Comparative Efficacy of Microwave versus Radiofrequency Ablation in Hepatocellular Carcinoma: Systematic Review and Meta-Analysis of Randomized-Controlled Trials.

Introduction: Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related deaths. Thermal ablation techniques, especially radiofrequency ablation (RFA) and microwave ablation (MWA), have become pivotal treatments for HCC. This systematic review and meta-analysis aim to compare these modalities, highlighting their efficacy, strengths, and limitations in treating HCC. Methods: A comprehensive literature search was conducted across major databases (PubMed, MEDLINE, Springer, ProQuest, EBSCOhost, Cochrane, and EMBASE) targeting studies on hepatocellular carcinoma with RFA and MWA. Heterogeneity analyses and pooled outcomes using random-effect models with were evaluated to compare both thermal ablation methods. Results: Nine studies, which consists of 368 patients underwent RFA and 387 patients underwent MWA, were included in review. The findings showed no significant differences in pooled analysis of volume of ablation, complete ablation rate, local tumor progression, survival rates, major complications, and adverse events. Subgroup analysis showed significantly higher risk of local tumor progression in RFA in African populations. Conclusion: No statistically significant difference was seen between outcomes across studies. MWA may offer a potential for longer therapeutic response with comparable risk of complications and adverse outcomes.

The Comparison of Serum Interleukin-8 Levels Based on Severity of Liver Cirrhosis.

Background: The molecule known as Interleukin-8 (IL-8), a chemotactic leukocyte, has been found to have a crucial role in the perpetuation of the inflammatory environment that is associated with hepatitis B virus (HBV) infection, as well as in the development of liver cirrhosis and cancer. Objective: The aim of this study was to carefully examine the role of IL-8 in the inflammatory reaction and to compare the levels based on the severity of liver cirrhosis. Methods: The study was conducted from February 2018 to September 2018 at the Gastroenterohepatology Division, Internal medicine Department, Faculty of Medicine, Universitas Sumatera Utara. The study was designed as an analytic comparative, cross-sectional study. The liver cirrhosis patients who participated in this study met the inclusion criteria and provided informed consent. Results: A total of 70 patients were included in the study, from which we identified 1 individual with child-pugh A, 28 individuals with child-pugh B, and 41 individuals with child-pugh C. The serum level of IL-8 was found to be 98 (11-320) (pg/ml). The IL-8 levels between child-pugh B and C patients did not exhibit any noteworthy differences during our analysis (p = 0.109, p>0.05). Conclusion: There is no notable inequality in the levels of IL-8 across different stages of liver cirrhosis.

Study of the Molecular Dynamics Stability in the Inhibitory Interaction of Tenofovir Disoproxil Fumarate against CTLA-4 in Chronic Hepatitis B Patients.

Background: Tenofovir disoproxil fumarate (TDF) is a first-line nucleotide analog (NA) drug for hepatitis B therapy. Long-term NA therapy increases peripheral T cell levels to enhance antiviral response, while CTLA-4 inhibits the activation. Objective: This study analyzed the interaction between TDF and CTLA-4 through molecular docking. Methods: Target protein and ligand data mining were performed, and proteins were prepared by removing water molecules in the Discovery Studio 2019 software. The energy minimization was performed on ligands using Pyrx v.0.9.8 software. Protein-ligand docking was performed using Autodock Vina integrated with Pyrx v.09.8. Meanwhile, the docking of proteins was accomplished using the Haddock server. The BioVia Discovery Studio 2019 software visualized the interaction between the compound and the docked protein. Molecular dynamics simulations were carried out using the YASARA Dynamic program developed by Biosciences GmbH. Results: TDF ligand has good and stable inhibitory activity against the CTLA-4/B7-1 and CTLA4/B7-2 complexes. TDF docking has been shown to initiate conformational changes, indicating the ligand's inhibitory activity. The significant conformational changes based on superimposition results were shown by the CTLA-4/TDF/B7-2 and CTLA-4/B7-1/TDF complexes. TDF in all ligands undergoes bonding and displacement of binding sites. Conclusion: Treatment with TDF was predicted to have inhibitory activity against CTLA-4, especially in its complex form with B7-1 and B7-2.

Association Between Serum Cytotoxic T Lymphocyte Antigen (CTLA)-4 Level and Disease Progression in Patients With Chronic Hepatitis B.

Backgroud: Immune impairment, marked by increased expression of cytotoxic T lymphocyte antigen (CTLA)-4, promotes the disease progression of chronic hepatitis B. Objective: This study aimed to determine the association between serum CTLA-4 level and disease progression in patients with chronic hepatitis B. Methods: A cross-sectional study was conducted at Haji Adam Malik General Hospital Medan, Indonesia between October 2021 to September 2022. A total of 150 participants were enrolled. Patients aged 18 years or older with evidence of chronic hepatitis B, HBV-related liver cirrhosis, and HBV-related hepatocellular carcinoma (HCC) were enrolled. Exclusion criteria were history of chronic hepatotoxic drug consumption, underlying liver abnormalities other than HBV infection, and liver injury due to metastasized malignancy from other sites. Serum CTLA-4 level was determined from serum using human CTLA-4 enzyme linked immunosorbent assay kit. Results: Most participants were males and aged between 40 and 60 years. Serum CTLA-4 level was positively associated with chronic hepatitis B progression (P<0.001). Serum CTLA-4 level was negatively correlated with serum platelet (P<0.001) and albumin levels (P<0.001) but positively correlated with serum ALT (P=0.045) and total bilirubin levels (P<0.001). Conclusions: Serum CTLA-4 level is associated with disease progression in patients with chronic hepatitis B.

