Skip to main content

Advertisement

SpringerLink
Log in

Addiction and Liver Disease: Exploring the Complex Relationship and Implications for Clinical Management

  • Published:
Current Hepatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The review focuses on addressing substance use disorders in individuals with chronic liver disease, specifically alcohol, tobacco, and cannabis.

Recent Findings

Psychological interventions and medications like naltrexone and acamprosate are effective in treating alcohol use disorder in patients with liver disease. Tobacco smoking has a negative impact on fibrosis progression, it is recommended to regularly screen and provide structured brief interventions in combination with medications like varenicline and nicotine replacement therapy. Cannabis use disorder is associated with adverse health outcomes, and psychological therapy is preferred; pharmaceutical agents are not currently recommended.

Summary

A combination of psychological interventions and medication is recommended for treating substance use disorders in patients with advanced liver disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

ALD:

Alcohol-associated liver disease

AH:

Alcohol-associated hepatitis

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. FastStats. 2022. https://www.cdc.gov/nchs/fastats/drug-use-illicit.htm. Accessed 8 May 2023.

  2. Kim D, Li AA, Gadiparthi C, Khan MA, Cholankeril G, Glenn JS, et al. Changing trends in etiology-based annual mortality from chronic liver disease, from 2007 through 2016. Gastroenterology. 2018;155(4):1154–63.e3.

    Article  PubMed  Google Scholar 

  3. Sepanlou SG, Safiri S, Bisignano C, Ikuta KS, Merat S, Saberifiroozi M, et al. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990--2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5(3):245–66.

    Article  Google Scholar 

  4. Zibbell JE, Asher AK, Patel RC, Kupronis B, Iqbal K, Ward JW, et al. Increases in acute hepatitis C virus infection related to a growing opioid epidemic and associated injection drug use, United States, 2004 to 2014. Am J Public Health. 2018;108(2):175–81.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hagan H, Pouget ER, Des Jarlais DC, Lelutiu-Weinberger C. Meta-regression of hepatitis C virus infection in relation to time since onset of illicit drug injection: the influence of time and place. Am J Epidemiol. 2008;168(10):1099–109.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Volkow ND, Gordon JA, Koob GF. Choosing appropriate language to reduce the stigma around mental illness and substance use disorders. Neuropsychopharmacology. 2021;46(13):2230–2.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Koob GF. Neurobiology of addiction. FOC. 2011;9(1):55–65.

    Article  Google Scholar 

  8. • Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry. 2016;3(8):760–73. Important overview of the neurobiology of substance use and a model for understanding substance use disorders

    Article  PubMed  PubMed Central  Google Scholar 

  9. Volkow ND, Fowler JS, Wang GJ. The addicted human brain: insights from imaging studies. J Clin Invest. 2003;111(10):1444–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. O’Brien C. Addiction and dependence in DSM-V. Addiction. 2011;106(5):866–7.

    Article  PubMed  Google Scholar 

  11. Martinez AD, Dimova R, Marks KM, Beeder AB, Zeremski M, Kreek MJ, et al. Integrated internist - addiction medicine - hepatology model for hepatitis C management for individuals on methadone maintenance. J Viral Hepat. 2012;19(1):47–54.

    Article  CAS  PubMed  Google Scholar 

  12. Elfeki MA, Abdallah MA, Leggio L, Singal AK. Simultaneous management of alcohol use disorder and liver disease: a systematic review and meta-analysis. J Addict Med. 2023;17(2):e119–28.

    Article  PubMed  Google Scholar 

  13. McLellan AT, Lewis DC, O’Brien CP, Kleber HD. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA. 2000;284(13):1689–95.

    Article  CAS  PubMed  Google Scholar 

  14. Garcia R. Understanding alcohol use disorder. Nurs Clin North Am. 2023;58(2):133–40.

    Article  PubMed  Google Scholar 

  15. Huang DQ, Mathurin P, Cortez-Pinto H, Loomba R. Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors. Nat Rev Gastroenterol Hepatol. 2023;20(1):37–49.

    Article  PubMed  Google Scholar 

  16. Morgan TR, Mandayam S, Jamal MM. Alcohol and hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S87–96.

    Article  CAS  PubMed  Google Scholar 

  17. Pollard MS, Tucker JS, Green HD. Changes in adult alcohol use and consequences during the COVID-19 pandemic in the US. JAMA Netw Open. 2020;3(9):e2022942.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Stanton R, To QG, Khalesi S, Williams SL, Alley SJ, Thwaite TL, et al. Depression, anxiety and stress during COVID-19: associations with changes in physical activity, sleep, tobacco and alcohol use in Australian adults. Int J Environ Res Public Health. 2020;17(11) https://doi.org/10.3390/ijerph17114065.

  19. Gadermann AC, Thomson KC, Richardson CG, Gagné M, McAuliffe C, Hirani S, et al. Examining the impacts of the COVID-19 pandemic on family mental health in Canada: findings from a national cross-sectional study. BMJ Open. 2021;11(1):e042871.

    Article  PubMed  Google Scholar 

  20. Jacob L, Smith L, Armstrong NC, Yakkundi A, Barnett Y, Butler L, et al. Alcohol use and mental health during COVID-19 lockdown: a cross-sectional study in a sample of UK adults. Drug Alcohol Depend. 2021;219:108488.

