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Non-alcoholic fatty liver disease differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2] Parth Vikram Singh, MBBS[3]

Overview

Usually, NAFLD presents with no or few symptomsΒ but if symptomatic NAFLD must be differentiated from other diseases that cause jaundice and abdominal pain which include Wilson’s disease, hemochromatosis, alcoholic hepatitis and cholestatic jaundice.

Differential Diagnosis

NAFLD must be differentiated from other diseases that cause jaundice and abdominal pain like including alcohol-associated liver disease, metabolic dysfunction and alcohol-related liver disease, drug-induced liver injury, hepatitis C virus infection, iron overload, celiac disease, HIV infection, malnutrition, Wilson disease, lysosomal acid lipase deficiency, hypobetalipoproteinemia, and inborn errors of metabolism.[1][2]

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 Hemochromatosis + – -/+ – ↑ ↑ ↑/N ↑/N N – Ferritin ↑ Liver biopsy
Wilson’s disease + – -/+ – ↑ ↑ N ↑/N N – Serum cerulloplasmin ↑ Liver biopsy
Alcoholic hepatitis – -/+ -/+ – ↑↑ ↑ N ↑/N N – – –
Cirrhosis -/+ -/+ -/+ – ↑ ↑ ↑/N ↑/N ↑/N -/+ Low platate Small liver on ultrasond
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 ↑ – Beading on MRCP Liver biopsy
Pancreatic carcinoma + – -/+ – N/↑ N/↑ ↑ N ↑ – Mass on ultrasond CT scan for diagnosis

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
Acute suppurative cholangitis RUQ + + + + βˆ’ βˆ’ βˆ’ βˆ’ + + + N
  • Abnormal LFT
  • WBC >10,000
  • Ultrasound shows biliary dilatation/stents/tumor
  • Septic shock occurs with features of SIRS
Acute cholangitis RUQ + βˆ’ βˆ’ + βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ N
  • Ultrasound shows biliary dilatation/stents/tumor
  • Biliary drainage (ERCP) + IV antibiotics
Acute cholecystitis RUQ + βˆ’ + + βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ Hypoactive Ultrasound shows:
  • Gallstone
  • Inflammation
Acute pancreatitis Epigastric + βˆ’ + Β± βˆ’ βˆ’ βˆ’ βˆ’ Β± βˆ’ βˆ’ N
  • Ultrasound shows evidence of inflammation
  • CT scan shows severity of pancreatitis
  • Pain radiation to back
Chronic pancreatitis Epigastric βˆ’ βˆ’ Β± Β± βˆ’ + + βˆ’ βˆ’ βˆ’ βˆ’ N
  • Increased amylase / lipase
  • Increased stool fat content
  • Pancreatic function test
 CT scan
  • Calcification
  • Pseudocyst
  • Dilation of main pancreatic duct
  • Predisposes to pancreatic cancer
Pancreatic carcinoma Epigastric βˆ’ βˆ’ + + βˆ’ + + βˆ’ βˆ’ βˆ’ βˆ’ N

SkinΒ manifestations may include:

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
Primary biliary cirrhosis RUQ/Epigastric βˆ’ βˆ’ βˆ’ + βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ N
  • Increased AMA level, abnormal LFTs
  • ERCP
  • Pruritis
Primary sclerosing cholangitis RUQ + βˆ’ βˆ’ + βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ N ERCP and MRCP shows
  • Multiple segmentalΒ strictures
  • Mural irregularities
  • BiliaryΒ dilatation and diverticula
  • Distortion of biliary tree
  • The risk ofΒ cholangiocarcinomaΒ in patients with primary sclerosing cholangitis is 400 times higher than the risk in the general population.
Cholelithiasis RUQ/Epigastric Β± βˆ’ Β± Β± βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ Normal to hyperactive for dislodged stone
  • Fatty food intolerance
Gastrointestinal perforation Diffuse + Β± – Β± βˆ’ βˆ’ βˆ’ + + + Β± Hyperactive/hypoactive
  • WBC> 10,000
Inflammatory bowel disease Diffuse Β± βˆ’ βˆ’ Β± βˆ’ + + + βˆ’ βˆ’ βˆ’ Normal or hyperactive

Extra intestinal findings:

Whipple’s disease Diffuse Β± βˆ’ βˆ’ Β± βˆ’ + + βˆ’ Β± βˆ’ βˆ’ N Endoscopy is used to confirm diagnosis.

Images used to find complications

Extra intestinal findings:
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
Viral hepatitis RUQ + βˆ’ + + βˆ’ Positive in Hep A and E + βˆ’ Positive in fulminant hepatitis Positive in acute + N
  • Abnormal LFTs
  • Viral serology
  • US
  • Hep A and E have fecal-oral route of transmission
  • Hep B and C transmits via blood transfusion and sexual contact.
Liver abscess RUQ + + + + βˆ’ Β± + βˆ’ + + Β± Normal or hypoactive
  • US
  • CT
Hepatocellular carcinoma/Metastasis RUQ + βˆ’ βˆ’ + βˆ’ βˆ’ + βˆ’ βˆ’ βˆ’ βˆ’
  • Normal
  • Hyperactive if obstruction present
  • US
  • CT
  • Liver biopsy

Other symptoms:

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
Budd-Chiari syndrome RUQ Β± βˆ’ βˆ’ Β± βˆ’ βˆ’ βˆ’ Positive in liver failure leading to varices βˆ’ βˆ’ βˆ’ N
Findings on CT scan suggestive of Budd-Chiari syndrome include:
Ascitic fluid examination shows:
Cirrhosis RUQ βˆ’ βˆ’ βˆ’ + βˆ’ βˆ’ + + + βˆ’ βˆ’ N US
  • Stigmata of liver disease
  • Cruveilhier- Baumgarten murmur
Spontaneous bacterial peritonitis Diffuse + βˆ’ βˆ’ Positive in cirrhotic patients βˆ’ + βˆ’ βˆ’ Β± + + Hypoactive
  • Ascitic fluid PMN>250 cells/mmΒ³
  • Culture: Positive for single organism
  • Ultrasound for evaluation of liver cirrhosis
Biliary colic RUQ βˆ’ βˆ’ + + βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ βˆ’ N
  • Ultrasound

References

  1. ↑ Abd El-Kader SM, El-Den Ashmawy EM (2015). “Non-alcoholic fatty liver disease: The diagnosis and management”. World J Hepatol. 7 (6): 846–58. doi:10.4254/wjh.v7.i6.846. PMCΒ 4411527. PMIDΒ 25937862.
  2. ↑ Tilg H, Petta S, Stefan N, Targher G (January 2026). “Metabolic Dysfunction-Associated Steatotic Liver Disease in Adults: A Review”. JAMA. 335 (2): 163–174. doi:10.1001/jama.2025.19615. PMIDΒ 41212550 Check |pmid= value (help).

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