Hepatic encephalopathy

Suggested reading

Here is a selection of the most up-to-date publications about developments in liver disease and hepatic encephalopathy:

  • Tiago Duarte, Pedro Fidalgo, Constantine J. Karvellas, Filipe S. Cardoso, What every Intensivist should know about … Ammonia in liver failure, Journal of Critical Care, Volume 81, 2024, 154456, ISSN 0883-9441, https://doi.org/10.1016/j.jcrc.2023.154456.
  • The Story of Ammonia in Liver Disease: An Unraveling Continuum Anand, Anil C. et al. Journal of Clinical and Experimental Hepatology, Volume 14, Issue 4, 101361https://doi.org/10.1016/j.jceh.2024.101361
  • Montagnese, S., Bajaj, J.S. Impact of Hepatic Encephalopathy in Cirrhosis on Quality-of-Life Issues. Drugs 79 (Suppl 1), 11–16 (2019). https://doi.org/10.1007/s40265-018-1019-y
  • Tapper EB, Parikh ND. Diagnosis and Management of Cirrhosis and Its Complications: A Review. JAMA. 2023 May 9;329(18):1589-1602. doi: 10.1001/jama.2023.5997. PMID: 37159031; PMCID: PMC10843851.
  • Faccioli J, Nardelli S, Gioia S, Riggio O, Ridola L. Minimal Hepatic Encephalopathy Affects Daily Life of Cirrhotic Patients: A Viewpoint on Clinical Consequences and Therapeutic Opportunities. J Clin Med. 2022 Dec 6;11(23):7246. doi: 10.3390/jcm11237246. PMID: 36498820; PMCID: PMC9736966.
  • Frenette CT, Levy C, Saab S. Hepatic Encephalopathy-Related Hospitalizations in Cirrhosis: Transition of Care and Closing the Revolving Door. Dig Dis Sci. 2022 Jun;67(6):1994-2004. doi: 10.1007/s10620-021-07075-2. Epub 2021 Jun 24. PMID: 34169435; PMCID: PMC9167177.
  • Torre A, Córdova-Gallardo J, Martínez-Sánchez FD. Hepatic encephalopathy: risk identification and prophylaxis approaches. Metab Brain Dis. 2025 Mar 7;40(3):138. doi: 10.1007/s11011-025-01531-y. PMID: 40053146.
  • Mishra AK, Dhiman RK. Hepatic encephalopathy in cirrhosis: therapies and developments. Metab Brain Dis. 2025 May 7;40(5):198. doi: 10.1007/s11011-025-01598-7. PMID: 40332628.
  • Gallego-Durán R, Hadjihambi A, Ampuero J, Rose CF, Jalan R, Romero-Gómez M. Ammonia-induced stress response in liver disease progression and hepatic encephalopathy. Nat Rev Gastroenterol Hepatol. 2024 Nov;21(11):774-791. doi: 10.1038/s41575-024-00970-9. Epub 2024 Sep 9. PMID: 39251708.
  • Shetty A, Saab EG, Choi G. Social Impact of Hepatic Encephalopathy. Clin Liver Dis. 2024 May;28(2):273-285. doi: 10.1016/j.cld.2024.01.011. Epub 2024 Feb 12. PMID: 38548439.
  • Badal BD, Bajaj JS. Hepatic Encephalopathy in Acute-on-Chronic Liver Failure. Clin Liver Dis. 2023 Aug;27(3):691-702. doi: 10.1016/j.cld.2023.03.012. Epub 2023 May 3. PMID: 37380292.
  • Trivedi S, Lam K, Ganesh A, Hasnain Y, Hassan W, Herren J, Gaba RC. Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Creation. Semin Intervent Radiol. 2023 May 4;40(1):9-14. doi: 10.1055/s-0043-1764282. PMID: 37152788; PMCID: PMC10159723.
  • Ochoa-Sanchez R, Tamnanloo F, Rose CF. Hepatic Encephalopathy: From Metabolic to Neurodegenerative. Neurochem Res. 2021 Oct;46(10):2612-2625. doi: 10.1007/s11064-021-03372-4. Epub 2021 Jun 15. PMID: 34129161.

Hepa-Merz® – Summary of prescribing information

Hepa-Merz® Granules. Composition: One sachet with 5 g of Granules contains: Active substance: 3 g L-ornithine- L-aspartate. Excipients: citric acid, aspartame (E951), povidone 25, fructose, flavorings, orange yellow S (E110). Note for diabetics: One sachet of Hepa-Merz® Granules contains 1.13 g of fructose (corresponds to approx. 0.11 BU). Therapeutic indications: Treatment of concomitant disease and sequelae due to impaired detoxification activity (e.g. in cirrhosis of the liver) with the symptoms of latent and manifest hepatic encephalopathy. Contraindications: Absolute: Hypersensitivity to L-ornithine-L-aspartate, orange yellow S or any of the other excipients. Severely impaired renal function (renal insufficiency). A serum creatinine value over 3 mg/100 ml can be used as a guideline value. Relative: Pregnancy and lactation: No clinical data are available relating to intake of Hepa-Merz® Granules in children and during pregnancy. No exhaustive animal studies have been performed for L-ornithine-L-aspartate, to investigate its toxicity in relation to reproduction. Administration of Hepa-Merz® Granules during pregnancy should therefore be avoided. If, however, treatment with Hepa-Merz® Granules is considered necessary, careful consideration should be given to the benefit versus risk ratio. It is not known whether L-ornithine-L-aspartate is excreted into the breast milk. Administration of Hepa-Merz® Granules should therefore be avoided during lactation. If, however, treatment with Hepa-Merz® Granules is considered necessary, careful consideration should be given to the benefit versus risk ratio. No data regarding fertility. Undesirable effects: Uncommon (³ 1/1,000 to < 1/100): Nausea, vomiting, stomach ache, flatulence, diarrhea. Very rare (< 1/10,000): Pain in the limbs. These undesirable effects are usually transient and do not require withdrawal of the medicine. Orange yellow S (E110) can trigger allergic reactions. Warnings: Hepa-Merz® Granules contain fructose. Patients with rare hereditary problems of fructose intolerance should not take this medicine. Aspartame (E951): Contains a source of phenylalanine. May be harmful for people with phenylketonuria. Further precautions: As a result of the disease, the ability to drive and operate machinery may be impaired during treatment with L-ornithine-L-aspartate.

