20th April 2024

Diseases of the Liver

Acute Liver Failure

Background

Functions of the liver include synthesis of albumin, clotting factors and bile, metabolism of drugs and toxins and glucose regulation. Liver failure refers to the development of severe liver injury with encephalopathy and impaired synthetic function. The most common cause of acute liver failure in the UK is paracetamol overdose, but it can also be due to drug reactions, viral infection or ischaemia.

Presentation

Acute liver failure can be hyperacute (<7 days), acute (7-21 days) or subacute (3-26 weeks). Patients are unwell with signs of hepatic encephalopathy and may develop jaundice, tachycardia and reduced blood pressure, mimicking sepsis. It can occur in isolation or on a background of underlying chronic liver disease (known as acute-on-chronic liver failure), which may be mistaken for acute liver failure if it is a first presentation.

Diagnosis

Acute liver failure is a clinical diagnosis based on the presence of hepatic encephalopathy in a patient with acute liver disease. Blood tests will show significantly elevated transaminases (ALT and AST) and bilirubin, prolonged prothrombin time (PT) and high INR (>1.5), and usually low platelet count and serum albumin. Hypoglycaemia is common and patients may develop metabolic acidosis. Paracetamol levels should be performed in patients with suspected overdose, as they can guide treatment. Signs of chronic liver disease (portal hypertension) are absent in acute liver failure.

Management

Acute liver failure can be life-threatening, and supportive management is key. Hepatotoxic drugs should be avoided and patients should receive IV fluid replacement, adequate nutrition (preferably enteral feeding) and vitamin K. Hepatic encephalopathy and renal failure should be monitored for and treated if present. N-acetylcysteine (NAC) is given for paracetamol-induced liver failure and should be considered in all causes of liver failure. A liver transplant may be required in severe cases.

References

• Aral SJ. Acute portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management [Online]. UpToDate. Last Updated 29 August 2022. Available at: https://www.uptodate.com/contents/acute-portal-vein-thrombosis-in-adults-clinical-manifestations-diagnosis-and-management [Accessed 8 December 2022]
• Bloom S, Webster G, Marks D. Oxford Handbook of Gastroenterology and Hepatology, 2nd Edition. Oxford. Oxford University Press. 2011
• Burns MJ, Friedman SL, Larson AM. Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and evaluation [Online]. UpToDate. Last Updated 20 May 2022. Available at: https://www.uptodate.com/contents/acetaminophen-paracetamol-poisoning-in-adults-pathophysiology-presentation-and-evaluation [Accessed 6 December 2022]
• European Association for the Study of the Liver. Guidelines on the management of acute (fulminant) liver failure. J Hepatol. 2017 May;66(5):1047-1081. doi: 10.1016/j.jhep.2016.12.003. PMID: 28417882. [Accessed 21 November 2022]
• Ferenci, P. Hepatic encephalopathy in adults: Clinical manifestations and diagnosis, UpToDate. Last Updated 27 April 2022. Available at: https://www.uptodate.com/contents/hepatic-encephalopathy-in-adults-clinical-manifestations-and-diagnosis [Accessed 28 November 2022]
• Ferenci, P. Hepatic encephalopathy in adults: Treatment, UpToDate. Last Updated 5 April 2022. Available at: https://www.uptodate.com/contents/hepatic-encephalopathy-in-adults-treatment [Accessed 28 November 2022]
• Friedman SL. Alcoholic hepatitis: Clinical manifestations and diagnosis [Online]. UpToDate. Last Updated: 29 July 2022. Available at: https://www.uptodate.com/contents/alcoholic-hepatitis-clinical-manifestations-and-diagnosis [Accessed 23 November 2022]
• Friedman SL. Management and prognosis of alcoholic hepatitis [Online]. UpToDate. Last Updates: 17 May 2022. Available at: https://www.uptodate.com/contents/management-and-prognosis-of-alcoholic-hepatitis [Accessed 23 November 2022]
• Goldberg E, Chopra S, Rubin JN. (2022). Acute liver failure in adults: Etiology, clinical manifestations, and diagnosis. [Online]. UpToDate. Last Updated: 12 May 2022. Available at: https://www.uptodate.com/contents/acute-liver-failure-in-adults-etiology-clinical-manifestations-and-diagnosis [Accessed 21 November 2022]
• Goldberg E, Chopra S, Rubin JN. (2022). Acute liver failure in adults: Management and prognosis. [Online]. Up To Date. Last Updated: 27 April 2022. Available at: https://www.uptodate.com/contents/acute-liver-failure-in-adults-management-and-prognosis?topicRef=35 [Accessed 21 November 2022]
• Lai M. Budd-Chiari syndrome: Epidemiology, clinical manifestations, and diagnosis [Online]. UpToDate. Last Updated 6 September 2022. Available at: https://www.uptodate.com/contents/budd-chiari-syndrome-epidemiology-clinical-manifestations-and-diagnosis [Accessed 7 December 2022]
• Larson AM. Drug-induced liver injury [Online]. UpToDate. Last updated 29 July 2022. Available at: https://www.uptodate.com/contents/drug-induced-liver-injury [Accessed 22 November 2022]
• Lee RH, Lockwood CJ. Acute fatty liver of pregnancy [Online]. UpToDate. Last Updated 12 July 2021. Available at: https://www.uptodate.com/contents/acute-fatty-liver-of-pregnancy [Accessed 7 December 2022]
• Newsome PN, Cramb R, Davison SM, Dillon JF, Foulerton M, Godfrey EM, et al. Guidelines on the management of abnormal liver blood tests. Gut. 2017;67(1):6-19
• Wendon J, Cordoba J, Dhawan A, Larsen FS, Manns M, Nevens F, et al. EASL clinical practical guidelines on the management of acute (fulminant) liver failure. Journal of Hepatology. 2017;May;66(5):1047-81

