Cirrhosis differential diagnosis: Difference between revisions

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==Differentiating Cirrhosis from other Diseases==
==Differentiating Cirrhosis from other Diseases==
Cirrhosis must be differentiated from other causes of abnormal liver function tests, altered liver architecture and size:
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Condition
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Differentiating signs and symptoms
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Differentiating Tests
|-
| style="background:#DCDCDC; + " |'''Cirrhosis'''
|
* [[Abdominal pain]] and bloating
* [[Menstrual disorder|Menstrual irregularities]]
* Symptoms of [[hypogonadism]]:
** [[Erectile dysfunction|Impotence]]
** [[Infertility]]
** [[Testicular atrophy]]
** Loss of [[libido]]
** Easy bruisability


* Decompensated [[cirrhosis]] may present with
** [[Jaundice]]
** Increase in abdominal girth due to [[ascites]]
** [[Itch|Pruritus]]
* Signs of [[upper gastrointestinal bleeding]]:
** [[Hematemesis]]
** [[Hematochezia]]
** [[Melena]]
** Symptoms due to [[hepatic encephalopathy]]:
** [[Altered mental status]]
** [[Confusion]]
** Sleep disturbances
|
[[Ultrasound]] findings in cirrhosis are as follows:<ref name="pmid22357834">{{cite journal |vauthors=Udell JA, Wang CS, Tinmouth J, FitzGerald JM, Ayas NT, Simel DL, Schulzer M, Mak E, Yoshida EM |title=Does this patient with liver disease have cirrhosis? |journal=JAMA |volume=307 |issue=8 |pages=832–42 |year=2012 |pmid=22357834 |doi=10.1001/jama.2012.186 |url=}}</ref><ref name="pmid3533689">{{cite journal |vauthors=Becker CD, Scheidegger J, Marincek B |title=Hepatic vein occlusion: morphologic features on computed tomography and ultrasonography |journal=Gastrointest Radiol |volume=11 |issue=4 |pages=305–11 |year=1986 |pmid=3533689 |doi= |url=}}</ref><ref name="pmid2526349">{{cite journal |vauthors=Di Lelio A, Cestari C, Lomazzi A, Beretta L |title=Cirrhosis: diagnosis with sonographic study of the liver surface |journal=Radiology |volume=172 |issue=2 |pages=389–92 |year=1989 |pmid=2526349 |doi=10.1148/radiology.172.2.2526349 |url=}}</ref><ref name="pmid3891495">{{cite journal |vauthors=Sanford NL, Walsh P, Matis C, Baddeley H, Powell LW |title=Is ultrasonography useful in the assessment of diffuse parenchymal liver disease? |journal=Gastroenterology |volume=89 |issue=1 |pages=186–91 |year=1985 |pmid=3891495 |doi= |url=}}</ref><ref name="pmid3532188">{{cite journal |vauthors=Giorgio A, Amoroso P, Lettieri G, Fico P, de Stefano G, Finelli L, Scala V, Tarantino L, Pierri P, Pesce G |title=Cirrhosis: value of caudate to right lobe ratio in diagnosis with US |journal=Radiology |volume=161 |issue=2 |pages=443–5 |year=1986 |pmid=3532188 |doi=10.1148/radiology.161.2.3532188 |url=}}</ref><ref name="pmid10341686">{{cite journal |vauthors=Simonovský V |title=The diagnosis of cirrhosis by high resolution ultrasound of the liver surface |journal=Br J Radiol |volume=72 |issue=853 |pages=29–34 |year=1999 |pmid=10341686 |doi=10.1259/bjr.72.853.10341686 |url=}}</ref><ref name="pmid22144108">{{cite journal |vauthors=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 |title=Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities |journal=Hepatology |volume=54 |issue=6 |pages=1987–97 |year=2011 |pmid=22144108 |doi=10.1002/hep.24545 |url=}}</ref><ref name="pmid22424438">{{cite journal |vauthors= |title=EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma |journal=J. Hepatol. |volume=56 |issue=4 |pages=908–43 |year=2012 |pmid=22424438 |doi=10.1016/j.jhep.2011.12.001 |url=}}</ref>
*Changes in [[liver]] contour: shrunken, irregular appearance
*Non [[Homogenization|homogeneous]] appearance of the [[Liver|hepatic]] tissue
*Increased [[Liver|surface]] [[Nodule (medicine)|nodularity]]
*Increase in echogenecity from focal fatty [[Infiltration (medical)|infiltration]]
*[[Atrophy]] of the right lobe and [[Hypertrophy (medical)|hypertrophy]] of the [[Caudate lobe of liver|caudate]] or left lobe
*[[Splenomegaly]]
*[[Ascites]]
*[[Varices]]
*[[Hepatic vein|Hepatic]] or [[portal vein]] [[thrombosis]]
