Cirrhosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sudarshana Datta, MD [2]

Overview

Cirrhosis may present in a similar way to some other diseases. History, physical examination, and diagnostic testing may help in differentiating cirrhosis from other diseases such as malignancy, constrictive pericarditis, Budd-Chiari syndrome, portal vein thrombosis and splenic vein thrombosis.

Differentiating Cirrhosis From Other Diseases

Differential diagnosis of jaundice

Differential diagnosis of jaundice are enlisted in the table below:[1][2][3][4][5]

Classification of jaundice based on etiology Disease History and clinical manifestations Diagnosis
Lab Findings Other blood tests Other diagnostic
Family history Fever Right upper quadrant (RUQ) Pain Pruritis Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) ALK Bilirubin (Indirect) Bilirubin (Direct) Viral serology
Jaundice Hepatocellular Jaundice Liver infiltration: Hemochromatosis, amyloidosis + - -/+ - ↑ ↑ ↑/N ↑/N N - Ferritin ↑ in hemochromatosis Liver biopsy
Wilson's disease + - -/+ - ↑ ↑ N ↑/N N - Serum ceruloplasmin ↑ Liver biopsy
Viral hepatitis - -/+ - - ↑ ↑ N ↑/N N + Specific viral antibody for each type -
Alcoholic hepatitis - -/+ -/+ - ↑↑ ↑ N ↑/N N - - -
Drug induced hepatitis - -/+ - - ↑ ↑ N ↑/N N - - -
Autoimmune hepatitis -/+ - - -/+ ↑ ↑ N ↑/N N - Anti-LKM antibody Liver biopsy
Cirrhosis -/+ -/+ -/+ - ↑ ↑ ↑/N ↑/N ↑/N -/+ Low platelet count Small liver on ultrasound
Nonalcoholic steatohepatitis -/+ - - - ↑ ↑ N ↑/N N - High lipids Liver biopsy
Ischemic hepatopathy -/+ - -/+ - ↑ ↑ N ↑/N N - Cardiovascular risk factors Clinical setting
Cholestatic Jaundice Common bile duct stone -/+ - + + N N ↑ N ↑ - Dilated ducts on sonography CT scan/ERCP
Hepatitis A (cholestatic type) - -/+ + + N N ↑ N ↑ + Anti-HAV antibody Abdominal ultrasound
EBV / CMV hepatitis - -/+ + + N N ↑ N ↑ + Positive serology -
Primary biliary cirrhosis -/+ - -/+ + N/↑ N/↑ ↑ N ↑ - Antimitochondrial antibody (AMA) positive Liver biopsy
Primary sclerosing cholangitis -/+ - -/+ + N/↑ N/↑ ↑ N ↑ - Positive autoantibodies (p-ANCA) Beading on MRCP,

Liver biopsy

Sickle cell disease + - - +/- N/↑ N/↑ ↑ N ↑ - Genetic testing
Pancreatic carcinoma + - -/+ -/+ N/↑ N/↑ ↑ N ↑ - - CT scan for diagnosis
AIDS cholangiopathy - - -/+ -/+ N/↑ N/↑ ↑ N ↑ - Positive HIV Sonography or ERCP for diagnosis
Parasite induces cholestasis - - -/+ -/+ N/↑ N/↑ ↑ N ↑ - Antibodies or parasite serology Sonography or ERCP for diagnosis
Intrahepatic cholestasis of pregnancy -/+ - -/+ + ↑ ↑ ↑ N ↑ - Low platelets, Negative viral serology Diagnosed clinically
Isolated Jaundice Crigler-Najjar type 2 + - - - N N N ↑ ↑ - Genetic testing
Gilbert syndrome + - - - N N N ↑ ↑ - Genetic testing
Rotor syndrome + - - - N N N N ↑ - Genetic testing Liver biopsy
Dubin-Johnson syndrome + - - - N N N N ↑ - Genetic testing Liver biopsy
Hereditary spherocytosis + - -/+ - N N N ↑ N - Genetic testing Osmotic fragility
Glucose 6 phosphate dehydrogenase (G6PD) deficiency + - - - N N N ↑ N - Genetic testing
Thalassemia + - - - N N N ↑ N - Genetic testing
Paroxysmal nocturnal hemoglobinuria (PNH) - - - - N N N ↑ N - Flow cytometery
Immune hemolysis - -/+ - - N N N ↑ N - Autoantibodies
Hematoma - -/+ - - N N N ↑ N - Anemia Trauma or surgery in history