Chronic Liver Disease and Liver Cirrhosis

Background

Cirrhosis is the final common pathway of many diseases that affect the liver. It is a histological diagnosis characterised by hepatic nodule formation and diffuse fibrosis. The most common causes in the UK include alcoholic liver disease, viral hepatitis (hepatitis C and B) and non-alcoholic fatty liver disease (NAFLD). Other causes include autoimmune liver disease (autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis), haemochromatosis, Wilson’s disease and α-1 antitrypsin deficiency.

Presentation

Cirrhosis can be picked up incidentally in patients with deranged LFTs. It can also present non-specifically or with features of decompensation. Features of decompensation include development of jaundice, hepatic encephalopathy, or ascites.

Diagnosis

Cirrhosis is diagnosed via imaging, with USS showing a small shrunken nodular liver. A liver biopsy can be used to confirm the diagnosis and establish the cause if uncertain. Patients should also be investigated for the presence of oesophageal varices and other features of portal hypertension.

Management

Management of cirrhosis is mostly supportive, with treatment aimed at avoiding complications. Good nutrition and avoidance of alcohol is vital regardless of aetiology and all patients should be prescribed thiamine. Treating the underlying cause can also slow down or even sometimes partially reverse disease progression. Patients should be screened for HCC with regular USS and α-fetoprotein levels. The only curative treatment for cirrhosis is a liver transplant.

