Thread by @theliverdr

1/ 'There's a self referred patient for you', ER doc tells me

'Self referred?'

'Yes, husband getting her discharged from multiple hospitals looking for a diagnosis'

Self referrals are nerve-racking, I thought, as I walked in, looking at the deeply jaundiced, disoriented woman

2/ The husband, Raj is by side of her bed

He is worried sick

Elsewhere, they were advised liver transplant

Docs weren't sure what was causing liver failure,
killing his wife, Meera

All he knew was that it was acute liver failure(ALF)

ALF is a terrifying, flummoxing disease

3/ It strikes without warning

A healthy person with healthy liver can be suddenly fighting for life on the ventilator in ALF

It is diagnosed when acute liver insult results in jaundice, followed by blood thinning (coagulation failure, represented by INR test >1.5) along with

4/ brain failure, also known as hepatic encephalopathy (HE) within weeks

HE is mandatory & liver MUST be normal prior to liver injury in ALF

In already diseased liver (chronic liver disease or cirrhosis) acute liver injury leads to acute-on-chronic liver failure(ACLF) not ALF

5/ The causes for ALF varies between countries

In India, it is acute hepatitis E
In UK, paracetamol poisoning (suicidal attempts)

Identifying and treating ALF requires that a specific set of questions be asked,

to look for reversible causes or plan life saving transplantation

6/ In ALF, the liver failure results in rapid shut down of other organs

The brain is affected first

Whole brain swells up

Pressure inside skull goes high

Leading to prolapse (herniation) of brain matte
Squeezing of brain structures across skull

This leads to irreversible..

7/ brain death.

Along with it, other organs also rapidly shut down - leading to multiple organ failure

With multiple organ failure, death is certain

Meera developed jaundice, brain failure and blood thinning within 4 weeks

This was preceded by loss of appetite and fatigue

8/ At multiple hospitals she was taken,

all causes of ALF were looked into

But none turned out positive

So she was diagnosed as ALF of indeterminate origin and advised a life saving liver transplant

But this wasn't an easy task

The family of 4, including two little children

9/ ..could not afford a transplant

Raj was just just making ends meet as a lab tech

The two kids were in lower grade school

They did not have a clue that their mother was fighting for her life

Adding to their woes,

A donor was not available and Raj was of another blood group

10/ I looked at the young mother - 32 y and tells Raj,

'My friend, she is slipping into a liver failure coma

& there is very little we can do if we cant protect her lungs

She needs to be on a ventilator.'

He asks, 'Will she come off the ventilator?'

& I say, 'I don't know'

11/ ALF requires quick management

A set of clinical and lab criteria decides who survives ONLY with an emergency transplant

- called King's College

- or Clichy criteria

- or ALFED Model Criteria (followed in India), developed by AIIMS docs at Delhi

12/ 'But it will buy us sometime, to find what is killing her liver'

Raj's mother is with him and he talks to her, briefly

He comes back to me and says, 'I agree'.

And I say, 'Please send mother and the kids home
We have a long drawn battle ahead of us.'

And he complies..

13/ ..goes to the kids and tells them,

'I'll come home with mother within a few days. You have to go to school. Go with grandmother. Don't worry, Papa is here'.

I hear that

And it feels like a ton of responsibility

As I look at the ER docs readying to put Meera on the machine

14/ Meera is now sedated & on ventilator,

Sleeping, without pain, suffering

The machines getting her organs the oxygen it requires

While she sleeps,

we sacrifice ours, to find the acute insult

that hides in plain sight

Was it something we could reverse?

Could we save..

15/ ..this young mother, for her kids to hug her once again?

A thorough review of records,

We find that the previous docs have left no stone unturned

Except one

A liver biopsy

Since Meera was in ALF, her blood was extremely thin

Which meant, a traditional biopsy would..

16/ ..cause intense bleeding into her liver

and she would not survive it

But we had another option - a transvenous biopsy

Where the liver is accessed through a vein in neck

And small liver tissue pulled out through vein

We could do this even in patients on the ventilator

17/ Raj gives us the green signal and we do it with ease

The small 1cm liver tissue is now rushed to the pathologist

It held all answers to what was killing the young mother of 2 kids

Tissue preparation and staining goes on at break neck speed

The pathologist knows..