Abdominal MRI may also be helpful in the diagnosis of [[portal hypertension]]. Findings on MRI suggestive of cirrhosis with [[portal hypertension]] include:<ref name="ProcopetBerzigotti2017">{{cite journal|last1=Procopet|first1=Bogdan|last2=Berzigotti|first2=Annalisa|title=Diagnosis of cirrhosis and portal hypertension: imaging, non-invasive markers of fibrosis and liver biopsy|journal=Gastroenterology Report|volume=5|issue=2|year=2017|pages=79–89|issn=2052-0034|doi=10.1093/gastro/gox012}}</ref><ref name="AagaardJensen1982">{{cite journal|last1=Aagaard|first1=J|last2=Jensen|first2=LI|last3=Sorensen|first3=TI|last4=Christensen|first4=U|last5=Burcharth|first5=F|title=Recanalized umbilical vein in portal hypertension|journal=American Journal of Roentgenology|volume=139|issue=6|year=1982|pages=1107–1110|issn=0361-803X|doi=10.2214/ajr.139.6.1107}}</ref><ref name="ChoPatel1995">{{cite journal|last1=Cho|first1=K C|last2=Patel|first2=Y D|last3=Wachsberg|first3=R H|last4=Seeff|first4=J|title=Varices in portal hypertension: evaluation with CT.|journal=RadioGraphics|volume=15|issue=3|year=1995|pages=609–622|issn=0271-5333|doi=10.1148/radiographics.15.3.7624566}}</ref><ref name="BandaliMirakhur2017">{{cite journal|last1=Bandali|first1=Murad Feroz|last2=Mirakhur|first2=Anirudh|last3=Lee|first3=Edward Wolfgang|last4=Ferris|first4=Mollie Clarke|last5=Sadler|first5=David James|last6=Gray|first6=Robin Ritchie|last7=Wong|first7=Jason Kam|title=Portal hypertension: Imaging of portosystemic collateral pathways and associated image-guided therapy|journal=World Journal of Gastroenterology|volume=23|issue=10|year=2017|pages=1735|issn=1007-9327|doi=10.3748/wjg.v23.i10.1735}}</ref>
*[[Cirrhosis|Cirrhotic liver]], as shrinkage and atrophy in liver
*Re-canalized [[umbilical vein]]--[[pathognomonic]]
*Dilated [[portal vein]] and/or [[splanchnic]] veins
*[[Esophageal varices]]
*[[Collaterals]] in any [[Abdominal organs|abdominal organ]]
*[[Splenomegaly]]
*[[Ascites]]
Transient [[elastography]] and the Acoustic Radiation Force Impulse (ARFI) technique are well-established methods for the staging of [[fibrosis]] in various [[liver]] diseases: <ref name="pmid20581229">{{cite journal |vauthors=Castera L, Pinzani M |title=Biopsy and non-invasive methods for the diagnosis of liver fibrosis: does it take two to tango? |journal=Gut |volume=59 |issue=7 |pages=861–6 |year=2010 |pmid=20581229 |doi=10.1136/gut.2010.214650 |url=}}</ref><ref name="pmid22239521">{{cite journal |vauthors=Friedrich-Rust M, Nierhoff J, Lupsor M, Sporea I, Fierbinteanu-Braticevici C, Strobel D, Takahashi H, Yoneda M, Suda T, Zeuzem S, Herrmann E |title=Performance of Acoustic Radiation Force Impulse imaging for the staging of liver fibrosis: a pooled meta-analysis |journal=J. Viral Hepat. |volume=19 |issue=2 |pages=e212–9 |year=2012 |pmid=22239521 |doi=10.1111/j.1365-2893.2011.01537.x |url=}}</ref><ref name="pmid18395077">{{cite journal |vauthors=Friedrich-Rust M, Ong MF, Martens S, Sarrazin C, Bojunga J, Zeuzem S, Herrmann E |title=Performance of transient elastography for the staging of liver fibrosis: a meta-analysis |journal=Gastroenterology |volume=134 |issue=4 |pages=960–74 |year=2008 |pmid=18395077 |doi=10.1053/j.gastro.2008.01.034 |url=}}</ref><ref name="pmid15690481">{{cite journal |vauthors=Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Lédinghen V, Marcellin P, Dhumeaux D, Trinchet JC, Beaugrand M |title=Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C |journal=Hepatology |volume=41 |issue=1 |pages=48–54 |year=2005 |pmid=15690481 |doi=10.1002/hep.20506 |url=}}</ref><ref name="pmid14698338">{{cite journal |vauthors=Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, Christidis C, Ziol M, Poulet B, Kazemi F, Beaugrand M, Palau R |title=Transient elastography: a new noninvasive method for assessment of hepatic fibrosis |journal=Ultrasound Med Biol |volume=29 |issue=12 |pages=1705–13 |year=2003 |pmid=14698338 |doi= |url=}}</ref><ref name="pmid23558397">{{cite journal |vauthors=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 |title=EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 1: Basic principles and technology |journal=Ultraschall Med |volume=34 |issue=2 |pages=169–84 |year=2013 |pmid=23558397 |doi=10.1055/s-0033-1335205 |url=}}</ref><ref name="pmid25911335">{{cite journal |vauthors= |title=EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis |journal=J. Hepatol. |volume=63 |issue=1 |pages=237–64 |year=2015 |pmid=25911335 |doi=10.1016/j.jhep.2015.04.006 |url=}}</ref><ref