Persistent hypoglycemia in patients with liver cancer.

Summary: Hypoglycemia is one of the paraneoplastic syndrome manifestations that arise from primary and secondary liver cancer. Hypoglycemia usually presents in the late stage of the disease and indicates a poor prognosis. This case series displays the characteristics profile of patients with primary and secondary liver cancer who are presented with hypoglycemia in a tertiary referral hospital in Indonesia. The study included 41 liver cancer patients who were presented with hypoglycemia. Hepatocellular carcinoma was diagnosed in 51.2% of patients, metastatic liver disease in 14.6% of patients, and undiagnosed liver cancer in 34.1% of patients. The mean age was 47.7 years with male predominance (65.9%). Jaundice was found in 58.5% and hepatomegaly in 70.7% of patients. The mean (± S.D.) initial blood glucose was 42.15 ± 17.11 mg/dL and the Child-Pugh score was 9.93 ± 2.11. Based on imaging, tumor diameter was 12.6 ± 6.9 cm, multiple (61%), and involving both lobes (61%). Treatments for hypoglycemia included oral/enteral feeding, intravenous dextrose, and steroids. No treatment was given for the cancer because all patients were in an advanced stage. The treatment resulted in 41.5% blood glucose being controlled, 56.1% refractory, and 2.4% persistent. Mortality was 70.7% and in average occurred 5.76 ± 4.99 days after hypoglycemia. The mainstay of treatment in these cases is treating the tumor with cytoreduction. However, it was difficult to do cytoreduction because the tumor was already in an advanced stage. Beneficial supportive treatments for maintaining normal blood glucose are frequent meals, dextrose infusion, steroids, and glucagon. Learning points: Hypoglycemia in liver cancer occurs due to the failure of the liver to fulfill body glucose demand because the liver parenchyma has been largely replaced by the tumor, in addition to the high production of insulin growth factor (IGF). Hypoglycemia is often caused by islet cell and non-islet cell tumors, with a higher occurrence in non-islet cell tumors due to paraneoplastic syndrome and the high metabolic requirements of the tumor. The mainstay of NICTH treatment is treating the tumor with cytoreduction. However, in an advanced stage, cytoreduction therapy is often challenging to conduct. Beneficial supportive treatments for controlling blood glucose are frequent meals, dextrose infusion, and the injection of steroids and glucagon. Steroids play a beneficial role in the treatment of persistent hypoglycemia in hepatocellular carcinoma by stimulating gluconeogenesis and increasing lipolysis. Steroids also have roles in the inhibition of peripheral glucose intake, suppression of big IGF-2 production, and modulation of the GH-IGF axis.

Correlation between controlled attenuation parameter values with SYNTAX score in patients with significant coronary artery disease.

Non-alcoholic fatty liver disease (NAFLD) is an emerging cause of chronic liver disease, with coronary artery disease (CAD) as the main cause of death in NAFLD patients. However, correlation between the severity of liver steatosis and coronary atherosclerosis is yet to be understood. Here we aim to explore the correlation between controlled attenuation parameter (CAP) values and SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score in adult patients with significant CAD, defined as ≥ 50% stenosis of the left main coronary artery, or ≥ 70% stenosis of the other major coronary arteries. A cross-sectional study was conducted on 124 adult patients with significant CAD who underwent coronary angiography. Transient elastography with CAP was used to assess liver steatosis severity, resulting in a mean CAP value of 256.5 ± 47.3 dB/m, with 52.5% subjects had significant steatosis (CAP value of ≥ 248 dB/m). Median SYNTAX score was 22. A statistically significant correlation was observed between CAP value and SYNTAX score (r = 0.245, p < 0.0001). The correlation was more pronounced in patients with prior history of PCI (r = 0.389, p = 0.037). Patients with high-risk SYNTAX score (> 32) had the highest CAP value (285.4 ± 42.6 dB/m), and it was significantly higher than those with low-risk SYNTAX score (0-22), with a mean difference of 38.76 dB/m (p = 0.006). Patients with significant liver steatosis should undergo periodic CAD assessment and lifestyle modification, especially those with severe liver steatosis.

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.

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease.