    Article  CAS  PubMed  Google Scholar 

  21. • Julien J, Ayer T, Tapper EB, Barbosa C, Dowd WN, Chhatwal J. Effect of increased alcohol consumption during COVID-19 pandemic on alcohol-associated liver disease: a modeling study. Hepatology. 2022, 75(6):1480–90. An important study investigating the application of a microsimulation model to forecast the anticipated short and long-term outcomes associated with increased rates of alcohol use during the COVID-19 pandemic.

  22. •• American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR. American Psychiatric Association Publishing; 2022. Important updated guideline on the diagnosis of substance use disorders using the DSM-5 standard.

    Book  Google Scholar 

  23. Arab JP, Izzy M, Leggio L, Bataller R, Shah VH. Management of alcohol use disorder in patients with cirrhosis in the setting of liver transplantation. Nat Rev Gastroenterol Hepatol. 2022;19(1):45–59.

    Article  CAS  PubMed  Google Scholar 

  24. Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption--II. Addiction. 1993 Jun;88(6):791–804.

    Article  CAS  PubMed  Google Scholar 

  25. Johnson JA, Lee A, Vinson D, Seale JP. Use of AUDIT-based measures to identify unhealthy alcohol use and alcohol dependence in primary care: a validation study. Alcohol Clin Exp Res. 2013;37:E253–9.

    Article  PubMed  Google Scholar 

  26. Bradley KA, DeBenedetti AF, Volk RJ, Williams EC, Frank D, Kivlahan DR. AUDIT-C as a brief screen for alcohol misuse in primary care. Alcohol Clin Exp Res. 2007;31(7):1208–17.

    Article  PubMed  Google Scholar 

  27. Lucey MR. Liver transplantation for alcoholic liver disease. Nat Rev Gastroenterol Hepatol. 2014;11(5):300–7.

    Article  PubMed  Google Scholar 

  28. Helander A, Eriksson CJP. WHO/ISBRA study on state and trait markers of alcohol use and dependence investigators. Laboratory tests for acute alcohol consumption: results of the WHO/ISBRA study on state and trait markers of alcohol use and dependence. Alcohol Clin Exp Res. 2002;26(7):1070–7.

    Article  PubMed  Google Scholar 

  29. Wurst FM, Skipper GE, Weinmann W. Ethyl glucuronide—the direct ethanol metabolite on the threshold from science to routine use. Addiction. 2003;98(s2):51–61.

    Article  PubMed  Google Scholar 

  30. Helander A, Böttcher M, Fehr C, Dahmen N, Beck O. Detection times for urinary ethyl glucuronide and ethyl sulfate in heavy drinkers during alcohol detoxification. Alcohol Alcohol. 2009;44(1):55–61.

    Article  CAS  PubMed  Google Scholar 

  31. Crabb DW, Im GY, Szabo G, Mellinger JL, Lucey MR. Diagnosis and treatment of alcohol-associated liver diseases: 2019 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2020;71(1):306.

    Article  PubMed  Google Scholar 

  32. Ting PS, Wheatley J, Chen PH. Behavioral treatment for patients with alcohol-related liver disease: a primer for hepatologists. Clin Liver Dis. 2020;15(1):31–5.

    Article  Google Scholar 

  33. Drumright LN, Hagan H, Thomas DL, Latka MH, Golub ET, Garfein RS, et al. Predictors and effects of alcohol use on liver function among young HCV-infected injection drug users in a behavioral intervention. J Hepatol. 2011;55(1):45–52.

    Article  PubMed  Google Scholar 

  34. Willenbring ML, Olson DH. A randomized trial of integrated outpatient treatment for medically ill alcoholic men. Arch Intern Med. 1999;159(16):1946–52.

    Article  CAS  PubMed  Google Scholar 

  35. • Addolorato G, Mirijello A, Leggio L, Ferrulli A, D’Angelo C, Vassallo G, et al. Liver transplantation in alcoholic patients: impact of an alcohol addiction unit within a liver transplant center. Alcohol Clin Exp Res. 2013;37(9):1601–8. An important study highlighting the utility of integration of an alcohol addiction unit within a liver transplant center.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Georgiou G, Webb K, Griggs K, Copello A, Neuberger J, Day E. First report of a psychosocial intervention for patients with alcohol-related liver disease undergoing liver transplantation. Liver Transpl. 2003;9(7):772–5.

    Article  PubMed  Google Scholar 

  37. Proeschold-Bell RJ, Patkar AA, Naggie S, Coward L, Mannelli P, Yao J, et al. An integrated alcohol abuse and medical treatment model for patients with hepatitis C. Dig Dis Sci. 2012;57(4):1083–91.

    Article  PubMed  Google Scholar 

  38. Lieber CS, Weiss DG, Groszmann R, Paronetto F, Schenker S, 391 Group VACS. II. Veterans Affairs Cooperative Study of polyenylphosphatidylcholine in alcoholic liver disease. Alcohol Clin Exp Res. 2003;27(11):1765–72.

