Hepatitis C differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Yazan Daaboul, Serge Korjian

Overview

Hepatitis C must be differentiated from other diseases that cause hepatic injury and abnormal liver function tests such as other viral hepatitides (Hepatitis A, Hepatitis B, and Hepatitis E) and non-viral etiologies such as alcoholic liver disease, non-alcoholic steatohepatitis, drug-induced liver injury, autoimmune hepatitis, hepatocellular carcinoma, liver abscess, pancreatitis, and bowel obstruction.

Differential Diagnosis

The differential diagnosis of hepatitis C includes other etiologies of viral hepatitis and non-viral etiologies:[1]

Viral Hepatitis Differential Diagnosis

Non-Viral Hepatitis Differential Diagnosis


Differential diagnosis of jaundice as one pf symptoms of hepatitic C are: [2][3][4][5][6]

Classification of jaundice based on etiology Disease History and clinical manifestations Diagnosis
Lab Findings Other blood tests Other diagnostic
Family history Fever RUQ Pain Pruritis AST ALT ALK BLR Indirect BLR 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 cerulloplasmin ↑ 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 platate Small liver on ultrasond
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 sono CT/ERCP
Hepatitis A cholestatic type - -/+ + + N N ↑ N ↑ + HAV- AB Abdominal ultrasound
EBV / CMV hepatitis - -/+ + + N N ↑ N ↑ + Positive serology -
Primary biliary cirrhosis -/+ - -/+ + N/↑ N/↑ ↑ N ↑ - AMA positive Liver biopsy
Primary sclerosing cholangitis -/+ - -/+ + N/↑ N/↑ ↑ N ↑ - Pos. autoantibodies 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 ↑ - Pos. HIV Sono or ERCP for diagnosis
Parasites induces cholestasis - - -/+ -/+ N/↑ N/↑ ↑ N ↑ - Ab or parasite serology Sono or ERCP for diagnosis
Intrahepatic cholestasis of pregnancy -/+ - -/+ + ↑ ↑ ↑ N ↑ - Low PLT, Neg viral serology Diagnosed clinically
Isolated Jaundice Crigler-Najjar type 2 + - - - N N N ↑ ↑ - Genetic testing
Gilbert + - - - 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
Hereditory spherocytosis + - -/+ - N N N ↑ N - Genetic testing Osmotic fragility
G6PD deficiency + - - - N N N ↑ N - Genetic testing
Thalassemia + - - - N N N ↑ N - Genetic testing
Paroxismal nocturnal hemoglobinoria - - - - N N N ↑ N - Flocytometery
Immune hemolysis - -/+ - - N N N ↑ N - Autoantibodies
Hematoma - -/+ - - N N N ↑ N - Anemia Truma or surgery in history

Differential diagnosis of cirrhosis if happened in hepatitis C based on altered hepatic function are:

Condition Differentiating signs and symptoms Differentiating Tests
Cirrhosis

Ultrasound findings in cirrhosis are as follows:[7][8][9][10][11][12][13][14]

Abdominal MRI may also be helpful in the diagnosis of portal hypertension. Findings on MRI suggestive of cirrhosis with portal hypertension include:[15][16][17][18]

Transient elastography and the Acoustic Radiation Force Impulse (ARFI) technique are well-established methods for the staging of fibrosis in various liver diseases: [19][20][21][22][23][24][25][26][27][28][29] 

  • 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:[30][31]
Constrictive pericarditis
Budd-Chiari Syndrome
  • Abdominal pain
  • Diarrhea
  • Ascites
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

References

  1. ↑ Giannini EG, Testa R, Savarino V (2005). "Liver enzyme alteration: a guide for clinicians". CMAJ. 172 (3): 367–79. doi:10.1503/cmaj.1040752. PMC 545762. PMID 15684121.
  2. ↑ Fargo MV, Grogan SP, Saguil A (2017). "Evaluation of Jaundice in Adults". Am Fam Physician. 95 (3): 164–168. PMID 28145671.
  3. ↑ 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.
  4. ↑ Hov JR, Boberg KM, Karlsen TH (2008). "Autoantibodies in primary sclerosing cholangitis". World J. Gastroenterol. 14 (24): 3781–91. PMC 2721433. PMID 18609700.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ "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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ "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.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ 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.
  30. ↑ 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.
  31. ↑ 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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