Table of Contents
Definition / general | Essential features | ICD coding | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Positive stains | Videos | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Rohit M, Mannan R. Hepatitis (acute and chronic)-general. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverhepatitisgeneral.html. Accessed June 7th, 2023.
Definition / general
- Acute hepatitis:
- Active hepatocellular damage and necrosis caused most often due to viral infection, autoimmune disease or adverse drug reaction
- Histologically characterized by lobular disarray and variable hepatocyte necrosis
- Usually self limited duration of < 6 months
- Chronic hepatitis:
- Persistent and progressive inflammation and injury of hepatocytes
- Histologically characterized by portal based chronic inflammation
- Elevated liver enzymes for > 6 months' duration
Essential features
- Hepatitis can be acute or chronic
- Variable etiology
- Morphologically characterized by lobular inflammation and necrosis, portal inflammation, interface hepatitis and fibrosis / cirrhosis
ICD coding
Sites
- Liver parenchyma
Pathophysiology
- Inflammation of hepatocytes is caused by many factors, such as viruses, autoimmune disorders, drugs and alcohol
- Inflammatory cells along with proinflammatory cytokines can cause hepatocyte degeneration and necrosis; can induce stellate cell activation resulting in fibrosis and even progressing to cirrhosis overtime (Alcohol Alcohol 2019;54:408, Cold Spring Harb Perspect Med 2018;8:a031708)
Etiology
- Viral hepatitis: A, B, C, D, E (World J Gastroenterol 2021;27:1691)
- Less often caused by CMV, EBV, HSV, adenovirus
- Autoimmune hepatitis (J Immunol Res 2019;2019:9437043)
- Drug induced hepatitis (J Clin Pathol 2009;62:481)
- Alcoholic hepatitis (Alcohol Alcohol 2019;54:408)
- Nonalcoholic steatohepatitis
- Metabolic causes:
- Wilson disease
- Alpha-1 antitrypsin deficiency
- Hemochromatosis
Clinical features
- Acute hepatitis:
- Nonspecific constitutional symptoms: fever, fatigue, malaise (World J Gastroenterol 2021;27:1691)
- Jaundice
- Nausea, vomiting, weight loss, abdominal pain
- May present with signs and symptoms of liver failure
- Nonspecific constitutional symptoms: fever, fatigue, malaise (World J Gastroenterol 2021;27:1691)
- Chronic hepatitis:
- Asymptomatic or nonspecific constitutional symptoms
- Often diagnosed on laboratory evaluation (World J Gastroenterol 2021;27:1691)
- May present with features of portal hypertension and cirrhosis in later stages
- Asymptomatic or nonspecific constitutional symptoms
Diagnosis
- Clinical history and physical examination for specific signs and symptoms
- Laboratory evaluation
- Biopsy for grade and stage in chronic hepatitis
Laboratory
- Elevated transaminases (Alcohol Alcohol 2019;54:408)
- Alkaline phosphatase is slightly elevated
- Viral hepatitis: viral serologies will be positive (World J Gastroenterol 2021;27:1691)
- Autoimmune hepatitis: autoimmune serologies will be positive (J Immunol Res 2019;2019:9437043)
- Disease specific tests: urinary copper, ceruloplasmin, alpha-1 antitrypsin levels are helpful
Radiology description
- Acute hepatitis (Radiopaedia: Acute hepatitis [Accessed 20 June 2022]):
- Ultrasound features:
- Hepatomegaly is the most sensitive sign
- Gallbladder wall thickening (most often seen in hepatitis A)
- Periportal edema
- Accentuated brightness of portal vein radicle walls
- Overall echotexture is decreased
- Color / spectral doppler is normal
- CT - not a first line imaging modality:
- Hepatomegaly
- Decreased attenuation around portal system and hepatic hilum
- Diffusely decreased parenchymal attenuation on noncontrast CT
- Periportal or hepatoduodenal lymphadenopathy
- MRI findings are nonspecific and often used to exclude other etiologies of abnormal liver function studies
- Ultrasound features:
- Chronic hepatitis (Radiopaedia: Cirrhosis [Accessed 20 June 2022]):
- Ultrasound:
- Surface nodularity
- Overall coarse and heterogenous echotexture
- Segmental hypertrophy / atrophy
- Signs of portal hypertension
- Splenomegaly
- Fatty change
- Ascites
- CT / MRI - insensitive in early cirrhosis:
- Surface and parenchymal nodularity
- Fatty change
- In advanced cirrhosis, nodular margin and lobar hypertrophy / atrophy may be seen
- Signs of portal hypertension
- Upper abdominal lymphadenopathy in advanced disease
- Ultrasound:
Radiology images
Case reports
- 28 year old woman with abdominal pain, fever and rash (J Family Med Prim Care 2020;9:3749)
- 30 year old man with generalized weakness (Case Rep Gastrointest Med 2018;2018:2139607)
- 45 year old woman with icterus, headache and confusion (ACG Case Rep J 2020;7:e00441)
- 50 year old woman with abnormal liver enzymes on routine labs (ACG Case Rep J 2020;7:e00440)
- 59 year old woman with right upper quadrant (RUQ) pain and intermittent fever (Ann Gastroenterol 2018;31:123)