Background: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no appropriate guidance on CKD in individuals with MAFLD. Furthermore, there has been little attention paid to the link between MAFLD and CKD in the Nephrology community. Methods and Results: Using a Delphi-based approach, a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD. Conclusions: This Delphi-based consensus statement provided guidance on the epidemiology, mechanisms, management and treatment of MAFLD and CKD, as well as the relationship between the severity of MAFLD and risk of CKD, which establish a framework for the early prevention and management of these two common and interconnected diseases.

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.

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.

The role of endoscopic ultrasound for portal hypertension in liver cirrhosis.

Chronic liver disease is still a major problem because disease progression will ultimately lead to liver cirrhosis. Portal hypertension is the hallmark in advanced liver disease management. By establishing portal vein access, endoscopic ultrasound (EUS) has been utilized in various clinical applications. In comparison to standard upper gastrointestinal endoscopy, EUS-Doppler has been shown to be a better modality for detecting esophageal and gastric varices along with peri-esophageal collateral veins, para-esophageal collateral veins, and perforating veins, and may be used to objectively predict the recurrence of bleeding. EUS-guided portal vein catheterization has also been proposed to overcome the limitations of trans-jugular approaches. The combination of EUS-elastography and azygos vein evaluation can also enhance the diagnostic accuracy of each modality. Another well-known implementation of EUS-guided procedures is in the management of ascites; particularly in paracentesis and ascitic fluid analysis. In addition, the most common clinical application of EUS in the treatment of portal hypertension is through vascular therapy or creation of intrahepatic portosystemic shunts. Major drawbacks of EUS mainly revolve around technical difficulties, the high cost of the procedure, as well as the requirement of more studies in humans to evaluate EUS-guided advanced therapeutic modalities in portal hypertension.

Contextual and individual factors associated with knowledge, awareness and attitude on liver diseases: A large-scale Asian study.

There are limited data to provide better understanding of the knowledge/awareness of general population towards liver health in Asia. We sought to identify the knowledge gaps and attitudes towards liver health and liver diseases as well as evaluate associated individual-level and macro-level factors based on contextual analysis. An online survey assessing knowledge, awareness and attitudes towards liver health and disease was conducted among 7500 respondents across 11 countries/territories in Asia. A liver index was created to measure the respondents' knowledge level and the degree of awareness and attitudes. Multilevel logistic regression was performed to identify individual factors and contextual effects that were associated with liver index. The overall liver index (0-100-point scale) was 62.4 with 6 countries/territories' liver indices greater than this. In the multilevel model, the inclusion of geographical information could explain for 9.6% of the variation. Residing in a country/territory with higher HBV prevalence (80% IOR: 1.20-2.79) or higher HCV death rate (80% IOR: 1.35-3.13) increased the individual probability of obtaining a high overall liver index. Individual factors like age, gender, education, household income, disease history and health screening behaviour were also associated with liver index (all p-values<0.001). The overall liver index was positively associated with the two macro-level factors viz. HBV prevalence and HCV death rate. There is a need to formulate policies especially in regions of lower HBV prevalence and HCV death rate to further improve the knowledge, awareness and attitudes of the general public towards liver diseases.

The Role of Interventional Endoscopic Ultrasound in Liver Diseases: What Have We Learnt?

Chronic liver disease (CLD) is still a major problem, where the disease progression will lead to liver cirrhosis (LC) or hepatocellular carcinoma (HCC). Portal hypertension (PH) management and loco-regional therapy for HCC have become the cornerstones in advanced liver disease management. Recently, there are studies looking at the potential role of interventional endoscopic ultrasound (EUS) in liver diseases. EUS may be useful in vascular changes of the digestive wall evaluation, performing dynamic assessment of hemodynamic changes, predicting variceal bleeding and rebleeding risk, and assessing the pharmacological effects. In PH management, EUS-guided vascular therapy-which revolves around glue injection, endovascular coil placement/embolization, and combination of both-has shown promising results. As a diagnostic modality for liver cancer, the implementation of EUS in liver diseases is currently not only limited to liver biopsy (EUS-LB) but also in shear-wave elastography (SWE) and portal pressure gradient measurement, as well as portal vein sampling. The application of EUS-guided radiofrequency ablation (EUS-RFA) and tumor injection can also overcome the limitations shown by both modalities without EUS. Nevertheless, establishing EUS as a firm diagnostic and therapeutic modality is still challenging since the performance of interventional EUS requires high expertise and adequate facilities.