    Article  CAS  PubMed  Google Scholar 

  39. Dieperink E, Ho SB, Heit S, Durfee JM, Thuras P, Willenbring ML. Significant reductions in drinking following brief alcohol treatment provided in a hepatitis C clinic. Psychosomatics. 2010;51(2):149–56.

    Article  PubMed  Google Scholar 

  40. Kuchipudi V, Hobein K, Flickinger A, Iber FL. Failure of a 2-hour motivational intervention to alter recurrent drinking behavior in alcoholics with gastrointestinal disease. J Stud Alcohol. 1990;51(4):356–60.

    Article  CAS  PubMed  Google Scholar 

  41. Verma M, Winder GS. Treatment of substance use disorders in patients with chronic liver disease. Clin Liver Dis. 2022;20(2):66–71.

    Article  Google Scholar 

  42. Schneekloth TD, Arab JP, Niazi SK, Simonetto DA. Impact of pre-and post-liver transplant addiction treatment and AA attendance on outcomes for recipients with alcoholic liver disease. J Psychosom Res. 2018;109:134.

    Article  Google Scholar 

  43. •• Leggio L, Lee MR. Treatment of alcohol use disorder in patients with alcoholic liver disease. Am J Med. 2017;130(2):124–34. Important guideline recommendations for the management of alcohol use disorder in patients with alcohol-associated liver disease.

    Article  PubMed  Google Scholar 

  44. Saitz R. Candidate performance measures for screening for, assessing, and treating unhealthy substance use in hospitals: advocacy or evidence-based practice? Ann Intern Med. 153(1):40–3.

  45. Khan A, Tansel A, White DL, Kayani WT, Bano S, Lindsay J, et al. Efficacy of psychosocial interventions in inducing and maintaining alcohol abstinence in patients with chronic liver disease: a systematic review. Clin Gastroenterol Hepatol. 2016;14(2):191–202.e1-4.

    Article  PubMed  Google Scholar 

  46. Swift RM. Drug therapy for alcohol dependence. N Engl J Med. 1999;340(19):1482–90.

    Article  CAS  PubMed  Google Scholar 

  47. Reus VI, Fochtmann LJ, Bukstein O, Eyler AE, Hilty DM, Horvitz-Lennon M, et al. The American Psychiatric Association practice guideline for the pharmacological treatment of patients with alcohol use disorder. Focus. 2019;17(2):158–62.

    Article  PubMed  PubMed Central  Google Scholar 

  48. De Sousa A. Disulfiram: side effects and toxicity. In: De Sousa A, editor. Disulfiram: its use in alcohol dependence and other disorders. Singapore: Springer Singapore; 2019. p. 59–67.

    Chapter  Google Scholar 

  49. Maisel NC, Blodgett JC, Wilbourne PL, Humphreys K, Finney JW. Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful? Addiction. 2013;108(2):275–93.

    Article  PubMed  Google Scholar 

  50. Ray LA, Chin PF, Miotto K. Naltrexone for the treatment of alcoholism: clinical findings, mechanisms of action, and pharmacogenetics. CNS Neurol Disord Drug Targets. 2010;9(1):13–22.

    Article  CAS  PubMed  Google Scholar 

  51. Ayyala D, Bottyan T, Tien C, Pimienta M, Yoo J, Stager K, et al. Naltrexone for alcohol use disorder: hepatic safety in patients with and without liver disease. Hepatol Commun. 2022;6(12):3433–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Heinälä P, Alho H, Kiianmaa K, Lönnqvist J, Kuoppasalmi K, Sinclair JD. Targeted use of naltrexone without prior detoxification in the treatment of alcohol dependence: a factorial double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2001;21(3):287–92.

    Article  PubMed  Google Scholar 

  53. Kalk NJ, Lingford-Hughes AR. The clinical pharmacology of acamprosate. Br J Clin Pharmacol. 2014 Feb;77(2):315–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mason BJ. Acamprosate in the treatment of alcohol dependence. Expert Opin Pharmacother. 2005;6(12):2103–15.

    Article  CAS  PubMed  Google Scholar 

  55. O’Shea RS, Dasarathy S, McCullough AJ. Practice Guideline Committee of the American Association for the study of liver diseases, Practice Parameters Committee of the American College of Gastroenterology. Alcoholic liver disease. Hepatology. 2010;51(1):307–28.

    PubMed  Google Scholar 

  56. Mason BJ, Heyser CJ. Acamprosate: a prototypic neuromodulator in the treatment of alcohol dependence. CNS Neurol Disord Drug Targets. 2010;9(1):23–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. National Institute of Diabetes and Digestive and Kidney Diseases. LiverTox. National Institute of Diabetes and Digestive and Kidney Diseases; 2012. https://www.ncbi.nlm.nih.gov/books/NBK547852/. Accessed 22 May 2023.

    Google Scholar 

  58. Delgrange T, Khater J, Capron D, Duron B, Capron JP. Effect of acute administration of acamprosate on the risk of encephalopathy and on arterial pressure in patients with alcoholic cirrhosis. Gastroenterol Clin Biol. 1992;16(8-9):687–91.

