Use and safety of prophylactic endoscopy from a single center serving urban and rural children with portal hypertension

Prophylactic endoscopy is routine in adults with portal hypertension (PHTN), but there is limited data in pediatrics. We sought to describe our experience with prophylactic endoscopy in pediatric PHTN. This is a retrospective study of 87 children who began surveillance endoscopy prior to gastrointestinal bleeding (primary prophylaxis) and 52 who began after an episode of bleeding (secondary prophylaxis) from 01/01/1994 to 07/01/2019. Patients who underwent primary prophylaxis had a lower mean number of endoscopies (3.897 vs 6.269, p = 0.001). The primary prophylaxis group was less likely to require a portosystemic shunt (6% vs 15%, p < 0.001) with no difference in immediate complications (1% vs 2%, p = 0.173) or 2-week complications (1% vs 2%, p = 0.097). No deaths were related to variceal bleeding or endoscopy. Kaplan–Meier Survival Curve suggests improved transplant and shunt free survival in the primary prophylaxis group (log-rank p < 0.001). Primary and secondary endoscopic prophylaxis should be considered safe for the prevention of variceal hemorrhage in pediatric portal hypertension. There are differences in outcomes in primary and secondary prophylaxis, but unclear if this is due to patient characteristics versus treatment strategy. Further study is needed to compare safety and efficacy to watchful waiting.

Esophageal Variceal Bleeding as the First Manifestation of COVID-19 Infection: A Case Report

Liver cirrhosis is a defined liver disease with a wide range of clinical manifestations. Variceal bleeding is the main source of gastrointestinal hemorrhage among cirrhotic patients induced by several factors, such as alcohol consumption or infections. This is a report of a cirrhotic patient presenting with esophageal variceal bleeding in the context of COVID-19 infection. We report the case of a 53-year-old patient with liver cirrhosis and multifocal hepatocellular carcinoma presenting with upper gastrointestinal bleeding as the first manifestation of COVID-19 infection. Upon admission, the patient had no symptoms suggestive of a respiratory tract infection or any contact with positive SARS-CoV-2 individual and upper gastrointestinal endoscopy revealed variceal hemorrhage. After a few hours the patient manifested with fever, cough and dyspnea and a SARS-CoV-2 polymerase chain reaction test obtained was positive. The patient was initially treated with endoscopic band ligation and transferred in the COVID-19 infection clinic, where after a few days of hospitalization he passed away. The devastating pandemic of coronavirus disease 2019 had altered the pathophysiology and clinical presentation of several chronic diseases. This case report suggests that coronavirus disease as a potential triggering factor of variceal bleeding.

Variceal Hemorrhage: Decompression, Obliteration, or Both?

Variceal hemorrhage is a morbid condition that frequently mandates the involvement of interventional radiology to achieve successful and sustained hemostasis. Primary image-guided therapies for variceal hemorrhage include a transjugular intrahepatic portosystemic shunt and transvenous obliteration. Knowledge of variceal pathophysiology and anatomy, current techniques, and the evidence supporting therapeutic selection is paramount to successful patient outcomes. The purpose of this review is to provide the reader a framework of the available literature on image-guided management of bleeding varices to assist in clinical management.

Rebalanced hemostasis in liver disease: a misunderstood coagulopathy

The combination of frequently abnormal hemostatic markers and catastrophic bleeding as seen with variceal hemorrhage has contributed to the longstanding misperception that chronic liver disease (CLD) constitutes a bleeding diathesis. Laboratory studies of hemostasis in liver disease consistently challenge this with global coagulation assays incorporating activation of the protein C pathway demonstrating rebalanced hemostasis. It is now recognized that bleeding in CLD is predominantly secondary to portal hypertension (rather than a coagulopathy) and additionally that these patients are at increased risk of venous thrombosis, particularly in the portal venous system. This narrative review describes the current understanding of hemostasis in liver disease, as well as the periprocedural management of hemostasis and anticoagulation for management of venous thromboembolism in patients with CLD.

Microbiota transplants from feces or gut content attenuated portal hypertension and portosystemic collaterals in cirrhotic rats

Liver cirrhosis and portal hypertension is the end of chronic liver injury with hepatic, splanchnic and portosystemic collateral systems dysregulation. Liver injury is accompanied by gut dysbiosis whereas dysbiosis induces liver fibrosis, splanchnic angiogenesis and dysregulated vascular tones vice versa, making portal hypertension aggravated. It has been proved that intestinal microbiota transplantation alleviates dysbiosis. Nevertheless, the influences of microbiota transplantation on cirrhosis related portal hypertension are not so clear. Liver cirrhosis with portal hypertension was induced by bile duct ligation in rats. Sham rats were surgical controls. Rats randomly received vehicle, fecal or gut (terminal ileum) material transplantation. The results showed that microbiota transplantation from feces or gut material significantly reduced portal pressure in cirrhotic rats (P = .010, .044). Hepatic resistance, vascular contractility, fibrosis and relevant protein expressions were not significantly different among cirrhotic rats. However, microbiota transplantation ameliorated splanchnic hyperdynamic flow and vasodilatation. Mesenteric angiogenesis, defined by whole mesenteric window vascular density, decreased in both transplantation groups and phosphorylated eNOS was downregulated. Portosystemic shunts determined by splenorenal shunt flow decreased in both transplantation groups (P = .037, .032). Shunting severity assessed by microsphere distribution method showed consistent results. Compared to sham rats, cirrhotic rats lacked Lachnospiraceae. Both microbiota transplants increased Bifidobacterium. In conclusion, microbiota transplantation in cirrhotic rats reduced portal pressure, alleviated splanchnic hyperdynamic circulation and portosystemic shunts. The main beneficial effects may be focused on portosystemic collaterals-related events, such as hepatic encephalopathy and gastroesophageal variceal hemorrhage. Further clinical investigations are mandatory.

