Comparative Immunohistochemical Analysis of Clinicopathological Subgroups in Hepatocellular Carcinomas from Japan and Indonesia.

Background: Standardized pathological evaluation based on immunohistochemical (IHC) analysis could improve hepatocellular carcinoma (HCC) diagnoses worldwide. We evaluated differences in clinicopathological subgroups in HCCs from two academic institutions in Tokyo-Japan, and Jakarta-Indonesia. Methods: Clinicopathological parameters and molecular expression patterns were evaluated in 35 HCCs from Indonesia and 41 HCCs from Japan. IHC analysis of biliary/stem cell (B/S) markers (cytokeratin 19, sal-like protein 4, epithelial cell adhesion molecule) and Wnt/ß-catenin (W/B) signaling-related molecules (ß-catenin, glutamine synthetase) could determine the IHC-based subgroups. For immuno-subtypes categorization, CD3/CD79α double immunohistochemistry was done to evaluate the infiltration of T and B cells. CD34 staining allowed identification of vessels that encapsulated tumor clusters (VETC). Results: Indonesian HCC patients were mostly <60 years old (66%) with a hepatitis B virus (HBV) background (82%), in contrast to Japanese HCC patients (8% and 19%, respectively, both P < 0.001). In comparison with Japanese, Indonesian cases more frequently had >5 cm tumor size (74% vs 23%, P = 0.001), poor differentiation (40% vs 24%), portal vein invasion (80% vs 61%), and α-fetoprotein levels >500 ng/ml (45% vs 13%, P = 0.005). No significant differences were found in the proportions of B/S, W/B, and -/- subgroups from both countries. No immune-high tumors were observed among Indonesian cases, and immune-low tumors (66%) were more common than in Japanese cases (54%). VETC-positive tumors in Indonesia were significantly more common (29%), and most were in the HBV (90%) and -/- subgroups (90%), whereas Japanese VETC cases (10%, P = 0.030) were nonviral (100%) and W/B subgroups (75%). Conclusion: IHC-based analysis more precisely reflected the clinicopathological differences of HCCs in Japan and Indonesia. These findings provide new insights into standardization attempts and HCC heterogeneity among countries.

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.

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.

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.