Clinical Review

Cirrhosis Complications: Keeping Them Under Control

Clinician Reviews. 2015 June;25(6):338-342

References

1. Scaglion S, Kliethermes S, Cao G, et al. The epidemiology of cirrhosis in the United States: A population-based study. J Clin Gastroenterol. 2014. October 8. [Epub ahead of print.]

2. Murphy SL, Xu JQ, Kochanek KD. Deaths: Final data for 2010. National Vital Statistics Reports. National Center for Health Statistics Web site. Available at: http://www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_04.pdf. Accessed April 30, 2015.

3. National Institute of Diabetes and Digestive and Kidney Diseases. Cirrhosis. National Institute of Diabetes and Digestive and Kidney Diseases Web site. Available at: http://www.niddk.nih.gov/health-information/health-topics/liver-disease/cirrhosis/Pages/facts.aspx. Accessed April 30, 2015.

4. Zhou WC, Zhang QB, Qiao L. Pathogenesis of liver cirrhosis. World J Gastroenterol. 2014;20:7312-7324.

5. Ginès P, Cárdenas A, Arroyo V, et al. Management of cirrhosis and ascites. N Eng J Med. 2004;350:1646-1654.

6. Grattagliano I, Ubaldi E, Bonfrate L, et al. Management of liver cirrhosis between primary care and specialists. World J Gastroenterol. 2011;17:2273-2282.

7. Centers for Disease Control and Prevention. 2015 recommended immunizations for adults: By age. Centers for Disease Control and Prevention Web site. Available from: http://www.cdc.gov/vaccines/schedules/downloads/adult/adult-schedule-easyread.pdf. Accessed April 28, 2015.

8. Bacon BR. Cirrhosis and its complications. In: Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012. Available from: http://accessmedicine.mhmedical.com/content.aspx?bookid=1130&sectionid=79748841. Accessed April 28, 2015.

9. O’Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Am J Gastroenterol. 2010;105:14-32.

10. National Institute on Alcohol Abuse and Alcoholism. Alcohol Alert. Alcoholic liver disease. U.S. Department of Health & Human Services. 2005. National Institute on Alcohol Abuse and Alcoholism Web site. Available at: http://pubs.niaaa.nih.gov/publications/aa64/aa64.htm. Accessed April 18, 2015.

11. Kashani A, Landaverde C, Medici V, et al. Fluid retention in cirrhosis: pathophysiology and management. QJM. 2008;101:71-85.

12. Chalasani NP, Vuppalanchi RK. Ascites: A common problem in people with cirrhosis. July 2013. American College of Gastroenterology Web site. Available at: http://patients.gi.org/topics/ascites/. Accessed April 28, 2015.

13. Kuiper JJ, van Buuren HR, de Man RA. Ascites in cirrhosis: a review of management and complications. Neth J Med. 2007;65:283-288.

14. Biecker E. Diagnosis and therapy of ascites in liver cirrhosis. World J Gastroentol. 2011;17:1237-1248.

15. Heidelbaugh JJ, Sherbondy M. Cirrhosis and chronic liver failure: Part II. Complications and treatment. Am Fam Physician. 2006;74:767-776.

16. Garcia-Tsao G, Lim JK; Members of Veterans Affairs Hepatitis C Resource Center Program. Management and treatment of patients with cirrhosis and portal hypertension: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program. Am J Gastroenterol. 2009;104:1802-1829.

17. Infante-Rivard C, Esnaola S, Villeneuve JP. Clinical and statistical validity of conventional prognostic factors in predicting shortterm survival among cirrhotics. Hepatology. 1987;7:660-664.

18. Garcia-Tsao G, Sanyal AJ, Grace ND, et al; Practice Guidelines Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46:922-938.

19. Serste T, Melot C, Francoz C, et al. Deleterious effects of betablockers on survival in patients with cirrhosis and refractory ascites. Hepatology. 2010;52:1017-1022.

20. Mandorfer M, Bota S, Schwabl P, et al. Nonselective b blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology. 2014;146:1680–1690.e1.

21. Sarin SK, Lamba GS, Kumar M, et al. Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding. N Engl J Med. 1999;340:988-993.

22. Garcia-Pagan JC, Feu F, Bosch J, et al. Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis. A randomized controlled study. Ann Intern Med. 1991;114:869-873.

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Take steps to prevent variceal bleeding

Soon after a patient is diagnosed with cirrhosis, he or she should undergo esophagogastroduodenoscopy to screen for the presence and size of varices.¹⁶ Although they can’t prevent esophagogastric varices, nonselective beta-blockers (NSBBs) are the gold standard for preventing first variceal hemorrhage in patients with small varices with red wale signs on the varices and/or Child-Pugh Class B or C cirrhosis (TABLE¹⁷), and in all patients with medium or large varices.¹⁸ Propranolol is usually started at 20 mg BID, or nadolol is started at 20 to 40 mg/d.¹⁶ The NSBB dose is adjusted to the maximum tolerated dose, which occurs when the patient's heart rate is reduced to 55 to 60 beats/min.

