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COVID Drugs and Liver Injuries

Feb 10 | 2:00 PM

Since December 2019, COVID-19 has been a severe global health concern worldwide. Healthcare professionals have been using antivirals, antibiotics, and steroids to treat infected patients. Although the medications' adverse effects are unknown, data from randomized control trials show detrimental effects on the liver. In this Medflix talk, Dr. Bipin Vibhute examines the hepatic manifestations of COVID-19 drugs, including their efficacy and adverse effects on liver function!

[Music] good evening everyone and welcome to netflix i'm dr naveeda and it's a pleasure uh to uh welcome uh dr bittenberg for this session that's on covert drugs and live injuries which is long overdue uh having said that because of kovat having been here for so many years uh need to understand the effects of the over drugs on liver uh so uh the guest for tonight is dr bipin who is the program director and head of the center for organ transplant at sayadri hospitals and sir was also the first one of the first people a person to start free um liver transplants for children uh up the age of 12. so basically uh everybody knows about kobe everybody knows about the drugs in first place second wave i third most of us are home current time home isolation and use the a lot of medicines a lot of ayurvedic so today i thought it's and its effect on the liver uh before i start my presentation i will just give us whatever medicines you take uh whatever infection you have to come out of it the liver has to work properly without leaving you it's very difficult it's very hard for from any disease to come out any drugs to metabolize to process so liver is an extremely important organ in this uh situation and um it is a regenerative organ so even if you cut half of the liver it grows back again so uh that's what god has gifted to us and probably that's why we don't care about it so and we should we should we should care about liver injuries liver disease because sometimes it will be very fatal so in the coming slides i will just try to explain what all drugs so uh this foreign cause drug induced liver injuries that is called as billy uh 19 what are the risk factor pathophysiology uh i'm not going into the details of pathophysiology but obviously i will uh talk about the management and its prevention of liver injuries and what if the take home message at the end so everybody knows about the liver disease how it started um i'm not going into detail and how and how we are facing uh this kovid 19 uh infection uh in third wave as well so uh uh i think i will i mean i will restrict myself to the liver instead of going into details of the overview but definitely there are some stages i want to highlight here because my discussion is based on the stages of this kuvi 19 infection stage 1 is the early infection very mild symptoms stage two is the lung phage or phase or you can say pulmonary phase stage three is the hyperinflammation phase and the most common and important clinical presentation is secondary to lung involvement like fever anchor but is the second most organ involved so why we call uh liver is involved second uh organ which is involved in the weight 19 is because uh there is a pre balance of 14 to 76 percent of patients with uh they will have a elevated liver enzymes i'll come back to it and there are meta-analysis also in the uh it is close to about it is a large study obviously it was more than 20 000 patients so there are again uh uh we need to know what is the mild liver injury moderate liver injury and severe injury severe liver injury so if there is a two times of upper limit of normal if alt and asd is increase then we call is a mild liver injury if it is a between two to five we call moderate and more than five we called as severe liver disease and that is what we are interested here so if you look at the demography of kovid 19 patient with abnormal liver enzymes so males are more affected severe uh kovet infections are definitely more affected but city score is an independent predictor of liver injury which is suggested by the city score if it is a more than of 44 or 32 definitely uh your liver is going to get involved and how i am going to uh discuss in the further slides so what is the spectrum of liver disease involved is the uh some patient will have an abnormal liver liver test like al increased alt or ast then uh coagulation abnormalities like increased prothrombin time or inr acute liver failure if somebody has existing hepatitis b infection or a pdc infection that can uh aggravate or reactivation of hepatitis b and bnc can happen alcoholic liver disease they also do bad uh in the kovid 19 ah similarly autoimmune disease non-alcoholic fatty liver and drug induced if there is a history of drug induced liver injury so which population is more prone to liver injury is the severe kovid 19 male elderly those initial symptoms are curved high bmi a patient with underlying liver diseases like fatty liver disease alcoholic liver disease and especially chronic liver disease like liver cirrhosis and patients with severe lung disease as well so lung injury as a liver injury is multifactorial so it could be a direct injury to the liver it could be ischemic hypo hypoxic re-perfusion injury sometimes there will be the bad hypotension uh hypoxia as well and that could also lead to a liver injury drugs which we use that is what we are going to discuss and uh there is a cytokine storm release as well so what what is actually a drug induced liver injury is increase in