Saturday, October 22, 2016


The quintessential question in liver transplant practice is whether a living donor liver is better than a cadaver liver option! Most live donor programs in India are vociferous in their support for living liver donation and claim living donor liver transplants are superior to cadaveric liver transplants. While living donor livers may be better in quality than a cadaver liver in India, the donor related risk and the higher technical complication rate negate this advantage.  In view of the risks to living donors, I have personally opted to wait for cadaver transplants unless the patient is too sick to wait. 

Having said that, there is an element of uncertainity with the cadver liver function.  Particularly in India where standards of critical care, infection control and lack of awareness about donor maintenance protocols, this issue takes the center stage.  There is no gold standard test to ascertain the viability of a cadver liver or the degree of damage sustained by it in the donor and ability to predict optimal function after transplantation. 

All in all around 20 - 30% of cadaver livers fail to function optimally after transplantation in India and this condition is termed early allograft dysfunction (EAD).  There are certain known associations for EAD, which are- older donors, prolonged ICU stay of donors, fatty liver (>30%), larger livers, those donors who sustain cardiac arrest during their ICU stay, longer cold preservation of the liver, excessive blood loss during recipient liver removal, high MELD score of the recipient and if the recipient was on a ventilator at the time of transplant.

By defenition EAD is present when the PT-INR is more than 1.6 after 7 days of transplant, AST/ ALT levels are higher than 2000 iu within the first 7 days and serum Bilurubin > 10 mg/ dl after 1 week of liver transplant.

A study 1930 cadver liver transplants published from Mayo clinic (Annals of Hepatology, Vol-15, No.1, 2016:53-60) clearly establishes the poor graft survival in EAD group.  The 1 year, 3 year and 5 year survival for non EAD vs those with EAD was 91.4% vs 78.6%, 83.5% vs 67.9% and 74.8% vs 57.2% respectively.  Clearly the graft failure rate and patient mortality continued into the fifth year after liver transplant.

This revelation raises a number of ethical issues in choosing marginal livers for liver transplant. Should the patient’s be given the choice to reject marginal livers? Which group of recipients can be transplanted with marginal livers? How does one decide on the issue of marginality?….. currently there are no guidelines and are left to individual surgeons or the center policy. Centers with larger number of waitlisted ptients assume this responsibility and are aggressive in using almost all livers.  the big question is how ethical is this decision making process….moreover usually the junior members of a team is sent to assess and retrieve livers and their assessment may be questionable.

Taking cognisance of the fact that cadaver organ resource is scarce, one should be able to utilize this resource with minimum discard rate.  Few options come to the fore, define degree of marginality based on the known risk factors and transplant livers with percieved risk of bad outcome only to those with higher risk (eg; HCC, high MELD, retransplants, those with living donor choice as a back up). Next the marginal livers could be maitained on pulsatile organ perfusion machines to study their function before transplantation (currently in expeimental stage). Yet another option that is gaining momentum is therapeutic plasma exchange in those with EAD.  early repots indicate a statistical benefit in graft and patient survival.

Monday, April 25, 2016

Acute on Chronic Liver Failure (ACLF): Dilemma in diagnosis and treatment

Acute on Chronic Liver Failure (ACLF): dilemma in diagnosis and treatment

A patient having known or unknown chronic liver disease, whose liver function worsens further with or without multiple organ dysfunction either while in hospital or presents to the hospital in that state is now called ACLF (Acute on Chronic Liver failure). It is classified based on severity into ACLF grade 0 to 4, depending on number of organ failures and its severity is predicted using CLIF-SOFA score. ACLF is now recognized as a distinct clinical entity and differs from decompensated liver disease. It is imperative to make this distinction as the prognosis and treatment approach vary significantly.
A vast majority of ACLF reported in western literature refers to alcoholic liver cirrhosis with alcoholic hepatitis. In Asian countries with a huge load of non alcoholic chronic liver disease, the causative factors for an acute insult would be viral hepatitis illness or drug induced hepatitis from myriad of drugs, anti tubercular drugs in particular. Whatever may be the trigger, the pathophysiology of this disease entity culminates in a common path of persistent immunity mediated inflammation that fails to settle or heal on its own.
This simmering inflammation of the liver may tilt the balance of liver destruction and regeneration adversely and various factors such as superadded systemic sepsis, liver reserve, and cause of primary chronic liver disease, state of immune system or the state of gut microbial flora might determine the ultimate prognosis.
Alcoholic liver cirrhosis with alcoholic hepatitis has a good prognosis as long as the ACLF is grade 0 to 2. They respond better to anti inflammatory strategy when the liver reserve is reasonable. In the absence of other co-morbidities, liver does regenerate and it is possible to achieve a steady and stable state for months to years. On the contrary, acute viral hepatitis induced ACLF tends to take a rapid downhill course.
I hypothesize that these patients have persistent inflammation due to delayed or no viral elimination. Many of them will have viral RNA (hepatitis A or E) detectable even 3 months after contracting the illness. Here antiviral strategies may improve the prognosis. If they don’t have RNA positivity then anti-inflamatory approach might help. Drug induced hepatitis may be due to direct liver toxicity or due to an idiosyncratic reaction.
I have seen even seemingly innocuous drugs like Atarvostatin causing severe hepatitis. Here the strategy of stopping the medication and using anti-oxidant agents might work. Role of steroids or other immune modulators are limited with current experience. However the ultimate recovery will depend on the liver reserve and the regenerative capacity. Those with ACLF grade 3 or 4 have one month mortality exceeding 80% and need to have a liver transplant.
Many centers offer plasma aphaeresis or MARS liver dialysis which is nothing short of cosmetic deception which will have no bearing on the prognosis of ACLF and may actually destabilize a patient by inducing sepsis or circulatory failure.
Sepsis= overwhelming infection
MARS = Molecular Adsorption and recirculation system
CLIF-SOFA = A scoring system based on grading organ system failure in critical illness Idiosyncratic = Immune system mediated cell injury