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
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
Traditionally severe alcoholic hepatitis (SAH) has been considered a contraindication for liver transplantation
for the following reasons
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.
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
- Serum bilirubin >5mg/dL
- AST (SGOT) > 300
- AST/ALT (SGOT/SGPT) >2
- INR >1.5
- 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
- Alcohol abstinence & Psychotherapy
- Corticosteroids ( controversial as results are equivocal, improves early survival if DF >32)
- Pentoxyfylline ( reduces renal dysfunction)
- Silymarine (no evidence of benefit)
- Infliximab /Etanercept (no benefit, may increase infection)
- 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
- Since patients have been drinking until recently, a period of abstinence will improve their condition
- Patients with SAH often have infection or liver failure and poor nutritional status and therefore are poor candidates for major surgery.
- 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.
2 comments:
The French study accrued a very small number of patients over a period of many years illustrating how careful and selective they were. Their results cannot be used to apply the modality to all patients with severe alcoholic hepatitis. They had not provided long term follow up in their study.
Yes indeed and that is why it is dangerous to extend the conclusion of this study in India which is still a living donor dependent systme
Post a Comment