NSBBs are associated with poor survival in patients with refractory ascites and thus are contraindicated in these patients.¹⁹ NSBBs also should not be taken by patients with SBP because use of these medications is associated with worse outcomes compared to those not receiving NSBBs.²⁰

Endoscopic variceal ligation is an alternative to NSBBs for the primary prophylaxis of variceal hemorrhage in patients with medium to large varices.¹⁸ In particular, ligation should be considered for patients with high-risk varices in whom beta-blockers are contraindicated or must be discontinued because of adverse effects.²¹

Avoid nitrates in patients with varices because these agents do not prevent first variceal hemorrhage and have been associated with higher mortality rates in patients older than 50.¹⁶ There is no significant additional benefit or mortality reduction associated with adding a nitrate to an NSBB.²² Transjugular intrahepatic portosystemic shunt (TIPS) or surgically created shunts are reserved for patients for whom medical therapy fails.¹⁸

Mental status changes suggest hepatic encephalopathy

Hepatic encephalopathy is a reversible impairment of neuropsychiatric function that is associated with impaired hepatic function. Because a patient with encephalopathy presents with an altered mental status, he or she may need to be admitted to the hospital for evaluation, diagnosis, and treatment.

The goals of hepatic encephalopathy treatment are to identify and correct precipitating causes and lower serum ammonia concentrations to improve mental status.¹⁵Nutritional support should be provided without protein restriction unless the patient is severely proteinintolerant.²³ The recommended initial therapy is lactulose 30 to 45 mL 2 to 4 times per day, to decrease absorption of ammonia in the gut. The dose should be titrated until patients have 2 to 3 soft stools daily.²⁴

For patients who can’t tolerate lactulose or whose mental status doesn’t improve within 48 hours, rifaximin 400 mg orally 3 times daily or 550 mg 2 times daily is recommended.²⁵ Neomycin 500 mg orally 3 times a day or 1 g twice daily is a second-line agent reserved for patients who are unable to take rifaximin; however, its efficacy is not well established, and neomycin has been associated with ototoxicity and nephrotoxicity.²⁴

Watch for signs of kidney failure

Hepatorenal syndrome is renal failure induced by severe hepatic injury and characterized by azotemia and decreased renal blood flow and glomerular filtration rate.¹⁵ It is a diagnosis of exclusion. Hepatorenal syndrome is typically caused by arterial vasodilation in the splanchnic circulation in patients with portal hypertension.^15,26,27 Type 1 hepatorenal syndrome is characterized by at least a 2-fold increase in serum creatinine to a level of >2.5 mg/dL over more than 2 weeks. Patients typically have urine output <400 to 500 mL/d. Type 2 hepatorenal syndrome is characterized by less severe renal impairment; it is associated with ascites that does not improve with diuretics.²⁸

Endoscopic variceal ligation is an alternative to nonselective beta-blockers for preventing variceal hemorrhage in patients with medium to large varices.

Patients with hepatorenal syndrome should not use any nephrotoxic agents, such as nonsteroidal anti-inflammatory drugs. Inpatient treatment is usually required and may include norepinephrine with albumin, terlipressin with midodrine, or octreotide and albumin. Patients who fail to respond to medical therapy may benefit from TIPS as a bridge until they can undergo liver transplantation.²⁹

When to consider liver transplantation

The appropriateness and timing of liver transplantation should be determined on a case-by-case basis. For some patients with cirrhosis, transplantation may be the definitive treatment. For example, in some patients with hepatocellular carcinoma (HCC), liver transplantation is an option because transplantation can cure the tumor and underlying cirrhosis. However, while transplantation is a suitable option for early HCC in patients with cirrhosis, it has been shown to have limited efficacy in patients with advanced disease who are not selected using specific criteria.³⁰

Referral for evaluation for transplantation should be considered once a patient with cirrhosis experiences a major complication (eg, ascites, variceal hemorrhage, or hepatic encephalopathy).³¹ Another criterion for timing and allocation of liver transplantation is based on the statistical model for end-stage liver disease (MELD), which is used to predict 3-month survival in patients with cirrhosis based on the relationships between serum bilirubin, serum creatinine, and international normalized ratio values.¹⁵ Liver transplantation should be considered for patients with a MELD score ≥15.^15,31 Such patients should be promptly referred to a liver transplantation specialist to allow sufficient time for the appropriate psychosocial assessments and medical evaluations, and for patients and their families to receive appropriate education on things like the risks and benefits of transplantation.¹⁵