Hepatitis D differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]; Jolanta Marszalek, M.D. [3]

Overview

Hepatitis D must be differentiated from other diseases that cause fever, nausea, vomiting, jaundice, hepatomegaly, icteric sclera, and elevated ALT and AST such as viral hepatitis (caused by other etiologic agents), alcoholic hepatitis, and autoimmune hepatitis.

Differential Diagnosis

Shown below is a table that summarizes the findings that differentiate hepatitis D from other conditions that cause fever, nausea, vomiting, jaundice, hepatomegaly, and icteric sclera.[1][2]

Disease Findings
Viral Hepatitis A Symptoms are similar to the ones of hepatitis D, however, hepatitis A, caused by the hepatitis A virus, produces a self-limited disease, rarely causing complications.
Viral Hepatitis B Symptoms are similar to the ones of hepatitis D, however, hepatitis B is a life-threatening condition caused by the hepatitis B virus, that may lead to the development of cirrhosis and liver cancer. Serologic testing will help differentiate these two conditions.
Viral Hepatitis C Symptoms are similar to the ones of hepatitis D, however, hepatitis C, caused by the hepatitis C virus, can cause acute and/or chronic hepatitis. Serologic testing will help differentiate these two conditions.
Viral Hepatitis E Symptoms are similar to the ones of hepatitis D, however, hepatitis E, caused by the hepatitis E virus, may complicate, in rare cases, into chronic hepatitis and liver failure. Serologic testing will help differentiate these two conditions.
Alcoholic Hepatitis Symptoms are similar to the ones of hepatitis D, however, alcoholic hepatitis is related to the excessive use of alcohol. Alcoholic hepatitis presents more often with ascites. Alcoholic hepatitis often leads to cirrhosis and liver failure, if alcohol use is not decreased. Serologic testing will help differentiate these two conditions. Also laboratory results show ALT<AST in alcoholic hepatitis (inverse from viral hepatitis, which is ALT>AST).
Autoimmune Hepatitis Autoimmune hepatitis occurs when the body's immune system attacks the hepatocytes. It often affects young females and may present with signs of acute hepatitis or chronic liver disease. Serologic testing will help differentiate these two conditions.

Differential diagnosis of jaundice are: [3][4][5][6][7]

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

References

  1. "Hepatitis D" (PDF).
  2. "Hepatitis D (CDC)".
  3. Fargo MV, Grogan SP, Saguil A (2017). "Evaluation of Jaundice in Adults". Am Fam Physician. 95 (3): 164–168. PMID 28145671.
  4. 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.
  5. Hov JR, Boberg KM, Karlsen TH (2008). "Autoantibodies in primary sclerosing cholangitis". World J. Gastroenterol. 14 (24): 3781–91. PMC 2721433. PMID 18609700.
  6. 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.
  7. 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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