Early liver transplantation for severe alcoholic hepatitis: cure or lure?

Alcoholic hepatitis is a clinical syndrome characterised by jaundice and liver failure following decades of significantly heavy alcohol consumption ( >100g daily).

Not uncommonly it results following abstinence periods of weeks to few months or following intermittent binge drinking interspersed by short periods of abstinence.

Although the diagnosis of alcoholic hepatitis is mainly clinical ( enlarged tender liver,  fever, ascites, jaundice, muscle wasting accompanied by renal failure and encephalopathy in more severe cases), the following laboratory criteria suggest its presence in absence of other causes

1. Serum bilirubin >5mg/dL
2. AST (SGOT) > 300
3. AST/ALT (SGOT/SGPT) >2
4. INR >1.5
5. White cell count >10000 cmm

Assessment of severity of alcoholic hepatitis is traditionally done using the Maddrey discriminant function ( 4.6* (PT-PTcontrol) + Serum bilirubin). It is believed that patients with a Maddrey Discriminant Function >32 may benefit from steroids and have poor prognosis.

The Lille model uses age, bilirubin (day 0,7) creatinine (day0), Prothrombin time (day 0) and albumin (day 0) to evaluate prognosis in SAH. A score > 0.45 predicted poor survival ( 30%) at 6 months very reliably.

The MELD score has also been found to be useful in patients with SAH where a score >21 significantly predicts high mortality at 90 days (<20 p="">
The Glasgow score for alcoholic hepatitis takes into account age, wbc count, urea, INR and bilirubin. A Glasgow score of >8 n day 1 or day7 of admission predicts poor prognosis.

Treatment for severe alcoholic hepatitis has evolved over the decades but is largely supportive.

Broadly the measures include

1. Alcohol abstinence & Psychotherapy
2. Corticosteroids ( controversial as results are equivocal, improves early survival if DF >32)
3. Pentoxyfylline  ( reduces renal dysfunction)
4. Silymarine (no evidence of benefit)
5. Infliximab /Etanercept (no benefit, may increase infection)
6. Vitamin E/ Parenteral nutrition / Oxandrolone (no survival benefit)

Traditionally severe alcoholic hepatitis (SAH) has been considered a contraindication for liver transplantation
for the following reasons

1. Since patients have been drinking until recently, a period of abstinence will improve their condition
2. Patients with SAH often have infection or liver failure and poor nutritional status and therefore are poor candidates for major surgery.
3. There is a significant chance that these patient not having had enough time to receive psychological assessment and counselling, have a significant chance of returning to alcohol

Most systems therefore have insisted on a six month period of abstinence before being listed for liver transplantation. Studies however have demonstrated that patients of SAH who do not improve significantly within three months of abstinence have reduced survival prompting a rethink of the six month rule.

Transplant physicians involved in the care of patients of SAH who continue to deteriorate despite abstinence and best supportive care, are often faced with an unenviable dilemma whether to transplant early or choose masterly inactivity till the patient has been abstinent for the period of at least three months. Since a deceased donor organ is a gift to society, waiting is probably just because early transplant diverts the scarce resource to a high risk patient who may waste the gift by early return to alcohol. Living donor organ however is a private gift and therefore using a living donor organ for early transplant conceptually does not deprive another potential recipient and is hence socially justifiable. The ethical foundation of living donor transplant is double equipoise ie the risk (however small) to the donor is justified only if the benefit to recipient is great. In this context recipient benefit cannot be equated to early survival alone but should also encompass recidivism and later issues. Despite this pleas and emotional pressures from a family of a deteriorating patient to perform an early living donor transplant can be unnerving.

Until recently a volume of scientific literature attested to the fact that early liver transplant in severe alcholic hepatitis was associated with either poorer early survival ( mean 55% vs 75% without SAH) or higher rates of recidivism (>33% vs 20%). Recent improvements in post-transplant management and critical care have led to improvement in survival of survival of critically ill transplant candidates including those with SAH and pre-transplant abstinence has been found not to be an unequivocal predictor of recidivism rates after transplant. Both these developments have prompted a re-evaluation of policies regarding liver transplant for SAH.