liver enzymes so there will be no hepatocellular necrosis cholestasis means increased bilirubin or it is associated with bode so there are drugs which directly affects the liver drugs which just elevate the liver enzymes but patient is completely asymptomatic drugs cause acute hepatitis like what what i told uh already about it and sometimes it is a dose dependent uh drug induced like a paracetamol if paracetamol is uh above a certain limit then definitely there will be then liver damage and drugs causing liver damage which has an independent uh dose so what is the pattern of uh liver injury is there are three patterns one is the hepatocellular pattern second is polystatic and uh third one is a mixed so there is a r ratio i i hope it is visible uh it is a little light in color because i i did it in a laptop but mobile it is coming as a little lighter in color but our ratio is the risk risk ratio so it is calculated by formula and depends on that uh score we decide whether it is a hepatocellular polystatic or mixed so that is this is uh important when we treat uh the drug induced liver injury because treatment is pertaining to uh especially hepatocellular and cholesterol is completely different so there will be the intrinsic liver uh liver injury or idiosyncratic liver injury intrinsic liver injury is an um is generally a uh is a typical drugs which we call as a paracetamol or acetaminophen and paracetamol produce massive hepatic necrosis when consuming in the large doses so the ideal dose of paracetamol if it is exceeds more than four grams per day it cause the uh liver injury and that depends on the uh how much of a dose of the paracetamol patient take that that lead to the hepatic necrosis idiosyncratic there is no dose dependent uh it takes from the few months few days to the several months as well and it is uh as i said it is not drug dependent so pathophysiology i am not going into detail as i said but uh just to touch a mitochondrial type there is a type of liver disturbance hypoxic liver disturbance holistic or hepatotoxic injury so why we need to know about the uh pathophysiology because treatment is completely depends uh how liver is uh getting injured by the drug but um for i think for this presentation i'm not going into detail how uh how actually a drug uh caused the liver injury so commonly used drugs in code 19 leads to hepatotoxic is uh especially corticosteroids like a methyl plateness salon or hydrocortisone is a very commonly uh use of dexamethasone for example so these steroids can cause or lead to a liver injury but our risk is low and it is a hepatocellular type of drug induced liver injury second commonly used a drug is the nac ideas like ibuprofen paracetamol iran like any naciods most of us we use the antibiotics like amoxilic clevelandic augmentin is very commonly used drugs uh uh and similarly uh azethromycin as well so these all these drugs can lead to a liver injury if you fall into the uh a risk category but if uh your a alt is already more than five times of upper limit then remedy severe is a contraindication or if you are existing uh chronic liver disease or severe liver injury then uh definitely these drugs you should avoid especially remedy severe is very commonly used drugs it is an hepatotoxic i will come back to it because i have a separate slide on it but azithromycin cause a cholestatic hepatitis corticosteroids i said if it is overused uh and uh it is a for long term then it cause the uh hepatotoxicity as well as exacerbation of the existing infections like hepatitis b c or cytomegalovirus paracetamol as i said uh is a intrinsic liver injury if you exceed the dose and similarly other biological agents as well so especially two drugs i want to discuss here is the glucocorticoid that is the steroid and second is the remedy severe so alt level in uv 19 treated patients with corticosteroids were significantly higher than uh they were without a glucocorticoid treatment similarly ast levels were also high so if you use glucocorticoids in the higher doses and for long term definitely there will be the liver injury so pattern of uh uh this is just an one case report uh remedies related uh liver injury so once we started uh it goes up liver enzymes slowly up to the fifth day onward and if you stop then it comes down so it depends on the severity of the liver disease so this is how remedy severe caused the liver injury that is the uh p glycoside a glycoprotein which uh all these active metabolites should go uh come out and go to the buy or excrete to the buy and through the bile it should excrete out of the body so remedy severe uh there is a if there is a deficiency in the transporter protein like a peak glycoprotein then uh there is a possibility that ram received might cause a liver injury so these are the published data about the toxicity and the case reports about the remedicity uh so i'm not going into the details of the all the uh case studies but certainly uh if your patient is a febrile respiratory symptom sore throat nasal sneezing breathlessness should undoubtedly be evaluated for covert 19 and coed 19 patients with trans aminities like increased hiv sgpt or alt or asd either they are symptomatic or asymptomatic should uh offer a code 19 standard test like viral hepatitis autoimmune markers copper studies and all because we need to know whether there is a pre-existing uh liver disease or uh there or not because if there is a pre-existing disease then we have to be little careful while using the drug and treating these patients uh symptomatically similarly patient with underlying