Cirrhosis: Diagnosis and Management

 

Cirrhosis is the 12th leading cause of death in the United States. Newer research has established that liver fibrosis is a dynamic process and that early cirrhosis may be reversible. Only one in three people with cirrhosis knows they have it. Most patients with cirrhosis remain asymptomatic until the onset of decompensation. When clinical signs, symptoms, or abnormal liver function tests are discovered, further evaluation should be pursued promptly. The most common causes of cirrhosis are viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis. Initial workup includes viral hepatitis serologies, ferritin, transferrin saturation, and abdominal ultrasonography as well as complete blood count, liver function tests, and prothrombin time/international normalized ratio, if not already ordered. Additional testing is based on demographics and risk factors. Common serum and ultrasound-based screening tests to assess fibrosis include the aspartate transaminase to platelet ratio index score, Fibrosis 4 score, FibroTest/FibroSure, nonalcoholic fatty liver fibrosis score, standard ultrasonography, and transient elastography. Generally, noninvasive tests are most useful in identifying patients with no to minimal fibrosis or advanced fibrosis. Chronic liver disease management includes directed counseling, laboratory testing, and ultrasound monitoring. Treatment goals are preventing cirrhosis, decompensation, and death. Varices are monitored with endoscopy and often require prophylaxis with nonselective beta blockers. Ascites treatment includes diuresis, salt restriction, and antibiotic prophylaxis for spontaneous bacterial peritonitis, when indicated. Hepatic encephalopathy is managed with lifestyle and nutritional modifications and, as needed, with lactulose and rifaximin. Hepatocellular carcinoma screening includes ultrasound screening every six months for patients with cirrhosis.

Cirrhosis is a diffuse process of liver damage considered irreversible in its advanced stages. In 2016, more than 40,000 Americans died because of complications related to cirrhosis, making it the 12th leading cause of death in the United States.1 Recent projections suggest that this number is likely to grow.2 An estimated 630,000 Americans have cirrhosis, yet less than one in three knows it.3 Important racial and socioeconomic disparities exist, with prevalence highest among non-Hispanic blacks, Mexican Americans, and those living below the poverty level.3 Cirrhosis and advanced liver disease cost the United States between $12 billion and $23 billion dollars in health care expenses annually.4,5

WHAT'S NEW ON THIS TOPIC

Cirrhosis

Estimates suggest that nonalcoholic steatohepatitis will become the leading cause of cirrhosis in U.S. patients awaiting liver transplantation sometime between 2025 and 2035.

Liver biopsy remains the reference standard; however, transient elastography has become more widely available and is rapidly replacing biopsy as the preferred method for liver fibrosis staging.

Newer guidelines suggest targeted screening for esophageal varices in patients with clinically significant portal hypertension rather than screening all patients with cirrhosis.

 Enlarge     Print

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComments

Further evaluation of patients with clinical signs or symptoms of liver disease or abnormal liver function tests should be pursued to determine the potential etiology, regardless of duration of the abnormality.19,20

C

Expert opinion and consensus guidelines in the absence of clinical trials

All patients with cirrhosis should be evaluated for hepatocellular carcinoma with ultrasonography every six months.43

C

Expert opinion and consensus guidelines with low-quality trials

Patients with cirrhosis who have a Model for End-Stage Liver Disease score of 15 or more, or complications of cirrhosis that include ascites, hepatic encephalopathy, or variceal hemorrhage, should be referred to a transplant center.37

B

Randomized controlled trials demonstrate acceptable survival benefits based on clinical criteria and Model for End-Stage Liver Disease results with some variability

Patients with clinically apparent (i.e., moderate to severe) ascites should be managed with salt restriction and spironolactone with or without loop diuretics.49

B

Data from multiple randomized controlled trials demonstrate more benefit than harm regarding patient comfort and reduced hospitalization times

Patients with cirrhosis who have medium, large, or high-risk varices (red wale markings) should be treated with nonselective beta blockers and/or endoscopic band ligation for primary prevention of variceal bleeds.7,9,46,53

B

Randomized controlled trials and meta-analyses comparing nonselective beta blockers, endoscopic band ligation, and placebo or no therapy, which generally show a reduction in variceal hemorrhage

Persistent hepatic

The Authors

show all author info

ANDREW SMITH, MD, is the director of obstetrics curriculum and a core faculty member of the Lawrence Family Medicine Residency Program at the Greater Lawrence (Mass.) Family Health Center and is an assistant professor at Tufts University Medical School, Boston, Mass....

KATRINA BAUMGARTNER, MD, is an HIV specialist and staff family physician and community faculty of the Lawrence Family Medicine Residency Program at the Greater Lawrence Family Health Center and is a clinical instructor at Tufts University Medical School.

CHRISTOPHER BOSITIS, MD, is the clinical program director of the HIV and Viral Hepatitis programs at Greater Lawrence Family Health Center, a core faculty member of the Lawrence Family Medicine Residency Program at the Greater Lawrence Family Health Center, and an assistant professor at Tufts University Medical School.