Factors affecting HBV DNA suppression in chronic hepatitis B patients treated with tenofovir disoproxil fumarate.

Background: This study aims to determine the factors affecting HBV DNA suppression in chronic hepatitis B patients with tenofovir disoproxil fumarate (TDF). Methods: A case-control was carried out from October 2021 to August 2022 on 182 chronic hepatitis B patients who had TDF therapy regularly for 24 weeks at H. Adam Malik and USU Hospitals in Medan, Indonesia. The history of the samples was obtained, followed by physical examination, and blood collection. CTLA-4 polymorphism examination was carried out using real-time PCR, while the serum CTLA-4 levels were assessed with ELISA. Results: The CTLA-4 -1661G>A polymorphism, genotype GG+AG, increased 1.52 times risk of not achieving HBV DNA suppression to TDF compared to genotype AA (p=0.041). High CTLA-4 levels increased 2.28 times risk, high HBV DNA levels increased 2.09 times risk, low ALT levels increased 1.95 times risk of not achieving HBV DNA suppression (p= 0.009, 0.026, 0.036, respectively). There was no relationship between gender, age, ethnicity, obesity, baseline AST, HBeAg, genotype, liver fibrosis and HBV DNA suppression after 24 weeks of treatment (p>0.05). Conclusions: The levels of CTLA-4, HBV DNA, ALT, and CTLA-4 -1661G>A polymorphism have a potential relationship with the suppression of HBV DNA in chronic hepatitis B patients with TDF.

Association Between Serum IL-6, IL-10, IL-12, and IL-23 Levels and Severity of Liver Cirrhosis.

BACKGROUND: Liver cirrhosis contributes to high liver-related mortality globally. Systemic inflammation mediated by immune cells contributes to the progression of liver cirrhosis. Growing evidence shows that several pro- and anti-inflammatory cytokines might have an important role in liver cirrhosis. OBJECTIVE: To evaluate the association between serum IL-6, IL-10, IL-12, and IL-23 levels and severity of liver cirrhosis. METHODS: This observational study was carried out at the Department of Internal Medicine, Universitas Sumatera Utara, Indonesia from March 2018 to August 2019. The severity of liver cirrhosis was assessed by using the Child-Pugh score. IL-6, IL-10, IL-12, and IL-23 levels, hepatitis and renal function were measured in all study subjects. Independent t-test and Mann-Whitney tests were conducted to observe differences between groups. RESULTS: A total of 78 liver cirrhosis patients were enrolled, mean age was 50.6±11.4. Median serum IL-6, IL-10, IL-12, and IL-23 levels were 24.5(2.6-46.4)pg/ml, 2.1(0.4-9.3)pg/ml, 3.5(1.4-20.8)pg/ml and 20.3(9.2-218)pg/ml, respectively. A higher IL-6 level was associated with more severe liver cirrhosis (p=0.001) and the presence of hepatic encephalopathy (p=0.018). Higher IL-23 level was found in patients with no hepatic encephalopathy (p=0.049). There was no association between serum cytokines levels and hepatitis viral infection status. CONCLUSION: IL-6 is associated with the severity of liver cirrhosis.

Association between CD133 expression and clinicopathological profile in colorectal cancer.

Aim To investigate CD133 expression and its relationship to clinicopathological profile in colorectal cancer (CRC) patients. Methods This cross-sectional study was performed at the Internal Medicine Department, School of Medicine, Adam Malik General Hospital. The colorectal cancer tissue was taken from surgical resection and colonoscopy biopsy from CRC patients. Clinical profile was obtained by a questionnaire. Histopathology examination was done using hematoxylin and eosin staining. Immunohistochemistry (distribution score and intensity score) combined with ROC analysis were conducted to determine CD133 expression. An association between CD133 expression and clinicopathological profile was then analyzed. Results Out of 118 patients, 690 (58.5%) were male. The high and low level of CD133 expression were found in 44 (37.3%) and 74 (62.7%) patients, respectively. No difference between gender, age, body mass index, hemoglobin, leucocytes, platelets, and histopathology with CD133 expression was found. There was a significant difference between CD133 and different CRC locations (p=0.002). CD133 expression was higher in the proximal colon than the rectum (p=0.002), and it was higher in the distal colon than the rectum (p=0.008), especially in terms of percentages of stained cancer cells (distribution score). Conclusion CD133 expression was associated with the tumour location, but not with other clinicopathological factors.

Endoscopic Submucosal Dissection for Colitis-Associated Dysplasia.

Dysplasia is a precancerous lesion of colorectal cancer in patients with long-standing inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn's disease. Recent guidelines suggest endoscopic resection as a key modality for the treatment of endoscopically resectable dysplasia in patients with colitis. Endoscopic submucosal dissection (ESD) has been suggested as one of the therapeutic options for dysplasia that is potentially resectable but not suitable for the conventional endoscopic mucosal resection technique. Several recent studies supported the feasibility of ESD for the treatment of colitis-associated dysplasia in terms of the en bloc and complete resection rates and the risk of procedure-related complications. However, these studies were performed exclusively in expert centers. Moreover, the local and metachronous recurrence rates were relatively high, and long-term outcome data are still lacking. Endoscopists should be highly skilled in colorectal ESD and have an intensive understanding of not only the lesions but also the conditions of patients with IBDs. Therefore, the decision to perform ESD for colitis-associated dysplasia should be made scrupulously after careful discussion with patients, in collaboration with a multidisciplinary IBD team including physicians, surgeons, and pathologists specialized in IBDs.