Treatment
- Based on the underlying etiology
Gross description
- Acute hepatitis:
- Liver is homogenously enlarged and congested, stretching Glisson capsule
- Necrosis and collapse of the liver lobules maybe seen
- Surface is usually reddish brown
- In cholestatic cases, a spectrum of brown to green may be seen
- Chronic hepatitis:
- Nonspecific in early stages
- Can be enlarged with yellow (fatty change in steatosis) to green (in cholestasis)
- In advanced stages the liver is cirrhotic with a firm, nodular appearance; they can have a micronodular or macronodular pattern (World J Gastroenterol 2016;22:1357)
Gross images
Microscopic (histologic) description
- Histological features are broad ranging and can vary based on etiology
- Acute hepatitis:
- Predominantly lobular injury pattern
- Chronic hepatitis:
- Predominantly portal / periportal inflammation, with varying degrees of fibrosis (World J Gastroenterol 2016;22:1357)
- Lobular inflammation and necrosis:
- Necrosis may be spotty, confluent or bridging
- Apoptotic bodies (acidophilic bodies / Councilman bodies)
- Ballooned hepatocytes (Alcohol Alcohol 2019;54:408)
- Canalicular cholestasis
- Portal inflammation (World J Gastroenterol 2016;22:1357):
- Viral hepatitis: primarily composed of lymphocytes, admixed plasma cells, histiocytes; lymphoid follicles are common in hepatitis C
- Autoimmune hepatitis: prominent plasma cell infiltrate with interface activity
- Drug induced: variable histology, mixed inflammatory cells, often rich in eosinophils
- Interface hepatitis (piecemeal necrosis) (Gut Liver 2020;14:430):
- Destruction of hepatocytes in the interface with inflammation extending into the adjacent liver parenchyma
- Fibrosis / cirrhosis (varying degrees, depending on stage of the disease)
Microscopic (histologic) images
Contributed by Rifat Mannan, M.B.B.S., M.D., Alexander Boyd, M.B.Ch.B., Owen Cain, M.B.Ch.B.,
Abhishek Chauhan, Ph.D. and Gwilym J. Webb, M.B.Ch.B., M.A.
Positive stains
- Trichrome stain / reticulin stain: highlights fibrosis / cirrhosis
- PASD: highlights cytoplasmic globules in alpha-1 antitrypsin deficiency
- Hepatitis B surface antigen (HBsAg) immunohistochemistry
- Other viral stains: CMV, adenovirus, HSV, EBER
Videos
Histopathology of liver in viral hepatitis
Histopathology of liver in chronic hepatitis
Sample pathology report
- Liver, needle biopsy:
- Chronic hepatitis B, with mild portal fibrosis (see comment)
- Histologic grade: A1 (METAVIR system)
- Histologic stage: 1/4 (Scheuer system)
- Comment: The patient's clinical history of hepatitis B virus infection (HBV DNA positive by report) is noted.
Differential diagnosis
- Primary biliary cholangitis, primary sclerosing cholangitis:
- Cholestasis with bile duct damage or loss
- Portal inflammation without interface hepatitis
- Alkaline phosphatase is elevated more than transaminases
- Lymphoma / leukemia:
- Portal tract inflammation with severe interface activity
- Infiltrates comprised of atypical lymphocytes
- Gene rearrangement studies and immunohistochemistry can help with diagnosis
- Graft rejection:
- Liver transplant patients
- Portal inflammation with mixed inflammatory cells, including eosinophils
- Lymphocytic cholangitis with duct damage, endothelialitis
Board review style question #1
An asymptomatic 50 year old woman presented with elevated transaminases (aspartate aminotransferase and alanine aminotransferase) on routine laboratory tests. The image above is a micrograph of the liver biopsy. What are the predominant inflammatory cells seen and what could be the underlying etiology?
- Lymphocytic predominance seen in viral hepatitis
- Lymphoid follicles seen in chronic hepatitis C infection
- Mixed inflammatory cells with eosinophils seen in drug induced hepatitis
- Plasma cell predominance seen in autoimmune hepatitis
Board review style answer #1
D. Plasma cell predominance seen in autoimmune hepatitis
Comment Here
Reference: Hepatitis (acute and chronic)-general
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Reference: Hepatitis (acute and chronic)-general
Board review style question #2
A 45 year old woman presented with jaundice, vomiting and abdominal pain. Elevated transaminases were found on laboratory testing. Patient is diagnosed with acute viral hepatitis. What would be the microscopic findings in this patient?
- Bile duct proliferation with extensive fibrosis and brown, green plugs
- Lobular disarray with interface hepatitis and plasma cell rich portal inflammation
- Lobular inflammation with confluent necrosis and balloon degeneration
- Necrosis of hepatocytes with atypical lymphocytic infiltration
Board review style answer #2
C. Lobular inflammation with confluent necrosis and balloon degeneration
Comment Here
Reference: Hepatitis (acute and chronic)-general
Comment Here
Reference: Hepatitis (acute and chronic)-general