Stemness markers in hepatocellular carcinoma of Eastern vs. Western population: Etiology matters?

Hepatocellular carcinoma (HCC) is one of the most common cancers with a high mortality rate. HCC development is associated with its underlying etiologies, mostly caused by infection of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV), alcohol, non-alcoholic fatty liver disease, and exposure to aflatoxins. These variables, together with human genetic susceptibility, contribute to HCC molecular heterogeneity, including at the cellular level. HCC initiation, tumor recurrence, and drug resistance rates have been attributed to the presence of liver cancer stem cells (CSC). This review summarizes available data regarding whether various HCC etiologies may be associated to the appearance of CSC biomarkers. It also described the genetic variations of tumoral tissues obtained from Western and Eastern populations, in particular to the oncogenic effect of HBV in the human genome.

Performance of EncephalApp Stroop Test in Cirrhotic Patients for Evaluating Covert Hepatic Encephalopathy.

BACKGROUND: Covert hepatic encephalopathy (HE) is the mildest HE spectrum that is difficult to detect, but associated with significant decrease in quality of life. Currently, there is no gold standard to detect covert HE. EncephalApp Stroop Test as a newer diagnostic tool is easier, faster and its ease of availability in various health institutions is expected to be applied in Indonesia for covert HE detection. This study aimed to validate and test the reliability and diagnostic ability of EncephalApp Stroop Test to diagnose covert HE, compared to the Psychometric Hepatic Encephalopathy Score (PHES) and critical flicker frequency (CFF). METHODS: This study is a cross-sectional test, conducted from August to September 2018, targeted at patient with cirrhosis in Jakarta, to obtain Area Under The Curve (AUC), sensitivity, specificity, cut-off point, predictive value, likelihood ratio, and post-test probability of the EncephalApp Stroop Test, compared to PHES and CFF. The Validity and reliability tests were done before diagnostic study. Translation of the EncephalApp Stroop Test were first carried out using WHO protocol. All patients first underwent a Mini Mental State Examination and Ishihara Test to rule out color blindness. RESULTS: Thirty subjects participated in validity and reliability tests, and eighty in diagnostic tests. The translated application showed excellent internal consistency (Chronbach's Alpha of 0.942) and correlation coefficient of 0.82. The diagnostic study showed OnTime + OffTime as the best parameter (AUC: 0.897 (95% CI: 82.9% - 96.5%); sensitivity: 88.6%; specificity: 80%; positive predictive value (PPV): 0.77; negative predictive value (NPV): 0.9; positive likelihood ratio (LK+): 4.4; negative likelihood ratio (LK-): 1.4; positive post-test probability: 0,775; negative post-test probability: 0,1; and cut-off point ≥ 188.8 seconds. CONCLUSION: The EncephalApp Stroop Test is valid and reliable, with good AUC value, sensitivity, specificity, PPV, NPV and likelihood ratio in diagnosing covert hepatic encephalopathy in patients with cirrhosis in Indonesia.

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.

Endoscopic Management Using Novel Haemostatic Agents for Immediate Bleeding during Endoscopic Retrograde Cholangio-Pancreatography.

Bleeding after endoscopic sphincterotomy (ES) remains as a major challenge during ERCP procedure. Standard endoscopic haemostatic procedures have demonstrated good performance for bleeding control. Novel endoscopic haemostatic agents have also been widely used in gastrointestinal bleeding management. Regardless, there is still a paucity of high-quality evidence evaluating the practicality of these agents in ERCP. This case series study was performed on the patients who underwent ERCP procedure in a tertiary referral private hospital within 2 years period. Post-ES immediate bleeding is defined as the onset of bleeding at the time of sphincterotomy. Treatment groups for post-ES bleeding are divided into (1) standard haemostatic methods and (2) novel haemostatic agents. There were 40 patients who received standard haemostatic treatment and 60 patients who received novel haemostatic agents. Initial haemostasis was achieved in all patients. Two patients who received standard haemostatic treatment had rebleeding. Meanwhile, no patients in novel haemostatic treatment group had rebleeding. In conclusion, novel haemostatic agent can be considered as an easy and practical method in daily practice, especially when an ERCP procedure is performed. Further studies with larger sample size which, if possible, can also include a cost-effectiveness analysis are still required to implement these agents as a standard procedure in clinical practice. (This abstract has been presented at the American College of Gastroenterology meeting October 2021).

