Liver & intrahepatic bile ducts
Acute and chronic hepatitis
Chronic hepatitis
Editor-in-Chief: Debra L. Zynger, M.D.
Topic Completed: 29 August 2019
Minor changes: 25 December 2020
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PubMed Search: Chronic hepatitis[TI] general[TI]
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: March J, Evason KJ. Chronic hepatitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverchronichepgeneral.html. Accessed January 18th, 2021.
Definition / general
- Liver fibrosis occurring as a result of hepatocyte based injury and inflammation, most commonly due to viral or autoimmune hepatitis or alcoholic or non-alcoholic fatty liver disease
Essential features
- Progressive fibrosis that ultimately leads to liver cirrhosis
- Morphologically characterized by portal inflammation with interface activity, lobular necroinflammatory activity and fibrosis
Terminology
- Chronic active hepatitis
- Chronic persistent hepatitis
- Chronic lobular hepatitis (Am J Surg Pathol 1995;19:1409)
ICD coding
ICD-10 coding:
B18.0 - chronic viral hepatitis B with delta-agent
B18.1 - chronic viral hepatitis B without delta-agent
B18.2 - chronic viral hepatitis C
B18.8 - other chronic viral hepatitis
B18.9 - chronic viral hepatitis, unspecified
K73.0 - chronic persistent hepatitis, not elsewhere classified
K73.1 - chronic lobular hepatitis, not elsewhere classified
K73.2 - chronic active hepatitis, not elsewhere classified
K73.8 - other chronic hepatitis, not elsewhere classified
K73.9 - chronic hepatitis, unspecified
Sites
- Liver parenchyma
Pathophysiology
- Hepatocytes are injured by viral infection, drugs, deregulated inflammatory cells or abnormal accumulation of metabolites, leading to activation of hepatic stellate cells, which produce increased extracellular matrix resulting in fibrosis (Middle East J Dig Dis 2016;8:166, Physiol Rev 2008;88:125)
Etiology
- Chronic viral hepatitis
- Hepatitis B virus (HBV)
- Hepatitis C virus (HCV)
- Hepatitis D virus (HDV)
- Autoimmune hepatitis
- Metabolic disease
- Drug induced chronic hepatitis (rare) (J Clin Pathol 2009;62:481)
- Lisinopril
- Sulfonamides
- Trazodone
- Uracil
- Tegafur
- Tamoxifen
- Methotrexate
- Minocycline
- Clometacin
- Methyldopa
- Nitrofurantoin
- Nonalcoholic steatohepatitis (NASH)
- Alcoholic liver disease
Clinical features
- May lack symptoms until end stage (cirrhosis)
- Associated signs and symptoms include:
- General: fatigue (most common), malaise, mild discomfort in the right upper quadrant, anorexia
- Impaired biliary tract function: jaundice, pruritus
- Portal hypertension: gastroesophageal varices, ascites, edema, splenomegaly
- Impaired hepatocyte metabolism: spider angiomata, hepatic encephalopathy, easy bleeding / bruising
Diagnosis
- Biopsy is gold standard for determining grade and stage
- Clinical history and exam looking for associated signs and symptoms (see above)
- Laboratory testing (see below)
- Transient elastography (Fibroscan) (World J Gastroenterol 2014;20:11033, World J Gastroenterol 2014;20:2854)
Laboratory
- Aminotransferase levels (AST, ALT may be elevated)
- Serological testing for hepatitis B, C and D and autoantibodies (may be positive, depending on etiology)
- Several serum markers for evaluating liver fibrosis have been proposed but none are widely used (World J Gastroenterol 2014;20:11033, World J Gastroenterol 2014;20:2854)
Radiology description
- MRI and CT findings in cirrhosis
- Surface and parenchymal nodularity
- Hypertrophy of the caudate lobe and lateral segments of the left lobe
- Atrophy of the posterior segments of the right lobe
- Ultrasound findings in cirrhosis
- Surface nodularity
- Course and heterogeneous echotexture
- Segmental hypertrophy / atrophy
- Doppler flow changes indicative of portal hypertension
- Splenomegaly
- Ascites (Radiopaedia.org: Cirrhosis | Radiology Reference Article [Accessed 17 July 2019])
Radiology images
Image hosted on other servers:
Nodular liver in patient with hepatitis B
Prognostic factors
- Amount of fibrosis (stage) is a key predictor of progression to end-stage liver disease (cirrhosis) (World J Gastroenterol 2014;20:2854) and adverse clinical outcomes including need for liver transplant and liver related death in patients with hepatitis C (Hepatology 2010;51:585)
- Amount of inflammation (grade) is associated with fibrosis progression (stage) in patients with hepatitis C (Pathol Int 2002;52:683)
- Rate of progression to end-stage liver disease depends on many other factors including age, sex (J Interferon Cytokine Res 2017;37:97), underlying etiology of liver injury and response to treatment (Gut Liver 2016;10:429)
Case reports
- 28 year old man with acute on chronic liver failure and hemolysis (EJIFCC 2019;30:99)
- 46 year old man with HBV cirrhosis and dermatomyositis (World J Clin Cases 2019;7:1206)
- 55 year old man with jaundice (N Engl J Med 2019;380:1955)
- 56 year old man with Guillain-Barré syndrome and chronic active hepatitis C (BMC Infect Dis 2019;19:636)
- 72 year old man successfully treated for HBV, HCV, and HEV (J Infect Public Health 2019 Jun 21 [Epub ahead of print])