    CAS  PubMed  Google Scholar 

  59. Phimarn W, Chamnanjit P, Anunworapunya W, Saramunee K, Sungthong B. Efficacy and safety of baclofen for treatment of alcohol dependence: an updated meta-analysis and meta-regression study. Indian J Pharm Sci. 2022;84(1). https://www.ijpsonline.com/articles/efficacy-and-safety-of-baclofen-for-treatment-of-alcohol-dependence-an-updated-metaanalysis-and-metaregression-study-4507.html?view=mobile. Accessed 8 May 2023.

  60. Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet. 2007;370(9603):1915–22.

    Article  CAS  PubMed  Google Scholar 

  61. Garbutt JC, Kampov-Polevoy AB, Gallop R, Kalka-Juhl L, Flannery BA. Efficacy and safety of baclofen for alcohol dependence: a randomized, double-blind, placebo-controlled trial. Alcohol Clin Exp Res. 2010;34(11):1849–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Reynaud M, Aubin HJ, Trinquet F, Zakine B, Dano C, Dematteis M, et al. A randomized, placebo-controlled study of high-dose baclofen in alcohol-dependent patients—the ALPADIR study. Alcohol Alcohol. 2017;52(4):439–46.

    Article  CAS  PubMed  Google Scholar 

  63. Rose AK, Jones A. Baclofen: its effectiveness in reducing harmful drinking, craving, and negative mood. A meta-analysis. Addiction. 2018;113(8):1396–406.

    Article  PubMed  Google Scholar 

  64. Fairbanks J, Umbreit A, Kolla BP, Karpyak VM, Schneekloth TD, Loukianova LL, et al. Evidence-based pharmacotherapies for alcohol use disorder: clinical pearls. Mayo Clin Proc. 2020;95(9):1964–77.

    Article  CAS  PubMed  Google Scholar 

  65. Fariba KA, Saadabadi A. Topiramate. StatPearls Publishing; 2023.

    Google Scholar 

  66. Brown SA, Izzy M, Watt KD. Pharmacotherapy for weight loss in cirrhosis and liver transplantation: translating the data and underused potential. Hepatology. 2021;73(5):2051–62.

    Article  CAS  PubMed  Google Scholar 

  67. Fluyau D, Kailasam VK, Pierre CG. A Bayesian meta-analysis of topiramate’s effectiveness for individuals with alcohol use disorder. J Psychopharmacol. 2023;37(2):155–63.

    Article  CAS  PubMed  Google Scholar 

  68. Vannier AGL, Shay JES, Fomin V, Patel SJ, Schaefer E, Goodman RP, et al. Incidence and progression of alcohol-associated liver disease after medical therapy for alcohol use disorder. JAMA Netw Open. 2022;5(5):e2213014.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014;174(1):70–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kranzler HR, Feinn R, Morris P, Hartwell EE. A meta-analysis of the efficacy of gabapentin for treating alcohol use disorder. Addiction. 2019;114(9):1547–55.

    Article  PubMed  PubMed Central  Google Scholar 

  71. • Anton RF, Latham P, Voronin K, Book S, Hoffman M, Prisciandaro J, et al. Efficacy of gabapentin for the treatment of alcohol use disorder in patients with alcohol withdrawal symptoms: a randomized clinical trial. JAMA Intern Med. 2020;180(5):728–36. An important randomized controlled trial that demonstrated the efficacy of gabapentin for managing alcohol use disorder.

    Article  CAS  PubMed  Google Scholar 

  72. Mariani JJ, Pavlicova M, Basaraba C, Mamczur-Fuller A, Brooks DJ, Bisaga A, et al. Pilot randomized placebo-controlled clinical trial of high-dose gabapentin for alcohol use disorder. Alcohol Clin Exp Res. 2021;45(8):1639–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Smith RV, Havens JR, Walsh SL. Gabapentin misuse, abuse and diversion: a systematic review. Addiction. 2016;111(7):1160–74.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Fischler PV, Soyka M, Seifritz E, Mutschler J. Off-label and investigational drugs in the treatment of alcohol use disorder: a critical review. Front Pharmacol. 2022;(13):927703.

  75. Rutledge SM, Asgharpour A. Smoking and liver disease. Gastroenterol Hepatol. 2020;16(12):617–25.

    Google Scholar 

  76. El-Zayadi AR. Heavy smoking and liver. World J Gastroenterol. 2006;12(38):6098–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Abdulkader RT, Kadhim SA. The effect of smoking on liver enzymes and its functions. J Pharm Negat Results. 2022;20:690–700.

    Article  Google Scholar 

  78. Petrick JL, Campbell PT, Koshiol J, Thistle JE, Andreotti G, Beane-Freeman LE, et al. Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: the Liver Cancer Pooling Project. Br J Cancer. 2018;118(7):1005–12.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Marti-Aguado D, Clemente-Sanchez A, Bataller R. Cigarette smoking and liver diseases. J Hepatol. 2022;77(1):191–205.

    Article  CAS  PubMed  Google Scholar 

  80. Jung HS, Chang Y, Kwon MJ, Sung E, Yun KE, Cho YK, et al. Smoking and the risk of non-alcoholic fatty liver disease: a cohort study. Am J Gastroenterol. 2019;114(3):453–63.

    Article  PubMed  Google Scholar 

  81. Zein CO, Unalp A, Colvin R, Liu YC, McCullough AJ. Nonalcoholic Steatohepatitis Clinical Research Network. Smoking and severity of hepatic fibrosis in nonalcoholic fatty liver disease. J Hepatol. 2011;54(4):753–9.

