Therapeutic interventions of acute and chronic liver disorders:A comprehensive review

Liver disorders are one of the most common pathological problems worldwide.It affects more than 1.5 billion worldwide.Many types of hepatic cells have been reported to be involved in the initiation and propagation of both acute and chronic liver diseases,including hepatocytes,Kupffer cells,sinusoidal endothelial cells,and hepatic stellate cells(HSCs).In addition,oxidative stress,cytokines,fibrogenic factors,microRNAs,and autophagy are also involved.Understanding the molecular mechanisms of liver diseases leads to discovering new therapeutic interventions that can be used in clinics.Recently,antioxidant,anti-inflammatory,anti-HSCs therapy,gene therapy,cell therapy,gut microbiota,and nanoparticles have great potential for preventing and treating liver diseases.Here,we explored the recent possible molecular mechanisms involved in the pathogenesis of acute and chronic liver diseases.Besides,we overviewed the recent therapeutic interventions that targeted liver diseases and summarized the recent studies concerning liver disorders therapy.

Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders

Inherited genetic disorders of the liver pose a significant public health burden.Liver transplantation is often limited by the availability of donor livers and the exorbitant costs of immunosuppressive therapy.To overcome these limitations,nucleic acid therapy provides a hopeful alternative that enables gene repair,gene supplementation,and gene silencing with suitable vectors.Though viral vectors are the most efficient and preferred for gene therapy,pre-existing immunity debilitating immune responses limit their use.As a potential alternative,lipid nanoparticle-mediated vectors are being explored to deliver multiple nucleic acid forms,including pDNA,mRNA,siRNA,and proteins.Herein,we discuss the broader applications of lipid nanoparticles,from protein replacement therapy to restoring the disease mechanism through nucleic acid delivery and gene editing,as well as multiple preclinical and clinical studies as a potential alternative to liver transplantation.

Periprocedural management of hemostatic alterations in patients with cirrhosis and vascular liver disorders: a step forward of the American Association for the Study of Liver Diseases

“Time flies over us,but leaves its shadow behind”(Nathaniel Hawthorne,1860,The Marble Faun).The shadow that separates the latest guidance on vascular liver disorders of the American Association for the Study of Liver Diseases(AASLD)from its former counterpart is 12 years long(1,2).Along the course,several guidelines from different societies have been published on this topic(3-7).As acknowledged in the preamble,the lack of high-quality evidence in the field led the AASLD to commission a guidance from an expert panel based on formal review and analysis of the literature.It thus differs from other guidelines that perform systematic reviews with explicit methods of searching,selection,and rating the quality of evidence and,if appropriate,meta-analysis on certain clinical questions(2).

Implications of metabolic dysfunction associated fatty liver disease in COVID-19

Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the world population.In 2020,the coronavirus disease 2019(COVID-19)crisis was unprecedented,and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2.MAFLD patients are frequently obese with added metabolic menace like diabetes,hypertension,and dyslipidemia leading to greater jeopardy of COVID-19.MAFLD patients are 4 to 6-fold more prone towards infections.COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin.Hence,MAFLD in COVID-19 patients worsens the condition significantly.The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission.Direct hepatic injury,enhanced levels of inflammatory cytokines,declined hepatic mitochondrial activity,and compromised immunity are considered as some underlying mechanisms.The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients.The review systematically analyzes the effect of striking two worldwide pandemics(MAFLD and COVID-19)together in the present era.

Liver transplantation for pediatric inherited metabolic liver diseases

Liver transplantation(LT)remains the gold standard treatment for end stage liver disease in the pediatric population.For liver based metabolic disorders(LBMDs),the decision for LT is predicated on a different set of paradigms.With improved outcomes post-transplantation,LT is no longer merely life saving,but has the potential to also significantly improve quality of life.This review summarizes the clinical presentation,medical treatment and indications for LT for some of the common LBMDs.We also provide a practical update on the dilemmas and controversies surrounding the indications for transplantation,surgical considerations and prognosis and long terms outcomes for pediatric LT in LBMDs.Important progress has been made in understanding these diseases in recent years and with that we outline some of the new therapies that have emerged.

