Surveillance and treatment of primary hepatocellular carcinoma (aka. STOP HCC): protocol for a prospective cohort study of high-risk patients for HCC using GALAD-score.

BACKGROUND: Vietnam and Saudi Arabia have high disease burden of primary hepatocellular carcinoma (HCC). Early detection in asymptomatic patients at risk for HCC is a strategy to improve survival outcomes in HCC management. GALAD score, a serum-based panel, has demonstrated promising clinical utility in HCC management. However, in order to ascertain its potential role in the surveillance of the early detection of HCC, GALAD needs to be validated prospectively for clinical surveillance of HCC (i.e., phase IV biomarker validation study). Thus, we propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients with advanced fibrosis or compensated cirrhosis, irrespective of etiologies, using semi-annual abdominal ultrasound and GALAD score for five years. METHODS: We plan to recruit a cohort of 1,600 patients, male or female, with advanced fibrosis or cirrhosis (i.e., F3 or F4) and MELD ≤ 15, in Vietnam and Saudi Arabia (n = 800 each). Individuals with a liver mass ≥ 1 cm in diameter, elevated alpha-fetoprotein (AFP) (≥ 9 ng/mL), and/or elevated GALAD score (≥ -0.63) will be scanned with dynamic contrast-enhanced magnetic resonance imaging (MRI), and a diagnosis of HCC will be made by Liver Imaging Reporting and Data System (LiRADS) assessment (LiRADS-5). Additionally, those who do not exhibit abnormal imaging findings, elevated AFP titer, and/or elevated GALAD score will obtain a dynamic contrast-enhanced MRI annually for five years to assess for HCC. Only MRI nearest to the time of GALAD score measurement, ultrasound and/or AFP evaluation will be included in the diagnostic validation analysis. MRI will be replaced with an abdominal computed tomography scan when MRI results are poor due to patient conditions such as movement etc. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI will not be carried out in study sites in both countries. Bootstrap resampling technique will be used to account for repeated measures to estimate standard errors and confidence intervals. Additionally, we will use the Cox proportional hazards regression model with covariates tailored to the hypothesis under investigation for time-to-HCC data as predicted by time-varying biomarker data. DISCUSSION: The present work will evaluate the performance of GALAD score in early detection of liver cancer. Furthermore, by leveraging the prospective cohort, we will establish a biorepository of longitudinally collected biospecimens from patients with advanced fibrosis or cirrhosis to be used as a reference set for future research in early detection of HCC in the two countries. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov Registration date: 22 April 2022 Trial registration number: NCT05342350 URL of trial registry record.

Investigating the Role of Non-Coding RNA in Non-Alcoholic Fatty Liver Disease.

Non-coding RNAs (ncRNAs) are RNA molecules that do not code for protein but play key roles in regulating cellular processes. NcRNAs globally affect gene expression in diverse physiological and pathological contexts. Functionally important ncRNAs act in chromatin modifications, in mRNA stabilization and translation, and in regulation of various signaling pathways. Non-alcoholic fatty liver disease (NAFLD) is a set of conditions caused by the accumulation of triacylglycerol in the liver. Studies of ncRNA in NAFLD are limited but have demonstrated that ncRNAs play a critical role in the pathogenesis of NAFLD. In this review, we summarize NAFLD's pathogenesis and clinical features, discuss current treatment options, and review the involvement of ncRNAs as regulatory molecules in NAFLD and its progression to non-alcoholic steatohepatitis (NASH). In addition, we highlight signaling pathways dysregulated in NAFLD and review their crosstalk with ncRNAs. Having a thorough understanding of the disease process's molecular mechanisms will facilitate development of highly effective diagnostic and therapeutic treatments. Such insights can also inform preventive strategies to minimize the disease's future development.

Candida Cardiac Tamponade Secondary to Oesophageal-Pericardial Fistula: A Rare Presentation of Oesophageal Squamous Cell Carcinoma.

Candida is a rare cause of purulent pericarditis. Oesophago-pericardial fistula is an uncommon and potentially life-threatening complication of both benign and malignant oesophageal tumours. Here we report the case of 40-year-old woman who presented with symptoms and signs suggestive of acute pericarditis complicated by cardiac tamponade which required acute management with paracentesis. Pericardial fluid analysis was positive for Candida albicans. Oesophagogastroduodenoscopy was performed and revealed a small fistula in the proximal oesophagus extending into the retrocardiac space. Multiple biopsy specimens of the fistula site and oesophageal stricture were obtained. Histopathological findings were consistent with poorly differentiated squamous cell carcinoma of the oesophagus complicated by fistulation to the retrocardiac space. LEARNING POINTS: Purulent pericarditis with atypical organisms should raise the suspicion of oesophago-pericardial fistula.Oesophago-pericardial fistula in oesophageal squamous cell carcinoma is rare and associated with high mortality and a poor prognosis.This is one of the few cases where a gastro-pericardial fistula has been diagnosed by endoscopy.

