Management of non-cirrhotic variceal bleeding in pregnant women with Budd-Chiari syndrome in the early second trimester: A case report.

Budd-Chiari syndrome is one of the post-hepatic causes of portal hypertension and a potential obstruction causes liver fibrosis. In pregnancy, obstruction of hepatic veins could occur due to stenosis or thrombosis. Variceal bleeding is the most fatal complication in pregnancy with co-existing Budd-Chiari syndrome, with 29.4% incidence of abortion and 33.3% perinatal mortality. The aim of this case report was to present the management of non-cirrhotic variceal bleeding in pregnant women with Budd-Chiari syndrome in the early second trimester. We report a pregnant female at 13-14 weeks gestation presented to the hospital with profuse hematemesis. Doppler ultrasonography (USG) was utilized to confirm the diagnosis of Budd-Chiari syndrome-hepatic vein occlusion type in pregnancy. Abdominal USG revealed hepatomegaly with hepatic veins dilation, while endoscopy showed grade IV esophageal varices and grade IV gastric varices. Laboratory results indicated disseminated intravascular coagulation due to hemorrhage. The patient was given strict fluid resuscitation and three packed red cells transfusion to stabilize the hemodynamic. Bleeding was successfully managed by intravenous octreotide, tranexamic acid, and vitamin K. The case highlights that the management of non-cirrhotic variceal bleeding in pregnancy with Budd-Chiari syndrome requires a multidisciplinary approach and regular fetal monitoring to ensure optimal outcomes.

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.

Management of dyspepsia and Helicobacter pylori infection: the 2022 Indonesian Consensus Report.

Dyspepsia still becomes a major challenge in upper gastrointestinal disease in Indonesia. This disease often correlated with Helicobacter pylori infection. However, the prevalence of this bacterium is generally low in Indonesia. Therefore, several considerations should be taken into consideration during the management of dyspepsia and H. pylori infection. "Management of dyspepsia and H. pylori infection in Indonesia: The Indonesian consensus report" comprises information gathered from 22 gastroenterology centers across Indonesia. The experts gathered to evolve a consensus, that consists of the statements, grades of recommendations, evidence levels, and rationales for the dyspepsia and H. pylori infection management for daily clinical practice. The report explains several aspects from the updated epidemiology information to comprehensive management therapy. After the experts worked together on all statements in the recommendations, the results are presented with the final agreement as a consensus to help clinicians in understanding, diagnosing, and treating dyspepsia and H. pylori infection patients in daily clinical practice in Indonesia.

Gastrointestinal mucosal damages caused by ingestion of corrosive substances: A case study of hydrochloric acid and sodium hydroxide.

Ingestion of corrosive substances is most common in children, while in adults causes more severe damages. Massive ingestion of corrosive substances results in severe damage to the gastrointestinal tract and oropharynx if not treated properly. Corrosive substances with pH<2 or >12 can result in severe esophageal damage with either colliquative (alkaline) or coagulative (acidic) necrosis and, at the same time various gastrointestinal injuries could lead to late post-corrosive complications. The aim of the case study was to report the gastrointestinal mucosal damages due to hydrochloric acid (HCl) and sodium hydroxide (NaOH) ingestion. A 55-year-old male patient was presented to the emergency room with a chief complaint of vomiting an hour before admission. Continuous vomiting with a volume of approximately 10-20 cc per vomit. The vomit was initially bluish and turned in to blackish brown over time. Other complaints included nausea, rapid breathing, heartburn, and burning mouth and throat, and had weakness and dizziness. The patient accidentally drank floor cleaning liquid containing HCl. The patient was diagnosed with hematemesis due to ulceration of esophageal, gastric, and duodenal mucosa induced by HCl. Tracheoesophageal fistula developed later in the patient as a long-term complication. Another a 22-year-old male patient was presented to the emergency room with chief complaints of nausea and vomiting an hour before admission. Headache and slight tightness were also experienced. The patient mouth felt burned pain in the solar plexus and frothy saliva. An hour earlier, the patient attempted suicide by drinking two bottles of floor cleaning liquid due to economic problems. The patient was diagnosed with erosive mucosal esophagogastroduodenum induced by NaOH. These cases highlight that intoxication with corrosive substances can complicate damage to the gastrointestinal mucosal and damage features depend on the type of substance concentration and quantity of the corrosive substance.

Co-incidence of COVID-19 and hepatocellular carcinoma during pregnancy: Double punches to disease severity and mortality?