Differentiating cirrhosis from other diseases based on serum-ascites albumin gradient (SAAG)

Cirrhosis must be differentiated from other causes of abnormal liver function tests, altered liver architecture and size:

Condition Differentiating signs and symptoms Differentiating Tests
Cirrhosis

Ultrasound findings in cirrhosis are as follows:[6][7][8][9][10][11][12][13]

Abdominal MRI may also be helpful in the diagnosis of portal hypertension. Findings on MRI suggestive of cirrhosis with portal hypertension include:[14][15][16][17]

Transient elastography and the Acoustic Radiation Force Impulse (ARFI) technique are well-established methods for the staging of fibrosis in various liver diseases: [18][19][20][21][22][23][24][25][26][27][28] 

  • The FibroScan (transient elastography) uses elastic waves to determine liver stiffness which theoretically may be converted into a liver score.
  • The FibroScan produces an ultrasound image of the liver (from 20-80mm) along with a pressure reading (in kPa).
  • Transient elastography is much faster than a biopsy (usually lasts 2.5-5 minutes) and is completely painless.
  • Findings on transient elastography may show reasonable correlation with the severity of cirrhosis:[29][30]
Constrictive pericarditis
Budd-Chiari Syndrome
Splenic vein thrombosis Signs and symptoms of:
Portal vein thrombosis
Schistosomiasis
Sarcoidosis
Inferior vena cava obstruction
Nodular regenerative hyperplasia None
Idiopathic portal hypertension (hepatoportal sclerosis) None
Vitamin A intoxication, arsenic, and vinyl chloride toxicity None
  • History generally reveals exposure

Differentiating Cirrhosis from other causes of jaundice and abdominal pain

Cirrhosis must be differentiated from other diseases that cause jaundice, abdominal pain, weight loss, and fever such as Gallbladder cancer, hepatocellular carcinoma, pancreatic cancer, cholecystitis, choledochitis and liver fluke infections.


Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram

Disease Clinical manifestations Diagnosis Comments
Symptoms Signs
Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo-

tension

Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging
Cholangiocarcinoma RUQ + − + + − − + − − − + Normal
  • Predisposes to pancreatic cancer
Hepatocellular carcinoma/Metastasis RUQ + − + + + + + + + − +
  • Normal
  • Hyperactive if obstruction present

Other symptoms:

Pancreatic carcinoma MidEpigastric − − + + + − + − − − + Normal

Skin manifestations may include:

Focal nodular hyperplasia Diffuse ± − − ± − − + + − − − Normal
  • Open biopsy if diagnosis can not be established
Disease Abdominal Pain Fever Rigors and chills Nausea or vomiting Jaundice Constipation Diarrhea Weight loss GI bleeding Hypo-

tension

Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Comments
Gallbladder cancer Midepigastric − − + + − + + − − − − Normal
Liver hemangioma Intermittent RUQ − − + + − − − − − − − Normal
  • Abnormal LFTs
Liver abscess RUQ + − + + − − + − − − − Normal
  • US
  • CT
Cirrhosis RUQ+Bloating + − + + − − + − − − − Normal US
  • Stigmata of liver disease
  • Cruveilhier- Baumgarten murmur
Inflammatory lesions RUQ ± − + + − − − − − − − Normal US
  • Nodular,shrunken or coarse liver
  • Stigmata of liver disease