Gastrointestinal tract post-transplant lymphoproliferative disorder after liver transplantation

To the Editor:Post-transplant lymphoproliferative disorder（PTLD）is a rare and potentially fatal complication occurring after all types of solid organ transplantation.;PTLD accounts for 20%of all de novo post-transplant tumors.;The most important risk factors for PTLD are prolonged intense immunosuppression and Epstein-Barr virus（EBV）

Case Report-Early Detection of Acute Fatty Liver of Pregnancy in Urgent Care Department with Nonspecific Symptoms

Acute fatty liver of pregnancy is a rare but serious disorder affecting pregnancy. The rarity of this situation along with nonspecific symptoms makes it difficult to diagnose and thus causes catastrophic events. Biochemical parameters are required to diagnose this condition and differentiate it from other life threatening causes of pregnancy like HELLP syndrome and Preeclampsia. To avoid complications it is imperative to diagnose this condition at the earliest by doing blood test investigation and symptomatic management and delivery. We present a case in our hospital which came to urgent care with nonspecific symptoms and was diagnosed on blood tests and managed promptly and thus averted a catastrophic event.

The Human Microbiota in Health and Disease

Trillions of microbes have evolved with and continue to live on and within human beings. A variety of environmental factors can affect intestinal microbial imbalance, which has a close relationship with human health and disease. Here, we focus on the interactions between the human microbiota and the host in order to provide an overview of the microbial role in basic biological processes and in the development and progression of major human diseases such as infectious diseases, liver diseases, gastrointestinal cancers, metabolic diseases, respiratory diseases, mental or psychological diseases, and autoimmune diseases. We also review important advances in techniques associated with microbial research, such as DNA sequencing, metabonomics, and proteomics combined with computation-based bioinformatics.Current research on the human microbiota has become much more sophisticated and more comprehensive.Therefore, we propose that research should focus on the host-microbe interaction and on causeeffect mechanisms, which could pave the way to an understanding of the role of gut microbiota in health and disease, and provide new therapeutic targets and treatment approaches in clinical practice.

Flexible Factor Model for Handling Missing Data in Supervised Learning

This paper presents an extension of the factor analysis model based on the normal mean-variance mixture of the Birnbaum-Saunders in the presence of nonresponses and missing data.This model can be used as a powerful tool to model non-normal features observed from data such as strongly skewed and heavy-tailed noises.Missing data may occur due to operator error or incomplete data capturing therefore cannot be ignored in factor analysis modeling.We implement an EM-type algorithm for maximum likelihood estimation and propose single imputation of possible missing values under a missing at random mechanism.The potential and applicability of our proposed method are illustrated through analyzing both simulated and real datasets.

Hepatoprotective and antioxidant activity of Bombax ceiba flowers against carbon tetrachloride-induced hepatotoxicity in rats

Aim:The flowers of Bombax ceiba are traditionally used as home remedy in the treatment of jaundice and spleen enlargement.The present work investigated the effect of aqueous extract of flowers of Bombax ceiba(BCAE)on experimentally induced hepatotoxicity in rats to substantiate its traditional use as hepatoprotective agent.Methods:Hepatotoxicity was induced in rats by carbon tetrachloride(CCl_(4))treatment;at the same time vehicle or BCAE(250 or 500 mg/kg)or silymarin(25 mg/kg)were administered daily orally for seven days.Hepatotoxicity was assessed by estimating the activities of marker enzymes and by histological studies.The antioxidant effect of BCAE was assessed by measuring amount of antioxidant phytochemicals(total phenolics and flavonoids),and DPPH free radical scavenging assay of the extract.Results:BCAE treatment significantly prevented the CCl_(4)-induced elevations in levels of glutamate oxaloacatate transaminase,glutamic pyruvic transaminase,alkaline phosphatase,bilirubin,and triglycerides,and decreased the total protein levels.Treatment with BCAE attenuated the CCl_(4)-induced cytotoxic damage to liver.BCAE exhibited presence of antioxidant phytochemicals and showed scavanging action on DPPH radicals.The hepatoprotective effect of BCAE was comparable to that of the standard antioxidant hepatoprotective agent,silymarin.These findings indicated that BCAE showed hepatoprotective effect against CCl_(4)-induced hepatotoxicity and exhibited in vitro antioxidant effects.Conclusion:Bombax ceiba flowers exhibited hepatoprotective effect which may be attributed to antioxidant potential.This study also validated their traditional medicinal use in liver disorders.

Hepatic disorder in Zika virus infection

Zika virus infection is the present global problem.This arbovirus infection can cause acute illness and affect fetus in utero.However,there can be other additional clinical manifestation including to the hepatic disorder.In this short commentary article,the author briefly discusses on the liver problem due to Zika virus infection.