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 influence of insulin resistance in the occurence of non-alcoholic fatty liver disease among first degree relatives of type 2 diabetes.

BACKGROUND: First degree relatives (FDR) of type 2 diabetes mellitus (T2DM) predisposes individuals to have earlier metabolic and vascular disorders independent of insulin resistance (IR) such as thicker carotid intima media thickness than that of non-FDR. Non-alcoholic fatty liver disease (NAFLD) is the most commonly found chronic liver disease in T2DM which is IR dependent. Studies about NAFLD in FDR of T2DM populations are very limited and inconclusive. It is unclear whether the occurrence of NAFLD in FDR of T2DM is IR dependent or due to genetic vulnerability. AIMS: The aim of this study is to determine the association between NAFLD and FDR of T2DM. METHOD AND MATERIALS: A total of 118 young adults (19-39 years old) with normal glucose tolerance (59 FDR of T2DM and age-sex matched 59 non-FDR subjects) were included in this cross-sectional study. Anthropometric measurement and routine laboratory analysis (fasting blood glucose/FBG, HbA1c, lipid profile, alanine aminotransferase (ALT), aspartate transaminase (AST)) were examined. Fatty liver was diagnosed by ultrasonography (US) using standard criteria. RESULTS: Twenty-six (22,03%) subjects with NAFLD were detected by ultrasound with similar proportion for each group. Low HDL-C level and metabolic syndrome were found higher in FDR group (p = 0.004, OR 3.81, CI95 = 1.47-9,91; p = 0.023, OR 4.28, CI95 = 1.13-16.23). Based on logistic regression analysis, central obesity and obesity had statistically significant influence towards NAFLD. CONCLUSION: The occurrence of NAFLD in FDR of T2DM was influenced by IR (central obesity and obesity).

Gut Microbiota Profiles in Nonalcoholic Fatty Liver Disease and Its Possible Impact on Disease Progression Evaluated with Transient Elastography: Lesson Learnt from 60 Cases.

BACKGROUND: Dysbiosis of the gut microbiota has been considered to have a role in nonalcoholic fatty liver disease (NAFLD) progression. However, there is still lack of studies regarding this phenomenon. AIM: To find the difference in the proportion of gut microbiota in NAFLD patients based on the stages of liver fibrosis. PATIENTS AND METHODS: A cross-sectional study was conducted at Dr. Cipto Mangunkusumo Hospital, which is the largest tertiary referral center. Human fecal samples from NAFLD patients who came to the outpatient clinic were collected consecutively. The stool sample examination was performed using an isolation DNA kit (Tiangen) and quantitative real-time polymerase chain reaction (Fast 7500). Clinical and laboratory data were also collected. The stage of fibrosis was diagnosed based on transient elastography (FibroScan® 502 Touch; Echosens, France). RESULTS: Of 60 NAFLD human fecal samples, 35 patients had nonsignificant fibrosis and 25 patients had significant fibrosis (46.7% male and 53.3% female; median age 56 years). Most patients had diabetes (85%), dyslipidemia (58.3%), obesity (58.3%), and central obesity (90%). The proportion of Bacteroides was higher when compared to Lactobacillus and Bifidobacteria. Of these 3 microbiota, the proportion of Bacteroides was significantly higher in the significant fibrosis group when compared to the nonsignificant fibrosis group. CONCLUSION: There is a change in the composition of gut microbiota in NAFLD patients. The proportion of Bacteroides is significantly higher in significant liver fibrosis, which may play a role in NAFLD progression.

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.

Hepatocellular Carcinoma in a Tertiary Referral Hospital in Indonesia: Lack of Improvement of One-Year Survival Rates between 1998-1999 and 2013-2014.

BACKGROUND: The survival of hepatocellular carcinoma (HCC) patients is usually low due to late diagnosis. Cipto Mangunkusumo Hospital as the largest tertiary referral hospital in Indonesia, has recently improved its modalities for advanced HCC management, but there has not been any evaluation on any improvement in HCC patient survival. MATERIALS AND METHODS: A retrospective analysis on 114 HCC patients in 2013-2014 were conducted and compared with the database for 77 HCC patients in 1998-1999. Clinical characteristics and treatment received were recorded and the survival of both groups was analyzed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: The percentage of HBV positive patients had increased after fifteen years from 32.5% to 67.5%. Only two patients (1.8%) in 2013-2014 were diagnosed with HCC during surveillance program. Proportions of Barcelona Clinic Liver Cancer A, B, C, and D in 2013-2014 were 1.8%, 42%, 28.1%, and 28.1%, respectively. There was an increase in the use of potentially curative treatment, such as surgical resection or combination of loco-regional therapies. The one-year survival rate increased from 24.1% in 1998-1999 to 29.4% in 2013-2014, while the median survival decreased from 146 days to 138 days, but the difference was not statistically significant (p=0.913). CONCLUSIONS: There was no improvement in the median survival of HCC patients after fifteen years because most continued to present at late stages. There is an urgent need for a nationwide implementation of a hepatitis screening program and HCC surveillance education.