name="pmid21205132">{{cite journal |vauthors=Castera L, Bedossa P |title=How to assess liver fibrosis in chronic hepatitis C: serum markers or transient elastography vs. liver biopsy? |journal=Liver Int. |volume=31 Suppl 1 |issue= |pages=13–7 |year=2011 |pmid=21205132 |doi=10.1111/j.1478-3231.2010.02380.x |url=}}</ref><ref name="pmid23732714">{{cite journal |vauthors=Chou R, Wasson N |title=Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection: a systematic review |journal=Ann. Intern. Med. |volume=158 |issue=11 |pages=807–20 |year=2013 |pmid=23732714 |doi=10.7326/0003-4819-158-11-201306040-00005 |url=}}</ref><ref name="pmid26779260">{{cite journal |vauthors=Khallafi H, Qureshi K |title=Imaging Based Methods of Liver Fibrosis Assessment in Viral Hepatitis: A Practical Approach |journal=Interdiscip Perspect Infect Dis |volume=2015 |issue= |pages=809289 |year=2015 |pmid=26779260 |pmc=4686715 |doi=10.1155/2015/809289 |url=}}</ref><ref name="pmid23954643">{{cite journal |vauthors=Singh S, Fujii LL, Murad MH, Wang Z, Asrani SK, Ehman RL, Kamath PS, Talwalkar JA |title=Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and meta-analysis |journal=Clin. Gastroenterol. Hepatol. |volume=11 |issue=12 |pages=1573–84.e1–2; quiz e88–9 |year=2013 |pmid=23954643 |pmc=3900882 |doi=10.1016/j.cgh.2013.07.034 |url=}}</ref> 
*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:<ref>{{cite journal |author=Foucher J, Chanteloup E, Vergniol J, ''et al'' |title=Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study |journal=Gut |volume=55|issue=3 |pages=403-8 |year=2006 |pmid=16020491 |doi=10.1136/gut.2005.069153}}</ref><ref name="pmid22733854">{{cite journal |author=Xie L, Chen X, Guo Q, Dong Y, Guang Y, Zhang X |title=Real-time elastography for diagnosis of liver fibrosis in chronic hepatitis B |journal=[[Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine]] |volume=31 |issue=7 |pages=1053–60 |year=2012|pmid=22733854 |doi= |url=}}</ref>
**Increasing [[Scar|scarring]] of the [[liver]] is associated with increasing "stiffness" of the [[Tissue (biology)|tissue]].
|-
| style="background:#DCDCDC; + " | '''Constrictive pericarditis'''
|
* Increased [[jugular venous pressure]]
* [[atrial fibrillation]]
* [[tachycardia]]
* Quiet heart sounds with a third heart sound (ventricular knock)
|
* [[EKG]] will show:
** [[tachycardia]]
** [[Atrial fibrillation]]
** Low-voltage QRS complexes
** [[T wave]] abnormalities
* [[Doppler ultrasound]] shows [[Ventricle (heart)|ventricular]] filling abnormalities
|-
| style="background:#DCDCDC; + " | '''Budd-Chiari Syndrome'''
|
* Abdominal pain
* Diarrhea
* Ascites
|
* [[Doppler ultrasound]] and [[CT]] of the abdomen shows absence of the [[hepatic vein]] filling
* Abdominal CT will show a rapid clearing of the [[Caudate lobe of liver|caudate lobe]] of the liver
|-
| style="background:#DCDCDC; + " | '''Splenic vein thrombosis'''
|Signs and symptoms of:
* Upper abdominal pain radiating to the back
* Vomiting
* Poor bowel sounds
* Fever
* Shock
* [[Cullen's sign]]
* [[Grey-Turner's sign]]
|
* Ultrasound of the abdomen and CT will show evidence of a [[splenic vein thrombosis]]
* Normal [[Hepatic vein|hepatic venous]] pressure gradient is present
|-
| style="background:#DCDCDC; + " | '''Portal vein thrombosis'''
|
* Symptoms depend on the underlying cause:
* If pancreatitis is present, the patient may develop:
** Upper abdominal pain radiating to the back
** Vomiting
** Poor bowel sounds
** [[fever]]
** [[shock]]
** [[Cullen's sign]]
** [[Grey-Turner's sign]]
* If the cause is [[ascending cholangitis]], symptoms include:
** Fever
** [[rigors]]
** Right upper quadrant pain
** Dark urine
** Pale stools
* If abdominal sepsis is the cause, symptoms include:
* [[fever]]
* [[abdominal pain]]
* Signs of [[peritonitis]]
|
* [[Doppler ultrasound]] and abdominal CT show a [[portal vein]] filling defect and absence of flow in the [[portal vein]].
* MR or direct [[Angiogram|angiography]] show a normal [[Hepatic vein|hepatic venous]] pressure gradient.
|-
| style="background:#DCDCDC; + " | '''Schistosomiasis'''
|
* Patients may have a history of travel to endemic areas
* Constitutional symptoms such as
** Malaise
** [[rigors]]
** [[anorexia]]
** [[weight loss]]
** [[vomiting]]
** D[[diarrhea|iarrhea]]
** [[headache]]
** Muscular aches
** [[weakness]]
** [[abdominal pain]]
** [[urticaria]]
** [[fever]]
** [[lymphadenopathy]]
|