Assessment of Non-invasive Markers for the Prediction of Esophageal Variceal Hemorrhage

Background: Esophageal variceal (EV) hemorrhage is a life-threatening consequence of portal hypertension in cirrhotic patients. Screening upper endoscopy and endoscopic variceal ligation to identify and treat EVs have contraindications, complications, and high costs. We sought to identify non-invasive tests (NITs) as alternatives to endoscopic EV screening.Methods: In this case-control study, we retrospectively analyzed 286 cirrhotic patients treated for EVs at the Second People's Hospital of Fuyang City, China from January to December 2019. We applied ROC curve analysis to assess the accuracy of various NITs in predicting EV hemorrhage.Results: There were significant differences between the hemorrhage and non-hemorrhage groups in median serum albumin (ALB) (p &lt; 0.001), median bilirubin (TBIL) (p &lt; 0.046), prothrombin (PT) time (p &lt; 0.001), Golgi protein 73 (GP73; p = 0.012) and Child-Pugh (C-P) scores (p &lt; 0.001). For ALB (cutoff &lt;33.2g/L), PT time (cutoff &gt; 14.2 seconds), GP73 (cutoff &gt; 126.4 ng/ml), and C-P scores, the areas under the ROC curves (AUCs) were 73.4% (95% CI: 67.5–79.2), 68.6% (95% CI: 62.4–74.8), 62.2% (95% CI: 52.8–71.5) and 69.8% (95%CI: 63.8–75.8), respectively, with corresponding sensitives of 71.5, 59.8, 69.8, and 92.2% and specificities of 65.6%, 70.1%, 56.5%, and 38.6%. When ALB was combined with GP73, the AUC was 74.3% (95% CI: 66.1–82.5) with a sensitivity of 65.1% and specificity of 76.5%. When ALB, PT, and C-P scores were combined, the AUC was 76.5% (95% CI: 70.9–82.1) with a sensitivity of 79.5% and specificity of 64.3%. When ALB, PT, GP73, and C-P scores were combined, the AUC was 75.2% (95% CI: 67.3–83.1) with a sensitivity of 54.0% and specificity of 86.9%.Conclusion: ALB, TBIL, GP73, and C-P scores, may be used to predict EV hemorrhage in cirrhotic patients. The combination of multiple NITs is better than a single index and can increase diagnostic performance.

Platelet count can predict the grade of esophageal varices in cirrhotic patients: a cross-sectional study

Background: Bleeding from esophageal varices is a life-threatening complication in cirrhosis. Screening endoscopy is recommended in cirrhotic patients to identify patients at risk of variceal hemorrhage, but this is an invasive procedure and has limitations. Therefore, thrombocytopenia has been proposed to predict the existence and grade of esophageal varices. The aim of the current study was to determine a correlation between platelet count and grades of esophageal varices in patients with liver cirrhosis. Methods: This cross-sectional study was conducted at the POF Hospital, Wah Cantt from 1st October, 2017 to 30th May, 2018. Newly diagnosed cases of cirrhosis having varices of any grade on endoscopy were included. Endoscopic findings of patients were standardized using Paquet grading system. On the basis of platelet count, patients were divided into four subgroups. Platelet count groups were correlated with grading of esophageal varices using Spearman rank correlations. Chi Square test was used to see association between the platelet count and grade of esophageal varices. Results: 110 patients were included in the study, 55.5% (n=61) were male. Mean age of the patients was 59.89±9.01 years. Platelet count was <50,000/uL in 35.5% patients, 50,000-99,000/uL in 26.4%, 100,000-150000 in 12.7%, and >150,000/uL in 25.5% patients. Grade I esophageal varices were found in 23.6% of patients, whereas grade II, III and IV were found in 24.5%, 33.6% and 18.2% of patients, respectively. Mean platelet count was 213884.62/mm3 in patients with grade I varices, whereas it was 119518.52/mm3, 58386.49/mm3 and 21600.00/mm3 in patients with grade II, III and IV varices, respectively (p=<0.0001). A significant negative correlation between platelet count and grades of esophageal varices was found (p<0.001). Conclusion: Platelet count can predict the grade of esophageal varices in cirrhotic patients. There is significant negative correlation between platelet count and grades of esophageal varices.

Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

Acute-on-chronic liver failure (ACLF) is a multifaceted condition with poor treatment options and high short-term mortality. ACLF can develop in patients with or without liver cirrhosis, where patients with decompensated cirrhosis display a higher risk of short-term mortality. Pathophysiological mechanisms include systemic inflammation due to bacterial and fungal infections and acute hepatic insult with drug, alcohol, and viral hepatitis. Cryptogenic factors also contribute to the development of ACLF. The clinical outcome of patients with ACLF gets further complicated by the occurrence of variceal hemorrhage, hepatorenal syndrome, hepatic encephalopathy, and systemic immune dysfunction. Regardless of the better understanding of pathophysiological mechanisms, no specific and definitive treatment is available except for liver transplantation. The recent approach of regenerative medicine using mesenchymal stem cells (MSCs) could be advantageous for the treatment of ACLF as these cells can downregulate inflammatory response by inducing antiinflammatory events and prevent hepatic damage and fibrosis by inhibiting hepatic stellate cell activation and collagen synthesis. Moreover, MSCs are involved in tissue repair by the process of liver regeneration. Considering the broad therapeutic potential of MSCs, it can serve as an alternative treatment to liver transplant in the near future, if promising results are achieved.