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Wilson Disease Presenting as Acute on Chronic Liver Failure: A Mystery yet to be Solved!!

      Dear Sir,
      We read with interest, the article by Devarbhavi H et al.
      • Devarbhavi H.
      • Reddy V.V.
      • Singh R.
      Wilson disease presenting with Acute on chronic liver failure: a single center experience of outcome and predictors of mortality in 68 patients.
      published in the Journal of Clinical and Experimental Hepatology. We congratulate the authors for reporting one of the largest case series of Wilson disease (WD) with a significant number of patients (68 of 272; 25%) presenting as acute on chronic liver failure (ACLF). The data were collected over a period of 20 years and retrospectively analyzed. The key messages we could gather from the study were that children constituted 80% of the study population with a mean age of 14.4 years, highlighting that most observations in the study are likely to be appropriated to children. Twenty-three liver biopsy samples in their series had an underlying chronic liver disease providing important information that though WD can have an acute liver failure (ALF) such as presentation, most of them in fact have an underlying liver disease suggesting a working diagnosis of ACLF as more appropriate than ALF.
      • Sarin S.K.
      • Kedarisetty C.K.
      • Abbas Z.
      • et al.
      For APASL ACLF Working Party
      Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL).
      As per the world gastroenterology organization (WGO) definition,
      • Jalan R.
      • Yurdaydin C.
      • Bajaj J.S.
      • et al.
      Toward an improved definition of acute-on-chronic liver failure.
      ACLF is a distinct entity presenting as liver failure along with one or more extrahepatic organ failures that are associated with increased mortality within a period of 28 days and up to 3 months from onset. The definition of ACLF used by the authors is not clear as also details on organ failures. While they have highlighted risk factors associated with acute precipitating results as viral or drug induced, namely nonsteroidal antiinflammatory drugs and anti-tuberculous therapy in 11.7%, the result was unknown in the remaining. Nonadherence and improper dosage of medications for WD can be an important precipitant for Wilsonian crises and flares and a hepatotropic insult for ACLF.
      • Sarin S.K.
      • Kedarisetty C.K.
      • Abbas Z.
      • et al.
      For APASL ACLF Working Party
      Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL).
      This should have been addressed by the authors.
      In the entire cohort of 272 patients, 68 presented with ACLF. The survival curves of these patients were compared with those with total bilirubin <5 or international normalized ratio (INR) <1.5. It showed the steep differences in the outcome between ACLF and others. However, the authors could have classified the entire cohort as ACLF (n – 68) and non-ACLF (n – 204). Because WD has varied presentation from chronic hepatitis to cirrhosis of liver and ACLF, a subclassification and survival analysis would have thrown more light into the natural history of patients with WD, presenting as ACLF. Interesting also would be to know the survival in these patients with ACLF based on the number of organ failures as assessed by the CLIF – SOFA score
      • Moreau R.
      • Jalan R.
      • Gines P.
      • et al.
      Acute on chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.
      and AARC dynamic score.
      • Choudhury A.
      • Jindal A.
      • Maiwall R.
      • et al.
      Liver failure determines the outcome in patients with acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF- SOFA models.
      In both EASL-CLIF consortium cohort and APASL consortium cohorts, the most common extrahepatic organ failure reported is renal involvement. So much so, that in the AARC dynamic score, serum creatinine >0.7 mg/dl was given 2 points and >1.5 mg/dl was given 3 points, reiterating that these small increments in creatinine, which appear normal, actually predict mortality. Even in the present study,
      • Devarbhavi H.
      • Reddy V.V.
      • Singh R.
      Wilson disease presenting with Acute on chronic liver failure: a single center experience of outcome and predictors of mortality in 68 patients.
      the mean creatinine in nonsurvivors was 1.2 ± 0.6 mg/dl and 1 ± 0.4 in survivors.
      The overall three-month mortality was 73.1% with maximal mortality in the first 2–4 weeks of presentation with encephalopathy being the single predictor in 96% cases. This is important in clinical practice to triage these patients for liver transplantation. More information could have been provided on grades of encephalopathy in both survivors and nonsurvivors. The ROC curve to predict mortality is not appropriate. This is essentially used for evaluating the performance of diagnostic tests and not for predicting mortality.
      Finally, it would have been intriguing to see the outcome in those three patients who underwent therapeutic plasmapheresis. More data are needed to understand the intricacies of presentation of WD as ACLF, which is itself a distinct entity.

      Conflicts of interest

      The authors have no conflicts of interest to disclose.

      References

        • Devarbhavi H.
        • Reddy V.V.
        • Singh R.
        Wilson disease presenting with Acute on chronic liver failure: a single center experience of outcome and predictors of mortality in 68 patients.
        J Clin Exp Hepatol. 2019; 9: 569-573
        • Sarin S.K.
        • Kedarisetty C.K.
        • Abbas Z.
        • et al.
        • For APASL ACLF Working Party
        Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL).
        Hepatol Int. 2014; 8: 453-471
        • Jalan R.
        • Yurdaydin C.
        • Bajaj J.S.
        • et al.
        Toward an improved definition of acute-on-chronic liver failure.
        Gastroenterology. 2014 Jul; 147: 4-10
        • Moreau R.
        • Jalan R.
        • Gines P.
        • et al.
        Acute on chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.
        Gastroenterology. 2013; 144: 1426-1437
        • Choudhury A.
        • Jindal A.
        • Maiwall R.
        • et al.
        Liver failure determines the outcome in patients with acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF- SOFA models.
        Hepatol Int. 2017; 11: 461-471