Hepatocellular carcinoma (HCC), a considerable leading cause of cancer-related deaths worldwide, is the most common primary liver cancer with poor prognosis and outcome. Many advances in prevention, screening, and new technologies in diagnostics and therapy have been achieved, but its incidence and mortality remain increasing. Co-infection of another viral disease in HCC patients with pregnancy might exacerbate the condition and double the mortality rate. The aim of this case report was to describe the co-infection of coronavirus disease 2019 (COVID-19) in an HCC patient during pregnancy. A 26-year-old woman with 16-17 weeks of gestation was admitted to Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia with shortness of breath. The patient also reported that the abdomen expanded rapidly in the last three weeks, followed by severe pain and collateral vein appearance. Laboratory findings revealed anemia, leukocytosis, HBsAg reactive, hypoalbuminemia, hyperbilirubinemia, elevated liver enzymes, increased alpha-fetoprotein (AFP), and cancer antigen 125 (CA-125). Ultrasonography indicated gestation with a single fetus, an enlarged liver with a 9.9 × 9.4 cm nodule, and massive ascites. The patient was also RT-PCR-confirmed COVID-19. On day 8 of hospitalization, the patient suddenly reported severe abdominal pain. Ultrasonography revealed fetal distress immediately followed by fetal death. Adequate management of cancer pain, continuous evacuation of ascites, and other supportive care could not save the patient who died on the day 17 of hospitalization. In this case, we found no proof that the patient experienced cirrhosis prior to HCC. Pregnancy through hormonal alteration is thought to be the aggravating factor that accelerates the progression of pre-existing liver disease into carcinoma and infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worsened the outcome in this patient.

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.

Acute severe hepatitis of unknown etiology in children: A mini-review.

The emergence of acute, severe non hepA-E hepatitis of unknown etiology (ASHUE) has attracted global concern owing to the very young age of the patients and its unknown etiology. Although this condition has been linked to several possible causes, including viral infection, drugs and/or toxin exposure, the exact cause remains unknown; this makes treatment recommendation very difficult. In this review, we summarize recent updates on the clinical manifestations, complemented with laboratory results, case numbers with the global distribution and other epidemiological characteristics, and the possible etiologies. We also provide the proposed actions that could be undertaken to control and prevent further spread of this hepatitis. Since many etiological and pathological aspects of the acute non hepA-E hepatitis remain unclear, further research is needed to minimize the severe impact of this disease.

Global prevalence of prolonged gastrointestinal symptoms in COVID-19 survivors and potential pathogenesis: A systematic review and meta-analysis.

Background: This study aimed to determine the cumulative prevalence of prolonged gastrointestinal (GI) symptoms, including nausea, vomiting, diarrhea, lack of appetite, abdominal pain, and dysgeusia, in survivors of both mild and severe COVID-19 worldwide and to discuss the potential pathogenesis.   Methods: Three databases (PubMed, Scopus, and Web of Science) were searched for relevant articles up to January 30, 2021. Data on study characteristics, clinical characteristics during follow-up, the number of patients with prolonged GI symptoms, and total number of COVID-19 survivors were retrieved according to PRISMA guidelines. The quality of eligible studies was assessed using the Newcastle-Ottawa scale. The pooled prevalence of specific prolonged GI symptoms was calculated and the association between COVID-19 severity and the occurrence of prolonged GI symptoms was assessed if appropriate.   Results: The global prevalence of prolonged nausea was 3.23% (95% CI: 0.54%-16.53%) among 527 COVID-19 survivors. Vomiting persisted in 93 of 2,238 COVID-19 survivors (3.19%, 95% CI: 1.62%-6.17%) and prolonged diarrhea was found in 34 of 1,073 survivors (4.12%, 95% CI: 1.07%-14.64%). A total of 156 patients among 2,238 COVID-19 survivors (4.41%, 95% CI: 1.91%-9.94%) complained of persistent decreased or loss of appetite. The cumulative prevalence of prolonged abdominal pain was 1.68% (95% CI: 0.84%-3.32%), whereas persistent dysgeusia was identified in 130 cases among 1,887 COVID-19 survivors (7.04%, 95% CI: 5.96%-8.30%). Data was insufficient to assess the relationship between COVID-19 severity and the occurrence of all prolonged GI symptoms.   Conclusion: Persistent GI symptoms among COVID-19 survivors after discharge or recovery raises a concern regarding the long-term impact of the COVID-19 infection on the quality of life of the survivors. Despite several potential explanations proposed, studies that aim to follow patients after recovery from COVID-19 and determine the pathogenesis of the prolonged symptoms of COVID-19 survivors are warranted.   PROSPERO registration: CRD42021239187.