Address correspondence to Andrew Smith, MD, Greater Lawrence Family Health Center, 34 Haverhill St., Lawrence, MA 01841 (email: asmith@glfhc.org). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

References

show all references

1. Kochanek KD, Murphy S, Xu J, et al. Mortality in the United States, 2016. NCHS Data Brief. 2017;(293):1–8....

2. Best AF, Haozous EA, Berrington de Gonzalez A, et al. Premature mortality projections in the USA through 2030: a modelling study [published correction appears in Lancet Public Health. 2018;3(8):e364]. Lancet Public Health. 2018;3(8):e374–e384.

3. Scaglione S, Kliethermes S, Cao G, et al. The epidemiology of cirrhosis in the United States: a population-based study. J Clin Gastroenterol. 2015;49(8):690–696.

4. Peery AF, Crockett SD, Murphy CC, et al. Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: update 2018 [published correction appears in Gastroenterology. 2019;156(6):1936]. Gastroenterology. 2019;156(1):254–272.e11.

5. National Institute of Diabetes and Digestive and Kidney Diseases. The burden of digestive diseases in the United States. January 2008. Accessed January 4, 2019. https://www.niddk.nih.gov/about-niddk/strategic-plans-reports/burden-of-digestive-diseases-in-united-states

6. Wong RJ, Aguilar M, Cheung R, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148(3):547–555.

7. Ge PS, Runyon BA. Treatment of patients with cirrhosis. N Engl J Med. 2016;375(8):767–777.

8. Wiegand J, Berg T. The etiology, diagnosis and prevention of liver cirrhosis: part 1 of a series on liver cirrhosis. Dtsch Arztebl Int. 2013;110(6):85–91.

9. National Institute for Health and Care Excellence. Cirrhosis in over 16s: assessment and management. NICE guideline [NG50]. July 2016. Accessed May 28, 2019. https://www.nice.org.uk/guidance/ng50

10. Poynard T, Mathurin P, Lai CL, et al.; PANFIBROSIS Group. A comparison of fibrosis progression in chronic liver diseases. J Hepatol. 2003;38(3):257–265.

11. Bonis PA, Friedman SL, Kaplan MM. Is liver fibrosis reversible? N Engl JMed. 2001;344(6):452–454.

12. Jung YK, Yim HJ. Reversal of liver cirrhosis: current evidence and expectations. Korean J Intern Med. 2017;32(2):213–228.

13. Lassailly G, Caiazzo R, Buob D, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149(2):379–388.

14. Asrani SK, Kamath PS. Natural history of cirrhosis. Curr Gastroenterol Rep. 2013;15(2):308.

15. D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44(1):217–231.

16. Stanford Medicine. Liver disease, head to foot. Accessed January 4, 2019. http://stanfordmedicine25.stanford.edu/the25/liverdisease.html

17. Reuben A. The liver has a body—a Cook's tour. Hepatology. 2005;41(2):408–415.

18. Udell JA, Wang CS, Tinmouth J, et al. Does this patient with liver disease have cirrhosis? JAMA. 2012;307(8):832–842.

19. Oh RC, Hustead TR, Ali SM, et al. Mildly elevated liver transaminase levels: causes and evaluation. Am Fam Physician. 2017;96(11):709–715. Accessed August 28, 2019. https://www.aafp.org/afp/2017/1201/p709.html

20. Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut. 2018;67(1):6–19.

21. O'Shea RS, Dasarathy S, McCullough AJ; Practice Guideline Committee of the American Association for the Study of Liver Diseases; Practice Parameters Committee of the American College of Gastroenterology. Alcoholic liver disease. Hepatology. 2010;51(1):307–328.

22. Bacon BR, Adams PC, Kowdley KV, et al.; American Association for the Study of Liver Diseases. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54(1):328–343.

23. Wilkins T, Akhtar M, Gititu E, et al. Diagnosis and management of hepatitis C. Am Fam Physician. 2015;91(12):835–842. Accessed August 28, 2019. https://www.aafp.org/afp/2015/0615/p835.html

24. Lurie Y, Webb M, Cytter-Kuint R, et al. Non-invasive diagnosis of liver fibrosis and cirrhosis. World J Gastroenterol. 2015;21(41):11567–11583.

25. Lin ZH, Xin YN, Dong QJ, et al. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011;53(3):726–736.

26. Parikh P, Ryan JD, Tsochatzis EA. Fibrosis assessment in patients with chronic hepatitis B virus (HBV) infection. Ann Transl Med. 2017;5(3):40.

27. World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. March 2015. Accessed January 4, 2019. https://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en/

28. Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and Fibrotest. Hepatology. 2007;46(1):32–36.

