Autoimmune hepatitis:Towards a personalized treatment

Autoimmune hepatitis is an uncommon condition that affects both adults and children and is characterized by chronic and recurrent inflammatory activity in the liver.This inflammation is accompanied by elevated IgG and autoantibody levels.Historically,treatment consists of steroids with the addition of azathioprine,which results in remission in approximately 80%of patients.Despite significant advancements in our understanding of the immune system over the past two decades,few modifications have been made to treatment algorithms,which have remained largely unchanged since they were first proposed more than 40 years ago.This review summarized the various treatment options currently available as well as our experiences using them.Although steroids are the standard treatment for induction therapy,other medications may be considered.Cyclosporin A,a calcineurin inhibitor that decreases T cell activation,has proven effective for induction of remission,but its long-term side effects limit its appeal for maintenance.Tacrolimus,a drug belonging to the same family,has been used in patients with refractory diseases with fewer side effects.Sirolimus and everolimus have interesting effects on regulatory T cell populations and may become viable options in the future.Mycophenolate mofetil is not effective for induction but is a valid alternative for patients who are intolerant to azathioprine.B celldepleting drugs,such as rituximab and belimumab,have been successfully used in refractory cases and are useful in both the short and long term.Other promising treatments include anti-tumor necrosis factors,Janus kinases inhibitors,and chimeric antigen receptor T cell therapy.This growing armamentarium allows us to imagine a more tailored approach to the treatment of autoimmune hepatitis in the near future.

COVID-19 associated liver injury:A general review with special consideration of pregnancy and obstetric outcomes

Liver injury is an increasingly recognized extra-pulmonary manifestation of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Coronavirus disease 2019(COVID-19)associated liver injury(COVALI)is a clinical syndrome encompassing all patients with biochemical liver injury identified in the setting of SARS-CoV-2 infection.Despite profound clinical implications,its pathophysiology is poorly understood.Unfortunately,most information on COVALI is derived from the general population and may not be applicable to individuals under-represented in research,including pregnant individuals.This manuscript reviews:Clinical features of COVALI,leading theories of COVALI,and existing literature on COVALI during pregnancy,a topic not widely explored in the literature.Ultimately,we synthesized data from the general and perinatal populations that demonstrates COVALI to be a hepatocellular transaminitis that is likely induced by systemic inflammation and that is strongly associated with disease severity and poorer clinical outcome,and offered perspective on approaching transaminitis in the potentially COVID-19 positive patient in the obstetric setting.

Sex ratio of mirid populations shifts in response to hostplant co-infestation or altered cytokinin signaling

Herbivore species sharing a host plant often compete. In this study, we show that host plant-mediated interaction between two insect herbivores-a generalist and a specialist-results in a sex ratio shift of the specialist＇s offspring. We studied demographic parameters of the specialist Tupiocoris notatus（Hemiptera： Miridae）when co-infesting the host plant Nicotiana attenuata（Solanaceae） with the generalist leafhopper Empoasca sp.（Hemiptera： Cicadellidae）. We show that the usually female-biased sex ratio of T. notatus shifts toward a higher male proportion in the offspring on plants coinfested by Empoasca sp. This sex ratio change did not occur after oviposition, nor is it due differential mortality of female and male nymphs. Based on pyrosequencing and PCR of bacterial 16 S rRNA amplicons, we concluded that sex ratio shifts were unlikely to be due to infection with Wolbachia or other known sex ratio-distorting endosymbionts. Finally, we used transgenic lines of N.attenuata to evaluate if the sex ratio shift could be mediated by changes in general or specialized host plant metabolites. We found that the sex ratio shift occurred on plants deficient in two cytokinin receptors（irCHK2/3）.Thus, cytokinin-regulated traits can alter the offspring sex ratio of the specialist T.notatus.