Hepa-Merz® Granules. Composition: One sachet with 5 g of Granules contains: Active substance: 3 g L-ornithine- L-aspartate. Excipients: citric acid, saccharin sodium, sodium cyclamate, povidone 25, fructose, flavorings, orange yellow S (E110). Note for diabetics: One sachet of Hepa-Merz® Granules contains 1.13 g of fructose (corresponds to approx. 0.11 BU). Therapeutic indications: Treatment of concomitant disease and sequelae due to impaired detoxification activity (e.g. in cirrhosis of the liver) with the symptoms of latent and manifest hepatic encephalopathy. Contraindications: Absolute: Hypersensitivity to L-ornithine-L-aspartate, orange yellow S or any of the other excipients. Severely impaired renal function (renal insufficiency). A serum creatinine value over 3 mg/100 ml can be used as a guideline value. Relative: Pregnancy and lactation: No clinical data are available relating to intake of Hepa-Merz® Granules in children and during pregnancy. No exhaustive animal studies have been performed for L-ornithine-L-aspartate, to investigate its toxicity in relation to reproduction. Administration of Hepa-Merz® Granules during pregnancy should therefore be avoided. If, however, treatment with Hepa-Merz® Granules is considered necessary, careful consideration should be given to the benefit versus risk ratio. It is not known whether L-ornithine-L-aspartate is excreted into the breast milk. Administration of Hepa-Merz® Granules should therefore be avoided during lactation. If, however, treatment with Hepa-Merz® Granules is considered necessary, careful consideration should be given to the benefit versus risk ratio. No data regarding fertility. Undesirable effects: Uncommon (³ 1/1,000 to < 1/100): Nausea, vomiting, stomach ache, flatulence, diarrhea. Very rare (< 1/10,000): Pain in the limbs. These undesirable effects are usually transient and do not require withdrawal of the medicine. Orange yellow S (E110) can trigger allergic reactions. Warnings : Hepa-Merz® Granules contain fructose. Patients with rare hereditary problems of fructose intolerance should not take this medicine. Further precautions: As a result of the disease, the ability to drive and operate machinery may be impaired during treatment with L-ornithine-L-aspartate.

Hepa-Merz® Infusion concentrate. Composition: One ampoule of 10 ml contains: Active substance: 5 g L-ornithine-L-aspartate. Excipients: Water for injections. Therapeutic indications: Latent and manifest hepatic encephalopathy. Contraindications: Absolute: Hypersensitivity to L-ornithine-L-aspartate. Severe renal impairment (renal failure). A serum creatinine level in excess of 3 mg/100 ml can be taken as a guide. Relative: Pregnancy and lactation: There are no clinical data available on the use of Hepa-Merz® Infusion concentrate in children and during pregnancy. L-ornithine L-aspartate has been investigated for reproduction toxicity only to a limited extent in experimental animal studies. The administration of Hepa-Merz® Infusion concentrate in pregnancy should therefore be avoided. If treatment with Hepa-Merz® is nevertheless thought to be necessary, the benefits and risks should be carefully assessed. It is not known whether L-ornithine-L-aspartate passes into breast milk. Administration of Hepa-Merz® should therefore be avoided during lactation. If treatment with Hepa-Merz® is nevertheless thought to be necessary, the benefits and risks should be carefully assessed. No data regarding fertility. Undesirable effects: Uncommon (³ 1/1,000 to < 1/100): Nausea. Rare (³ 1/10,000 to < 1/1,000): vomiting. Frequency not known (frequency cannot be estimated from the available data): hypersensitivity, anaphylactic reaction. Generally however, the gastrointestinal symptoms are transient, and do not necessitate discontinuation of treatment. They disappear on reduction of the dose or the infusion rate. Further precautions: Hepa-Merz concentrate for solution for infusion can be mixed with the usual infusion solutions. So far, no peculiarities have been observed with regard to miscibility. However, the ampoules should be admixed to the infusion solution only immediately before application. At high doses of Hepa-Merz® Infusion concentrate, serum and urine urea levels should be monitored. If liver function is substantially impaired, the infusion rate must be adjusted to the individual patient in order to prevent nausea and vomiting. Depending on the underlying disease, the ability to drive and operate machines may also be impaired on treatment with L-ornithine L-aspartate. Hepa-Merz® Infusion concentrate must not be injected into an artery. Status: January 2016. Merz Pharmaceuticals GmbH, 60048 Frankfurt.