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.

Identifying the early predictors of non-response to steroids in patients with flare of autoimmune hepatitis causing acute-on-chronic liver failure.

BACKGROUND AND AIMS: Early identification of non-response to steroids is critical in patients with autoimmune hepatitis (AIH) causing acute-on-chronic liver failure (ACLF). We assessed if this non-response can be accurately identified within first few days of treatment. METHODS: Patients with AIH-ACLF without baseline infection/hepatic encephalopathy were identified from APASL ACLF research consortium (AARC) database. Diagnosis of AIH-ACLF was based mainly on histology. Those treated with steroids were assessed for non-response (defined as death or liver transplant at 90 days for present study). Laboratory parameters, AARC, and model for end-stage liver disease (MELD) scores were assessed at baseline and day 3 to identify early non-response. Utility of dynamic SURFASA score [- 6.80 + 1.92*(D0-INR) + 1.94*(∆%3-INR) + 1.64*(∆%3-bilirubin)] was also evaluated. The performance of early predictors was compared with changes in MELD score at 2 weeks. RESULTS: Fifty-five out of one hundred and sixty-five patients (age-38.2 ± 15.0 years, 67.2% females) with AIH-ACLF [median MELD 24 (IQR: 22-27); median AARC score 7 (6-9)] given oral prednisolone 40 (20-40) mg per day were analyzed. The 90 day transplant-free survival in this cohort was 45.7% with worse outcomes in those with incident infections (56% vs 28.0%, p = 0.03). The AUROC of pre-therapy AARC score [0.842 (95% CI 0.754-0.93)], MELD [0.837 (95% CI 0.733-0.94)] score and SURFASA score [0.795 (95% CI 0.678-0.911)] were as accurate as ∆MELD at 2 weeks [0.770 (95% CI 0.687-0.845), p = 0.526] and better than ∆MELD at 3 days [0.541 (95% CI 0.395, 0.687), p < 0.001] to predict non-response. Combination of AARC score > 6, MELD score > 24 with SURFASA score ≥ - 1.2, could identify non-responders at day 3 (concomitant- 75% vs either - 42%, p < 0.001). CONCLUSION: Baseline AARC score, MELD score, and the dynamic SURFASA score on day 3 can accurately identify early non-response to steroids in AIH-ACLF.

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.

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.

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.

Therapeutic interventional endoscopic ultrasound in pancreato-biliary disorders: Does it really replace the surgical/percutaneous approach?

Pancreato-biliary disorders are still incredibly challenging in the field of gastroenterology, as they would sometimes require multi-approach interventional procedures. Recently, therapeutic interventional endoscopic ultrasound (EUS) has emerged as a potential alternative to surgical or percutaneous approaches. Unfortunately, considering the high cost of EUS, lack of facility and expertise, most gastroenterologists still often refer cases to undergo surgical interventions without contemplating the possibility of utilizing EUS first. EUS-guided biliary drainage has become one of the best choices for establishing access to biliary system, given the clear visualization of pancreas, gallbladder, and common bile duct. Although there are still only a few studies which directly compare EUS-guided and surgical approaches for biliary drainage, current evidence demonstrated the superiority of EUS-guided approach in terms of adverse events and re-intervention rates, with similarly high technical and clinical success rates compared to percutaneous and surgical approaches, especially in patients with history of failed endoscopic retrograde cholangiopancreatography attempt. Comparable success rates with shorter length of hospital stay between endoscopic and surgical approaches have also been exhibited for pancreatic pseudocysts and walled-off necrosis. Recent findings about the progress of EUS approach in gastroenterostomy/jejunostomy also indicated a promising potential of EUS, as a less invasive approach, for managing gastric outlet obstruction.

An expert review on the use of tenofovir alafenamide for the treatment of chronic hepatitis B virus infection in Asia.