    Article  CAS  PubMed  Google Scholar 

  82. Munsterman ID, Smits MM, Andriessen R, van Nieuwkerk CMJ, Bloemena E, Mulder CJJ, et al. Smoking is associated with severity of liver fibrosis but not with histological severity in nonalcoholic fatty liver disease. Results from a cross-sectional study. Scand J Gastroenterol. 2017;52(8):881–5.

    Article  PubMed  Google Scholar 

  83. Wang YH, Chuang YH, Wu CF, Jan MC, Wu WJ, Lin CL, et al. Smoking and hepatitis B virus-related hepatocellular carcinoma risk: the mediating roles of viral load and alanine aminotransferase. Hepatology. 2019;69(4):1412–25.

    Article  CAS  PubMed  Google Scholar 

  84. Wijarnpreecha K, Werlang M, Panjawatanan P, Pungpapong S, Lukens FJ, Harnois DM, et al. Smoking & risk of advanced liver fibrosis among patients with primary biliary cholangitis: a systematic review & meta-analysis. Indian J Med Res. 2021;154(6):806–12.

    Article  PubMed  PubMed Central  Google Scholar 

  85. •• Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update Panel, Liaisons, and Staff. A clinical practice guideline for treating tobacco use and dependence: 2008 update. A U.S. Public Health Service report. Am J Prev Med. 2008;35(2):158–76. Important clinical practice guideline on the management of tobacco use disorder.

    Article  Google Scholar 

  86. Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO. The Fagerstrom test for nicotine dependence: a revision of the Fagerstrom tolerance questionnaire. Addiction. 1991;86(9):1119–27.

    CAS  Google Scholar 

  87. Ehlers SL, Rodrigue JR, Widows MR, Reed AI, Nelson DR. Tobacco use before and after liver transplantation: a single center survey and implications for clinical practice and research. Liver Transpl. 2004;10(3):412–7.

    Article  PubMed  Google Scholar 

  88. van der Heide F, Dijkstra G, Porte RJ, Kleibeuker JH, Haagsma EB. Smoking behavior in liver transplant recipients. Liver Transpl. 2009;15(6):648–55.

    Article  PubMed  Google Scholar 

  89. Valero JM, Rubio E, Moreno JM, Pons F, Sanchez-Turrion V, Cuervas-Mons V. De novo malignancies in liver transplantation. Transplant Proc. 2003;35(2):709–11.

    Article  CAS  PubMed  Google Scholar 

  90. Scheifele C, Reichart PA, Hippler-Benscheidt M, Neuhaus P, Neuhaus R. Incidence of oral, pharyngeal, and laryngeal squamous cell carcinomas among 1515 patients after liver transplantation. Oral Oncol. 2005;41(7):670–6.

    Article  CAS  PubMed  Google Scholar 

  91. Jiménez C, Manrique A, Marqués E, Ortega P, Loinaz C, Gómez R, et al. Incidence and risk factors for the development of lung tumors after liver transplantation. Transpl Int. 2007;20(1):57–63.

    Article  PubMed  Google Scholar 

  92. Dumortier J, Guillaud O, Adham M, Boucaud C, Delafosse B, Bouffard Y, et al. Negative impact of de novo malignancies rather than alcohol relapse on survival after liver transplantation for alcoholic cirrhosis: a retrospective analysis of 305 patients in a single center. Am J Gastroenterol. 2007;102(5):1032–41.

    Article  PubMed  Google Scholar 

  93. Leithead JA, Ferguson JW, Hayes PC. Smoking-related morbidity and mortality following liver transplantation. Liver Transpl. 2008;14(8):1159–64.

    Article  PubMed  Google Scholar 

  94. Li Q, Wang Y, Ma T, Liu X, Wang B, Wu Z, et al. Impact of cigarette smoking on early complications after liver transplantation: a single-center experience and a meta-analysis. PloS One. 2017;12(5):e0178570.

    Article  PubMed  PubMed Central  Google Scholar 

  95. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu. EASL Clinical Practice Guidelines: Liver transplantation. J Hepatol. 2016;64(2):433–85.

    Article  Google Scholar 

  96. Benowitz NL, Bernert JT, Foulds J, Hecht SS, Jacob P, Jarvis MJ, et al. Biochemical verification of tobacco use and abstinence: 2019 update. Nicotine Tob Res. 2020;22(7):1086–97.

    Article  PubMed  Google Scholar 

  97. Bright RP, Civalier KM, Krahn L. Reliability of self-reported nicotine use as determined by serum cotinine levels in patients referred for liver transplantation. Psychosomatics. 2010;51(5):395–400.

    Article  PubMed  Google Scholar 

  98. Jaén CR, Benowitz NL, Curry SJ, Parsippany N, Kottke TE, Mermelstein RJ, et al. A clinical practice guideline for treating tobacco use and dependence: 2008 update. Am J Prev Med. 2008;35(2):158–76.

    Article  Google Scholar 

  99. • Stead LF, Buitrago D, Preciado N, Sanchez G, Hartmann-Boyce J, Lancaster T. Physician advice for smoking cessation. Cochrane Database Syst Rev. 2013;31(5):CD000165. An important systematic review of the utility of physician advice and brief interventions for tobacco use disorder.

