#100: Cirrhosis: Initial Evaluation and Management

June 18, 2018 | By Cyrus Askin

Cirrhosis. Finally. Take your liver game to the next level with tips from @liverprof, Scott Matherly MD, Assistant Professor of Medicine at Virginia Commonwealth University. Topics include: exam findings in cirrhosis, interpreting liver function tests, incidental cirrhosis on imaging, fatty liver disease, steatohepatitis, hep c, shear wave elastography, screening for varices and hepatocellular carcinoma, pathophysiology, and lifestyle measures for initial management. This episode is sponsored for CME-MOC credit by the American College of Physicians. ACP members can claim free credit at acponline.org/curbsiders (goes live at 9am on release date).

Credits:
Written by: Cyrus Askin MD
CME questions by: Cyrus Askin MD
Produced by: Cyrus Askin MD and Matthew Watto MD
Hosts: Cyrus Askin MD, Matthew Watto MD, Stuart Brigham MD, Paul Williams MD
Guest: Scott Matherly MD

Shear wave elastography: Can effectively diagnosis cirrhosis in thin patients with hepatitis C. More useful for negative predictive value in obese patients with diabetes and/or fatty liver disease (i.e. a negative test is reassuring, but an intermediate or high risk test needs liver biopsy to confirm). –Dr Matherly

Red flags on lab testing:  Low albumin, low platelets, and/or prolonged INR. –Dr Matherly

Screen for varices in cirrhosis at the time of diagnosis. Subsequent testing every 1-3 years based on size. -Dr Matherly

Screen for hepatocellular carcinoma with hepatic ultrasound every 6 months after a diagnosis of cirrhosis. Alpha fetoprotein was removed from the guidelines, but some experts still use it to augment screening. -Dr Matherly

Diet: High protein diet (at least 1 gm/kg body weight/day) is recommended due to cirrhosis being a catabolic state. Low sodium diet is not useful for cirrhotics unless ascites is present. -Dr Matherly

In-depth Show Notes

The seven hand findings of cirrhosis: 

1. Palmar Erythema ¹
2. Dupuytren’s contracture² 
3. Asterixis ³ 
4. Terry’s Nails ⁴ 
5. Clubbing ⁵ 
6. Spider angiomas ⁶ 
7. Muscle wasting ⁷ 

Laboratory Assessment – AST, ALT & Beyond

1. Normal ALT – most lab values are NOT evidence based ⁸
   1. Female: 19-25 IU/L
   2. Male: 29-33 IU/L
2. Thrombocytopenia: an immediate red flag when evaluating a patient for liver disease (<150×10⁹) ⁹
   1. This may indicate advanced disease as the thrombocytopenia is often due to portal hypertension, which develops in the setting of cirrhosis and leads to splenic sequestration of platelets/ hypersplenism
3. Albumin: hypoalbuminemia due to liver disease suggests advanced liver disease ¹⁰ 
4. PT/INR: One of the most sensitive markers for hepatic function, elongated INR suggests advanced liver disease, readily available virtually anywhere ¹¹ 
5. FIB-4: First developed for estimating degree of fibrosis in HIV/HCV co-infection; later found to be more generalizable. Useful when imaging is not already available, to screen patients when there is concern for cirrhosis ¹² 
   1. FIB-4=Age×ASTPLT×ALT
   2. <1.45 has NPV of 90% for advanced fibrosis (sens. 81%)
   3. >3.25 has PPV of 65% for advanced fibrosis (sens. 97%)
   4. Fib4, and other non-invasive tests, are “good at the margins” – indeterminate scores need to be invasively evaluated – Dr. Matherly
6. Don’t forget hepatitis C testing!
   1. HCV: If born 1945-1965, CDC recommends Hep C testing ¹³ 

Beyond Blood Tests

1. Shear-wave elastography/vibration controlled transient elastography ¹⁴ 
   1. Non-invasive means to determine “liver stiffness” and from there, extrapolate extent of fatty infiltration and/or fibrosis
   2. Dr. Matherly: “Essentially replaced liver biopsy (in hepatitis C)”
   3. Fatty liver disease: negative predictive tool
2. Ultrasound: with respect to fibrosis shows changes when disease is advanced, not useful for identifying early fibrosis ¹⁵ 
3. Liver biopsy: the gold standard, limited by sampling bias ^16,17

Cirrhosis can kill you in three ways

1. Liver failure
   1. Check & trend MELD scores ¹⁸
2. Variceal Bleeding ¹⁹ 
   1. > ¼ patients who have an index variceal bleed will die of variceal bleeding
   2. Baveno VI: PLT > 150 and shear-wave elastography demonstrating liver stiffness < 20 kPa, EGD can be circumvented as risk of varices is < 5%^19,20 
   3. EGD is gold standard ¹⁹ 
      1. Allows you to quantify and characterize varices
      2. If no varices: repeat in 3 years
      3. Small varices: repeat EGD every 1-2 years
   4. It boils down to how large they are (correlates with bleeding risk)
3. Hepatocellular carcinoma ²¹
   1. Risk of liver cancer in a cirrhotic is anywhere from 3-5% per year
   2. Ultrasound surveillance every 6 months following initial diagnosis

Disclosures: Dr. Matherly reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.