Helicobacter pylori in the Indonesian Malay's descendants might be imported from other ethnicities.

BACKGROUND: Even though the incidence of H. pylori infection among Malays in the Malay Peninsula is low, we observed a high H. pylori prevalence in Sumatra, which is the main residence of Indonesian Malays. H. pylori prevalence among Indonesian Malay descendants was investigated. RESULTS: Using a combination of five tests, 232 recruited participants were tested for H- pylori and participants were considered positive if at least one test positive. The results showed that the overall H. pylori prevalence was 17.2%. Participants were then categorized into Malay (Aceh, Malay, and Minang), Java (Javanese and Sundanese), Nias, and Bataknese groups. The prevalence of H. pylori was very low among the Malay group (2.8%) and no H. pylori was observed among the Aceh. Similarly, no H. pylori was observed among the Java group. However, the prevalence of H. pylori was high among the Bataknese (52.2%) and moderate among the Nias (6.1%). Multilocus sequence typing showed that H. pylori in Indonesian Malays classified as hpEastAsia with a subpopulation of hspMaori, suggesting that the isolated H. pylori were not a specific Malays H. pylori. CONCLUSIONS: Even though the ethnic groups live together as a community, we observed an extremely low H. pylori infection rate among Indonesian Malay descendants with no specific Indonesian Malay H. pylori. The results suggest that H. pylori was not originally among these groups and H. pylori was imported from other ethnic groups.

Ulcerative Colitis in Hemophilia A Patient: Case Report.

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory disease that affects colon while the incidence is increasing worldwide. The pathogenesis of the disease is complex and involves multi factors such genetic predisposition, defects in epithelial barrier and immune response as well as environmental factors. Combination UC with Hemophilia A, a hereditary hemorrhagic disorder, is very rare but can lead massive rectal bleeding that will be fatal for the patients. AIM: The case report present a case of a man with hemophilia A with rectal bleeding and recently diagnosed with ulcerative colitis. CASE REPORT: A 52 years old man presented with massive rectal bleeding since 3 days before admitted to hospital. The patient reported recurrent rectal bleeding for years but never continue for more than a week. He was previously diagnosed with hemophilia A since 34 years ago with factor VIII between 5 to 8 percent and receive recombinant human factor VIII routinely. Colonoscopy examination showed redness and ulcer along colon descendent and was confirmed for ulcerative colitis with histopathology analysis. The patient showed clinical improvement after administered with sulfasalazine and tranexamide acid. CONCLUSION: UC can cause fatal bleeding in patient with hemophilia A therefore early diagnosis of UC altogether with UC flare prevention, continuing FVII infusion and anti-hemorrhagic administration are the most important strategy in management UC in hemophilia A patient.

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.

Analysis of risks of gastric cancer by gastric mucosa among Indonesian ethnic groups.

Indonesia is a big country with multiethnic populations whose gastric cancer risks have not been elucidated. We performed a nationwide survey and obtained histological specimens from 1053 individuals in 19 cities across the country. We examined the gastric mucosa, the topography, the atrophic gastritis risk factors, and the gastric cancer risk scores. Almost half (46.1%) of the patients with dyspeptic symptoms had histological abnormalities; chronic (36.3%) and atrophic gastritis (28.9%) being the most frequent. Individuals of the Timor ethnicity had the highest prevalence of acute (52.6%) and chronic gastritis (68.4%), even those negative for H. pylori. Our topographic analysis showed the majority of patients had predominantly antral acute and chronic gastritis. A multivariate logistic regression model showed age (Odds ratio [OR], 1.107), Timor ethnicity (OR, 8.531), and H. pylori infection (OR, 22.643) as independent risk factors for presence of atrophic gastritis. In addition, the gastric cancer risk score was highest in those from Timor, Papuan, and Bugis ethnic populations. Overall, Indonesia is a low-risk gastric cancer country. However, several ethnic groups displayed severe gastric mucosa symptoms suggesting policy makers should focus on those ethnic groups to perform gastric cancer screenings and to eradicate H. pylori.

The Level Short Chain Fatty Acids and HSP 70 in Colorectal Cancer and Non-Colorectal Cancer.

