Pathology Outlines

Liver and intrahepatic bile ducts - nontumor
General concepts
Cirrhosis

Author: Anthony W.H. Chan, F.R.C.P.A.

Topic Completed: 1 June 2017

Minor changes: 24 May 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: Liver cirrhosis[TI] liver[mh] free full text[sb]

Related topics: Alcoholic Cirrhosis, Biliary tract disease related

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Table of Contents

Cite this page: Chan A. Cirrhosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livercirrhosis.html. Accessed May 24th, 2020.

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

Diagrams / tables

Images hosted on other servers:

Regression of cirrhosis

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

Images contributed by Anthony W.H. Chan, FRCPA:

Cirrhosis images

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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

Images contributed by Anthony W.H. Chan, FRCPA:

Images hosted on other servers:

Fibrosis (trichrome)

Bridging fibrosis types (left to right): portal - portal; central - central; portal - central

Alcoholic cirrhosis

Regression of cirrhosis

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 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.