References

  1. ↑ Fargo MV, Grogan SP, Saguil A (2017). "Evaluation of Jaundice in Adults". Am Fam Physician. 95 (3): 164–168. PMID 28145671.
  2. ↑ Leevy CB, Koneru B, Klein KM (1997). "Recurrent familial prolonged intrahepatic cholestasis of pregnancy associated with chronic liver disease". Gastroenterology. 113 (3): 966–72. PMID 9287990.
  3. ↑ Hov JR, Boberg KM, Karlsen TH (2008). "Autoantibodies in primary sclerosing cholangitis". World J. Gastroenterol. 14 (24): 3781–91. PMC 2721433. PMID 18609700.
  4. ↑ Bond LR, Hatty SR, Horn ME, Dick M, Meire HB, Bellingham AJ (1987). "Gall stones in sickle cell disease in the United Kingdom". Br Med J (Clin Res Ed). 295 (6592): 234–6. PMC 1247079. PMID 3115390.
  5. ↑ Malakouti M, Kataria A, Ali SK, Schenker S (2017). "Elevated Liver Enzymes in Asymptomatic Patients - What Should I Do?". J Clin Transl Hepatol. 5 (4): 394–403. doi:10.14218/JCTH.2017.00027. PMC 5719197. PMID 29226106.
  6. ↑ Udell JA, Wang CS, Tinmouth J, FitzGerald JM, Ayas NT, Simel DL, Schulzer M, Mak E, Yoshida EM (2012). "Does this patient with liver disease have cirrhosis?". JAMA. 307 (8): 832–42. doi:10.1001/jama.2012.186. PMID 22357834.
  7. ↑ Becker CD, Scheidegger J, Marincek B (1986). "Hepatic vein occlusion: morphologic features on computed tomography and ultrasonography". Gastrointest Radiol. 11 (4): 305–11. PMID 3533689.
  8. ↑ Di Lelio A, Cestari C, Lomazzi A, Beretta L (1989). "Cirrhosis: diagnosis with sonographic study of the liver surface". Radiology. 172 (2): 389–92. doi:10.1148/radiology.172.2.2526349. PMID 2526349.
  9. ↑ Sanford NL, Walsh P, Matis C, Baddeley H, Powell LW (1985). "Is ultrasonography useful in the assessment of diffuse parenchymal liver disease?". Gastroenterology. 89 (1): 186–91. PMID 3891495.
  10. ↑ Giorgio A, Amoroso P, Lettieri G, Fico P, de Stefano G, Finelli L, Scala V, Tarantino L, Pierri P, Pesce G (1986). "Cirrhosis: value of caudate to right lobe ratio in diagnosis with US". Radiology. 161 (2): 443–5. doi:10.1148/radiology.161.2.3532188. PMID 3532188.
  11. ↑ Simonovský V (1999). "The diagnosis of cirrhosis by high resolution ultrasound of the liver surface". Br J Radiol. 72 (853): 29–34. doi:10.1259/bjr.72.853.10341686. PMID 10341686.
  12. ↑ Trinchet JC, Chaffaut C, Bourcier V, Degos F, Henrion J, Fontaine H, Roulot D, Mallat A, Hillaire S, Cales P, Ollivier I, Vinel JP, Mathurin P, Bronowicki JP, Vilgrain V, N'Kontchou G, Beaugrand M, Chevret S (2011). "Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities". Hepatology. 54 (6): 1987–97. doi:10.1002/hep.24545. PMID 22144108.
  13. ↑ "EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma". J. Hepatol. 56 (4): 908–43. 2012. doi:10.1016/j.jhep.2011.12.001. PMID 22424438.
  14. ↑ Procopet, Bogdan; Berzigotti, Annalisa (2017). "Diagnosis of cirrhosis and portal hypertension: imaging, non-invasive markers of fibrosis and liver biopsy". Gastroenterology Report. 5 (2): 79–89. doi:10.1093/gastro/gox012. ISSN 2052-0034.
  15. ↑ Aagaard, J; Jensen, LI; Sorensen, TI; Christensen, U; Burcharth, F (1982). "Recanalized umbilical vein in portal hypertension". American Journal of Roentgenology. 139 (6): 1107–1110. doi:10.2214/ajr.139.6.1107. ISSN 0361-803X.
  16. ↑ Cho, K C; Patel, Y D; Wachsberg, R H; Seeff, J (1995). "Varices in portal hypertension: evaluation with CT". RadioGraphics. 15 (3): 609–622. doi:10.1148/radiographics.15.3.7624566. ISSN 0271-5333.