liver disease as i already told academic liver disease should be uh tested for over 19 despite ongoing pandemic uh tropical diseases like dengue malaria also uh we should not uh forget to test if there is a kovid 19 negative so overall uh whenever there is a involvement of the liver with certain symptoms like kovi apart from the kovid you should get tested for the other things as well so what is the approach how we should approach to the elevated liver enzymes if you find uh uh kuvid 19 positive so we should consider as i said whether it is a mild moderate or severe second thing we should consider whether it is a hepatocellular or polystatic or mix depends on that you should have your approach your approach must be targeted you cannot do n number of uh tests uh to rule out uh why are lt or asd or regulativity is elevated so you do the investigations which is uh which will change your management or change your treatment plan then only you do otherwise don't do it so uh most of the time we as i we try to uh stop the if it is expected if that stopping drugs which probably cause the liver injury if it is not enzymes are not coming then uh we need to rule out infections like hepatitis b c as i said copper uh pre-existing alcoholic liver disease fatty liver disease uh wilson's disease and uh and all so general algorithm for suspected drug induced liver injuries if you find uh abnormal liver enzymes then there is a you take a thorough history now there is no alternative to it then you calculate the risk value if it is a risk or r ratio if uh our r value if it is a more than five it is a hepatocellular then you need to find out whether it is a acute viral hepatitis associated with kovid or not and second line test is based on uh if you don't find any virus positive then we need to know whether if it is a cme ebv celluloplasmin autoimmune markers and all so if it is a mixed lab r value is less than five more than two then first line again is the hepatitis acute viral hepatitis if hcv rna autoimmune so all these things we need to rule out and if it is less than two then uh just get an uh ultrasound to find out whether your liver is normal or not and just wait and watch sorry so what is the flow chart uh when whenever you suspect a drug induced liver injury is on admission uh if there is a liver injury then take a proper history do a differential diagnosis if your first diagnosis if it is uv 90 or stars p2 infection then you carry out the rtpcr or whatever taste you do at your center if not then you need to know whether it is a alcohol any medicines causing the liver injury viral or autoimmune hepatitis any uh structural abnormalities i mean liver is getting secondary involved because of the cardiac issues kidney issues and all then hemodynamic disorders and hereditary metabolic diseases i'm not going into detail so uh when patient is in the hospital already this what i told flowchart is on admission you can follow this is once patient get hospitalized then there are two scenarios one there is a clinical improvement and decrease the implementary parameters then first think of drug induced liver injury second scenario in a severe or critical coed 19 patients uh admitted at um on admission or deteriorated during the hospitalization then think of fluid infection severe covet infection i mean so liver biopsy there are very few indications of liver biopsy if there is a strong suspicion of drug induced liver injury but whatever measures you supposed to do it you're already done it but still your alt and asd levels are not decreasing by more than 50 percent in 30 to 60 days uh or your alp is not fallen by more than 50 at uh 180 days then you need to suspect uh something else and the in that case liver biopsy might help you casualty assessment method i'm i'm not going to uh discuss here but what i would like to uh discuss is the management of the liver injury in kovid 19 uh patient so uh correction of hypoxia uh i i i don't have to go into the detail uh oxygen supplement and ventilations and all this but avoid hypoxia and hypoxia and hypotension will avoid the hypoxia and hypotension related hepatocellular injury if there is a severe cytokine strong with liver injury then crrt or continuous renal replacement therapy is recommended then as i said if there is a intravascular volume is low in that case uh you need to manage the hypotension then prompt identification and discont continuation or those reduction of the drugs responsible for the drug induced liver injury so an adjuvant therapy whatever you have to protect your anti-liberty drugs we give that uh supportive medicines we have to uh continue but for drug induced liver injury you need to be very highly highly suspicious because it needs little bit of clinical experience and because um every time you cannot do all these types of investigations as well as you uh uh like you you if there is a severe pov patient is deteriorating your liver function is deteriorating the patient is deteriorating um liver parameter wise then you cannot wait for the further reports to come to act out so yeah with the high suspicious you have to uh do all these majors so there are some special consideration since kobe 19 patients especially those hospitalized are particularly prone for liver injury up to the 44 percent patients from the mild to severe infection so symptomatic treatment with nacids or paracetamol should be administered with caution with proper history whether he has a proper uh prior liver disease prior liver injury prior history of drug induced liver injury so we have to be very cautious in these