One disease, many faces-typical and atypical presentations of SARS-CoV-2 infection-related COVID-19 disease

Since the appearance of the novel coronavirus(severe acute respiratory syndrome-coronavirus-2)and related coronavirus disease 2019(COVID-19)in China in December 2019,a very high number of small and large patient series have been published in literature from around the world.Even though the classical presentation of COVID-19 is one with respiratory symptoms with or without pneumonia that can be self-limiting or evolve into severe respiratory distress syndrome with multiple organ failure,and secondary bacterial sepsis,a large body of evidence suggests a plethora of other types of clinical presentation.In this exhaustive review,we reviewed all of the published literature on COVID-19 to identify different types of clinical presentations affecting various organ systems,to provide an in-depth analysis that may prove useful for clinicians and health-workers on the frontline,battling the severe pandemic.

Transjugular intrahepatic portosystemic shunt in cirrhosis: An exhaustive critical update

More than five decades after it was originally conceptualized as rescue therapy for patients with intractable variceal bleeding,the transjugular intrahepatic portosystemic shunt(TIPS)procedure continues to remain a focus of intense clinical and biomedical research.By the impressive reduction in portal pressure achieved by this intervention,coupled with its minimally invasive nature,TIPS has gained increasing acceptance in the treatment of complications of portal hypertension.The early years of TIPS were plagued by poor long-term patency of the stents and increased incidence of hepatic encephalopathy.Moreover,the diversion of portal flow after placement of TIPS often resulted in derangement of hepatic functions,which was occasionally severe.While the incidence of shunt dysfunction has markedly reduced with the advent of covered stents,hepatic encephalopathy and instances of early liver failure continue to remain a significant issue after TIPS.It has emerged over the years that careful selection of patients and diligent post-procedural care is of paramount importance to optimize the outcome after TIPS.The past twenty years have seen multiple studies redefining the role of TIPS in the management of variceal bleeding and refractory ascites while exploring its application in other complications of cirrhosis like hepatic hydrothorax,portal hypertensive gastropathy,ectopic varices,hepatorenal and hepatopulmonary syndromes,non-tumoral portal vein thrombosis and chylous ascites.It has also been utilized to good effect before extrahepatic abdominal surgery to reduce perioperative morbidity and mortality.The current article aims to review the updated literature on the status of TIPS in the management of patients with liver cirrhosis.

Still'dwelling in the possibility'-critical update on stem cell therapy for acute on chronic liver failure

Stem cells therapy could improve survival in patients with liver failure.Studies on stem cell therapy and related growth factors in decompensated cirrhosis has been on the forefront but has shown heterogenous results.Recent high-quality studies have shown a lack of efficacy and safety.Patients with acute-on-chronic liver failure(ACLF)are a unique group with high mortality in the short-term associated with rapid onset extrahepatic organ failures.In these patients,there is an urgent need to identify treatments that can improve liver cell function and mass,prevent sepsis/organ failure,ameliorate systemic inflammation,and increase transplant-free survival.Stem cells are a novel treatment in ACLF but with unclear efficacy and safety.In this narrative review,we discuss the basics of liver regeneration in patients with ACLF and update current clinical status of stem cell use in patients with ACLF for improving our understanding of future directions.

Comprehensive review of hepatotoxicity associated with traditional Indian Ayurvedic herbs

With growing antipathy toward conventional prescription drugs due to the fear of adverse events,the general and patient populations have been increasingly using complementary and alternative medications(CAMs)for managing acute and chronic diseases.The general misconception is that natural herbal-based preparations are devoid of toxicity,and hence short-and long-term use remain justified among people as well as the CAM practitioners who prescribe these medicines.In this regard,Ayurvedic herbal medications have become one of the most utilized in the East,specifically the Indian sub-continent,with increasing use in the West.Recent well-performed observational studies have confirmed the hepatotoxic potential of Ayurvedic drugs.Toxicity stems from direct effects or from indirect effects through herbal metabolites,unknown herb-herb and herbdrug interactions,adulteration of Ayurvedic drugs with other prescription medicines,and contamination due to poor manufacturing practices.In this exhaustive review,we present details on their hepatotoxic potential,discuss the mechanisms,clinical presentation,liver histology and patient outcomes of certain commonly used Ayurvedic herbs which will serve as a knowledge bank for physicians caring for liver disease patients,to support early identification and treatment of those who present with CAM-induced liver injury.

