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Usefulness of nutritional therapy recommended in the Japanese Society of Gastroenterology/Japan Society of Hepatology evidence-based clinical practice guidelines for liver cirrhosis 2020

Abstract

Background

The JSGE/JSH guidelines for the management of patients with liver cirrhosis revised in 2020 recommends new strategies for nutritional assessment and intervention, although their usefulness in daily clinical practice is unclear.

Methods

A total of 769 patients with cirrhosis were classified into low-, intermediate-, and high-risk groups according to hypoalbuminemia and sarcopenia, the criteria established for initiating the nutritional therapy algorithm in the guidelines. The association between these groups and mortality was analyzed using a Cox proportional hazards model. The effect of branched-chain amino acids (BCAAs) on survival was evaluated using propensity score matching.

Results

Of the enrolled patients, 495 (64%) were men with a median age of 73 years, 428 (56%) had hypoalbuminemia, 156 (20%) had sarcopenia, and 288 (37%) were receiving BCAAs. During a median follow-up period of 1.5 years, 276 (36%) patients died. The intermediate-risk [hazard ratio (HR), 1.60; 95% confidence interval (CI), 1.18–2.18] and high-risk (HR, 2.85; 95% CI, 1.92–4.23) groups independently predicted mortality. Among the propensity score-matched 250 patients, 49 (39%) BCAA-treated and 58 (46%) untreated died. Overall survival was higher in BCAA-treated patients than in untreated patients (HR, 0.67; 95% CI, 0.46–0.98). The survival benefit of BCAAs was pronounced in the intermediate-risk (HR, 0.50; 95% CI, 0.31–0.80) and high-risk (HR, 0.38; 95% CI, 0.16–0.91) groups.

Conclusions

The 2020 JSGE/JSH guidelines for liver cirrhosis are useful in stratifying the mortality risk and providing effective nutritional interventions for malnourished patients with cirrhosis.

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References

  1. 1.

    Periyalwar P, Dasarathy S. Malnutrition in cirrhosis: contribution and consequences of sarcopenia on metabolic and clinical responses. Clin Liver Dis. 2012;16:95–131.

    Article  Google Scholar 

  2. 2.

    Hanai T, Shiraki M, Nishimura K, et al. Sarcopenia impairs prognosis of patients with liver cirrhosis. Nutrition. 2015;31:193–9.

    Article  Google Scholar 

  3. 3.

    Bischoff SC, Bernal W, Dasarathy S, et al. ESPEN practical guideline: clinical nutrition in liver disease. Clin Nutr. 2020;39:3533–62.

    Article  Google Scholar 

  4. 4.

    European Association for the Study of the Liver. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol. 2019;70:172–93.

    Article  Google Scholar 

  5. 5.

    Yoshiji H, Nagoshi S, Akahane T, et al. Evidence-based clinical practice guidelines for Liver Cirrhosis 2020. J Gastroenterol. 2021;56:593–619.

    Article  Google Scholar 

  6. 6.

    Yoshiji H, Nagoshi S, Akahane T, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2020. Hepatol Res. 2021;51:725–49.

    Article  Google Scholar 

  7. 7.

    Moriwaki H, Miwa Y, Tajika M, et al. Branched-chain amino acids as a protein- and energy-source in liver cirrhosis. Biochem Biophys Res Commun. 2004;313:405–9.

    CAS  Article  Google Scholar 

  8. 8.

    Dasarathy S, Merli M. Sarcopenia from mechanism to diagnosis and treatment in liver disease. J Hepatol. 2016;65:1232–44.

    Article  Google Scholar 

  9. 9.

    Lai JC, Tandon P, Bernal W, et al. Malnutrition, frailty, and sarcopenia in patients with cirrhosis: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021 (in press).

  10. 10.

    Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723–50.

    Article  Google Scholar 

  11. 11.

    Nishikawa H, Shiraki M, Hiramatsu A, et al. Japan Society of Hepatology guidelines for sarcopenia in liver disease (1st edition): Recommendation from the working group for creation of sarcopenia assessment criteria. Hepatol Res. 2016;46:951–63.

    Article  Google Scholar 

  12. 12.

    Haukoos JS, Lewis RJ. The propensity score. JAMA. 2015;314:1637–8.

    CAS  Article  Google Scholar 

  13. 13.

    Kawaguchi T, Izumi N, Charlton MR, et al. Branched-chain amino acids as pharmacological nutrients in chronic liver disease. Hepatology. 2011;54:1063–70.

    CAS  Article  Google Scholar 

  14. 14.

    Hey P, Gow P, Testro AG, et al. Nutraceuticals for the treatment of sarcopenia in chronic liver disease. Clin Nutr ESPEN. 2021;41:13–22.

    Article  Google Scholar 

  15. 15.

    Hanai T, Shiraki M, Miwa T, et al. Effect of loop diuretics on skeletal muscle depletion in patients with liver cirrhosis. Hepatol Res. 2019;49:82–95.

    CAS  Article  Google Scholar 

  16. 16.

