidney transplant recipients who had HCV genotype 1a infection without liver fibrosis. CASE PRESENTATION: Case 1 describes a 13-year-old Indonesian boy who had undergone hemodialysis since 2014 after being diagnosed with end-stage renal disease (ESRD) secondary to bilateral renal hypoplasia. Later, he had HCV infection and was treated with interferon-based therapy with ribavirin prior to living-related renal transplantation (LRRT). The HCV was undetected and his liver function normalized six months after treatment initiation. However, 10 months after treatment initiation, he had HCV virological breakthrough, leading to cessation of interferon therapy. Plans for LRRT were continued and HCV treatment using DAAs was set up to be given post LRRT. Case 2 describes a 14-year-old Indonesian girl who also had hemodialysis prior to LRRT after she was diagnosed with ESRD secondary to nephrotic syndrome. Later, she had HCV infection and was treated with interferon and ribavirin prior to the live-unrelated renal transplantation. HCV infection did not resolve, in addition, she experienced thrombocytopenia-which is a side effect of interferon-resulting in termination of interferon treatment. Both cases were treated with DAAs one year following renal transplantation after reaching stable graft function, leading to achievement of sustained virological response at 24 weeks. CONCLUSION: Post-transplantation treatment of chronic HCV is preferred in KTRs. The sofosbuvir/daclatasvir regimen as an interferon-free therapy is a safe, effective option for HCV infection in pediatric KTRs, who can tolerate sofosbuvir/daclatasvir well and respond favorably without significant adverse events.