patients in addition there is a widespread administration of antibiotic coverage so now i have seen many patients uh in fact we have operated three of them transplanted free of three patients with drug induced liver injuries so invariably all the patients i must have been seen around 40 odd patients in last couple of years so uh they were they were on antibiotics they were on steroids with asymptomatic very mild uh symptoms so we have to avoid the you know over judicious uh uh use of uh medicines uh like antibiotics nsads and all given importance to therapy with systemic steroids and other immunomodulators heparin remdi severe nib when indicated for a rds complications decision to discontinue one or more of them should be thoroughly examined because both are important liver injury is important and covid19 infection is important so we have to judge upon the patient's clinical parameters and patients clinical condition which drugs to continue and which treatment we need to give the preference in patient with severe nine severe covet 19 particularly existing liver this is just too many drugs with um delhi potentially uh generally not more than two should be administered so that is the advice from the liver committee so uh and whenever you advise you should not exceed you should not accept again i am mentioning you should not exceed the maximum possible dose if you need to exceed then we have to find out some alternative solution to it or we have to monitor our liver functions liver enzymes very strictly the problem hardly arises in cases with drugs with biological agents like tackling zuma sarlis remedy severe generally five days however when suspicious of uh delhi involves the other treatments that needs prolonged administration and their then their discontinuation is mandatory if there is an acute level failure it should uh it should be elevated if alt level increase more than 10 times of upper limit of normal or there is a lt elevation associated with clinical worsening of the liver inflammation similarly in patient with core 19 being administered antiviral anti-inflammatory drugs the liver parameters should be monitored how frequently it uh completely depends on how what is your initial uh liver functions whether it is a mild moderate or severe how and what are parameters monitor that also you decide on the patient's clinical parameters as well as liver parameters in patients with ongoing uh anti uh hepatitis b apparently c treatment should not be discontinued at all because uh uh it is said that whenever there is a koi 19 infection your liver gets an a very hard time uh hard time during that period because of drugs medicines and infection so these infection tend to recover and add uh add into the additional damage to the liver because i repeated this aparity c so carefully monitoring these patients with therapies and avoid nephrotoxic drugs which use for hepatitis b and c you can change the treatment plan accordingly so in presence of hepatic fibrotic tissue in presence of hepatic fibrotic tissue even in the post kovid 19 period drug therapy should be considered to reduce the fibrotic and implementary state of the liver which i already told you so how to prevention is the rational use of the drugs vigilance of symptoms depends on the symptoms we need to train uh treat and re-exposure to the drugs that is thought to have caused hepatotoxicity is strongly uh discouraged during this uh period and monitoring of the liver enzymes like alt asd or hot hgbt frequently so take home message is liver injury in patient with kv19 infection is higher than what we think liver injury in kovid19 patient may cause a multifactorial it is a direct effect or immune related or drug related drug related hepatotoxins toxicity generally idiosyncratic it is not necessary always it is a overdose or what you call uh it is a pre-existing uh drug injury pathogenesis of uh drug into sliver injury remains an enigmatic area and but involves exposure to the toxic agents mitochondrial injury failure to adaptation innate and adaptive immune responses due to its protein manifestation uh delhi must be included in differential diagnosis of all patients with abnormal liver panel so that's what i told uh before also you need a very high suspicious if you find your alt asd or alp is raised then then you need to uh be on your toes uh to diagnose why liver enzymes and always think why why liver enzymes are increased then probably you might get some answer management of drug induced liver injury is completely symptomatic and if it is getting worse then please refer to liver transplant unit where these patients can be monitored uh better and if required the process of liver transplantation can be expedited little uh fast so uh especially in non-parasitable induced injuries liver injuries so as i always say we are the instruments in the heads of hands of god so always we require uh some blessings whenever we treat other patients and whenever we do the surgery many times life is like this picture you have a lot of resources a lot of things in our hand but we take a very poor decision at the end uh if for example if we patients are asymptomatic mild symptoms still we tend to uh forcefully uh sometimes because for patients he wants some medicines we prescribe this guy for a long time so distance doesn't matter when your roots are connected i'm always there and available or now if you have any questions any queries uh regarding any liver uh related problems or especially these drugs i have a youtube channel around 50 000 odd subscribers this is completely started because