Performance of Alpha Fetoprotein in Combination with Alpha-1-acid Glycoprotein for Diagnosis of Hepatocellular Carcinoma Among Liver Cirrhosis Patients.

AIM: to evaluate the use of alpha-1-acid glycoprotein (AAG) for diagnosing hepatocellular carcinoma (HCC), and to combine with alpha fetoprotein (AFP) as part of routine examination in liver cirrhosis patients. METHODS: this is a diagnostic study using cross-sectional design. A hundred and six patients were included in this study. Baseline data such as age, gender, AFP, AAG, peripheral blood count, AST and ALT were consecutively collected from liver cirrhosis patients with or without HCC. Serum AAG were measured quantitatively using immunoturboditimetric assay and AFP with enzyme immune assay (EIA). Statistical analysis were done using SPSS 13.0. Data comparisons between group were done using Mann-Whitney test. Diagnostic performance for each marker alone was compared to the surrogate use of both markers (combined parallel approach) in HCC cases. RESULTS: receiver operating characteristic (ROC) analysis showed that area under the curve for AFP-AAG combination was 88.1% and higher than AFP only (86.2%) or AAG only (76.5%) with sensitivity of 83%, 73% and 44%, respectively, at specificity of >80%. CONCLUSION: our study showed that combination of AFP and AAG is superior than either marker alone in diagnosing HCC in liver cirrhosis patients. Combination of AFP and AAG may be used to prompt early diagnosis screening of HCC.

Impact of Endoscopic Ultrasound Procedures in Various Pancreatobiliary Disorders in Indonesia Based on a Case Series in a Private Hospital.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a common technique for assessing the pancreas and the biliary system; however, the potential complications have raised concern among endoscopists and patients. Recently, the need of endoscopic ultrasound (EUS) as an additional tool of assessment before the ERCP procedure has been increasing. The need of EUS in developing countries is still a matter of debate regarding the cost, investment, and training. Here, we report the significant impact of EUS on several unselected interesting cases of pancreatobiliary disorders. METHOD: We selected several interesting cases from the patients who underwent EUS at our private hospital in Jakarta, Indonesia. The EUS procedures were performed by one experienced endosonographer and one EUS trainee who are very experienced with transabdominal ultrasound. The equipment was an Olympus JF UCT 180 EUS scope which was connected to an Aloka IPF-1701C ultrasound machine (Tokyo, Japan). RESULTS: Five interesting cases were included from patients who underwent EUS due to pancreatobiliary disorders. The cases included recurrent pancreatitis due to pancreatic stone at the small branch that obstructed the main pancreatic duct, common bile duct (CBD) stone with insignificant duct dilatation, pancreatic head cancer with total obstruction at the distal CBD and portal vein infiltration, pancreas divisum in a young girl, and distal CBD mass that caused obstructive jaundice. CONCLUSIONS: The EUS procedure has shown a significant impact in managing patients with pancreatobiliary diseases. In most developing countries, EUS needs to be evaluated further regarding the cost, investment, and training.

Reimbursement policies in the Asia-Pacific for chronic hepatitis B.

BACKGROUND: There is considerable variation in reimbursement policies in Asian countries and this is likely to have an impact on treatment practice for chronic hepatitis B (CHB). Consequently a survey of leading hepatologists was performed to evaluate such policies and their impact on management of CHB in the Asia Pacific region. METHODS: A questionnaire was sent to key hepatologists in Asia Pacific for information on CHB reimbursement policy-its nature, coverage, funding source, duration, review strategy and impact on Asia Pacific Association for the Study of the Liver (APASL) CHB guidelines. The results were analysed and described. RESULTS: Leading hepatologists from 16 Asia Pacific countries responded. Almost all of the countries have reimbursement policies but eligibility varied from only a limited group (e.g. civil servants only) to universal access. In most instances reimbursement was from the central government (except China, Pakistan and Hong Kong). Reimbursement policies were usually created by Ministry of Health committees, who received input from medical professionals, although they may not be aware of the APASL guidelines. Policies were limited by available resources, funds and prioritization. Where there was a regular review this occurred between 1 and 5 years. The quantum of reimbursement varied from 50% in Singapore to 100% in the majority of other countries. The criteria for treatment reimbursement were based on doctor's opinion alone (Bangladesh, India, Pakistan, Philippines, Singapore and Vietnam) or specific clinical/laboratory criteria in the rest of the countries. In general, most countries offered unlimited duration for reimbursement except Taiwan, Indonesia and Pakistan. Monitoring tests for treatment response were reimbursed in all countries other than Vietnam. Viral resistance was diagnosed by viral or biochemical breakthrough, and viral resistance testing was uncommon. The main rescue therapy was adefovir. CONCLUSION: Reimbursement policies differed from country to country, the quantum and the proportion of patients who received reimbursement also varied significantly. Asia Pacific countries were able to follow APASL guidelines with variable success based on their reimbursement policies.