18/ that we were running out of time

Meanwhile, Meera starts showing clinical signs of increased brain swelling and pressure

There is high chances of her brain squeezing out of the skull, killing her

There is a method of measuring the brain pressure and its called 'Bolting'

19/ ..where in a pressure transducer probe is placed into the fluid filled cavity of the brain (called ventricles)

through a hole burrowed in the skull

Critical care docs contemplate bolting to see for pressures

But, we decide against it as clinical signs were suggestive of...

20/ raised pressure in the skull

High ammonia is what makes the brain cells swell up

& cause HE in ALF

So we decide to tackle the ammonia aggressively

Through a procedure called plasma exchange therapy

Meera goes on a high volume plasma exchange session

To remove the bad..

21/ ammonia-rich plasma.

Plasma therapy high or standard volume removal

Buys time for dying patients, for the liver to regenerate

And this was the only way we could keep Meera alive, for now

She stabilized after two sessions

Meaning, no further clinical deterioration

22/ While we struggled to keep Meera alive on the ventilator

The pathologist calls me in 48 hours, to come down to the lab

I rush there, hoping for an answer

A final diagnosis for which we could do something

The kids were waiting back home

She says, 'Look at it yourself'..

23/ And I peep into the microscope & see things bizarre

Was it viral hepatitis?
Was it autoimmune hepatitis?
Some areas looked like severe fatty liver!
Others areas had severe bile duct damage!

And I turn to the pathologist and ask her,

'What am I looking at?'

24/ & she says - 'Its everything you can think of

There is damage due to viruses, autoimmune disease, toxins, drugs, bacterial infections, you name it.'

'Only 1 thing can mimic everything

& thats drug induced liver injury (DILI)

Time for you to find out which'

I'm exhausted.

25/ Bcoz we have been asking for every drug under the sun to Raj so many times

Common liver toxic prescription drugs, OTC meds, herbal drugs, Homeopathic tinctures

Raj denied everything

& I ask him about diet changes

Any changes to food, fad diets, mushroom use and then..

26/ Raj sits up and asks,

'Does food cause liver damage?'

To which I say, 'Yes, certain foods can - like mushrooms', aloe vera, green tea extracts.

webmd.com/hepatitis/toxi…

'What about protein supplements?', Raj asks me.

And I turn around and ask him, 'What do you mean?'

27/ Herbal and dietary supplements also called HDS

Are now an upcoming cause of liver injury and liver failure

In the United States alone,

More patients underwent transplantation for HDS liver injury, last decade

Herbalife products containing various potentially toxic herbs

28/ ..have been described to cause severe liver injury and liver failure

The National Institute of Diabetes & Digestive and Kidney Diseases, USA, calls Herbalife

"A well established cause of clinically apparent liver injury"

ncbi.nlm.nih.gov/books/NBK54844…

They also list various..

29/ ..other HDS that has caused liver failure,

Some requiring transplant or leading to death

Such as Hydroxycut, Move Free, Oxylite Pro and SlimQuick

ncbi.nlm.nih.gov/books/NBK54844…

Meera was overweight & hypothyroid

One day, the couple came across a nutritional club that advertised

30/ ..healthy weight loss through meal replacements

Raj bought Meera 2 months (INR 10,000 or $130) worth protein supplements as meal replacement for weight loss

2 months into using these products,

some containing green tea extracts,

a common cause for liver failure, Meera..

31/ ..started to develop severe fatigue and loss of appetite

In a few weeks time, she was jaundice and a month later,

on the ventilator, fighting for her life

The biggest issue with HDS liver failure is that they are irreversible

Almost 100% patients die without a transplant

32/ And I knew this

Because published literature on HDS liver failure is depressing

The culprits are multiple since HDS has complex ingredients & there is no antidote

[Like we have for paracetamol poisoning, N acetyl cysteine is the antidote]

This meant, plasma exchange wont

33/ ..work for long in keeping Meera alive

So I call Raj and tell him, that he had to beg, borrow or steal

For Meera to get better and take her back home, to the kids

Since we did not have a transplant unit functioning at the time,

I referred her to the best center nearby..