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.

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.

APASL practical recommendations for the management of hepatocellular carcinoma in the era of COVID-19.

BACKGROUND: COVID-19 has been giving the devastating impact on the current medical care system. There are quite many guidelines on COVID-19, but only a few on the management of hepatocellular carcinoma (HCC) during COVID-19 pandemic. AIMS: We develop these recommendations to preserve adequate clinical practice for the management of HCC. METHODS: Experts of HCC in the Asia-Pacific region exchanged opinions via webinar, and these recommendations were formed. RESULTS: Close contact should be minimized to reduce possible exposure of both medical staff and patients to the novel coronavirus. To prevent transmission of the virus, meticulous hygiene measures are important. With the decrease in regular medical service, the medical staff may be mobilized to provide COVID-19-related patient care. However, diagnosis and treatment of HCC should not be delayed because of COVID-19 pandemic. The management of HCC should be the same as in non-pandemic circumstances. HCC is highly malignant, thus it is recommended not to delay curative treatment such as surgery and ablation. However, a kind of triage is necessary even among patients with HCC when resources are insufficient for all to be treated. Curative treatments should be periodized and cytoreductive or non-curative treatment such as vascular interventions and systemic therapy may be postponed until it can be performed safely with sufficient resources. For patients with confirmed or suspected to be infected with the novel coronavirus, diagnosis and treatment should be postponed until the virus is eliminated or they are confirmed as not being infected with it. CONCLUSIONS: These are collection of measures implemented by front-line medical professionals. We would evolve these recommendations over time as more real-world data becomes available.

Clinical significance of isolated gastric varices in liver cirrhotic patients: A single-referral-centre retrospective cohort study.

INTRODUCTION: Gastric varices (GVs) occur in 10-30% of liver cirrhotic patients, with a mortality rate of up to 45%. Rupture of isolated GVs (IGVs) is less prevalent but often results in more severe hemorrhage and a higher risk of mortality than rupture of esophageal varices (EVs). However, there is no clear consensus yet about the optimal management for incidentally discovered IGVs. OBJECTIVE: To determine the clinical significance of IGVs in liver cirrhotic patients. METHODS: This was a retrospective cohort endoscopy database study within a 2-year period (2016-2017). All study subjects were liver cirrhotic patients with OVs or GVs. The exclusion criteria were noncirrhotic portal hypertension, presence of malignancy, absence of varices, and incomplete data. Statistical analysis was performed using IBM SPSS 23. RESULTS: A total of 153 patients were included in this study. IGVs were found in 13 (8.49%) patients, whereas OVs were found in 112 (73.20%) patients and gastro-OVs were found in 28 (18.30%) patients. Child-Pugh class C (CP C) score was the strongest independent risk factor for variceal bleeding in bivariate analysis (hazard ratio [HR]: 10.21, 95% confidence interval [CI]: 4.15-25.12, P = 0.001) and multivariate analysis (HR: 12.49, 95% CI: 4.95-31.54, P 0.001); however, the presence of IGVs was not an independent risk factor. CP C score was also the only significant risk factor associated with 1-year mortality in liver cirrhotic patients on multivariate analysis (HR: 26.77, 95% CI: 6.01-119.34, P 0.001). CONCLUSION: The presence of IGVs has no clinical significance in the occurrence of 1-year rebleeding and in patient survival.

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.

The Improvement in 1-Year Survival Rate of Patients with Hepatocellular Carcinoma BCLC Stage A and B after the Implementation of Comprehensive Management.

BACKGROUND: The previous study showed lack of improvement in survival rate of hepatocellular carcinoma (HCC) patients in 2013-2014 period compared to 1998-1999 period in Indonesia due to late diagnosis. Comprehensive management of HCC has been implemented since 2015 in Cipto Mangunkusumo National General Hospital. This aims to provide better screening and surveillance in HCC patients and prioritizing of more proactive approach, such as online patient's group discussion and social media education. AIM: To compare the survival rates in HCC BCLC stage A and B before and after the implementation of comprehensive management. METHODS: A retrospective study design was conducted in this study. We compared the database of HCC BCLC A and B patients between the 2015-2017 period and the 2013-2014 period. Clinical parameters, modality of treatment, and 1-year survival rate were analyzed. RESULTS: A total of 50 patients from 2013 to 2014 period and 143 patients from 2015 to 2017 period were included in this study. After the implementation of comprehensive management, the number of patients detected in BCLC class A increased significantly (p = 0.003). In 2015-2017 period, the number of patients that received curative treatment increased significantly (p = 0.018). The 1-year survival rate of the 2015-2017 group and the 2013-2014 group was 73.9% and 47.9%, respectively, with p value 0.002. CONCLUSIONS: The 1-year survival rate of BCLC A and BCLC B HCC patients in Cipto Mangunkusumo National Hospital improved significantly after the implementation of comprehensive management of HCC in 2015.