    Google Scholar 

  100. Stead LF, Koilpillai P, Fanshawe TR, Lancaster T. Combined pharmacotherapy and behavioural interventions for smoking cessation. Cochrane Database Syst Rev. 2016;3(3):CD008286.

    PubMed  Google Scholar 

  101. Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. 1999;340(9):685–91.

    Article  CAS  PubMed  Google Scholar 

  102. Ebbert JO, Hughes JR, West RJ, Rennard SI, Russ C, McRae TD, et al. Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial. JAMA. 2015;313(7):687–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Baker TB, Piper ME, Stein JH, Smith SS, Bolt DM, Fraser DL, et al. Effects of nicotine patch vs varenicline vs combination nicotine replacement therapy on smoking cessation at 26 weeks: a randomized clinical trial. JAMA. 2016;315(4):371–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. • Anthenelli RM, Benowitz NL, West R, St Aubin L, McRae T, Lawrence D, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016;387(10037):2507–20. Important randomized clinical trial demonstrating the efficacy of varenicline therapy for management of tobacco use disorder.

    Article  CAS  PubMed  Google Scholar 

  105. Franck AJ, Sliter LR. Acute hepatic injury associated with varenicline in a patient with underlying liver disease. Ann Pharmacother. 2009;43(9):1539–43.

    Article  PubMed  Google Scholar 

  106. Sprague D, Bambha K. Drug-induced liver injury due to varenicline: a case report. BMC Gastroenterol. 2012;12:65.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Mogensen H, Björnsson ES. Varenicline-induced acute liver injury with jaundice. Hepatology. 2015;61(6):2110–1.

    Article  CAS  PubMed  Google Scholar 

  108. Sakakibara M, Ohkawa K, Nawa T, Abe Y, Kusakabe A, Imai T, et al. Two-step progression of varenicline-induced autoimmune hepatitis. Clin J Gastroenterol. 2018;11(3):184–7.

    Article  PubMed  Google Scholar 

  109. Wilkes S. The use of bupropion SR in cigarette smoking cessation. Int J Chron Obstruct Pulmon Dis. 2008;3(1):45–53.

    Article  MathSciNet  CAS  PubMed  PubMed Central  Google Scholar 

  110. Richmond R, Zwar N. Review of bupropion for smoking cessation. Drug Alcohol Rev. 2003;22(2):203–20.

    Article  PubMed  Google Scholar 

  111. Oslin DW, Duffy K. The rise of serum aminotransferases in a patient treated with bupropion. J Clin Psychopharmacol. 1993;13(5):364–5.

    Article  CAS  PubMed  Google Scholar 

  112. Tiyyagura L, Kanel G, Redeker AG. Case report: acute hepatitis induced by bupropion. Dig Dis. 2000;42(1997):1872–3.

    Google Scholar 

  113. Alvaro D, Onetti-Muda A, Moscatelli R, Atili AF. Acute cholestatic hepatitis induced by bupropion prescribed as pharmacological support to stop smoking. A case report. Dig Liver Dis. 2001;33(8):703–6.

    Article  CAS  PubMed  Google Scholar 

  114. Tang DM, Koh C, Twaddell WS, von Rosenvinge EC, Han H. Acute hepatocellular drug-induced liver injury from bupropion and doxycycline. ACG Case Rep J. 2015;3(1):66–8.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Ai-Leng K, Lai-San T, Kang-Hoe L, Gek-Kee L. Acute liver failure with concurrent bupropion and carbimazole therapy. Ann Pharmacother. 2003;37(2):220–3.

    Article  Google Scholar 

  116. Humayun F, Shehab TM, Tworek JA, Fontana RJ. A fatal case of bupropion (Zyban) hepatotoxicity with autoimmune features: case report. J Med Case Reports. 2007;1:88.

    Article  PubMed Central  Google Scholar 

  117. Connarn JN, Zhang X, Babiskin A, Sun D. Metabolism of bupropion by carbonyl reductases in liver and intestine. Drug Metab Dispos. 2015;43(7):1019–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Moore D, Aveyard P, Connock M, Wang D, Fry-Smith A, Barton P. Effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis. BMJ. 2009;338:b1024.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Wadgave U, Nagesh L. Nicotine replacement therapy: an overview. Int J Health Sci. 2016;10(3):425–35.

    Google Scholar 

  120. Fagerström KO, Schneider NG, Lunell E. Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms. Psychopharmacology. 1993;111(3):271–7.

    Article  PubMed  Google Scholar 

  121. Kornitzer M, Boutsen M, Dramaix M, Thijs J, Gustavsson G. Combined use of nicotine patch and gum in smoking cessation: a placebo-controlled clinical trial. Prev Med. 1995;24(1):41–7.

    Article  CAS  PubMed  Google Scholar 

  122. Leone FT, Zhang Y, Evers-Casey S, Evins AE, Eakin MN, Fathi J, et al. Initiating pharmacologic treatment in tobacco-dependent adults. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202(2):e5–31.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Hajek P, Phillips-Waller A, Przulj D, Pesola F, Myers Smith K, Bisal N, et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med. 2019;380(7):629–37.