* MR or direct [[Angiogram|angiography]] shows a normal [[Hepatic vein|hepatic venous]] pressure gradient
|-
| style="background:#DCDCDC; + " | '''Sarcoidosis'''
|
* Dry cough with [[dyspnea]]
* Anterior or posterior [[uveitis]]
* [[dry eyes]]
* [[glaucoma]]
* Skin findings may include:
** Maculopapular lesions on the face, back, arms and legs
** [[erythema nodosum]] on the legs
|
* Chest x ray may show:
** [[hilar lymphadenopathy]]
** Upper lobe [[fibrosis]]
** Diffuse reticulonodular shadowing
** [[Liver biopsy]] shows non-necrotizing, non-caseating [[Granuloma|granulomas]]
|-
| style="background:#DCDCDC; + " | '''Inferior vena cava obstruction'''
|
* Signs and symptoms of [[renal cell carcinoma]]:
* Hematuria
* [[flank pain]]
* Flank or abdominal mass
* Weight loss
* [[hypertension]]
|
* [[Ultrasound]] of the abdomen shows evidence of [[inferior vena cava]] obstruction
|-
| style="background:#DCDCDC; + " | '''Nodular regenerative hyperplasia'''
|None
|
* [[Liver biopsy]] shows small regenerative [[Nodule (medicine)|nodules]] with little or no [[fibrosis]] on reticulin staining
|-
| style="background:#DCDCDC; + " | '''Idiopathic portal hypertension (hepatoportal sclerosis)'''
|None
|
* [[Liver biopsy]] shows no evidence of cirrhosis
|-
| style="background:#DCDCDC; + " | '''Vitamin A intoxication, arsenic, and vinyl chloride toxicity'''
|None
|
* History generally reveals exposure
|}
Differential diagnosis of jaundice are: <ref name="pmid28145671">{{cite journal |vauthors=Fargo MV, Grogan SP, Saguil A |title=Evaluation of Jaundice in Adults |journal=Am Fam Physician |volume=95 |issue=3 |pages=164–168 |year=2017 |pmid=28145671 |doi= |url=}}</ref><ref name="pmid9287990">{{cite journal |vauthors=Leevy CB, Koneru B, Klein KM |title=Recurrent familial prolonged intrahepatic cholestasis of pregnancy associated with chronic liver disease |journal=Gastroenterology |volume=113 |issue=3 |pages=966–72 |year=1997 |pmid=9287990 |doi= |url=}}</ref><ref name="pmid18609700">{{cite journal |vauthors=Hov JR, Boberg KM, Karlsen TH |title=Autoantibodies in primary sclerosing cholangitis |journal=World J. Gastroenterol. |volume=14 |issue=24 |pages=3781–91 |year=2008 |pmid=18609700 |pmc=2721433 |doi= |url=}}</ref><ref name="pmid3115390">{{cite journal |vauthors=Bond LR, Hatty SR, Horn ME, Dick M, Meire HB, Bellingham AJ |title=Gall stones in sickle cell disease in the United Kingdom |journal=Br Med J (Clin Res Ed) |volume=295 |issue=6592 |pages=234–6 |year=1987 |pmid=3115390 |pmc=1247079 |doi= |url=}}</ref><ref name="pmid29226106">{{cite journal |vauthors=Malakouti M, Kataria A, Ali SK, Schenker S |title=Elevated Liver Enzymes in Asymptomatic Patients - What Should I Do? |journal=J Clin Transl Hepatol |volume=5 |issue=4 |pages=394–403 |year=2017 |pmid=29226106 |pmc=5719197 |doi=10.14218/JCTH.2017.00027 |url=}}</ref>
Differential diagnosis of jaundice are: <ref name="pmid28145671">{{cite journal |vauthors=Fargo MV, Grogan SP, Saguil A |title=Evaluation of Jaundice in Adults |journal=Am Fam Physician |volume=95 |issue=3 |pages=164–168 |year=2017 |pmid=28145671 |doi= |url=}}</ref><ref name="pmid9287990">{{cite journal |vauthors=Leevy CB, Koneru B, Klein KM |title=Recurrent familial prolonged intrahepatic cholestasis of pregnancy associated with chronic liver disease |journal=Gastroenterology |volume=113 |issue=3 |pages=966–72 |year=1997 |pmid=9287990 |doi= |url=}}</ref><ref name="pmid18609700">{{cite journal |vauthors=Hov JR, Boberg KM, Karlsen TH |title=Autoantibodies in primary sclerosing cholangitis |journal=World J. Gastroenterol. |volume=14 |issue=24 |pages=3781–91 |year=2008 |pmid=18609700 |pmc=2721433 |doi= |url=}}</ref><ref name="pmid3115390">{{cite journal |vauthors=Bond LR, Hatty SR, Horn ME, Dick M, Meire HB, Bellingham AJ |title=Gall stones in sickle cell disease in the United Kingdom |journal=Br Med J (Clin Res Ed) |volume=295 |issue=6592 |pages=234–6 |year=1987 |pmid=3115390 |pmc=1247079 |doi= |url=}}</ref><ref name="pmid29226106">{{cite journal |vauthors=Malakouti M, Kataria A, Ali SK, Schenker S |title=Elevated Liver Enzymes in Asymptomatic Patients - What Should I Do? |journal=J Clin Transl Hepatol |volume=5 |issue=4 |pages=394–403 |year=2017 |pmid=29226106 |pmc=5719197 |doi=10.14218/JCTH.2017.00027 |url=}}</ref>