Detection rate of colorectal adenoma or cancer in unselected colonoscopy patients: Indonesian experience in a private hospital.

BACKGROUND: Colorectal cancer is currently the third most common cancer in Indonesia, yet colonoscopy--the most accepted mode of screening to date--is not done routinely and national data are still lacking. OBJECTIVE: To determine the detection rate of colorectal cancers and adenomas in unselected patients undergoing colonoscopy for various large bowel symptoms at the Digestive Disease and GI Oncology Centre, Medistra Hospital in Jakarta, Indonesia. MATERIALS AND METHODS: Colonoscopy data from January 2009 to December 2012 were reviewed. New patients referred for colonoscopy were included. Data collected were patient demographic and significant colonoscopy findings such as the presence of hemorrhoids, colonic polyps, colonic diverticula, inflammation, and tumor mass. Histopathological data were obtained for specimens taken by biopsy. Associations between categorical variables were analyzed using chi-square test, while mean differences were tested using the t-test. RESULTS: A total of, 1659 cases were included in this study, 889 (53.6%) of them being men. Polyps or masses were found in 495 (29.8%) patients while malignancy was confirmed in 74 (4.5%). Patients with a polyp or mass were significantly older (60.2 vs 50.8 years; p<0.001; t-test) and their presence was significantly associated with male gender (35.0% vs 23.9%; prevalent ratio [PR] 1.71; 95% confidence interval [CI] 1.38-2.12; p<0.001) and age>50 years (39.6% vs 16.6%; PR 3.29; 95% CI 2.59-4.12; p<0.001). Neoplastic lesions was found in 257 (16.1%), comprising 180 (11.3%) adenomas, 10 (0.6%) in situ carcinomas, and 67 (4.2%) carcinomas. CONCLUSIONS: Polyps or masses were found in 30% of colonoscopy patients and malignancies in 16.1%. These figures do not represent the nation-wide demographic status of colorectal cancer, but may reflect a potentially increasing major health problem with colorectal cancer in Indonesia.

Advances in the molecular diagnosis of hepatitis B infection: providing insight into the next generation of disease.

Hepatitis B virus (HBV) infection continues to represent a significant health threat, affecting over 400 million people worldwide. Historically, the diagnosis and treatment of chronic hepatitis B (CHB) relied in detection of the hepatitis B surface antigen (HBsAg) and more recently realtime polymerase chain reaction (PCR) analysis. The advent of novel technologies and equipment for the identification and staging of the different stages of HBV infection has resulted in dramatic changes to patient monitoring and management. Through the use of rapid, quantitative HBsAg immunoassays, it is now possible to predict the likelihood of patient response to treatment as well as the clinical course of disease. Ultradeep sequencing technologies (also known as next-generation sequencing) overcome many of the traditional limitations associated with population-based sequencing approaches, and have provided significant insight into the viral response to therapeutic intervention and the molecular pathogenesis of CHB. The authors discuss recent developments in the molecular diagnosis of HBV infection, as well as potential advantages and caveats resultant of this rapid progression of technology.

Significant hepatic histopathology in chronic hepatitis B patients with serum ALT less than twice ULN and high HBV-DNA levels in Indonesia.