Asia has intermediate-to-high prevalence and high morbidity of hepatitis B virus (HBV) infection. The use of guideline-recommended nucleos(t)ide analogs with high barrier to resistance, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), is one of the key interventions for curbing HBV infection and associated morbidity in Asia. However, there are some challenges to the use of ETV and TDF; while ETV is associated with high resistance in lamivudine (LAM)-exposed (especially LAM-refractory) patients; bone and renal safety issues are a major concern with TDF. Hence, a panel of twenty-eight expert hepatologists from Asia convened, reviewed the literature, and developed the current expert opinion-based review article for the use of TAF in the resource-constrained settings in Asia. This article provides a comprehensive review of two large, phase 3, double-blind, randomized controlled trials of TAF versus TDF in HBeAg-negative (study 0108) and HBeAg-positive (study 0110) chronic HBV patients (> 70% Asians). These studies revealed as follows: (1) non-inferiority for the proportion of patients who had HBV DNA < 29 IU/mL; (2) significantly high rate of normalization of alanine aminotransferase levels; (3) no incidence of resistance; and (4) significantly better bone and renal safety, with TAF vs. TDF up to 144 weeks. Considering the benefits of TAF, the expert panel proposed recommendations for optimizing the use of TAF in Asia, along with guidance on specific patient groups at risk of renal or bone disease suitable for TAF therapy. The guidance provided in this article may help clinicians optimize the use of TAF in Asia.

Risk factors of mortality in the patients with hepatocellular carcinoma: A multicenter study in Indonesia.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is considered a significant burden, and its associated rate of mortality is increasing. Therefore, a population-based cancer registry is considered an essential element in the baseline and comprehensive analysis of the risk factors associated with HCC. We present a multicenter analysis of HCC registry from 2 hospitals in Indonesia. METHODS: We performed a follow-up on patients with HCC who were admitted between January 2015 and November 2017 in Cipto Mangunkusumo National General Hospital and Dharmais Hospital, Jakarta, Indonesia. Patient's death was considered the primary outcome of the study. A multivariate analysis was conducted using logistic regression, and odds ratio (OR) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 282 patients with HCC included. At the last follow-up, 136 (48.2%) patients had died. Mortality rate was not significantly affected by sex, age, etiology, the presence of cirrhosis, nor surveillance of HCC. Based on the Child-Pugh (CP) classification, the OR increased progressively in CP C patients (OR 1.95; 95% CI 1.08-3.53; P = 0.026). The progressive increase was also found in patients with a higher Barcelona Clinic Liver Cancer stage, and the OR for CP C and D patients were 3.50 (95% CI 1.18-10.38; P = 0.024) and 3.41 (95% CI 1.02-11.41; P = 0.047), respectively. Supportive treatment was the most common treatment modality with an OR of 2.17 (95% CI 1.14-4.16; P = 0.019), and it was associated with the mortality rate of HCC. CONCLUSIONS: The CP classification, Barcelona Clinic Liver Cancer staging system, and treatment modality might predict mortality in patients with HCC. Moreover, other parameters must be further evaluated.

Asian consensus recommendations on optimizing the diagnosis and initiation of treatment of hepatitis B virus infection in resource-limited settings.

Asia has an intermediate-to-high prevalence of and high morbidity and mortality from hepatitis B virus (HBV) infection. Optimization of diagnosis and initiation of treatment is one of the crucial strategies for lowering disease burden in this region. Therefore, a panel of 24 experts from 10 Asian countries convened, and reviewed the literature, to develop consensus guidance on diagnosis and initiation of treatment of HBV infection in resource-limited Asian settings. The panel proposed 11 recommendations related to diagnosis, pre-treatment assessment, and indications of therapy of HBV infection, and management of HBV-infected patients with co-infections. In resource-limited Asian settings, testing for hepatitis B surface antigen may be considered as the primary test for diagnosis of HBV infection. Pre-treatment assessments should include tests for complete blood count, liver and renal function, hepatitis B e-antigen (HBeAg), anti-HBe, HBV DNA, co-infection markers and assessment of severity of liver disease. Noninvasive tests such as AST-to-platelet ratio index, fibrosis score 4 or transient elastography may be used as alternatives to liver biopsy for assessing disease severity. Considering the high burden of HBV infection in Asia, the panel adopted an aggressive approach, and recommended initiation of antiviral therapy in all HBV-infected, compensated or decompensated cirrhotic individuals with detectable HBV DNA levels, regardless of HBeAg status or alanine transaminase levels. The panel also developed a simple algorithm for guiding the initiation of treatment in noncirrhotic, HBV-infected individuals. The recommendations proposed herein, may help guide clinicians, to optimize the diagnosis and improvise the treatment rates for HBV infection in Asia.