Identification and Analysis of Gut Microbiota and Functional Metabolism in Decompensated Cirrhosis with Infection

Background and Aims:Intestinal dysbiosis play a role in the adverse outcomes of sepsis and septic shock.However,variations in bacterial diversity and microbiota-related functional metabolic alterations within the gut microbiome in decompensated cirrhosis(DC)patients with infection remain unknown.Methods:We conducted 16-srRNA sequencing on stool samples(n=51:sepsis,27/no sepsis,24)collected from consecutive DC patients upon admission.Bacterial diversity,significant taxa,and respective metabolic profiling were performed based on subgroup comparisons.Conet/Cytoscape was utilized to identify significant non-random patterns of bacterial copresence and mutual exclusion for clinical events.Results:Genera associated with pathogenicity in conditions of immune exhaustion(Corynebacterium,Lautropia)were predominant in patients with sepsis.Metabolic pathways associated with oxidative stress and endotoxemia[lipopolysaccharide(LPS)synthesis and sulfur relay]were significantly upregulated in sepsis.Specific taxa were associated with sites of infection in DC patients.Protective oxidant pathways that increase glutathione were upregulated in those without sepsis.Gammaproteobacteria family of sulfur-metabolizing bacteria,exaggeration of orally predominant pathogens(Prevotella),and pathways of severe LPS-related hyperinflammatory stress were notable in those with interleukin-6 levels>1,000 pg/dL.Pathogenic genera related to an immune deficient state was significant in DC with≥2 infection episodes.Megamonas was associated with survival during the same admission.Conclusions:Specific gut microbiota and their metabolites were associated with sepsis and related events in patients with DC.Identifying beneficial strains that reduce immune exhaustion and supplementation of favorable metabolites could improve therapeutics for DC and sepsis,for which larger prospective,well controlled population-based studies remain an unmet need.

Clinical outcomes and gut microbiota analysis of severe alcohol-associated hepatitis patients undergoing healthy donor fecal transplant or pentoxifylline therapy:single-center experience from Kerala

Background Severe alcohol-associated hepatitis(SAH)patients with infections have a high short-term mortality rate.Gut microbiota dysbiosis plays an important role in the pathogenesis of SAH.Preliminary studies have demonstrated long-term benefits with healthy donor fecal microbiota transplantation(FMT).Data on FMT compared with pentoxifylline for SAH and relevant gut microbial changes are lacking in literature.Methods From January 2019 to February 2021,retrospective analysis of a single hospital’s records revealed 47 SAH patients undergoing FMT(100mL/day via nasoduodenal tube for 7days)and 25matched patients receiving pentoxifylline(400mg/8 h for 28days).The primary end point was a 6-month survival rate.Secondary end points included incidence of ascites,hepatic encephalopathy,infections,acute kidney injury,and gutmicrobiota changes between post-therapy groups.Biomarker discovery and network analysis were also performed to identify significant taxa of gutmicrobiota in post-treatment groups in retrospectively stored stool samples.Results All were males.The 6-month survival rate was higher in the patients undergoing FMT than in patients receiving pentoxifylline(83.0%vs 56.0%,P=0.012).At the end of 6-month follow-up,the incidences of clinically significant ascites(56.0%vs 25.5%,P=0.011),hepatic encephalopathy(40.0%vs 10.6%,P=0.003),and critical infections(52.0%vs 14.9%,P<0.001)in patients administered pentoxifylline were significantly higher than those in patients treated with FMT.At 3 months,biomarker analysis revealed a significant abundance of Bifidobacterium and Eggerthella in the FMT group and the pentoxifylline group,respectively.At 6 months,Bifidobacterium in the FMT group and pathogenic Aerococcaceae in the pentoxifylline group were notable.Network analysis showed beneficial taxa(Bifidobacterium)as a central influencer in those undergoing FMT at 6 months.Conclusions Healthy donor FMT improved survival rate and reduced liver-related complications compared with pentoxifylline.These clinical benefits were associated with favorable modulation of intestinal bacterial communities.Difficult-totreat SAH patients may be safely bridged to transplantation using FMT.Controlled trials evaluating long-term outcomes are an unmet need.