Time Stamps 

• 00:00 Announcements
• 00:45 Disclaimer
• 01:19 Intro to the show and our guest
• 04:15 Guest one liner, books recommendations, and career advice
• 09:04 Cyrus’ pick of the week
• 10:14 Clinical case of abnormal liver functions tests
• 11:12 Seven hand findings of cirrhosis
• 13:28 Should we screen for NASH?
• 15:28 Incidental finding of cirrhosis on imaging
• 17:47 Next steps after diagnosis of cirrhosis
• 20:36 Non-invasive scoring systems to predict cirrhosis
• 23:55 Liver biopsy
• 25:33 Shear wave elastography
• 29:10 Recap of what we learned so far
• 31:58 Three ways cirrhosis can kill you
• 33:56 Counseling patients about cirrhosis
• 36:05 Management of NASH and early  cirrhosis
• 42:55 Screening for varices and hepatocellular carcinoma
• 46:28 Outro

Goal: Listeners will know the basics regarding pathophysiology in cirrhotic patients, know how to approach a patient with elevated liver-associated enzymes when cirrhosis is on the differential and know about scoring systems / tests to identify / grade cirrhosis. Importantly, they will know what evidence-based interventions they can make at the primary care level which may improve morbidity and mortality.  They will know the complications of cirrhosis and how to screen for them based on the most recent evidence.

Learning objectives:

After listening to this episode listeners will…

1. Understand the pathophysiology of cirrhosis, specifically the process through which fatty-infiltration develops into fibrosis and ultimately into the disease known as cirrhosis
2. Be able to identify the common causes for cirrhosis: HBV, HCV, Alcoholism, non-alcoholic steatohepatitis
3. Know what primary care interventions can be made to help prevent the development of cirrhosis
4. Know who to screen and how to screen for cirrhosis in asymptomatic patients with risk factors
5. Know the appropriate work up for a patient who presents with elevated liver-associated enzymes when there is concern for cirrhosis
6. Recall the tools/labs/studies are available for evaluating a patient when concerned for cirrhosis
7. Be comfortable with evidence-based interventions the primary care provider may use to treat the cirrhotic patient
8.  Know the complications associated with cirrhosis, how/when to screen for them and the basics regarding their management
9. When to refer to a hepatologist and what role do hepatologists play in the outpatient management of a cirrhotic patient

Links

• Attending: Medicine, Mindfulness, and Humanity (book) by Ronald Epstein
• Battlefield 1 (video game)
• The Art of Racing in the Rain (book) by Garth Stein
• Ge PS, Runyon BA. Treatment of Patients with Cirrhosis. N Engl J Med. 2016;375(8):767-77.

Sources

1. Serrao R, Zirwas M, English JC. Palmar erythema. Am J Clin Dermatol. 2007;8(6):347-56.
2. Davidson CS, Summerskill WH, Wolfe SJ. Thickening and contraction of the palmar fascia (Dupuytren’s contracture) associated with alcoholism and hepatic cirrhosis. N Engl J Med. 1956;255(12):559-63.
3. Butz M, Timmermann L, Gross J, et al. Cortical activation associated with asterixis in manifest hepatic encephalopathy. Acta Neurol Scand. 2014;130(4):260-7.
4. Baran B, Soyer OM, Karaca C. Terry’s nail: an overlooked physical finding in cirrhosis. HBPD INT. 2013;12(1):109.
5. Callemeyn J, Van haecke P, Peetermans WE, Blockmans D. Clubbing and hypertrophic osteoarthropathy: insights in diagnosis, pathophysiology, and clinical significance. Acta Clin Belg. 2016;71(3):123-30.
6. Li CP, Lee FY, Hwang SJ, et al. Spider angiomas in patients with liver cirrhosis: role of vascular endothelial growth factor and basic fibroblast growth factor. World J Gastroenterol. 2003;9(12):2832-5.
7. Montano-loza AJ. Clinical relevance of sarcopenia in patients with cirrhosis. World J Gastroenterol. 2014;20(25):8061-71.
8. Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol. 2017;112(1):18-35.
9. Gangireddy VG, Kanneganti PC, Sridhar S, Talla S, Coleman T. Management of thrombocytopenia in advanced liver disease. Can J Gastroenterol Hepatol. 2014;28(10):558-64.
10. Spinella R, Sawhney R, Jalan R. Albumin in chronic liver disease: structure, functions and therapeutic implications. Hepatol Int. 2016;10(1):124-32.
11. Schuppan D, Afdhal N. Liver cirrhosis. Lancet. 2008;371: 838-51.
12. Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317-25.
13. Testing Recommendations for Hepatitis C Infection. Centers for Disease Control and Prevention. https://www.cdc.gov/hepatitis/hcv/guidelinesc.htm. Last update 10/2015. Accessed 6/2018.
14. De lédinghen V, Vergniol J. Transient elastography (FibroScan). Gastroenterol Clin Biol. 2008;32(6 Suppl 1):58-67.
15. 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):13-5.
16. Germani G, Hytiroglou P, Fotiadu A, Burroughs AK, Dhillon AP. Assessment of fibrosis and cirrhosis in liver biopsies: an update. Semin Liver Dis. 2011;31(1):82-90.
17. Rockey D, et al. Liver Biopsy. 2009 position paper by the American Association for the study of liver diseases. Hepatology 2009;49(3):1017-43 
18. Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33(2):464-70.
19. Garcia-tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology. 2017;65(1):310-335.
20. De franchis R. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743-52.
21. Heimbach J, Kulik L, et al. Guidelines for the Treatment of Hepatocellular Carcinoma: 2018 practice guidance by the American Association for the study of liver diseases. Hepatology. 2018;67(1):358-80.