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.

Palliative Endoscopic Ultrasound Biliary Drainage for Advanced Malignant Biliary Obstruction: Should It Replace the Percutaneous Approach?

Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD) are the standard of care in malignant biliary obstruction cases. Recently, endoscopic ultrasound-guided biliary drainage (EUS-BD) has been widely used after unsuccessful ERCP. However, the patient's clinical impact of EUS-BD over PTBD is still not obvious. Therefore, this case series study aims to evaluate the clinical outcomes of patients with advanced malignant biliary obstruction who underwent EUS-BD after failed ERCP. A retrospective database study was performed between January 2016 and June 2018 in patients with advanced malignant biliary obstruction. Patients were consecutively enrolled without randomization. Treatment options consisted of ERCP and PTBD or EUS-BD if ERCP failed. Based on 144 biliary obstruction cases, 38 patients were enrolled; 24 (63.2%) were men. The patients' mean age was 66.8 ± 12.36 years. The most common cause of malignant biliary obstruction was pancreatic cancer (44.7%). Biliary drainage was achieved by ERCP (39.5%), PTBD (39.5%), and EUS-BD (21.1%). The technical success rate was 86.7% by PTBD and 87.5% by EUS-BD (p = 1.000), while the clinical success rate was 93.3% by PTBD and 62.5% by EUS-BD (p = 0.500). The median survival in patients who underwent PTBD versus those wo underwent EUS-BD was 11 versus 3 months (log-rank p = 0.455). In conclusion, there is no significant advantage of EUS-BD when compared to PTBD in terms of clinical success and survival benefit in advanced malignant biliary obstruction.

The role of Small Intestinal Bacterial Overgrowth (SIBO) in Non-alcoholic Fatty Liver Disease (NAFLD) patients evaluated using Controlled Attenuation Parameter (CAP) Transient Elastography (TE): a tertiary referral center experience.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an emerging disease, where it can progress to non-alcoholic steatohepatitis (NASH) and lead to liver cirrhosis or liver cancer. Small intestinal bacterial overgrowth (SIBO) has been hypothesized to play an important role in NAFLD development and progression, however, there is still conflicting data about this phenomenon. Transient Elastography (TE) examination using controlled attenuation parameter (CAP) has been validated for liver disease progression assessment in NAFLD. It is non-invasive method and easy to perform in clinical practice. Therefore, we would like to know the role of SIBO in NAFLD and its possible impact on disease progression. METHODS: A cross-sectional design study performed at outpatient's Hepatobiliary clinic at tertiary referral university hospital in Jakarta. All recruited study subjects based on inclusions criteria underwent laboratory examination, transabdominal ultrasound examination, CAP-TE 502 (by Echosens, France), and glucose hydrogen breath test (GHBT) using portable hydrogen breath test apparatus (Gastro+™ Gastrolyzer by Bedfont Scientific Ltd). Stool sample examination was performed using RT-PCR. RESULTS: This study recruited 160 subjects with median age of 58 (22-78) years and 108 (67.5%) of them are female. SIBO (65,5%), DM (70.8%), dyslipidemia (75.2%), obesity (76.6%), and metabolic syndrome (73%) were more prevalent in NAFLD than non-NAFLD population. Bivariate analysis showed no significant association between SIBO and NAFLD development (p = 0.191; PR 0.871; CI 95% [0.306-1.269]). SIBO was also not associated with significant hepatic steatosis (p = 0.951; PR = 0.951; CI 95% [0.452-2.239]) and fibrosis (p = 0.371; PR = 1.369; CI 95% [0.608-3.772]). However, the presence of central obesity has significantly associated with the presence of SIBO (p = 0.001; PR = 0.378; CI 95% [0.021-0.478]). Based on stool sample analysis from 60 NAFLD patients, there is a significant correlation using Spearmen test between the presence of Bacteroides and the stage of fibrosis (p .037). Further analysis between obese NAFLD patients and non-obese NAFLD patients showing that there is a significant decrease of Bifidobacteria (p .047) and Lactobacillus (p .038) in obese NAFLD patients and a tendency of increase Bacteroides in obese NAFLD patients (p .572). CONCLUSIONS: SIBO is not associated with NAFLD development and progression.

