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