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|}
|}


Cirrhosis must be differentiated from other causes of abnormal liver function tests, altered liver architecture and size:
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Condition
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Differentiating signs and symptoms
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Differentiating Tests
|-
| style="background:#DCDCDC; + " |'''Cirrhosis'''
|
* [[Abdominal pain]] and bloating
* [[Menstrual disorder|Menstrual irregularities]]
* Symptoms of [[hypogonadism]]:
** [[Erectile dysfunction|Impotence]]
** [[Infertility]]
** [[Testicular atrophy]]
** Loss of [[libido]]
** Easy bruisability
* Decompensated [[cirrhosis]] may present with
** [[Jaundice]]
** Increase in abdominal girth due to [[ascites]]
** [[Itch|Pruritus]]
* Signs of [[upper gastrointestinal bleeding]]:
** [[Hematemesis]]
** [[Hematochezia]]
** [[Melena]]
** Symptoms due to [[hepatic encephalopathy]]:
** [[Altered mental status]]
** [[Confusion]]
** Sleep disturbances
|
[[Ultrasound]] findings in cirrhosis are as follows:<ref name="pmid22357834">{{cite journal |vauthors=Udell JA, Wang CS, Tinmouth J, FitzGerald JM, Ayas NT, Simel DL, Schulzer M, Mak E, Yoshida EM |title=Does this patient with liver disease have cirrhosis? |journal=JAMA |volume=307 |issue=8 |pages=832–42 |year=2012 |pmid=22357834 |doi=10.1001/jama.2012.186 |url=}}</ref><ref name="pmid3533689">{{cite journal |vauthors=Becker CD, Scheidegger J, Marincek B |title=Hepatic vein occlusion: morphologic features on computed tomography and ultrasonography |journal=Gastrointest Radiol |volume=11 |issue=4 |pages=305–11 |year=1986 |pmid=3533689 |doi= |url=}}</ref><ref name="pmid2526349">{{cite journal |vauthors=Di Lelio A, Cestari C, Lomazzi A, Beretta L |title=Cirrhosis: diagnosis with sonographic study of the liver surface |journal=Radiology |volume=172 |issue=2 |pages=389–92 |year=1989 |pmid=2526349 |doi=10.1148/radiology.172.2.2526349 |url=}}</ref><ref name="pmid3891495">{{cite journal |vauthors=Sanford NL, Walsh P, Matis C, Baddeley H, Powell LW |title=Is ultrasonography useful in the assessment of diffuse parenchymal liver disease? |journal=Gastroenterology |volume=89 |issue=1 |pages=186–91 |year=1985 |pmid=3891495 |doi= |url=}}</ref><ref name="pmid3532188">{{cite journal |vauthors=Giorgio A, Amoroso P, Lettieri G, Fico P, de Stefano G, Finelli L, Scala V, Tarantino L, Pierri P, Pesce G |title=Cirrhosis: value of caudate to right lobe ratio in diagnosis with US |journal=Radiology |volume=161 |issue=2 |pages=443–5 |year=1986 |pmid=3532188 |doi=10.1148/radiology.161.2.3532188 |url=}}</ref><ref name="pmid10341686">{{cite journal |vauthors=Simonovský V |title=The diagnosis of cirrhosis by high resolution ultrasound of the liver surface |journal=Br J Radiol |volume=72 |issue=853 |pages=29–34 |year=1999 |pmid=10341686 |doi=10.1259/bjr.72.853.10341686 |url=}}</ref><ref name="pmid22144108">{{cite journal |vauthors=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 |title=Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities |journal=Hepatology |volume=54 |issue=6 |pages=1987–97 |year=2011 |pmid=22144108 |doi=10.1002/hep.24545 |url=}}</ref><ref name="pmid22424438">{{cite journal |vauthors= |title=EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma |journal=J. Hepatol. |volume=56 |issue=4 |pages=908–43 |year=2012 |pmid=22424438 |doi=10.1016/j.jhep.2011.12.001 |url=}}</ref>
*Changes in [[liver]] contour: shrunken, irregular appearance
*Non [[Homogenization|homogeneous]] appearance of the [[Liver|hepatic]] tissue
*Increased [[Liver|surface]] [[Nodule (medicine)|nodularity]]
*Increase in echogenecity from focal fatty [[Infiltration (medical)|infiltration]]
*[[Atrophy]] of the right lobe and [[Hypertrophy (medical)|hypertrophy]] of the [[Caudate lobe of liver|caudate]] or left lobe
*[[Splenomegaly]]
*[[Ascites]]
*[[Varices]]
*[[Hepatic vein|Hepatic]] or [[portal vein]] [[thrombosis]]
