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.

Meta analysis of radiofrequency ablation versus surgical resection in small and large nodule of hepatocellular carcinoma.

INTRODUCTION: Although studies have indicated comparable outcomes between RFA and surgical resection in early HCC, there is still unclear evidence of benefit in larger tumor sizes. This study aimed to assess the efficacy and safety of RFA versus surgical resection in HCC patients, considering nodule size with a cutoff at 3 cm. METHODS: A comprehensive search of multiple databases was conducted. The systematic review and meta-analysis followed the PRISMA guidelines. RESULT: Surgical resection showed superior OS (HR = 1.18, 95% CI: 1.11-1.27, p = 0.008) and RFS (HR = 1.17, 95% CI: 1.11-1.25, p < 0.00001), compared to RFA. For nodules less than 3 cm or larger than 5 cm, the OS and RFS in the surgical resection group were significantly higher than those in the RFA group, while no significant differences were observed for nodules sized 3-5 cm. However, significantly more adverse events occurred following surgical resection (OR = 0.43, 95% CI: 0.33-0.56, P < 0.00001). CONCLUSION: Surgical resection has better OS and RFS compared to RFA for liver tumors less than 3 cm or larger than 5 cm. For liver tumors sized 3-5 cm, RFA and surgical resection yield similar findings. RFA may become a preferable option in these 3-5 cm tumors due to its comparable efficacy and fewer adverse events for patients unsuitable for surgery.

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.

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.

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.

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.

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 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.

Predictive scoring systems for in-hospital mortality due to acutely decompensated liver cirrhosis in Indonesia.

BACKGROUND: Acutely decompensated liver cirrhosis is associated with high medical costs and negatively affects productivity and quality of life. Data on factors associated with in-hospital mortality due to acutely decompensated liver cirrhosis in Indonesia are scarce. This study aims to identify predictors of in-hospital mortality and develop predictive scoring systems for clinical application in acutely decompensated liver cirrhosis patients. METHODS: This was a retrospective cohort study using a hospital database of acutely decompensated liver cirrhosis data at Cipto Mangunkusumo National General Hospital, Jakarta (2016-2019). Bivariate and multivariate logistic regression analyses were performed to identify the predictors of in-hospital mortality. Two scoring systems were developed based on the identified predictors. RESULTS: A total of 241 patients were analysed; patients were predominantly male (74.3%), had hepatitis B (38.6%), and had Child-Pugh class B or C cirrhosis (40% and 38%, respectively). Gastrointestinal bleeding was observed in 171 patients (70.9%), and 29 patients (12.03%) died during hospitalization. The independent predictors of in-hospital mortality were age (adjusted OR: 1.09 [1.03-1.14]; p = 0.001), bacterial infection (adjusted OR: 6.25 [2.31-16.92]; p < 0.001), total bilirubin level (adjusted OR: 3.01 [1.85-4.89]; p < 0.001) and creatinine level (adjusted OR: 2.70 [1.20-6.05]; p = 0.016). The logistic and additive scoring systems, which were developed based on the identified predictors, had AUROC values of 0.899 and 0.868, respectively. CONCLUSION: The in-hospital mortality rate of acutely decompensated liver cirrhosis in Indonesia is high. We have developed two predictive scoring systems for in-hospital mortality in acutely decompensated liver cirrhosis patients.

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 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.

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.

The Role of Hepatitis C Virus NS5A Region Mutation and SNP IL-28B of Host to Support Successful Pegylated Interferon and Ribavirin Treatment in Patients with HCV-HIV Coinfection: A Prospective Cohort Study.

BACKGROUND: HIV infection in HCV-infected patients accelerates disease progression and reduces the success rate of Peg-IFN/RBV treatment. HCV mutation in NS5A-ISDR/PKR-BD region improved the outcome in HCV monoinfection treated with Peg-IFN/RBV. SNP-IL28B polymorphism is predicted to have an effect on HCV quasispecies evolution. However, the role of NS5A mutation and SNP IL-28B in HIV-HCV coinfection is still unclear. The aim of the study is to determine the role of HCV NS5A-ISDR/PKR-BD mutation and SNP IL-28 polymorphism on the successfulness of Peg-IFN/RBV therapy in HCV-HIV coinfection. METHODS: prospective cohort was performed in this study. Plasma sample were obtained from 30 and 8 patients with HCV-HIV coinfection and HCV monoinfection, respectively. PCR nucleotide sequencing was performed after RNA virus extraction and cDNA synthesis. Protein secondary structure and prediction of mutation function were analyzed using PredictProtein (PP) program. RESULTS: sixteen HCV-HIV coinfected patients and none from eight HCV patients achieved sustained virological response (SVR). ≥1 non-neutral mutation was found in 24/30 HCV-HIV coinfection and more frequent in SVR group (14 patients). ≥1 non-neutral mutation were found statistically significant for overall SVR achievement (p<0.05) in all patients regardless of coinfection or monoinfection status. Of the 27 HCV-HIV coinfected patients with CC-gene, 21 subjects had non-neutral mutation. The structure which was expected as NS5A binding site structure was different from consensus (wild type) in SVR group, while the structure was similar to consensus in non-SVR group. CONCLUSION: having ≥1 non-neutral mutation was associated with SVR achievement in Peg-IFN/RBV therapy, regardless of monoinfection and coinfection status.