34/ We shifted Meera quickly, onto an ambulance,

as Raj sat nearby with docs present to assure her safe passage to transplant center

Raj held my hand, but did not say anything

His eyes thanked me for the diagnosis

But his mind morose, heart exhausted

And I said,

35/ 'You will take her home to the kids soon. All will be well'

He faked a smile as we closed the ambulance doors

A few days later, Raj messages me,

tells me that a nephew was ready for donation,

work up was ongoing and funds slowly came in.

Plasma therapy was continued..

36/ and I was glad, the fire still burned

8 days after I said goodbye to Raj,

I received a message late evening, from him

Just 3 words & he went offline

'She is gone'

It was late Feb-March 2018

Meera's brain herniated, leading to brain death, killing her on the ventilator..

37/ Donor was not fit, couldn't find others

Meera's heart beat as long as it could,

for the love of her kids,

but had became weary,

as she battled a persistent enemy.

'Every good thing must come to an end'

& Raj brought Meera's body back home to their children

As promised.

38/ We published Meera's report in August 2018 titled:

Slimming to the Death: Herbalife-Associated Fatal Acute Liver Failure—Heavy Metals, Toxic Compounds, Bacterial Contaminants and Psychotropic Agents in Products Sold in India

Not just Meera's report, we assessed similar..

39/ ..products & found contamination within products sold online

And from then on, our lives changed.

Late Oct & Nov 2019,

Herbalife send legal letters threatening to sue us for defamation

and asked us to prove our credibility, and convince THEM that we were real doctors.

40/ They made 'Scientists' on their payroll write

'critical letters' to the journal, trying to discredit our report

But the journal gave us a chance to refute their allegations

& both their letter and our responses were published

Evidence trumped fear mongering

41/ But it didn't end there

Company sent their trump card, Prof Steven Newmaster to destroy our credibility via a 10-12 page criticism

Which we destroyed with a 24 page response
retractionwatch.com/wp-content/upl…

Newmaster was himself later accused of data fraud..
science.org/content/articl…

42/ ..but then cleared of 'misconduct',

while the investigation found that he “displayed a pattern of poor judgement and failed to apply the standards reasonably expected in research activity in his discipline,” (Oh well)

And we thought that was it...

science.org/content/articl…

43/ But the company had more surprises for us

They sent threatening legal letters to the Journal, The Editorial Board, The Publisher Elsevier,

flexing more muscle in the process

And even after a second investigational peer review which concluded our report was credible,

44/ Through more legal pressure, Herbalife succeeded in removing our report from all web sources and the Journal

Elisabeth Bik wrote about how science lost and money won in her blog scienceintegritydigest.com/2020/12/20/pap…

Retraction Watch featured our battle for science and Meera on theirs..

45/ retractionwatch.com/2020/12/22/aft…

So we published it on Zenodo a free to upload data repository which Herbalife again removed after threatening Zenodo



So we uploaded it on ResearchGate for posterity..

46/
And Herbalife threatened ResearchGate
and removed it from there too


After our report came out, multiple other large reports on HDS causing liver injury was reported from world over, many featuring Herbalife products

47/ Our report was the first from Asia

I tweeted about new cases recently,

& Herbalife again threatened me with a 'Cease and Desist' notice



Tussle over HDS industry, public health & science will continue
until the day, science will win

I may not..

48/ witness this during my lifetime,

but I hope, future scientists/clinicians

watch over their patients & family and protect them

from this avoidable public health risk.

I spoke to Raj 2y after that last message

He found a new job, moved to a new place

49/ I called him because a New York Times reporter wanted to run this story and she wanted Raj's interview

This is a great chance, I had a selfish thought

My work would get highlighted

But at the expense of digging up the dark past of another man

The reporter was sweet, she..

50/ ..travelled all the way from Mumbai to speak to me,

took my pics & spoke to Raj via a translator

I called Raj thereafter

And asked him how it went

He said he had to relive that gloom, but he did it only for me, because I was family

I ask him about his kids
He says they..

51/ ..were busy with studies

& they miss their mother
Everyday

He says he thinks of Meera
only when he thinks about hospitals & ME

Over phone, his voice breaks

And I feel miserable

So I talk to the reporter & call it off

Because NYT has a three tier fact checking and Raj..

52/ ..will have to relive his tragedy again & again

& it wasn't worth it.

I didn't want to burden him with the past.

During our last conversation, I thanked Raj,

But tell him the NYT story is off

& that he could call me anytime for any help

But I dont call him

Not anymore