Abdominal MRI may also be helpful in the diagnosis of [[portal hypertension]]. Findings on MRI suggestive of cirrhosis with [[portal hypertension]] include:<ref name="ProcopetBerzigotti2017">{{cite journal|last1=Procopet|first1=Bogdan|last2=Berzigotti|first2=Annalisa|title=Diagnosis of cirrhosis and portal hypertension: imaging, non-invasive markers of fibrosis and liver biopsy|journal=Gastroenterology Report|volume=5|issue=2|year=2017|pages=79–89|issn=2052-0034|doi=10.1093/gastro/gox012}}</ref><ref name="AagaardJensen1982">{{cite journal|last1=Aagaard|first1=J|last2=Jensen|first2=LI|last3=Sorensen|first3=TI|last4=Christensen|first4=U|last5=Burcharth|first5=F|title=Recanalized umbilical vein in portal hypertension|journal=American Journal of Roentgenology|volume=139|issue=6|year=1982|pages=1107–1110|issn=0361-803X|doi=10.2214/ajr.139.6.1107}}</ref><ref name="ChoPatel1995">{{cite journal|last1=Cho|first1=K C|last2=Patel|first2=Y D|last3=Wachsberg|first3=R H|last4=Seeff|first4=J|title=Varices in portal hypertension: evaluation with CT.|journal=RadioGraphics|volume=15|issue=3|year=1995|pages=609–622|issn=0271-5333|doi=10.1148/radiographics.15.3.7624566}}</ref><ref name="BandaliMirakhur2017">{{cite journal|last1=Bandali|first1=Murad Feroz|last2=Mirakhur|first2=Anirudh|last3=Lee|first3=Edward Wolfgang|last4=Ferris|first4=Mollie Clarke|last5=Sadler|first5=David James|last6=Gray|first6=Robin Ritchie|last7=Wong|first7=Jason Kam|title=Portal hypertension: Imaging of portosystemic collateral pathways and associated image-guided therapy|journal=World Journal of Gastroenterology|volume=23|issue=10|year=2017|pages=1735|issn=1007-9327|doi=10.3748/wjg.v23.i10.1735}}</ref>
*[[Cirrhosis|Cirrhotic liver]], as shrinkage and atrophy in liver
*Re-canalized [[umbilical vein]]--[[pathognomonic]]
*Dilated [[portal vein]] and/or [[splanchnic]] veins
*[[Esophageal varices]]
*[[Collaterals]] in any [[Abdominal organs|abdominal organ]]
*[[Splenomegaly]]
*[[Ascites]]
Transient [[elastography]] and the Acoustic Radiation Force Impulse (ARFI) technique are well-established methods for the staging of [[fibrosis]] in various [[liver]] diseases: <ref name="pmid20581229">{{cite journal |vauthors=Castera L, Pinzani M |title=Biopsy and non-invasive methods for the diagnosis of liver fibrosis: does it take two to tango? |journal=Gut |volume=59 |issue=7 |pages=861–6 |year=2010 |pmid=20581229 |doi=10.1136/gut.2010.214650 |url=}}</ref><ref name="pmid22239521">{{cite journal |vauthors=Friedrich-Rust M, Nierhoff J, Lupsor M, Sporea I, Fierbinteanu-Braticevici C, Strobel D, Takahashi H, Yoneda M, Suda T, Zeuzem S, Herrmann E |title=Performance of Acoustic Radiation Force Impulse imaging for the staging of liver fibrosis: a pooled meta-analysis |journal=J. Viral Hepat. |volume=19 |issue=2 |pages=e212–9 |year=2012 |pmid=22239521 |doi=10.1111/j.1365-2893.2011.01537.x |url=}}</ref><ref name="pmid18395077">{{cite journal |vauthors=Friedrich-Rust M, Ong MF, Martens S, Sarrazin C, Bojunga J, Zeuzem S, Herrmann E |title=Performance of transient elastography for the staging of liver fibrosis: a meta-analysis |journal=Gastroenterology |volume=134 |issue=4 |pages=960–74 |year=2008 |pmid=18395077 |doi=10.1053/j.gastro.2008.01.034 |url=}}</ref><ref name="pmid15690481">{{cite journal |vauthors=Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Lédinghen V, Marcellin P, Dhumeaux D, Trinchet JC, Beaugrand M |title=Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C |journal=Hepatology |volume=41 |issue=1 |pages=48–54 |year=2005 |pmid=15690481 |doi=10.1002/hep.20506 |url=}}</ref><ref name="pmid14698338">{{cite journal |vauthors=Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, Christidis C, Ziol M, Poulet B, Kazemi F, Beaugrand M, Palau R |title=Transient elastography: a new noninvasive method for assessment of hepatic fibrosis |journal=Ultrasound Med Biol |volume=29 |issue=12 |pages=1705–13 |year=2003 |pmid=14698338 |doi= |url=}}</ref><ref name="pmid23558397">{{cite journal |vauthors=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 |title=EFSUMB guidelines and recommendations on the clinical use of ultrasound elastography. Part 1: Basic principles and technology |journal=Ultraschall Med |volume=34 |issue=2 |pages=169–84 |year=2013 |pmid=23558397 |doi=10.1055/s-0033-1335205 |url=}}</ref><ref name="pmid25911335">{{cite journal |vauthors= |title=EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis |journal=J. Hepatol. |volume=63 |issue=1 |pages=237–64 |year=2015 |pmid=25911335 |doi=10.1016/j.jhep.2015.04.006 |url=}}</ref><ref name="pmid21205132">{{cite journal |vauthors=Castera L, Bedossa P |title=How to assess liver fibrosis in chronic hepatitis C: serum markers or transient elastography vs. liver biopsy? |journal=Liver Int. |volume=31 Suppl 1 |issue= |pages=13–7 |year=2011 |pmid=21205132 |doi=10.1111/j.1478-3231.2010.02380.x |url=}}</ref><ref name="pmid23732714">{{cite journal |vauthors=Chou R, Wasson N |title=Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection: a systematic review |journal=Ann. Intern. Med. |volume=158 |issue=11 |pages=807–20 |year=2013 |pmid=23732714 |doi=10.7326/0003-4819-158-11-201306040-00005 |url=}}</ref><ref name="pmid26779260">{{cite journal |vauthors=Khallafi H, Qureshi K |title=Imaging Based Methods of Liver Fibrosis Assessment in Viral Hepatitis: A Practical Approach |journal=Interdiscip Perspect Infect Dis |volume=2015 |issue= |pages=809289 |year=2015 |pmid=26779260 |pmc=4686715 |doi=10.1155/2015/809289 |url=}}</ref><ref name="pmid23954643">{{cite journal |vauthors=Singh S, Fujii LL, Murad MH, Wang Z, Asrani SK, Ehman RL, Kamath PS, Talwalkar JA |title=Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and meta-analysis |journal=Clin. Gastroenterol. Hepatol. |volume=11 |issue=12 |pages=1573–84.e1–2; quiz e88–9 |year=2013 |pmid=23954643 |pmc=3900882 |doi=10.1016/j.cgh.2013.07.034 |url=}}</ref> 
*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:<ref>{{cite journal |author=Foucher J, Chanteloup E, Vergniol J, ''et al'' |title=Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study |journal=Gut |volume=55|issue=3 |pages=403-8 |year=2006 |pmid=16020491 |doi=10.1136/gut.2005.069153}}</ref><ref name="pmid22733854">{{cite journal |author=Xie L, Chen X, Guo Q, Dong Y, Guang Y, Zhang X |title=Real-time elastography for diagnosis of liver fibrosis in chronic hepatitis B |journal=[[Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine]] |volume=31 |issue=7 |pages=1053–60 |year=2012|pmid=22733854 |doi= |url=}}</ref>
**Increasing [[Scar|scarring]] of the [[liver]] is associated with increasing "stiffness" of the [[Tissue (biology)|tissue]].
|-
| style="background:#DCDCDC; + " | '''Constrictive pericarditis'''
|
* Increased [[jugular venous pressure]]
* [[atrial fibrillation]]
* [[tachycardia]]
* Quiet heart sounds with a third heart sound (ventricular knock)
|
* [[EKG]] will show:
** [[tachycardia]]
** [[Atrial fibrillation]]
** Low-voltage QRS complexes
** [[T wave]] abnormalities
* [[Doppler ultrasound]] shows [[Ventricle (heart)|ventricular]] filling abnormalities
|-
| style="background:#DCDCDC; + " | '''Budd-Chiari Syndrome'''
|
* Abdominal pain
* Diarrhea
* Ascites
|
* [[Doppler ultrasound]] and [[CT]] of the abdomen shows absence of the [[hepatic vein]] filling
* Abdominal CT will show a rapid clearing of the [[Caudate lobe of liver|caudate lobe]] of the liver
|-
| style="background:#DCDCDC; + " | '''Splenic vein thrombosis'''
|Signs and symptoms of:
* Upper abdominal pain radiating to the back
* Vomiting
* Poor bowel sounds
* Fever
* Shock
* [[Cullen's sign]]
* [[Grey-Turner's sign]]
|
* Ultrasound of the abdomen and CT will show evidence of a [[splenic vein thrombosis]]
* Normal [[Hepatic vein|hepatic venous]] pressure gradient is present
|-
| style="background:#DCDCDC; + " | '''Portal vein thrombosis'''
|
* Symptoms depend on the underlying cause:
* If pancreatitis is present, the patient may develop:
** Upper abdominal pain radiating to the back
** Vomiting
** Poor bowel sounds
** [[fever]]
** [[shock]]
** [[Cullen's sign]]
** [[Grey-Turner's sign]]
* If the cause is [[ascending cholangitis]], symptoms include:
** Fever
** [[rigors]]
** Right upper quadrant pain
** Dark urine
** Pale stools
* If abdominal sepsis is the cause, symptoms include:
* [[fever]]
* [[abdominal pain]]
* Signs of [[peritonitis]]
|
* [[Doppler ultrasound]] and abdominal CT show a [[portal vein]] filling defect and absence of flow in the [[portal vein]].
* MR or direct [[Angiogram|angiography]] show a normal [[Hepatic vein|hepatic venous]] pressure gradient.
|-
| style="background:#DCDCDC; + " | '''Schistosomiasis'''
|
* Patients may have a history of travel to endemic areas
* Constitutional symptoms such as