    Article  PubMed  Google Scholar 

  124. Hedman L, Galanti MR, Ryk L, Gilljam H, Adermark L. Electronic cigarette use and smoking cessation in cohort studies and randomized trials: a systematic review and meta-analysis. Tob Prev Cessat. 2021;7:62.

    Article  PubMed  PubMed Central  Google Scholar 

  125. El Golli N, Jrad-Lamine A, Neffati H, Rahali D, Dallagi Y, Dkhili H, et al. Impact of e-cigarette refill liquid with or without nicotine on liver function in adult rats. Toxicol Mech Methods. 2016;26(6):419–26.

    Article  PubMed  Google Scholar 

  126. Fan T, DuBose L, Wayne C, Sisniega C. E-cigarette, or vaping, associated lung and hepatic injury. J Pediatr Gastroenterol Nutr. 2020;71(3):e98–100.

    Article  PubMed  Google Scholar 

  127. Chakinala RC, Dawoodi S, Fabara SP, Asad M, Khayyat A, Chandramohan S, et al. Association of smoking and e-cigarette in chronic liver disease: an NHANES study. Gastroenterol Res Pract. 2022;15(3):113–9.

    Article  Google Scholar 

  128. Werner AK, Koumans EH, Chatham-Stephens K, Salvatore PP, Armatas C, Byers P, et al. Hospitalizations and deaths associated with EVALI. N Engl J Med. 2020;382(17):1589–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Guorgui J, Ito T, Markovic D, Aziz A, Younan S, Severance A, et al. The impact of marijuana use on liver transplant recipients: a 900 patient single center experience. Clin Transplant. 2021;35(4):e14215.

    Article  PubMed  Google Scholar 

  130. Yan K, Forman L. Cannabinoid use among liver transplant recipients. Liver Transpl. 2021;27(11):1623–32.

    Article  PubMed  Google Scholar 

  131. Serrano Rodriguez P, Strassle PD, Barritt AS 4th, Watkins R, Gerber DA, Hayashi PH, et al. Marijuana consumption in liver transplant recipients. Liver Transpl. 2019;25(5):734–40.

    Article  PubMed  Google Scholar 

  132. Wijarnpreecha K, Panjawatanan P, Ungprasert P. Use of cannabis and risk of advanced liver fibrosis in patients with chronic hepatitis C virus infection: a systematic review and meta-analysis. J Evid Based Med. 2018;11(4):272–7.

    Article  PubMed  Google Scholar 

  133. Farooqui MT, Khan MA, Cholankeril G, Khan Z, Mohammed Abdul MK, Li AA, et al. Marijuana is not associated with progression of hepatic fibrosis in liver disease: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2019;31(2):149–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Brunet L, Moodie EEM, Rollet K, Cooper C, Walmsley S, Potter M, et al. Marijuana smoking does not accelerate progression of liver disease in HIV-hepatitis C coinfection: a longitudinal cohort analysis. Clin Infect Dis. 2013;57(5):663–70.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Maselli DB, Camilleri M. Pharmacology, clinical effects, and therapeutic potential of cannabinoids for gastrointestinal and liver diseases. Clin Gastroenterol Hepatol. 2021;19(9):1748–58.e2.

    Article  CAS  PubMed  Google Scholar 

  136. Anthony JC, Warner LA, Kessler RC. Comparative epidemiology of dependence on tobacco, alcohol, controlled substances, and inhalants: basic findings from the National Comorbidity Survey. In: Marlatt GA, editor. Addictive behaviors: readings on etiology, prevention, and treatment. Washington, DC, US: American Psychological Association; 1997. p. 3–39.

    Chapter  Google Scholar 

  137. Lopera V, Rodríguez A, Amariles P. Clinical relevance of drug interactions with cannabis: a systematic review. J Clin Med Res. 2022;11(5) https://doi.org/10.3390/jcm11051154.

  138. Adamson SJ, Kay-Lambkin FJ, Baker AL, Lewin TJ, Thornton L, Kelly BJ, et al. An improved brief measure of cannabis misuse: the Cannabis Use Disorders Identification Test-Revised (CUDIT-R). Drug Alcohol Depend. 2010;110(1-2):137–43.

    Article  PubMed  Google Scholar 

  139. • Sherman BJ, McRae-Clark AL. Treatment of cannabis use disorder: current science and future outlook. Pharmacotherapy. 2016;36(5):511–35. Important review on the current approach to the management of cannabis use disorder.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Budney AJ, Moore BA, Rocha HL, Higgins ST. Clinical trial of abstinence-based vouchers and cognitive-behavioral therapy for cannabis dependence. J Consult Clin Psychol. 2006;74(2):307–16.

    Article  PubMed  Google Scholar 

  141. Copeland J, Swift W, Roffman R, Stephens R. A randomized controlled trial of brief cognitive–behavioral interventions for cannabis use disorder. J Subst Abuse Treat. 2001;21(2):55–64.

    Article  CAS  PubMed  Google Scholar 

  142. Stephens RS, Roffman RA, Fearer SA, Williams C, Picciano JF, Burke RS. The marijuana check-up: reaching users who are ambivalent about change. Addiction. 2004;99(10):1323–32.