Saudi association for the study of liver diseases and transplantation position statement on the hepatology workforce in Saudi Arabia.

The field of hepatology has evolved significantly over the last two decades. Hepatology practice in Saudi Arabia (SA) was dominated by hepatitis B and C viruses but is now being overtaken by patients with non-alcoholic fatty liver disease. These patients require greater medical attention as their care is more complex compared to patients with viral hepatitis. In addition, liver transplantation (LT) has expanded significantly in SA over the last three decades. There is a necessity to increase the hepatology workforce to meet the demand in SA. The time has come to reinforce the transplant hepatology fellowship program, that was launched recently, and to develop a nurse practitioner practice model to meet these demands. In addition, SA is going through a health care reform to enhance health care delivery which may affect the financial compensation polices of various specialties including gastroenterology and hepatology. Therefore, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) established a task force to discuss the current and future demands in the hepatology workforce in SA, as well as to discuss different avenues of financial compensation for transplant hepatologists in LT centers.

Acute reversible rhabdomyolysis during direct-acting antiviral hepatitis C virus treatment: a case report.

INTRODUCTION: Treatment of hepatitis C infection has evolved dramatically since 2011. Previous conventional therapy with interferon and ribavirin used to have a low sustained virological response rate of less than 40%. In the new direct-acting antiviral therapy era, a sustained virological response can be achieved in more than 90% of cases. CASE PRESENTATION: We report a rare case of severe reversible acute rhabdomyolysis in a 31-year-old Saudi male patient with very long-chain acyl-coenzyme A dehydrogenase deficiency and chronic hepatitis C infection. The patient was clinically asymptomatic with no signs of decompensated liver disease. The patient received new direct-acting antiviral agents: sofosbuvir and daclatasvir. Fourteen days after initiation of direct-acting antiviral agents, the patient was found to have asymptomatic rhabdomyolysis. His creatine kinase peaked at 2572 IU/l, and he was treated conservatively; the direct-acting antiviral agents were discontinued and within 7 days, the patient's creatine kinase levels normalized. CONCLUSION: This case highlights possible direct-acting antiviral agent-induced rhabdomyolysis in a patient with very-long-chain acyl-CoA dehydrogenase deficiency, presumably through alteration of mitochondrial membrane potential. Further studies are required to assess the possible impact and associations.

An unusual case of collagenous gastritis in a middle- aged woman with systemic lupus erythromatosis: a case report.

INTRODUCTION: Collagenous gastritis is a rare histopathologic disease. It is characterized by marked subepithelial collagen deposition with associated inflammatory infiltrate. It is considered an uncommon disease among the general population. Collagenous gastritis without colonic involvement is an extremely rare disease. It is not known to be associated with systemic lupus erythromatosis. This is the first report of this type of association. CASE PRESENTATION: We present a 47-year-old woman from southeast Asia with dyspepsia and mild anemia. Her past medical history was significant for systemic lupus erythromatosis, autoimmune hemolytic anemia as well as hypothyroidism. Her gastroscopy and colonoscopy results were normal from an endoscopic point of view. However, the histopathology showed collagenous gastritis. CONCLUSIONS: To the best of our knowledge, this is the first case reported of a patient with systemic lupus erythromatosis associated with collagenous gastritis. Further studies are needed to evaluate the association between both diseases from a pathophysiological and immunological perspective.

The clinical consequences of utilizing donation after cardiac death liver grafts into hepatitis C recipients.

UNLABELLED: Chronic liver failure from hepatitis C virus (HCV) remains the leading indication for liver transplantation (LT). Donation after cardiac death (DCD) donors are becoming a more frequent source of liver grafts. Hepatitis C recipients of standard donation after brain death (DBD) allografts may have inferior long-term results, and more so when expanded criteria organs are used. Given the nature of DCD grafts, a focus on the consequences to HCV recipients is of major importance. We analyzed the graft outcomes in HCV and non-HCV liver transplant recipients of DCD grafts. RESULTS: 21 patients underwent LT using a DCD grafts (9 HCV, 12 non-HCV) the donor body mass index and age was similar in both groups. One non-HCV recipient was retransplanted for primary non-function (PNF 8%). Biliary complications occurred in 22% (2/9) of the HCV group, 50% (6/12) in the non-HCV group (p = 0.21). After a mean of 19 months follow up, excellent patient and graft survival was seen in the non-HCV recipients of DCD grafts (100 and 92%, respectively). These outcomes were numerically less in HCV recipients (78, 67%). In the HCV recipients of DCD grafts, 33% (3/9) suffered graft loss, two from fatal aggressive fibrosing cholestatic (FCH) HCV and one due to ischemic cholangiopathy. CONCLUSION: Although a statistically significant difference in patient/graft survival for HCV and non-HCV recipients of DCD organs was not shown, it is clear that more dire consequences exist for HCV recipients of DCD grafts, highlighting the need for larger data sets for evaluating this patient population.