The role of gut microbiota in non-alcoholic fatty liver disease: pathways of mechanisms.

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Its prevalence increases with increasing rates of obesity, insulin resistance, and diabetes mellitus. The pathogenesis of NAFLD involves many factors, including the gastrointestinal microbiota. However, there is still debate about the impact of gut dysbiosis in the NAFLD disease progression. Therefore, this paper aims to review the relationship between gut microbiota and other risk factors for NAFLD and how gut dysbiosis plays a role in the pathogenesis of NAFLD. Hopefully, this paper can make an appropriate contribution to the development of NAFLD research in the future.

Visceral fat thickness of erosive and non-erosive reflux disease subjects in Indonesia's tertiary referral hospital.

BACKGROUND: There has been an increasing number of reports regarding the correlation between obesity and gastroesophageal reflux disease (GERD). Visceral fat thickness is thought to be a risk factor for GERD and its severity. Several studies have conflicting results, so this study aimed to determine visceral fat thickness difference between erosive and non-erosive reflux disease. METHODS: A cross-sectional study of 56 adult subjects with GERD symptoms was held at Cipto Mangunkusumo National General Hospital between April and November 2018. Gastroesophageal Reflux Disease Questionnaires (GERDQ) were utilized to determine the presence of GERD. Ultrasonography was used to determine visceral fat thickness. Esophageal erosions were diagnosed using upper gastrointestinal endoscopy. The difference in visceral fat thickness between esophagitis and non-esophagitis group was analysed using T-test. RESULTS: From 56 total subjects, 55.4% have erosive reflux disease (ERD), in which were dominated by subjects with grade A esophagitis (64.5%) based on Los Angeles Classification of Esophagitis (LA classifications). There was no significant difference of visceral fat thickness between non-erosive reflux disease (NERD) and ERD (p = 0,831). There was, however, an increasing trend of visceral fat thickness with the advancing severity of esophagitis, although statistical significance was not reached. CONCLUSION: Visceral fat thickness as measured by ultrasonography has no significant difference between NERD and ERD.

Hyperuricemia as an independent risk factor for non-alcoholic fatty liver disease (NAFLD) progression evaluated using controlled attenuation parameter-transient elastography: Lesson learnt from tertiary referral center.

BACKGROUND AND AIM: Hyperuricemia is one of the metabolic parameter which has been considered to play an important role in non-alcoholic fatty liver disease (NAFLD). However, there is still lack of studies about association between serum uric acid with liver disease progression in NAFLD. This study aimed to know the association between hyperuricemia with moderate to severe steatosis and significant fibrosis along with other metabolic factors in NAFLD patients evaluated using Controlled Attenuation Parameter (CAP) - Transient Elastography (TE). METHODS: This is a prospective study in NAFLD patients who came to our tertiary referral center University hospital hepatobiliary outpatient's clinic. All patients underwent metabolic parameters measurement including serum uric acid level and CAP-TE examination. Cutoff value used for significant liver fibrosis ≥7 kPa and ≥285 dB/m for moderate-severe steatosis. RESULTS: Of 113 NAFLD patients, there were 45 patients with moderate-severe steatosis and 34 patients with significant fibrosis. Multivariate analysis showed only high level of fasting blood glucose (OR 2756; 95% CI 1.131-6.717) and low HDL level (OR 4.196, 95% CI 1.22-14.430) to be independent risk factors of moderate-severe steatosis. High level of fasting blood glucose (OR 3.98, 95% CI 1.105-14.389) and hyperuricemia (OR 2.501, 95% CI 1.095-5.714) were found to be independent risk factors for significant liver fibrosis. CONCLUSION: Hyperuricemia is found to be an independent risk factor for significant liver fibrosis.