References

• Aithal GP, Palaniyappan N, China L, Harmala S, Macken L, Ryan JM, et al. Guidelines on the management of ascites in cirrhosis. Gut. 2020. Oct 16;70(1):gutjnl-2020-321790
• Bacon BR, Phatak P. Clinical manifestations and diagnosis of hereditary hemochromatosis, UpToDate. Last Updated 14 November 2022. Available at: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemochromatosis. [Accessed 13 December 2022]
• Bleibel W, Chopra S, Curry M. Portal hypertension in adults, UpToDate. Last Updated 6 September 2022. Available at: https://www.uptodate.com/contents/portal-hypertension-in-adults [Accessed 8 December 2022]
• Bloom S, Webster G, Marks D. Oxford Handbook of Gastroenterology and Hepatology, 2nd Edition. Oxford. Oxford University Press. 2011
• Chapman MH, Thorburn D, Hirschfield GM, Webster GGJ, Rushbrook SM, Alexander G, et al. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut. 2019 Jun 1;68(8):1356-78
• Gleeson D, Heneghan MA. British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis. Gut. 2011 Jul 13;60(12):1611-29
• Goldberg, E. and Chopra, S. Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis, UpToDate. Last Updated 1 December 2022. Available at: https://www.uptodate.com/contents/cirrhosis-in-adults-etiologies-clinical-manifestations-and-diagnosis [Accessed 21 November 2022]
• Heneghan MA. Overview of autoimmune hepatitis, UpToDate. Last Updated 4 April 2022. Available at: https://www.uptodate.com/contents/overview-of-autoimmune-hepatitis. [Accessed 15 December 2022]
• Hirschfield GM, Dyson JK, Alexander GJM, Chapman MH, Collier J, Hubscher S, et al. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut [Internet]. 2018 Mar 28 [cited 2019 Nov 6];67(9):1568-94. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109281/
• Lok ASF. Hepatitis B virus: Clinical manifestations and natural history, UpToDate. Last Updated 29 April 2020. Available at: https://www.uptodate.com/contents/hepatitis-b-virus-clinical-manifestations-and-natural-history [Accessed 7 December 2022]
• Newsome P, Cramb R, Davison S et al. Guidelines on the management of abnormal liver blood tests. Gut. 2017. gutjnl-2017. 10.1136/gutjnl-2017-314924
• NICE. Cirrhosis. NICE CKS. Last Updated June 2018. Available at: https://cks.nice.org.uk/topics/cirrhosis. [Accessed 21 November 2022]
• NICE. Cirrhosis in over 16s: assessment and management. 6 July 2016. Available at: https://www.nice.org.uk/guidance/ng50/resources/cirrhosis-in-over-16s-assessment-and-management-pdf-1837506577093 [Accessed 22 November 2022]
• NICE. Hepatitis C. NICE CKS. Last Updated September 2022. Available at: https://cks.nice.org.uk/topics/hepatitis-c/ [Accessed 7 December 2022]
• Runyon B. Spontaneous bacterial peritonitis in adults: Clinical manifestations, UpToDate. Last Updated 5 August 2021. Available at: https://www.uptodate.com/contents/spontaneous-bacterial-peritonitis-in-adults-clinical-manifestations [Accessed 13 December 2022]
• Runyon B. Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis, UpToDate. Last Updated 21 March 2022. Available at: https://www.uptodate.com/contents/spontaneous-bacterial-peritonitis-in-adults-treatment-and-prophylaxis. [Accessed 13 December 2022]
• Ryder SD. Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults. Gut [Internet]. 2003 May 1;52(90003):1iii8. Available at: https://gut.bmj.com/content/52/suppl_3/iii1.full
• Tripathi D, Stanley AJ, Hayes PC, Patch D, Millson C, Mehrzad H, et al. UK guidelines on the management of variceal haemorrhage in cirrhotic patients. Gut. 2015 Apr 17;64(11):1680-704
• Tripathi D, Stanley AJ, Hayes PC, Travis S, Armstrong MJ, Tsochatzis EA, et al. Transjugular intrahepatic portosystemic stent-shunt in the management of portal hypertension. Gut. 2020 Feb 29;69(7):1173-92
• Runyon B. Hepatorenal syndrome, UpToDate. Last Updated 13 December 2022. Available at: https://www.uptodate.com/contents/hepatorenal-syndrome [Accessed 15 December 2022]