An open-label, controlled trial of the clinical effects of Laennec® in patients with nonalcoholic steatohepatitis or cirrhosis

Objective: to evaluate the efficacy and safety of human placenta hydrolysate (HPH) Laennec® in the treatment of nonalcoholic fatty liver disease (NAFLD) in a clinical trial.

Material and methods. The study involved hospitalized NAFLD patients (with non-alcoholic steatohepatitis, cirrhosis) (n=34, mean age 53±14 years). In the therapy group (n=17), patients received Laennec® HPH (4 ml intravenous drip infusion in a solution of 5% glucose 5 times a week for 2 weeks). In the control group (n=17), patients hospitalized in other departments of the clinic did not receive any therapy for NAFLD. The effectiveness of therapy was assessed after 2 and 3 weeks by subjective NAFLD symptoms (fatigue, anorexia, bloating, constipation, nausea, and pain in hypochondrium) and biochemical indicators of liver function: levels of blood serum aspartate aminotrans-ferase (AST), alanine notransferase (ALT), gamma-glutamyltransferase (GGT).

Results. At the start of the study, there were no significant differences between the groups in the values of the studied indicators of liver function: blood levels of AST, ALT, GGT, etc. By the end of Week 1, a significant decrease in AST levels was registered in the group receiving Laennec® (–35 U/l; control: –8 U/l; p<0.001), ALT (–45 U/l; control: –10 U/l; p<0.001), and GGT (–23 U/l; control: –8 U/l; p=0.084; trend). At the end of the study (Week 3), the decrease in AST, ALT and GGT levels towards the normal range was even more pronounced for all three biomarkers: AST (–62 U/l; control: –23 U/l; p<0.001), ALT (–78 U/l; control: –20 U/l; p<0.001), GGT (–40 U/l; control: –15 U/l; p=0.005). Subjective NAFLD symptoms significantly improved after 3 weeks. No adverse effects were identified with the use of HPH.

Conclusion. Laennec® is an effective and safe treatment for NAFLD.

1. Powell E.E., Wong V.W., Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021; 397 (10290): 2212–24. https://doi.org/10.1016/S01406736(20)32511-3.

2. Younossi Z.M., Koenig A.B., Abdelatif D., et al. Global epidemiology of nonalcoholic fatty liver disease – meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016; 64 (1): 73–84. https://doi.org/10.1002/hep.28431.

3. Ivashkin V.T., Drapkina O.M., Mayev I.V., et al. Prevalence of nonalcoholic fatty liver disease in out-patients of the Russian Federation: DIREG 2 study results. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2015; 25 (6): 31–41 (in Russ.).

4. Tsukanov V.V., Yurkina A.S., Ushakova T.A., Blinov D.V. Epidemiological features of non-alcoholic fatty liver disease in Novosibirsk (Siberian Federal District): regional data of open multicenter prospective study DIREG 2. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya / FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2016; 9 (2): 17–27 (in Russ.). https://doi.org/10.17749/2070-4909.2016.9.2.017-027.

5. Eguchi Y., Wong G., Lee E.I., et al. Epidemiology of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Japan: a focused literature review. JGH Open. 2020; 4 (5): 808–17. https://doi.org/10.1002/jgh3.12349.

6. Liu Y., Wang D.W., Wang D., et al. Exenatide attenuates non-alcoholic steatohepatitis by inhibiting the pyroptosis signaling pathway. Front Endocrinol (Lausanne). 2021; 12: 663039. https://doi.org/10.3389/fendo.2021.663039.

7. Xu X., Poulsen K.L., Wu L., et al. Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH). Signal Transduct Target Ther. 2022; 7 (1): 287. https://doi.org/10.1038/s41392-022-01119-3.

8. Gromova O.A., Torshin I.Yu., Chuchalin A.G., Maksimov V.A. Human placenta hydrolysates: from V.P. Filatov to the present day. Therapeutic Archive. 2022; 94 (3): 434–41 (in Russ.). https://doi.org/10.26442/00403660.2022.03.201408.

9. Gromova O.A., Torshin I.Yu., Zgoda V.G., Tikhonova O.V. Hepatoprotective peptides of the drug Laennec. Experimental and Clinical Gastroenterology. 2022; 203 (7): 21–30 (in Russ.). https://doi.org/10.31146/1682-8658-ecg-203-7-21-30.

10. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016; 64 (6): 1388–402. https://doi.org/10.1016/j.jhep.2015.11.004.

11. Nikonov E.L., Aksenov V.A. Current approaches to diagnosing and treating nonalcoholic fatty liver disease. Profilakticheskaya meditsina / Preventive Medicine. 2018; 21 (3): 62–9 (in Russ.). https://doi.org/10.17116/profmed201831262.

12. Clinical guidelines “Non-alcoholic fatty liver disease” (project). 2022. Available at: https://rsls.ru/files/PR2022.pdf (in Russ.) (accessed 10.08.2023).

13. Newsome P.N., Buchholtz K., Cusi K., et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021; 384 (12): 1113–24. https://doi.org/10.1056/NEJMoa2028395.

14. Cusi K., Orsak B., Bril F., et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann Intern Med. 2016; 165 (5): 305–15. https://doi.org/10.7326/M15-1774.

15. Lee C.H., Fu Y., Yang S.J., Chi C.C. Effects of omega-3 polyunsaturated fatty acid supplementation on non-alcoholic fatty liver: a systematic review and meta-analysis. Nutrients. 2020; 12 (9): 2769. https://doi.org/10.3390/nu12092769.

16. Xiang Z., Chen Y.P., Ma K.F., et al. The role of ursodeoxycholic acid in non-alcoholic steatohepatitis: a systematic review. BMC Gastroenterol. 2013; 23 (13): 140. https://doi.org/10.1186/1471230X-13-140.

17. Nadinskaia M., Maevskaya M., Ivashkin V., et al. Ursodeoxycholic acid as a means of preventing atherosclerosis, steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2021; 27 (10): 959–75. https://doi.org/10.3748/wjg.27.i10.959.

18. Simental-Mendía M., Sánchez-García A., Simental-Mendía L.E. Effect of ursodeoxycholic acid on liver markers: a systematic review and meta-analysis of randomized placebo-controlled clinical trials. Br J Clin Pharmacol. 2020; 86 (8): 1476–88. https://doi.org/10.1111/bcp.14311.

19. Sanyal A.J., Chalasani N., Kowdley K.V., et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010; 362 (18): 1675–85. https://doi.org/10.1056/NEJMoa0907929.

20. Bril F., Biernacki D.M., Kalavalapalli S., et al. Role of vitamin E for nonalcoholic steatohepatitis in patients with type 2 diabetes: a randomized controlled trial. Diabetes Care. 2019; 42 (8): 1481–8. https://doi.org/10.2337/dc19-0167.

21. Manzillo G., Piccinino F., Surrenti C., et al. Multicentre double-blind placebo-controlled study of intravenous and oral S-adenosyl-L-methionine (SAMe) in cholestatic patients with liver disease. Drug Invest. 1994; 24: 90–100. https://doi.org/10.1007/BF03258369.