    Sano A, Kakazu E, Morosawa T, et al. The profiling of plasma free amino acids and the relationship between serum albumin and plasma-branched chain amino acids in chronic liver disease: a single-center retrospective study. J Gastroenterol. 2018;53:978–88.

    CAS  Article  Google Scholar 

  17. 17.

    Muto Y, Sato S, Watanabe A, et al. Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis. Clin Gastroenterol Hepatol. 2005;3:705–13.

    CAS  Article  Google Scholar 

  18. 18.

    Marchesini G, Bianchi G, Merli M, et al. Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology. 2003;124:1792–801.

    CAS  Article  Google Scholar 

  19. 19.

    Kawaguchi T, Shiraishi K, Ito T, et al. Branched-chain amino acids prevent hepatocarcinogenesis and prolong survival of patients with cirrhosis. Clin Gastroenterol Hepatol. 2014;12:1012-8.e1.

    CAS  Article  Google Scholar 

  20. 20.

    Hanai T, Shiraki M, Watanabe S, et al. Sarcopenia predicts minimal hepatic encephalopathy in patients with liver cirrhosis. Hepatol Res. 2017;47:1359–67.

    CAS  Article  Google Scholar 

  21. 21.

    Tsien C, Davuluri G, Singh D, et al. Metabolic and molecular responses to leucine-enriched branched chain amino acid supplementation in the skeletal muscle of alcoholic cirrhosis. Hepatology. 2015;61:2018–29.

    CAS  Article  Google Scholar 

  22. 22.

    Hernández-Conde M, Llop E, Gómez-Pimpollo L, et al. Adding branched-chain amino acids to an enhanced standard-of-care treatment improves muscle mass of patients with cirrhosis with sarcopenia: a placebo-controlled trial. Am J Gastroenterol. 2021 (in press).

  23. 23.

    Kitajima Y, Takahashi H, Akiyama T, et al. Supplementation with branched-chain amino acids ameliorates hypoalbuminemia, prevents sarcopenia, and reduces fat accumulation in the skeletal muscles of patients with liver cirrhosis. J Gastroenterol. 2018;53:427–37.

    CAS  Article  Google Scholar 

  24. 24.

    Gluud LL, Dam G, Les I, et al. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2017;5:CD001939.

    PubMed  Google Scholar 

  25. 25.

    Lok AS, McMahon BJ, Brown RS Jr, et al. Antiviral therapy for chronic hepatitis B viral infection in adults: a systematic review and meta-analysis. Hepatology. 2016;63:284–306.

    CAS  Article  Google Scholar 

  26. 26.

    Takehara T, Sakamoto N, Nishiguchi S, et al. Efficacy and safety of sofosbuvir-velpatasvir with or without ribavirin in HCV-infected Japanese patients with decompensated cirrhosis: an open-label phase 3 trial. J Gastroenterol. 2019;54:87–95.

    CAS  Article  Google Scholar 

  27. 27.

    Hiramine Y, Uto H, Mawatari S, et al. Effect of tolvaptan on the prognosis of patients with hepatic ascites. Hepatol Res. 2019;49:765–77.

    CAS  PubMed  Google Scholar 

  28. 28.

    Iwasa M, Iwata K, Hara N, et al. Nutrition therapy using a multidisciplinary team improves survival rates in patients with liver cirrhosis. Nutrition. 2013;29:1418–21.

    Article  Google Scholar 

  29. 29.

    Reuter B, Shaw J, Hanson J, et al. Nutritional assessment in inpatients with cirrhosis can be improved after training and is associated with lower readmissions. Liver Transpl. 2019;25:1790–9.

    Article  Google Scholar 

  30. 30.

    Fialla AD, Israelsen M, Hamberg O, et al. Nutritional therapy in cirrhosis or alcoholic hepatitis: a systematic review and meta-analysis. Liver Int. 2015;35:2072–8.

    Article  Google Scholar 

  31. 31.

    Tandon P, Dunn MA, Duarte-Rojo A. Resistance training reduces risk of sarcopenia in patients with cirrhosis. Clin Gastroenterol Hepatol. 2020;18:1036–9.

    Article  Google Scholar 

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Acknowledgements

The authors have had no financial support to produce this manuscript.

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Contributions

All authors contributed to the conception and design of this study. Data collection and analysis were performed by Tatsunori Hanai, Kayoko Nishimura, Takao Miwa, Toshihide Maeda, Yui Ogiso, Kenji Imai, Atsushi Suetsugu, and Koji Takai. The first draft of the manuscript was written by Tatsunori Hanai, and all authors commented on the previous versions of the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Tatsunori Hanai.

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Hanai, T., Nishimura, K., Miwa, T. et al. Usefulness of nutritional therapy recommended in the Japanese Society of Gastroenterology/Japan Society of Hepatology evidence-based clinical practice guidelines for liver cirrhosis 2020. J Gastroenterol 56, 928–937 (2021). https://doi.org/10.1007/s00535-021-01821-z

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Keywords

  • Branched-chain amino acids
  • Cirrhosis
  • Malnutrition
  • Nutritional intervention
  • Sarcopenia