29. Shah AG, Lydecker A, Murray K, et al.; Nash Clinical Research Network. Comparison of noninvasive markers of fibrosis in patients with non-alcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7(10):1104–1112.

30. Ratziu V, Massard J, Charlotte F, et al.; LIDO Study Group; CYTOL Study Group. Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol. 2006;6:6.

31. Imbert-Bismut F, Ratziu V, Pieroni L, et al.; MULTIVIRC Group. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet. 2001;357(9262):1069–1075.

32. Salkic NN, Jovanovic P, Hauser G, et al. FibroTest/Fibrosure for significant liver fibrosis and cirrhosis in chronic hepatitis B: a meta-analysis. Am J Gastroenterol. 2014;109(6):796–809.

33. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846–854.

34. Castéra L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128(2):343–350.

35. Hashemi SA, Alavian SM, Gholami-Fesharaki M. Assessment of transient elastography (FibroScan) for diagnosis of fibrosis in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Caspian J Intern Med. 2016;7(4):242–252.

36. Colli A, Fraquelli M, Andreoletti M, et al. Severe liver fibrosis or cirrhosis: accuracy of US for detection—analysis of 300 cases. Radiology. 2003;227(1):89–94.

37. Martin P, DiMartini A, Feng S, et al. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology. 2014;59(3):1144–1165.

38. European Association for Study of Liver; Asociacion Latinoamericana para el Estudio del Higado. EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015;63(1):237–264.

39. Noureddin M, Loomba R. Nonalcoholic fatty liver disease: indications for liver biopsy and noninvasive biomarkers. Clin Liver Dis (Hoboken). 2012;1(4):104–107.

40. Geng XX, Huang RG, Lin JM, et al. Transient elastography in clinical detection of liver cirrhosis: a systematic review and meta-analysis. Saudi J Gastroenterol. 2016;22(4):294–303.

41. Bonekamp S, Kamel I, Solga S, et al. Can imaging modalities diagnose and stage hepatic fibrosis and cirrhosis accurately? J Hepatol. 2009;50(1):17–35.

42. Saverymuttu SH, Joseph AE, Maxwell JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed). 1986;292(6512):13–15.

43. 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(2):723–750.

44. Afdhal NH. Diagnosing fibrosis in hepatitis C: is the pendulum swinging from biopsy to blood tests? Hepatology. 2003;37(5):972–974.

45. Herrera JL, Rodríguez R. Medical care of the patient with compensated cirrhosis. Gastroenterol Hepatol (N Y). 2006;2(2):124–133.

46. Garcia-Tsao G, Abraldes JG, Berzigotti A, et al. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the Study of Liver Diseases [published correction appears in Hepatology. 2017;66(1):304]. Hepatology. 2017;65(1):310–335.

47. Addolorato G, Mirijello A, Leggio L, et al. Management of alcohol dependence in patients with liver disease. CNS Drugs. 2013;27(4):287–299.

48. Addolorato G, Leggio L, Ferrulli A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet. 2007;370(9603):1915–1922.

49. Runyon BA. Management of adult patients with ascites due to cirrhosis: update 2012. Accessed August 20, 2019. https://www.aasld.org/sites/default/files/2019-06/141020_Guideline_Ascites_4UFb_2015.pdf

50. Wadhawan M, Anand AC. Coffee and liver disease. J Clin Exp Hepatol. 2016;6(1):40–46.

51. Zhang X, Harmsen WS, Mettler TA, et al. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology. 2014;60(6):2008–2016.

52. Glass LM, Dickson RC, Anderson JC, et al. Total body weight loss of ≥ 10% is associated with improved hepatic fibrosis in patients with non-alcoholic steatohepatitis. Dig Dis Sci. 2015;60(4):1024–1030.

53. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis [published correction appears in J Hepatol. 2018;69(5):1207]. J Hepatol. 2018;69(2):406–460.

54. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715–735.

55. Terrault NA, Lok AS, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560–1599.

56. Starr SP, Raines D. Cirrhosis: diagnosis, management, and prevention. Am Fam Physician. 2011;84(12):1353–1359. Accessed August 28, 2019. https://www.aafp.org/afp/2011/1215/p1353.html

57. Heidelbaugh JJ, Bruderly M. Cirrhosis and chronic liver failure: part I. Diagnosis and evaluation. Am Fam Physician. 2006;74(5):756–762. Accessed August 28, 2019. https://www.aafp.org/afp/2006/0901/p756.html

58. Riley TR III, Bhatti AM. Preventive strategies in chronic liver disease: part II. Cirrhosis. Am Fam Physician. 2001;64(10):1735–1740. Accessed August 28, 2019. https://www.aafp.org/afp/2001/1115/p1735.html

 

 

Copyright © 2019 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions

CME Quiz

More in AFP


Editor's Collections


Related Content


More in Pubmed

MOST RECENT ISSUE


Apr 1, 2020

Access the latest issue of American Family Physician

Read the Issue


Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article