  17. ↑ Bandali, Murad Feroz; Mirakhur, Anirudh; Lee, Edward Wolfgang; Ferris, Mollie Clarke; Sadler, David James; Gray, Robin Ritchie; Wong, Jason Kam (2017). "Portal hypertension: Imaging of portosystemic collateral pathways and associated image-guided therapy". World Journal of Gastroenterology. 23 (10): 1735. doi:10.3748/wjg.v23.i10.1735. ISSN 1007-9327.
  18. ↑ Castera L, Pinzani M (2010). "Biopsy and non-invasive methods for the diagnosis of liver fibrosis: does it take two to tango?". Gut. 59 (7): 861–6. doi:10.1136/gut.2010.214650. PMID 20581229.
  19. ↑ Friedrich-Rust M, Nierhoff J, Lupsor M, Sporea I, Fierbinteanu-Braticevici C, Strobel D, Takahashi H, Yoneda M, Suda T, Zeuzem S, Herrmann E (2012). "Performance of Acoustic Radiation Force Impulse imaging for the staging of liver fibrosis: a pooled meta-analysis". J. Viral Hepat. 19 (2): e212–9. doi:10.1111/j.1365-2893.2011.01537.x. PMID 22239521.
  20. ↑ Friedrich-Rust M, Ong MF, Martens S, Sarrazin C, Bojunga J, Zeuzem S, Herrmann E (2008). "Performance of transient elastography for the staging of liver fibrosis: a meta-analysis". Gastroenterology. 134 (4): 960–74. doi:10.1053/j.gastro.2008.01.034. PMID 18395077.
  21. ↑ Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Lédinghen V, Marcellin P, Dhumeaux D, Trinchet JC, Beaugrand M (2005). "Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C". Hepatology. 41 (1): 48–54. doi:10.1002/hep.20506. PMID 15690481.
  22. ↑ Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, Christidis C, Ziol M, Poulet B, Kazemi F, Beaugrand M, Palau R (2003). "Transient elastography: a new noninvasive method for assessment of hepatic fibrosis". Ultrasound Med Biol. 29 (12): 1705–13. PMID 14698338.
  23. ↑ Bamber J, Cosgrove D, Dietrich CF, Fromageau J, Bojunga J, Calliada F, Cantisani V, Correas JM, D'Onofrio M, Drakonaki EE, Fink M, Friedrich-Rust M, Gilja OH, Havre RF, Jenssen C, Klauser AS, Ohlinger R, Saftoiu A, Schaefer F, Sporea I, Piscaglia F (2013). "EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 1: Basic principles and technology". Ultraschall Med. 34 (2): 169–84. doi:10.1055/s-0033-1335205. PMID 23558397.
  24. ↑ "EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis". J. Hepatol. 63 (1): 237–64. 2015. doi:10.1016/j.jhep.2015.04.006. PMID 25911335.
  25. ↑ Castera L, Bedossa P (2011). "How to assess liver fibrosis in chronic hepatitis C: serum markers or transient elastography vs. liver biopsy?". Liver Int. 31 Suppl 1: 13–7. doi:10.1111/j.1478-3231.2010.02380.x. PMID 21205132.
  26. ↑ Chou R, Wasson N (2013). "Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection: a systematic review". Ann. Intern. Med. 158 (11): 807–20. doi:10.7326/0003-4819-158-11-201306040-00005. PMID 23732714.
  27. ↑ Khallafi H, Qureshi K (2015). "Imaging Based Methods of Liver Fibrosis Assessment in Viral Hepatitis: A Practical Approach". Interdiscip Perspect Infect Dis. 2015: 809289. doi:10.1155/2015/809289. PMC 4686715. PMID 26779260.
  28. ↑ Singh S, Fujii LL, Murad MH, Wang Z, Asrani SK, Ehman RL, Kamath PS, Talwalkar JA (2013). "Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and meta-analysis". Clin. Gastroenterol. Hepatol. 11 (12): 1573–84.e1–2, quiz e88–9. doi:10.1016/j.cgh.2013.07.034. PMC 3900882. PMID 23954643.
  29. ↑ Foucher J, Chanteloup E, Vergniol J; et al. (2006). "Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study". Gut. 55 (3): 403–8. doi:10.1136/gut.2005.069153. PMID 16020491.
  30. ↑ Xie L, Chen X, Guo Q, Dong Y, Guang Y, Zhang X (2012). "Real-time elastography for diagnosis of liver fibrosis in chronic hepatitis B". Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 31 (7): 1053–60. PMID 22733854.

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