** Malaise
** [[rigors]]
** [[anorexia]]
** [[weight loss]]
** [[vomiting]]
** D[[diarrhea|iarrhea]]
** [[headache]]
** Muscular aches
** [[weakness]]
** [[abdominal pain]]
** [[urticaria]]
** [[fever]]
** [[lymphadenopathy]]
|
* MR or direct [[Angiogram|angiography]] shows a normal [[Hepatic vein|hepatic venous]] pressure gradient
|-
| style="background:#DCDCDC; + " | '''Sarcoidosis'''
|
* Dry cough with [[dyspnea]]
* Anterior or posterior [[uveitis]]
* [[dry eyes]]
* [[glaucoma]]
* Skin findings may include:
** Maculopapular lesions on the face, back, arms and legs
** [[erythema nodosum]] on the legs
|
* Chest x ray may show:
** [[hilar lymphadenopathy]]
** Upper lobe [[fibrosis]]
** Diffuse reticulonodular shadowing
** [[Liver biopsy]] shows non-necrotizing, non-caseating [[Granuloma|granulomas]]
|-
| style="background:#DCDCDC; + " | '''Inferior vena cava obstruction'''
|
* Signs and symptoms of [[renal cell carcinoma]]:
* Hematuria
* [[flank pain]]
* Flank or abdominal mass
* Weight loss
* [[hypertension]]
|
* [[Ultrasound]] of the abdomen shows evidence of [[inferior vena cava]] obstruction
|-
| style="background:#DCDCDC; + " | '''Nodular regenerative hyperplasia'''
|None
|
* [[Liver biopsy]] shows small regenerative [[Nodule (medicine)|nodules]] with little or no [[fibrosis]] on reticulin staining
|-
| style="background:#DCDCDC; + " | '''Idiopathic portal hypertension (hepatoportal sclerosis)'''
|None
|
* [[Liver biopsy]] shows no evidence of cirrhosis
|-
| style="background:#DCDCDC; + " | '''Vitamin A intoxication, arsenic, and vinyl chloride toxicity'''
|None
|
* History generally reveals exposure
|}
===Differentiating Cirrhosis from other Diseases Based on Ascitic Fluid===
===Differentiating Cirrhosis from other Diseases Based on Ascitic Fluid===
[[Ascites]] may be caused by [[portal hypertension]] due to cirrhosis of [[liver]] or due to other causes such as [[Cancer|malignancy]]. [[Ascites|Ascitic]] fluid analysis should be done to broadly categorize the cause of [[ascites]].
[[Ascites]] may be caused by [[portal hypertension]] due to cirrhosis of [[liver]] or due to other causes such as [[Cancer|malignancy]]. [[Ascites|Ascitic]] fluid analysis should be done to broadly categorize the cause of [[ascites]].

Revision as of 19:22, 19 December 2017

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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 to differentiate cirrhosis from other diseases such as malignancy, constrictive pericarditis, Budd-Chiari syndrome, portal vein thrombosis and splenic vein thrombosis.

Differentiating Cirrhosis from other Diseases

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:[1][2][3][4][5][6][7][8]

Abdominal MRI may also be helpful in the diagnosis of portal hypertension. Findings on MRI suggestive of cirrhosis with portal hypertension include:[9][10][11][12]

Transient elastography and the Acoustic Radiation Force Impulse (ARFI) technique are well-established methods for the staging of fibrosis in various liver diseases: [13][14][15][16][17][18][19][20][21][22][23] 

  • 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:[24][25]
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

Differential diagnosis of jaundice are: [26][27][28][29][30]

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

Differentiating Cirrhosis from other Diseases Based on Ascitic Fluid

Ascites may be caused by portal hypertension due to cirrhosis of liver or due to other causes such as malignancy. Ascitic fluid analysis should be done to broadly categorize the cause of ascites.

Ascites is broadly classified as two types based on the serum-ascites albumin gradient (SAAG):

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ "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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ "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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ 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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  29. ↑ 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.
  30. ↑ 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.

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