Treatment
- Dependent on underlying etiology
Gross description
- In cirrhosis, the liver is generally firm and demonstrates a micronodular or macronodular pattern
- Color ranges from beefy red (normal) to dark green (cholestasis) or yellow (steatosis) (World J Gastroenterol 2016;22:1357)
Gross images
Image hosted on other servers:
Cirrhotic liver is diffusely nodular
Microscopic (histologic) description
- Fibrosis
- Required for pathologic diagnosis of chronic hepatitis
- Progressive fibrosis of limiting plate leads to enlargement of portal tracts and stellate periportal fibrous extension
- May lead to portal - portal or portal - central fibrous bridging, culminating in cirrhosis, which is usually micronodular (nodules < 3 mm in diameter) or mixed micronodular and macronodular type
- Portal inflammation
- Mononuclear infiltration of portal tracts (mostly CD4+ T lymphocytes with some plasma cells)
- Lymphoid aggregates or follicles may be present (most common in hepatitis C infection)
- Interface hepatitis
- Previously called “piecemeal necrosis”
- Hepatocyte apoptosis and inflammation at the stromal-parenchymal interface (interface of portal tract and lobule)
- Mononuclear infiltrate (mostly CD8+ T lymphocytes)
- Lobular hepatitis
- Mononuclear infiltrate of the hepatic parenchyma (lobules)
- Apoptotic / necrotic hepatocytes (Councilman bodies) in zones 2 and 3
Microscopic (histologic) images
Contributed by Kimberley J. Evason, M.D., Ph.D.
Chronic hepatitis C
Fibrosis in chronic hepatitis C
Cirrhosis (end stage)
Positive stains
- Trichrome stain can help with the assessment of the amount of scarring and fibrosis present (stage)
Sample pathology report
- Liver, core biopsy:
- Chronic hepatitis with mild activity (grade 2, scale 0-4, Batts-Ludwig methodology) and periportal fibrosis with septae formation (stage 2, scale 0-4, Batts-Ludwig methodology), consistent with clinical history of chronic hepatitis C
Differential diagnosis
- Primary biliary cirrhosis (PBC)
- Can have portal based inflammation with interface activity and lobular activity
- Florid duct lesions not seen in chronic hepatitis
- Clinical history may include elevated alkaline phosphatase, gamma-glutamyl transpeptidase, serum IgM and antimitochondrial autoantibodies
- Lymphoma or leukemia infiltrating into the liver
- Can have portal lymphocytic inflammation
- Lacks interface hepatitis and portal based fibrosis
- May have monomorphism and marked atypia of the infiltrating cells
- Active hepatitis with bridging necrosis
- Has portal inflammation with interface activity and lobular inflammation
- Bridging necrosis can cause a nodular appearance from low power, mimicking bridging fibrosis or cirrhosis
- Trichrome staining is paler in zones of dropout / necrosis than in fibrous areas
Additional references
Board review style question #1
- An asymptomatic 35 year old woman has elevated serum aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). A liver biopsy was performed. What is the most likely underlying etiology of these findings?
- Alcoholic liver disease would be expected to show steatohepatitis. There is no fat in this biopsy
- Infection with hepatitis C causes chronic hepatitis, which is characterized by fibrosis and periportal lymphocytic inflammation
- Oxaliplatin induced liver injury is characterized by a vascular injury pattern including sinusoidal dilatation, congestion, and centrizonal necrosis
- Tylenol associated liver injury is associated with centrizonal necrosis
- Valproic acid-associated liver injury is characterized by microvesicular steatosis
Board review style answer #1
B. Infection with hepatitis C causes chronic hepatitis, which is characterized by fibrosis and periportal lymphocytic inflammation
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Reference: Chronic hepatitis - general
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Reference: Chronic hepatitis - general
Board review style question #2
- A liver biopsy from a 54 year old man is shown below. What feature, required for the diagnosis of chronic hepatitis, is shown in the image?
- Bridging necrosis is not required for the diagnosis of chronic hepatitis. This biopsy shows bridging fibrosis, not bridging necrosis. Bridging necrosis would appear pale blue-gray on trichrome stain
- There is extensive fibrosis in this biopsy. Fibrosis is required for the histologic diagnosis of chronic hepatitis
- Interface hepatitis is often present in chronic viral hepatitis, but is not required for the diagnosis of chronic hepatitis
- Nodule formation is seen here and is required for the diagnosis of cirrhosis, but is not required for the diagnosis of chronic hepatitis
- Portal inflammation is often present in chronic viral hepatitis, but is not required for the diagnosis of chronic hepatitis
Board review style answer #2
B. There is extensive fibrosis in this biopsy. Fibrosis is required for the histologic diagnosis of chronic hepatitis
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Reference: Chronic hepatitis - general
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Reference: Chronic hepatitis - general