Comparative efficacy of sofosbuvir-ribavirin versus sofosbuvir-daclatasvir for treatment of chronic hepatitis C in an area with limited NS5A inhibitor availability.

INTRODUCTION: Sofosbuvir (SOF) and daclatasvir (DCV) regimens are recommended for all genotypes of hepatitis C virus (HCV) infection. However, DCV accessibility is still low in several low- and middle-income countries. Ribavirin (RBV) is more affordable and has been known for chronic HCV treatment along with SOF or interferon. The aim of this study was to assess the efficacy of SOF + RBV and SOF + DCV regimens for treatment of chronic HCV in Indonesia. METHODS: We conducted a retrospective study among patients with chronic HCV who were treated with SOF. Data on SOV + RBV were collected from 2015 to 2016, while those on SOF + DCV were collected from 2016 to 2017. The baseline characteristics were recorded from the medical record unit in Cipto Mangunkusumo General Hospital, Jakarta, Indonesia. The primary outcome was the achievement of sustained virological response at 12 weeks (SVR12). RESULTS: Of 309 patients, 64.4% (199/309) had genotype 1 infections, 29.8% (92/309) had cirrhosis, and 4.9% (15/309) had co-infection with human immunodeficiency virus (HIV). At the end of treatment (EOT), 99.3% (136/137) patients in the SOF + RBV group and 99.4% (164/165) in SOF + DCV group had no detectable viral load. The criterion for SVR12 was met in 90.8% (109/120) patients in SOF + RBV regimen and 98.2% (108/110) in SOF + DCV regimen. Among patients with cirrhosis, 84.4% (38/45) patients and 100% (27/27) achieved SVR12 in the SOF + RBV and SOF + DCV groups, respectively. CONCLUSION: SOF + DCV regimen had higher SVR rates compared to SOF + RBV regimen (p = 0.034). However, both the regimens showed an impressive outcome, with overall SVR12 rates above 90%, irrespective of presence of cirrhosis and HCV genotype. In non-structural protein 5A inhibitor limited setting, SOF + RBV regimen still can be used as treatment for HCV infection, particularly in non-cirrhotic patients.

Evaluation of Acoustic Radiation Force Impulse (ARFI) for Fibrosis Staging in Chronic Liver Diseases.

BACKGROUND: acoustic radiation force impulse (ARFI) is a new proposed noninvasive method for liver fibrosis staging. Integrated with B-mode ultrasonography, ARFI can be used to assess liver tissue condition. However its diagnostic accuracy is still being continuously evaluated. Also, there is lack of data regarding the utilization of ARFI in our population. This study aimed to evaluate the diagnostic value of ARFI as an alternative noninvasive modality for fibrosis staging in chronic hepatitis B and hepatitis C patients in our population. METHODS: we conducted cross-sectional comparison of ARFI imaging and transient elastography on patients who underwent liver biopsy at Cipto Mangunkusumo Hospital. Fibrosis staging using METAVIR scoring system presented as standard reference. A total of 43 patients underwent liver biopsy was evaluated by ARFI imaging and transient elastography. Cut-off values were determined using receiver-operating characteristic (ROC). RESULTS: both liver stiffness determined by ARFI and transient elastography (TE) were moderately correlated with METAVIR score with value of 0.581 and 0.613, respectively (both P<0.01). Diagnostic accuracy of ARFI predicted significant fibrosis (F≥2) with area under receiver operating characteristic curve (AUROC) of 0.773 (95% CI 0.616-0.930) and even better for cirrhosis (F4 fibrosis), expressed as AUROC of 0.856 (95% CI 0.736-0.975). Transient elastography was better for significant fibrosis with AUROC of 0.761 (95% CI 0.601-0.920) and was best for prediction of cirrhosis, expressed as AUROC of 0.845 (95% CI 0.722-0.968). CONCLUSION: ARFI is provided with more convenient evaluation of liver tissue condition, and its diagnostic accuracy is not significantly different from TE for staging liver fibrosis.