Liver & intrahepatic bile ducts
General
Cirrhosis
Author: Anthony W.H. Chan, F.R.C.P.A.
Topic Completed: 1 June 2017
Minor changes: 15 December 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Liver cirrhosis[TI] liver[mh] free full text[sb]
Table of Contents
Definition / general | Epidemiology | Causes | Pathophysiology | Clinical features | Laboratory | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Features to report | Differential diagnosis | Board review style question #1 | Board review style answer #1Cite this page: Chan A. Cirrhosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livercirrhosis.html. Accessed January 22nd, 2021.
Definition / general
- Diffuse nodulation of liver due to fibrous bands subdividing liver into regenerative nodules
Epidemiology
- Major cause of global health burden accounting for 1.2% of disability adjusted life years (DALYs) (Lancet 2012;380:2197) and 2% of deaths (Lancet 2012;380:2095) worldwide in 2010
Causes
- Prevalence of causes varies by location
- Common causes include
- Chronic viral hepatitis B (± D) and C
- Fatty liver disease: alcoholic and nonalcoholic
- Metabolic: genetic hemochromatosis, alpha-1-antitrypsin deficiency, Wilson disease
- Immune mediated: autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis
- Chronic biliary obstruction
- Drug induced liver injury
- Cryptogenic (idiopathic) cirrhosis: accounts for 8 - 9% of liver transplants in the US; "burnt out" NAFLD / NASH is a common cause of cryptogenic cirrhosis (Hepatology 2000;32:689)
Pathophysiology
- Combination of different processes (J Hepatol 2017;66:778)
- Fibrosis: excessive production of collagen type I / III by hepatic stellate cells ± portal fibroblasts through chronic inflammation (TNF alpha, TGF-beta, IL1), cytokines from Kupffer cells, endothelial cells, bile duct cells, hepatocytes and disruption of extracellular matrix and toxins
- Regeneration of hepatocytes through proliferation of progenitor cells of the ductular reaction
- Parenchymal extinction due to vascular disruption
- Regression (J Hepatol 2015;63:1038)
- Cirrhosis is potentially reversible after successful treatment of chronic liver disease, e.g. viral hepatitis
- Cessation of chronic damage allows hepatocyte recovery and modulates the microenvironment
- Shifting balance from inflammation to resolution results in phenotypic adjustments of immune cells
- Myofibroblasts are deactivated by senescence, apoptosis and inactivation
- Matrix degradation also occurs
Clinical features
- General (nonspecific): malaise, fatigue, anorexia, weight loss
- Specific (due to impaired liver function):
- Impaired protein synthesis (leukonychia [white nails], ascites, bruising)
- Impaired biliary excretion (jaundice, pruritus)
- Impaired nitrogen metabolism (hepatic encephalopathy)
- Impaired estrogen metabolism (palmar erythema, spider nevus, testicular atrophy, gynecomastia)
- Complications:
- Decompensation: development of jaundice, ascites, variceal hemorrhage or hepatic encephalopathy
- Portal hypertension: ascites (± spontaneous bacterial peritonitis), splenomegaly, esophageal / gastric varices
- Liver failure: coagulopathy, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, portopulmonary hypertension
- Hepatocellular carcinoma: cirrhosis is a key risk factor and the annual incidence of HCC among cirrhotic patients is 2 - 8% (Lancet 2014;384:2053, Hepatology 2010;51:1972)
Laboratory
- Clinical subclassification of cirrhosis uses blood ± clinical parameters
- Child-Pugh score / grade (J Hepatol 2005;42:S100)
- Five parameters: albumin, bilirubin, INR / prothrombin time, ascites and hepatic encephalopathy
- Each parameter is assigned from 1 - 3
- Total score ranges from 5 - 15 and is categorized as grade A (5, 6), B (7 - 9) and C (10 - 15)
- Model for end stage liver disease (MELD) score (J Hepatol 2005;42:S100)
- Three parameters: bilirubin, creatinine and INR
- Uses to prioritize need for liver transplantation
- Albumin-bilirubin (ALBI) score / grade (J Clin Oncol 2015;33:550)
- Two parameters: albumin, bilirubin
- Simple, objective and evidence based alternative of Child-Pugh score / grade
Gross images
Contributed by Anthony W.H. Chan, FRCPA
Cirrhosis images
Images hosted on other servers:
Micronodular and macronodular cirrhosis
Microscopic (histologic) description
- Nonbiliary type cirrhosis
- Diffuse disruption in architecture of the entire liver (loss of normal central - portal relationship)
- Bridging fibrous septa
- Roundish parenchymal nodules of regenerating hepatocytes
- Biliary type cirrhosis
- Diffuse disruption in architecture of the entire liver (loss of normal central - portal relationship)
- Bridging fibrous septa
- Irregular, jigsaw puzzle shaped parenchymal nodules of regenerating hepatocytes with peripheral pale halo (peripheral septal edema, loose packed fibrous tissue and chronic cholate stasis of periseptal hepatocytes)
- Alcoholic type cirrhosis
- Micronodular cirrhosis, Mallory bodies, fatty change
- Also perivenular and pericellular fibrosis (highlighted with trichrome stain) with partial / complete obliteration of central vein (identify as central vein due to lack of arterioles)
- More prominent bridging from central zone to central zone and central zone to portal zone than in other causes of cirrhosis
- Usually few inflammatory cells unless superimposed viral or alcoholic hepatitis
Microscopic (histologic) images
Contributed by Anthony W.H. Chan, FRCPA:
Micronodular and macronodular cirrhosis
Images hosted on other servers:
Fibrosis (trichrome)
Bridging fibrosis types (left to right): portal - portal; central - central; portal - central
Features to report
- Diagnosis: incomplete cirrhosis (Ishak stage 5) vs. probable / definite cirrhosis (Ishak stage 6) (J Hepatol 1995;22:696)
- Subclassification: micronodular (< 3 mm) vs. macronodular (≥ 3 mm)
- Classically but not very clinically significant
- Former is more commonly associated with alcoholic liver disease, genetic hemochromatosis and Wilson disease, whereas the later is more frequently associated with viral hepatitis
- Micronodular cirrhosis and macronodular cirrhosis may be transformed in either way depending on disease activity (Arch Pathol Lab Med 2000;124:1599)
- Difficult to assess in liver biopsy specimen
- Subclassification: Laennec fibrosis scoring system (J Hepatol 2011;55:1004)
- 4A: mild cirrhosis; marked septation with rounded contours or visible nodules; most septa are thin (one broad spectum allowed)
- 4B: moderate cirrhosis with at least two broad septa
- 4C: severe cirrhosis with at least one very broad septum or many minute nodules
- Excellent interobserver agreement (kappa 0.83)
- Correlate with severity of portal hypertension and Child-Pugh and MELD scores
- Etiology
- Clinical, biochemical and serological correlation is essential
- Cryptogenic (idiopathic) cirrhosis accounts for 8 - 9% of liver transplants in the US; "burnt out" NAFLD / NASH is a common cause of cryptogenic cirrhosis (Hepatology 2000;32:689)
Differential diagnosis
- Congenital hepatic fibrosis: absence of regenerative nodule
- Focal nodular hyperplasia: absence of diffuse nodulation
- Nodular regenerative hyperplasia: absence of fibrous septa
Board review style question #1
What are the two factors contributing to the periseptal halo in biliary type cirrhosis?
- Ballooning degeneration
- Bilirubinostasis
- Feathery degeneration
- Florid duct lesion
- Periseptal edema
Board review style answer #1
C. and E.
- Ballooning degeneration is a hallmark pathological change of steatohepatitis, which is not associated with biliary type cirrhosis.
- Bilirubinostasis may be present in late biliary type cirrhosis but is not associated with periseptal halo.
- Feathery degeneration is one of features of chronic cholate stasis contributing to the periseptal halo in biliary type cirrhosis.
- Florid duct lesion is one of characteristic features of primary biliary cholangitis, which is not associated with periseptal halo.
- Periseptal edema is one of characteristic features of biliary type cirrhosis, which is not associated with periseptal halo.
