Transplant;

My middle-age immunocompromised patient receiving immunosuppressants has had 3 doses of mRNA Covid vaccine and is now 4 months out from her 3rd dose.  Should she consider a fourth dose of Covid vaccine?

FA Manian MD, MPH, , , , , , , , , , , , , Leave a comment

Yes! According to the Centers for Disease Control and Prevention (CDC) of the U.S.,1 persons who are “moderately or severely immunocompromised” and have received 3 doses of an mRNA vaccine (either Pfizer [12+ years old) or Moderna (18+ years old]) should receive a 4th dose (“booster”) at least 3 months after the 3rd dose.  Similarly, those who initially received a J&J vaccine followed by one of the aforementioned mRNA vaccines and are at least 2 months from the 2nd dose should also receive a 3rd dose (booster. 

The following are considered moderately or severely immunocompromised conditions by CDC: 

  • Active cancer treatment for tumors or cancers of the blood
  • Organ transplant with immunosuppressants on board
  • Stem cell transplant within the last 2 years or taking immunosuppressants
  • Moderate or severe primary immunodeficiency (eg, DiGeorge or Wiskott-Aldrich syndromes)
  • Advanced or untreated HIV infection
  • Active treatment with high-dose corticosteroids or other immunosuppressants

A published study2 of Covid-19-associated emergency department (ED) and urgent care (UC) encounters and hospitalization among adults during a period including Omicron variant predominance in 10 states found vaccine effectiveness for ED/UC visits dropping to 66% and for hospitalization to 78% by the 4th month after a 3rd dose (vs 87% and 91%, respectively during the 2 months after a 3rd dose).  This study did not distinguish immunocompromised from non-immunocompromised persons, however.  More data on the vaccine effectiveness in non-immunocompromised persons at high risk of Covid-19 related complications would be welcome.

Bonus Pearl: Did you know that of American adults who are fully vaccinated against Covid-19, only about 30% have received an additional Covid vaccine dose beyond the primary series ? 3 

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References

  1. Covid-19 vaccines for moderately or severely immunocompromised people (Updated Feb 17, 2022). Accessed Feb 21, 2022.  https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html?s_cid=10483:immunocompromised%20and%20covid%20vaccine:sem.ga:p:RG:GM:gen:PTN:FY21
  2. Waning 2-doe and 3-dose effectiveness of mRNA vaccines against Covid-10-associated emergency department and urgent care encounters and hospitalizations among adults during periods of delta and omicron variant predominance—Vision Network, 10 states, August 2021-January 2022. MMWR 2022; 71:255-63. https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e2.htm?s_cid=mm7107e2_w
  3. Hubler S, Harman A. As Cov id surges, experts say U.S. booster effort is falling behind. NY Times, December 18, 2021. https://www.nytimes.com/2021/12/18/us/omicron-booster-shots-americans.html

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My middle-age immunocompromised patient receiving immunosuppressants has had 3 doses of mRNA Covid vaccine and is now 4 months out from her 3rd dose.  Should she consider a fourth dose of Covid vaccine?

Why can’t my patient with alcohol-related liver disease be placed on the liver transplant list for at least 6 months after his last drink?

FA Manian MD, MPH, , , , , , , , Leave a comment

Although many centers impose a 6-month sobriety rule before patients can be listed for liver transplant, this rule has been increasingly challenged based on the results of more recent studies and ethical issues. 1-10

The argument for enforcing a 6-month sobriety rule is in part based on earlier studies (often small and/or single center) that reported an association between less than 6 months of sobriety before liver transplantation and relapse.5-6 Another frequently cited reason for postponing liver transplantation is to allow the liver enough time to recover from adverse effect of recent alcohol consumption before assessing the need for transplantation.6

Arguments against the 6-month sobriety rule include the very limited life-expectancy (often 3 months or less) of patients with severe alcohol-related liver disease who do not respond to medical therapy and increasing number of studies supporting earlier transplantation particularly in selected patients (eg, severe acute alcoholic hepatitis [SAAH], acute-on-chronic liver failure [ACLF]).1,7,9,10,

Further supporting a less stringent transplantation rule are a low rate (about 4%) of death or graft loss in alcohol-related liver disease patients who experience a relapse and lack of significant differences in survival between non-relapsers, occasional drinkers and problem drinkers.1 A 2019 multicenter, prospective study in the U.S. also found that early liver transplant for alcohol-related  liver disease was associated with comparable patient and graft survival as those without alcohol-related liver disease at 5 years post-transplant but increased risk of death at 10 years. 10

Bonus Pearl: Did you know that alcohol-related liver disease is now the most common diagnosis among patients undergoing liver transplantation in the U.S.? 10