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.

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.

Mortality-related Factors in Patients with Malignant Obstructive Jaundice.

AIM: to obtain survival rate and mortality-related factors of malignant obstructive jaundice patients. METHODS: all medical records of obstructive jaundice inpatient at Cipto Mangunkusumo Hospital, Jakarta from January 2010 to December 2013 were reviewed retrospectively. The following factors were analyzed in terms of mortality: age, gender, sepsis, hypoalbumin, serum bilirubin level, serum CA 19-9 level, billiary drainage, non-ampulla Vateri carcinoma, and comorbid factors. RESULTS: total 181 out of 402 patients were enrolled in this study with male proportion was 58.6%, and patients aged 50 years or above was 57.5%. Multivariate analysis showed that only sepsis, unsuccessful or no prior biliary drainage and Charlson comorbid score ≥4 were independent predictors of mortality. Patients with significant prognostic factors had median survival 14 days compared with overall median survival 26 days. Score ≥2 identified as the highest prognostic score threshold with sensitivity 68%, specificity 75%, and AUC on ROC curve 0.769. CONCLUSION: sepsis, unsuccessful or no prior bilirary drainage, and Charlson comorbid score ≥4 are factors significantly associated with shortened survival in malignant obstructive jaundice patients. Prognostic score  ≥2 was determined to classify patients into high risk mortality group. Mortality of patients with those significant prognostic factors can be predicted in 76.9%.

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.

Periportal CD4+ cell infiltration increases in HIV/hepatitis C virus-coinfected patients commencing ART, whereas CD8+ cells clear from the liver.

Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common in Asia, but the effects of antiretroviral therapy (ART) are unclear. Histopathological changes in the liver are described in a prospective study of HCV-seropositive HIV-infected patients at Cipto Mangunkusomo Hospital (Jakarta, Indonesia). Liver biopsy specimens were collected at baseline (n = 48) and 48 weeks (n = 34). Ishak scores showed mild but detectable inflammation and/or fibrosis. Levels of portal inflammation declined during ART (P = .03), whereas fibrosis remained (P = .11). Portal infiltration of CD4(+) cells increased during ART (P < .0001), whereas infiltration of CD8(+) cells subsided. Numbers of CD4(+) cells in the liver at baseline correlated with circulating CD4(+) T-cell counts (P = .03-.05). Numbers of liver-infiltrating CD4(+) and CD8(+) cells at baseline were not associates with subsequent experience of an immune restoration disease, which is defined by a rise in alanine transaminase levels during ART.

Patients co-infected with hepatitis C virus (HCV) and human immunodeficiency virus recover genotype cross-reactive neutralising antibodies to HCV during antiretroviral therapy.

When severely immunodeficient HIV/HCV co-infected patients are treated with antiretroviral therapy, it is important to know whether HCV-specific antibody responses recover and whether antibody profiles predict the occurrence of HCV-associated immune restoration disease (IRD). In 50 HIV/HCV co-infected patients, we found that antibody reactivity and titres of neutralising antibodies (nAb) to JFH-1 (HCV genotype 2a virus) increased over 48 weeks of therapy. Development of HCV IRD was associated with elevated reactivity to JFH-1 before and during the first 12 weeks of therapy. Individual analyses of HCV IRD and non-HCV IRD patients revealed a lack of an association between nAb responses and HCV viral loads. These results showed that increased HCV-specific antibody levels during therapy were associated with CD4(+) T-cell recovery. Whilst genotype cross-reactive antibody responses may identify co-infected patients at risk of developing HCV IRD, neutralising antibodies to JFH-1 were not involved in suppression of HCV replication during therapy.

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.