A recent multi-centre study from Europe (New England Journal of Medicine) suggested that early (deceased donor) liver transplantation performed for  patients with first episode of SAH and who were steroid non-responders was associated with good survival (77% at 6 months) as compared to 23% in controls without liver transplant. The recidivism rate was 11% and no recidivism was seen in first 6 months. There was no significant diversion of organs to these cases as strict criteria and multidisciplinary consensus was mandatory for performing transplant.

Some centres in India have been conveniently using this study to justify early liver transplant in patients with SAH. Even the success of early living donor transplant for acute liver failure has been used to justify early living donor transplant in this totally uncomparable situation. The authors of the European study themselves have clarified that living donor transplant for the same situation is not justifiable and deceased donor transplant is justifiable only if deceased donor organs are not scarce. In India where deceased donation is rare, it is tempting (economically) to perform early transplant using a living donor since it does not deprive society of an organ and the distressed family often sees it as the only light at the end of the tunnel. Early transplant is even used as a lure to transfer such desperate patients from other centres that do not subscribe to this ethos.

Unfortunately the results of this exercise have been poor with unflattering survival and significantly higher recidivism among survivors, yet it continues to be offered as a last hope in an otherwise deteriorating situation either capitulating to pressure of family of for less honourable economic reasons.

This is one desperate situation that should not be dealt with by desperate measures.

CAVEAT LECTOR.

Liver Transplant Surgery: if you choose to travel the distance there is a price to pay

Liver transplantation is a complex procedure and the transplant operation is just one event in the journey that a patient and his caregivers have to embark on. In any long process, well begun is half done and therefore this event ie the operation, if performed and tolerated well, increases the chances of patient survival and eventual well-being. However it must be remembered that this in itself does not ensure a smooth course.

Nearly 10-20% liver transplant patients will need to have an intervention ( either radiological, endoscopic or surgical) during the same admission as their transplant procedure. Often these interventions if not performed emergently and by experienced personnel, can lead to loss of graft and indeed loss of life. It therefore follows that the transplant team should be available round the clock to anticipate, detect early and intervene in time to salvage the graft and the life of the patient.

In the first three months following discharge, at least 10% transplant recipients may need hospital admission under the care of the transplant team for problems related to infection, rejection or surgical complications. If these are not managed well, they can lead to graft as well as patient loss.

There is a tendency among Indian patients to jump on the bandwagon and travel great distances to few transplant centers for their surgery (often at an exploitatively elevated cost) or have transplants performed by commercially-motivated visiting teams attracted by real or exaggerated claims of success, aggressive marketing or through inducement of their referring physicians. While there is no doubt that the right to choose lies with the patient, there is often no consideration given to the availability of continuous surveillance once the patient returns to his community. Patients are lulled into a (false) sense of complacency by the promise of periodic visits by members of the transplant team or placement of inadequately trained minions in the community to look after them for which a 'follow up fee' is charged upfront.

I have recently come across several cases of these 'transplant orphans' who having undergone 'successful' surgery at centers far away from their communities, have suffered due to the lack of direct surveillance and landed up in graft damage or even graft loss. Travelling the distance for managing the complication, imposes an even greater financial burden and moreover patient status may not even allow safe travel in time even if one were to disregard the economics. These patients are frustrated and left to fend for themselves or cared inadequately by inexperienced personnel through telephonic or email directions from the transplant centre. They then have no alternative to running from pillar to post to get proper care from nearby transplant physicians who may not necessarily be willing to takeover the case.

I think anybody traveling to a distant center for a complex procedure like liver transplantation should really consider the availability of longterm experienced followup in his community and ensure that adequate provisions are made for this before the surgery (whenever possible).

There is often a price to pay for going the distance and sometimes the price can be just too high!