OBJECTIVE: To study the prevalence of significant hepatic histopathology in chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) ≤ twice upper limit of normal (ULN) and its association with age, HBeAg status, hepatitis B virus (HBV)-DNA level and viral genotype. METHODS: A prospective study was conducted over a 3-year period in treatment-naive CHB patients with ALT ≤ twice ULN. Patients with a history of acute flare hepatitis, use of alcohol and hepatotoxic drugs, hepatitis C, hepatitis D and human immunodeficiency virus (HIV) co-infection were excluded from the study. Hepatic histopathology was assessed according to the METAVIR scoring system. RESULTS: A total of 145 patients were recruited, 81 (55.9%) of whom were male. The patients' mean age was 41.50 ± 10.74 years (range 16-70 years). Significant hepatic inflammation was found in 59.3% of these patients, and significant hepatic fibrosis was found in 62.1%, the latter being associated with hepatitis B e antigen status, ALT levels and serum HBV-DNA, but not with their age group or viral genotype. Significant hepatic fibrosis was found in 24 of 35 CHB patients (68.6%) who were previously considered in an immunotolerance phase. CONCLUSIONS: The prevalence of significant hepatic histopathology in CHB patients with serum ALT levels ≤ twice ULN is high. Delayed antiviral treatment can be harmful.

Diagnostic accuracy of transient elastography (FibroScan) versus the aspartate transaminase to platelet ratio index in assessing liver fibrosis in chronic hepatitis B: the role in primary care setting.

BACKGROUND: A non-invasive method to assess liver fibrosis by measuring liver stiffness with transient elastography (TE) has been recently introduced. The role of TE among chronic hepatitis B (CHB) patients in starting antiviral therapy in the primary care setting is still controversial because of its high cost. The AST to platelet ratio index (APRI) could be a much cheaper alternative. OBJECTIVES: This study compares the diagnostic accuracy of TE and APRI in assessing liver fibrosis in CHB patients. PATIENTS AND METHODS: A cross-sectional study in CHB patients intending to start antiviral treatment. Liver fibrosis was staged according to the METAVIR scoring system. Liver stiffness was measured by TE performed on the same day with liver biopsy, while APRI was calculated as follows: APRI=(AST/upper limit of normal)×100/platelet count (10(9)/l). Cutoff levels of liver stiffness and APRI were calculated by using the receiver operating characteristic curve to detect significant liver fibrosis, defined as fibrosis stage F2 or more. RESULTS: 117 patients were enrolled in the study; their mean age was 40.6±10.97 years. The median liver stiffness was 5.9 kPa (2.5-48 kPa) and the median APRI was 0.239 (0.09-2.73). The cutoff level of liver stiffness was 5.85 kPa for ≥F2 with an AUC of 0.614, 60.3% sensitivity, 63.6% specificity, 73.3% PPV, 49.1% NPV and a LR+ of 1.66. The APRI cutoff level was 0.235 for F≥2 with an AUC of 0.693, 64.4% sensitivity, 70.5% specificity, 78.3% PPV, 54.4% NPV and a LR+ of 2.18. Both methods gave comparable diagnostic accuracy. CONCLUSION: APRI is a useful marker to screen liver fibrosis in the primary care setting when TE is not available.

Diagnostic value of a group of biochemical markers of liver fibrosis in patients with non-alcoholic steatohepatitis.

OBJECTIVE: The objectives of this study were to investigate the use of non-invasive biochemical markers to evaluate the severity of liver fibrosis in patients with non-alcoholic steatohepatitis (NASH). METHODS: This was a cross-sectional study of patients with histopathologically confirmed NASH between January 2005 and December 2006. The patients' characteristics were recorded and the body mass index was calculated for each patient. All patients underwent ultrasound-guided liver biopsy and a fibrosis assessment was performed using the Brunt criteria. The non-invasive laboratory markers measured were insulin resistance, tumor necrosis factor (TNF-alpha), type IV collagen and hyaluronic acid (HA). RESULTS: Thirty patients were recruited, of whom 18 (60%) were men. Their mean age was 45 +/- 13.9 (18-71) years. About 83% of patients had fibrosis stage 1-2. In bivariate analysis, age, TNF-alpha and type IV collagen concentrations showed a weak but significant correlation with the fibrosis stage. When the patients were grouped into mild fibrosis (stages 1-2) and advanced fibrosis (stages 3-4), the mean concentrations of HA and type IV collagen were significantly higher in those with advanced fibrosis than those with mild fibrosis (180.8 +/- 49.63 vs 543.6 +/- 360.45 ng/mL; for HA; P = 0.026 and 125.3 +/- 32.11 vs 288.0 +/- 171.22 ng/mL for type IV collagen; P = 0.010). CONCLUSION: Our study showed that the degree of liver fibrosis was significantly correlated with age, TNF-alpha and type IV collagen concentrations. The level of HA and type IV collagen could differentiate between mild (F1-2) and advanced fibrosis (F3-4).