    Article  PubMed  Google Scholar 

  143. Stephens RS, Roffman RA, Curtin L. Comparison of extended versus brief treatments for marijuana use. J Consult Clin Psychol. 2000;68(5):898–908.

    Article  CAS  PubMed  Google Scholar 

  144. Marijuana Treatment Project Research Group. Brief treatments for cannabis dependence: findings from a randomized multisite trial. J Consult Clin Psychol. 2004;72(3):455–66.

    Article  Google Scholar 

  145. Walker DD, Stephens RS, Towe S, Banes K, Roffman R. Maintenance check-ups following treatment for cannabis dependence. J Subst Abuse Treat. 2015;56:11–5.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Budney AJ, Higgins ST, Radonovich KJ, Novy PL. Adding voucher-based incentives to coping skills and motivational enhancement improves outcomes during treatment for marijuana dependence. J Consult Clin Psychol. 2000;68(6):1051–61.

    Article  CAS  PubMed  Google Scholar 

  147. Kondo KK, Morasco BJ, Nugent SM, Ayers CK, O’Neil ME, Freeman M, Kansagara D. Pharmacotherapy for the treatment of cannabis use disorder: A systematic review. Ann Intern Med. 2020;172(6):398–412.

    Article  PubMed  Google Scholar 

  148. Gray KM, Sonne SC, McClure EA, Ghitza UE, Matthews AG, McRae-Clark AL, et al. A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults. Drug Alcohol Depend. 2017;177:249–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. McRae-Clark AL, Gray KM, Baker NL, Sherman BJ, Squeglia L, Sahlem GL, et al. Varenicline as a treatment for cannabis use disorder: a placebo-controlled pilot trial. Drug Alcohol Depend. 2021;229(Pt B):109111

  150. Mason BJ, Crean R, Goodell V, Light JM, Quello S, Shadan F, et al. A proof-of-concept randomized controlled study of gabapentin: effects on cannabis use, withdrawal and executive function deficits in cannabis-dependent adults. Neuropsychopharmacology. 2012;37(7):1689–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Miranda R Jr, Treloar H, Blanchard A, Justus A, Monti PM, Chun T, et al. Topiramate and motivational enhancement therapy for cannabis use among youth: a randomized placebo-controlled pilot study. Addict Biol. 2017;22(3):779–90.

    Article  CAS  PubMed  Google Scholar 

  152. Levin FR, Mariani JJ, Brooks DJ, Pavlicova M, Cheng W, Nunes EV. Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend. 2011;116(1-3):142–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Levin FR, Mariani JJ, Pavlicova M, Brooks D, Glass A, Mahony A, et al. Dronabinol and lofexidine for cannabis use disorder: a randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend. 2016;159:53–60.

    Article  CAS  PubMed  Google Scholar 

  154. Hill KP, Palastro MD, Gruber SA, Fitzmaurice GM, Greenfield SF, Lukas SE, et al. Nabilone pharmacotherapy for cannabis dependence: a randomized, controlled pilot study. Am J Addict. 2017;26(8):795–801.

    Article  PubMed  PubMed Central  Google Scholar 

  155. • Trigo JM, Soliman A, Quilty LC, Fischer B, Rehm J, Selby P, et al. Nabiximols combined with motivational enhancement/cognitive behavioral therapy for the treatment of cannabis dependence: a pilot randomized clinical trial. PloS One. 2018;13(1):e0190768. An important randomized controlled trial that suggests efficacy for adjunctive nabiximols combined with psychological therapy for the treatment of cannabis use disorder.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This article was partially supported by the Chilean government through the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT 1200227 to JPA).

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, 339 Windermere Road, Room A10-224, University Hospital, London, Ontario, N6A 5A5, Canada

    David Hudson, Nisha Howarth, Yi Nong Song, Alvi Islam & Juan Pablo Arab

  2. Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile

    Francisco Idalsoaga, Luis Antonio Díaz & Juan Pablo Arab

  3. Department of Neuroscience, Schulich School of Medicine & Dentistry, Western University, London, Canada

    Saranya Theiventhiran

  4. Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada

    Juan Pablo Arab

Authors
  1. David Hudson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nisha Howarth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francisco Idalsoaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yi Nong Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alvi Islam
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Saranya Theiventhiran
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Luis Antonio Díaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Juan Pablo Arab
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors confirm their contribution to the article as follows: David Hudson: investigation, writing—original draft, writing—review and editing; Nisha Howarth, Francisco Idalsoaga, Yi Nong Song, Alvi Islam, Saranya Theiventhiran: investigation, writing—original draft, writing—review and editing. Luis Antonio Díaz and Juan Pablo Arab: conceptualization, writing—review, editing, and supervision

Corresponding author

Correspondence to Juan Pablo Arab.

Ethics declarations

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki Declaration and its amendments, institutional/national research committee standards, and international/national/international guidelines).

Conflict of Interest

The authors declare no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hudson, D., Howarth, N., Idalsoaga, F. et al. Addiction and Liver Disease: Exploring the Complex Relationship and Implications for Clinical Management. Curr Hepatology Rep 23, 110–122 (2024). https://doi.org/10.1007/s11901-024-00630-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11901-024-00630-1

Keywords

Search

Navigation