Non-alcoholic fatty pancreas disease as a risk factor for pancreatic cancer based on endoscopic ultrasound examination among pancreatic cancer patients: A single-center experience.

BACKGROUND AND AIM: Non-alcoholic fatty pancreas disease (NAFPD) is a disease that ranges from simple steatosis and can further lead to chronic pancreatitis and possible pancreatic cancer development. Its exact pathogenesis and impact on clinical practice are still largely unknown. Pancreatic cancer is still the most lethal malignancy in the world. Studies about the relationship between NAFPD and pancreatic cancer are still lacking. This study aims to find the possible role of endoscopic ultrasound (EUS) examination as a screening tool in NAFPD patients based on EUS examination among pancreatic cancer patients. METHODS: EUS hospital data were collected within a 2-year period, and all patients who underwent EUS procedures were analyzed. Pancreatic malignancy was diagnosed based on imaging and tumor markers and cytopathology using the endoscopic ultrasound fine needle aspiration (EUS-FNA) procedure. Patients with pre-existing pancreatic diseases, significant alcohol consumption, or other primary cancer with metastasis to the pancreas were excluded. Statistical analysis was performed using SPSS version 23.0. RESULTS: In total, 162 patients (75 females and 87 males) were recruited for database analysis.^ Pancreatic malignancy was found in 43 (26.5%) patients, whereas fatty pancreas was found in 53 (32.7%) patients, and this was commonly found among pancreatic cancer patients.^ Based on logistic regression analysis, factors such as age, gender, diabetes, and chronic pancreatitis were not found to be significant risk factors for pancreatic malignancy where fatty pancreas is the only significant risk factor for pancreatic cancer (odds ratio: 18.027 [95% CI: 7.288-44.588]). CONCLUSION: Prevalence of NAFPD among pancreatic cancer patients is high. Future studies can be conducted to show whether EUS can be considered a screening tool for the early detection of pancreatic malignancy in NAFPD patients; a cohort prospective study might also be needed to show clear causality between fatty pancreas and pancreatic cancer.

Treatment Response Monitoring of Chronic Hepatitis B Patients using Transient Elastography and Aspartate Aminotransferase-to-Platelet Ratio Index (APRI).

BACKGROUND: Hepatitis B is endemic in Indonesia and treatment response need to be monitored during and after antiviral therapy. Liver stiffness measurement and alanine aminotransferase-to-platelet ratio index (APRI) are noninvasive method to detect liver fibrosis available in Indonesia. However, little is known about their ability to evaluate treatment response in chronic hepatitis B (CHB) patients in Indonesia. This study aimed to investigate liver stiffness changes by transient elastography (TE) and APRI before and after one-year oral antiviral treatment in CHB patients and the correlation between TE and APRI. METHODS: this study was retrospective cohort on CHB patients in CiptoMangunkusumo Hospital, Jakarta who uderwent treatment between January 2012 and December 2014. Patients received oral antiviral treatment with newer nucleoside analogues (entecavir or telbivudine) for at least one year. TE and APRI were obtained before and after treatment. TE and APRI reductions were analyzed statistically with Spearman's test. RESULTS: a total of 41 patients were enrolled in this study. Median liver stiffness value was significantly reduced from 10.8 to 5.9 kPa after oral antiviral treatment (p<0.001, Wilcoxon's test). Median APRI was also significantly reduced from 1.13 to 0.43 after treatment (p<0.001, Wilcoxon's test). The correlation between liver stiffness and APRI before treatment was weak (r=0.40), but it was strong after treatment (r=0.73). CONCLUSION: the liver stiffness measured with transient elastography and APRI significantly decreased after one year of antiviral treatment in chronic HBV patients. There was a significant correlation between TE and APRI after one year of treatment.