INTRODUCTION: Microbial involvement in colorectal cancer (CRC) is now well established. Short Chain Fatty Acids (SCFA) is the main products of anaerobic microbial fermentation in the large intestine and affects colonic health. SCFA mainly produced as microbial metabolites, acetate, propionate, and butyrate acids. Several in vitro studies showed that butyrate induce expression of heat shock protein (HSP) 70 that has function in the beginning of apoptosis. AIM: The aim of this study was investigating the differences level SCFA and HSP 70 expression in CRC compared with non-CRC patients. MATERIAL AND METHODS: The study consists of 14 patients diagnosed with CRC and 14 non-CRC patients. Stool sample were analyzed for SCFA (acetate, propionate, and butyrate acids) with gas chromatography and the result is given as µg/mL and the protein expression of HSP70 was determined by immunohistochemistry (IHC) and haematoxylin-eosin staining to determine the morphological changes in colon tissue. RESULTS: We found that CRC patients had lower level of acetate, propionate and butyrate acids than non-CRC. Whereas in CRC patients, the mean concentration of acetate was 8,55 µg/mL, propionate was 5,61 µg/mL and butyrate acids were 3,79 µg/mL respectively (all P < 0.05). And among the samples of patients with colorectal cancer was obtained the highest expression of HSP-70. CONCLUSIONS: Short chain fatty acids were indirectly contributed in the role of pathogenesis in CRC despite another factor could affect for this disease.

Surveillance of Helicobacter pylori Antibiotic Susceptibility in Indonesia: Different Resistance Types among Regions and with Novel Genetic Mutations.

Information regarding Helicobacter pylori antibiotic resistance in Indonesia was previously inadequate. We assessed antibiotic susceptibility for H. pylori in Indonesia, and determined the association between virulence genes or genetic mutations and antibiotic resistance. We recruited 849 dyspeptic patients who underwent endoscopy in 11 cities in Indonesia. E-test was used to determine the minimum inhibitory concentration of five antibiotics. PCR-based sequencing assessed mutations in 23S rRNA, rdxA, gyrA, gyrB, and virulence genes. Next generation sequencing was used to obtain full-length sequences of 23S rRNA, infB, and rpl22. We cultured 77 strains and identified 9.1% with clarithromycin resistance. Low prevalence was also found for amoxicillin and tetracycline resistance (5.2% and 2.6%, respectively). In contrast, high resistance rates to metronidazole (46.7%) and levofloxacin (31.2%) were demonstrated. Strains isolated from Sumatera Island had significantly higher metronidazole resistance than those from other locations. Metronidazole resistant strains had highly distributed rdxA amino acid substitutions and the 23S rRNA A2143G mutation was associated with clarithromycin resistance (42.9%). However, one strain with the highest MIC value had a novel mutation in rpl22 without an A2143G mutation. Mutation at Asn-87 and/or Asp-91 of gyrA was associated with levofloxacin-resistance and was related to gyrB mutations. In conclusions, although this is a pilot study for a larger survey, our current data show that Indonesian strains had the high prevalence of metronidazole and levofloxacin resistance with low prevalence of clarithromycin, amoxicillin, and tetracycline resistance. Nevertheless, clarithromycin- or metronidazole-based triple therapy should be administered with caution in some regions of Indonesia.

Microbiota Composition, HSP70 and Caspase-3 Expression as Marker for Colorectal Cancer Patients in Aceh, Indonesia.

AIM: to investigate the relationship between microbiota composition with HSP70 and Caspase-3 expressions in colon tissue as an initial study to develop the candidate for early detection of colorectal cancer for Indonesian patients. METHODS: this is a cross-sectional study on 32 patients undergoing colonoscopy; 16 patients of colorectal cancer (CRC) while the other 16 patients are not (colitis and internal hemorrhoid). The composition of microbiota in stool samples was examined using 16S rRNA Denaturing Gradient Gel Electrophoresis (DDGE) while expression of HSP70 was examined by immunohistochemistry and Caspase-3 by using Haematoxylin-Eosin(HE) staining to determine the morphological changes in colon tissue. RESULTS: analysis of PCR-DDGE shows a different composition of microbiota between patients with CRC and non-CRC. All CRC patients showed disappearance of dominant band from Bifidobacterium groups. Histological observation based on Inter Class Correlation (ICC) test from all slide showed a high scores (5.2-9.2) in CRC patients and low scores (1.7-2.4) in non-CRC patients. HSP70 expression was increased significantly in CRC patients with the highest percentage of 84%, while expression of caspase-3 decreased with the highest percentage of 21%. Statistical analysis showed that the incidence of colorectal cancer was associated with the expression of HSP 70 (p<0.001), and Caspase 3 (p<0.001). CONCLUSION: bifidobacterium is an important indicator for colorectal cancer patients that show disappearance of dominant band, while expression of HSP70 increased and the Caspase-3 expression decreased significantly.