people don't know about the liver health how to take care of liver whether there is a need to take care of the liver which foods they should take away so such channel was not available so i started uh one year back and i i will continue to do that please go through if you have any queries and thank you so much for uh listening and me on this platform thank you so much for that wonderful performance [Music] sorry thank you so much for the wonderful session um very informative and really great uh youtube channel like you said uh which is the need of the eye like everybody needs to know about the liver we have a question by dr nirmalan who's asked is there any role for imaging modalities in the diagnosis of drug induced liver industries and its follower yeah which i i already mentioned but you should get an ultrasound done and ultrasound will give you and uh initial assessment of your liver whether somebody has a fatty liver or alcoholic liver disease or chronic liver disease and if not then you can go for the city or mri but i don't think so in drug induced city and mri is going to contribute much then probably i will go for the liver biopsy thank you sir [Music] let's go to the next question we have dr jayavalan who's asked um does over intake of paracetamol and amoxicillin affect the liver and to what extent is the damage [Music] it completely depends on paracetamol i think once in a while everybody use the paracetamol [Music] as i said if it is goes more than four grams per day it is a hepatotoxic or toxic to the liver and it can cause a liver injury so uh it completely depends on the what is the status of your liver how much dose you take if you are already pre-existing liver diseases like chronic liver disease autoimmune alcoholic liver disease or some wilson's then probably you might get an very early symptoms of liver and can get worse or mild to severe even if the small doses of paracetamol as well so it is uh as i said uh intrinsic uh hepatotoxic uh injury and mechanism is the same so it can go to the any extent okay thank you so i hope that answers your question uh we have dr ashok who's asked which uh what are uh which is the safe drugs in sevilla covered 19. all drugs are safe if you don't overuse it actually so that's what i told if you have a patient with mild moderate and severe or covered infection we have to treat it accordingly we should not exceed the drugs what we use if there is a pre-existing liver diseases uh even fatty liver for that matter so uh if and is if there are elevated hot sgpt or alt asd then we have to be very cautious when you use the drugs you can use but monitor the liver enzymes that is the uh advice and golden uh statement of from today's discussion don't just uh use it and forget about the liver so give some importance to liver and your experts also yeah definitely to both the points if the patient is previously diagnosed with the fatty liver disease uh and is under self medication uh like paracetamol uh for fever uh what can we suggest yeah if you are going to take a paracetamol for uh a couple of days or four or five days and if you are completely asymptomatic then i would recommend you to do once a liver function test if you are not done before starting the paracetamol so because we don't know your fatty liver status it is exactly only the fatty liver or it is uh there is a inflammation which we call as a non-alcoholic steroid hepatitis means there is a a raised heel to hgbt uh before kubi19. in that case uh your dose of paracetamol need to be restricted if it is a agility gpt or liver functions are normal and if your fatty liver alone grade one or grade two then you can safely use a paracetamol in a recommended dose of for uh four or five days if you need to take for more than five days or ten days you then then you need to monitor your liver function test okay uh thank you so and in connection with liver function test we have another question by dr spain how frequently the lfd should be done after admission of the patient and before starting drug i'm assuming this is for covert 19 related drug therapy that started yeah so that is what i i showed you the algorithm also and guidelines also so once patient on admission you should do one liver function test if on admission liver function test is normal then probably i would say inpatient is stable then once in a three months three days you should monitor your lft and couple of electricities are normal patient is getting getting better then probably you don't need to but if patient condition is getting worse and it is moderate to severe then probably uh your involvement of liver uh will be more so probably daily uh till you show the downward trends of asian agility sgpt or bilirubin you should monitor your left so to settle the drug induced liver injury takes around six months some patients takes around six months so you need to monitor and once patient is stable left is stable then probably once in a 15 days or once in a month till it becomes normal thank you so much sir i think we've covered mostly all of the questions in case we have uh uh missed any questions we will definitely uh try to get them answered by sir thank you so much sir for coming on to netflix

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dr. Bipin Vibhute

Dr. Bipin Vibhute

Program Director and Head of the Center for Organ Transplants | Sahyadri Hospitals, Pune

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dr. Bipin Vibhute

Dr. Bipin Vibhute

Program Director and Head of the Center for O...

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