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References

  1. Obed A, Stern S, Jarrad A, et al. Six month abstinence rule for liver transplantation in severe alcoholic liver disease patients. W J Gastroenterol 2015; 21:4423-26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394109/
  2. Bramstedt KA, Jabbour N. When alcohol abstinence criteria create ethical dilemmas for the liver transplant team. J Med Ethics 2006;32:263-65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2579412/
  3. Kollmann D, Rashoul-Rockenschaub S, Steiner I, et al. Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post-tranplantation CDT monitoring for alcohol relapse assement— a retrospective study. Transplant International 2016;29:559-67. https://onlinelibrary.wiley.com/doi/epdf/10.1111/tri.12756
  4. Osorio RW, Ascher NL, Avery M, et al. Predicting recidivism after orthoptic liver transplantation for alcoholic liver disease. Hepatoloty 1994;20:105-110. https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.1840200117
  5. Carbonneau M, Jensen LA, Bain VG. Alcohol use while on the liver transplant waiting list: a single-center experience. Liver Transplantation 2010;16:91-97. https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/lt.21957
  6. Harnanan A. Challenging the “six-month sober” rule for liver transplants in Canada. McGill Journal of Law and Health. Dec 12, 2019. https://mjlh.mcgill.ca/2019/12/12/challenging-the-six-month-sober-rule-for-liver-transplants-in-canada/
  7. Lee BP, Mehta N, Platt L, et al. Outcomes of early liver transplantation for patients with severe alcoholic hepatitis. Gastroenterology 2018;155:422-430.e1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460480/
  8. Rice JP, Lee BP. Early liver transplantation for alcohol-associated liver disease: need for engagement and education of all stakeholders. Hepatol Communications 2019;3: 1019-21. https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep4.1385
  9. Lee BP, Vittinghoff E, Pletcher MJ, et al. Medicaid policy and liver transplant for alcohol-related liver disease. Hepatology; November 8, 2019 https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.31027
  10. Lee BP, Vittinghoff E, Dodge JL, et al. National trends and long-term outcomes of liver transplant for alcohol-associated liver disease in the United States. JAMA Intern Med 2019;179:340-48. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2720757?widget=personalizedcontent&previousarticle=2720750

Contributed in part by Nneka Ufere, MD, GI Division, Massachusetts General Hospital, Boston, MA

Why can’t my patient with alcohol-related liver disease be placed on the liver transplant list for at least 6 months after his last drink?

What is the rationale for using N-acetylcysteine (NAC) in the treatment of non-acetaminophen-related liver failure (NALF)?

FA Manian MD, MPH, , , , , Leave a comment

Although  the evidence on the effectiveness of NAC in NALF has often been inconclusive, an 2021 meta-analysis and systematic review of the role of NAC in NALF concluded that NAC significantly improves overall survival, post-transplant survival and transplant-free survival while decreasing the overall length of hospital stay (1). 

This meta-analysis included 7 studies involving 883 patients with a mean age of 21 years in the NAC group. Significantly higher overall survival (O.R. 1.8), post-transplant survival (O.R. 2.4) and transplant-free survival (O.R. 2.9) were observed in the NAC group. 

Previously, a 2009 randomized-controlled study involving adults with NALF (including many due to drug toxicity, hepatitis B virus-HBV, and autoimmune causes) had found longer transplant-free survival—not overall survival—in the treatment group, especially among those with lower grade encephalopathy, or liver failure caused by drugs or HBV (2). 

Although it’s not clear how NAC might work in the setting of of NALF, possible effect on microcirculation or 02 delivery through interference with cytokines or other mechanisms have been suggested (2,3).  An interesting 2013 article reported lower serum levels of interleukin-17 among treated patients (3)!

Bonus Pearl: Did you know that acute liver failure affects 2000-3000 persons in the U.S. each year with a mortality as high as 30%? (3)

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References

  1. Walayat S, Shaoib H, Asghar M, et al. Role of N-acetylcysteine in non-acetominophen-related acute liver failure: an updated meta-analysis and systematic review. Ann Gastroenterol 2021;34, 1-6. http://www.annalsgastro.gr/files/journals/1/earlyview/2021/ev-01-2021-04-AG_5321-0571.pdf 
  2. Bass S, Zook N. Intravenous acetylcysteine for indications other than acetaminophen overdose. Am J Health-Syst Pharm 2013;70:1496-1501. https://www.ncbi.nlm.nih.gov/pubmed/23943180
  3. Stravitz RT, Sanyal AJ, Reisch J, et al. Effects of N-acetylcysteine on cytokines in non-acetaminophen acute liver failure: potential mechanism of improvement in transplant-free survival. Liver Int. 2013;33:1324-1331. https://utsouthwestern.pure.elsevier.com/en/publications/effects-of-n-acetylcysteine-on-cytokines-in-non-acetaminophen-acu

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

What is the rationale for using N-acetylcysteine (NAC) in the treatment of non-acetaminophen-related liver failure (NALF)?