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.

Portal Hypertension in Nonalcoholic Fatty Liver Disease: From Pathogenesis to Clinical Practice.

Portal hypertension in nonalcoholic fatty liver disease (NAFLD) mostly occur in cirrhotic stage. However, several experimental and clinical studies showed evidence of portal hypertension in NAFLD without significant or advance fibrosis. This early development of portal hypertension in NAFLD is associated with liver sinusoidal contraction by hepatocellular lipid accumulation and ballooning, which is also accompanied by capillarization and dysfunction of liver sinusoidal endothelial cells. Both of these impaired mechanical and molecular components can cause an increase in intrahepatic vascular resistance which lead to the increase of portal pressure in the absence of significant liver fibrosis. Extrahepatic factors such as insulin resistance and gut dysbiosis may also contribute to liver sinusoidal endothelial dysfunction and early portal hypertension in NAFLD. The clinical impact of early portal hypertension in NAFLD is still unclear. However, clinical tools for diagnosis and monitoring of portal hypertension in NAFLD are being investigated to predict high-risk patients and to guide therapy.

The Clinical Role of Endoscopic Ultrasound for Management of Bleeding Esophageal Varices in Liver Cirrhosis.

Bleeding esophageal varices (BEV) is a serious clinical condition and can potentially be life-threatening. Esophageal varices are caused by abnormal dilated submucosal and collateral veins in the esophagus wall as a result of portal hypertension due to liver cirrhosis. Consequently, it is important to administer appropriate preventive treatment for the disease in order to decrease morbidity and mortality rates. The current gold standard to identify esophageal varices is the use of esophagogastroduodenoscopy (EGD). However, EGD has limitations due to its inability in observing detailed information of varices morphology and esophagogastric hemodynamics. This report shares the potential role of endoscopic ultrasound (EUS) to overcome the limitation of EGD in clinical practices. Two cases of BEV in hepatitis B liver cirrhosis patients were described in the report. In case 1, large esophageal varices were found through EGD, and large paraesophageal varices were found through EUS. In case 2, small esophageal varices were found through EGD, and submucosal varices with a large periesophageal collateral vein and perforating vein in the distal esophagus were found through EUS. Cyanoacrylate injection guided by EUS was performed in both cases, and no rebleeding occurred after the procedure. In these cases, we showed that EUS is proven to be a potential tool in diagnosis and management of BEV in liver cirrhosis. EUS provides more accurate diagnostic aspects to find varices, assess bleeding risk, and predict bleeding recurrence. EUS also provides more beneficial treatment aspects to guide the treatment procedure and to monitor post treatment response.

Overall Survival of Hepatocellular Carcinoma Patients Underwent Radiofrequency Ablation (RFA) Treatment: a Retrospective Cohort Study from Two Referral Hospitals in Indonesia.

BACKGROUND: Radiofrequency ablation (RFA) is one of the curative modality therapies commonly used for the early stage of HCC management. Although numerous studies have reported the outcome of RFA around the world, the data regarding the usage of RFA for the early and intermediate stage of HCC remains limited. Hence, the study aimed to report the survival rate of the early and intermediate stage HCC patients who underwent RFA in two tertiary referral hospitals in Jakarta, Indonesia. METHODS: A retrospective cohort study was conducted in Cipto Mangunkusumo and Medistra multicenter hospital in Jakarta, Indonesia. The patients with HCC BCLC A and B who underwent RFA treatments between January 2015 to December 2017 were recruited for the study. Baseline characteristics of patients were collected from the medical record. Survival analysis was calculated using the Kaplan Meier. p value result was obtained from the log-rank test. Sub-analysis of factors associated with the survival was also included in this study. RESULTS: There were 62 patients enrolled in this study (32.3% were BCLC A and 67.7% were BCLC B). Forty-six out of 62 patients (74.2%) were reported to have RFA as their first line of treatment, while 12 (25.8%) were reported to have a combination of RFA and other therapy modalities. All these patients were follow-up with an average duration of 27 months. The survival rate of liver cancer due to HCC for 12 and 36 months in patients who received RFA was 82.3% and 57.8%, respectively. Moreover, BCLC staging of liver cancer and response after RFA was significantly associated with survival. CONCLUSION: RFA still can be used as initial modality therapy nor combination with another therapy for the early and intermediate stage of HCC. BCLC staging and response after RFA had shown to be the independent factors related to survival.

Diagnostic Performance of Mac-2-Binding Protein Glycosylation Isomer (M2BPGi), compared to Transient Elastography to Assess Liver Stiffness in Treatment Naïve Chronic Hepatitis C Patients.

BACKGROUND: Liver fibrosis is an essential factor in the management of Hepatitis C virus infection. Its assessment is crucial in decision-making regarding the therapeutic decisions, and the patients' follow up. However, the established liver measurement methods have several limitations. Therefore, this study aims to assess the role of Mac-2-Binding Protein Glycosylation Isomer (M2BPGi) as a novel biomarker to measure liver stiffness in treatment naïve Chronic Hepatitis C Indonesian patients. METHODS: This study used a cross-sectional design to determine the correlation between serum M2BPGi and the degree of liver stiffness, Transient Elastrography, and differences in serum M2BPGi levels in chronic hepatitis C patients. Serum M2BPGi level and Transient Elastography results were evaluated in 56 Chronic Hepatitis C patients and 48 healthy controls. Pearson correlation analysis was conducted to find the correlation between the level of M2BPGi and Transient Elastography result. ROC analysis was conducted to find the optimum cut-off to assess fibrosis's degree among Chronic Hepatitis C Patients. RESULTS: The level of serum M2BPGi and Transient Elastography result was strongly correlated with the median level of serum M2BPGi. It was also significantly higher among Chronic Hepatitis C Patients than among healthy controls (r: 0.708, p<0.001; 0.590 COI vs. 4.130 COI, p<0.001). Among the Chronic Hepatitis C patients, the median serum of M2BPGi increased according to the degree of liver fibrosis: 1.500 COI (F0-F1), 2.985 COI (F2-F3) and 8.785 COI (≥F4). The optimum cut-off value for diagnosing significant fibrosis (F2-F3) was 1.820 COI (AUC: 90.8%) and for diagnosing cirrhosis (≥F4) was 3.770 COI (AUC: 89.3%). CONCLUSION: Serum M2BPGi was a reliable diagnostic tool for identifying liver fibrosis in Indonesian patients with Chronic Hepatitis C.

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.

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.

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.

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

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

Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease.

BACKGROUND: This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). METHODS: We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1ß. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. RESULTS: The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal ß-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend <0.001). CONCLUSION: Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD.