Cirrhosis – A Thorough Walkthrough

“The word cirrhosis is a neologism from the Greek word “kirrhos,” meaning tawny (organ –yellow) colored.” 

The term cirrhosis was coined by Laennec in 1819 

It is a consequence of chronic liver disease characterized by the replacement of liver tissue by fibrous scar tissue and regenerative nodules that occur due to the process in which damaged liver is regenerated, leading to loss of liver function.

Pathogenesis

Cirrhosis of the liver starts with an injury of hepatocytes. Insult to the hepatocytes can have multiple causes. Some of the most typical causes of liver cell injury include chronic hepatitis C, alcoholic liver disease, non-alcoholic steatohepatitis, chronic hepatitis B in decreasing order of frequency. 

Wisdom: Cirrhosis caused by alcohol consumption is called “Laennec cirrhosis.”

Other causes include biliary cirrhosis, Budd-Chiari syndrome, Wilson’s disease, α1 antitrypsin deficiency, etc.

These injured liver cells initiate an inflammatory response in the organ, which further injures the hepatocytes. In an attempt to fix these damages, cellular proliferation and regeneration result in scar tissue formation. Cirrhosis, in most cases, may present with nodules. These are formed as a result of the regenerative process.

Clinical features

Symptoms are highly variable. While some present with symptoms, some are diagnosed incidentally by USG examination. Non-specific symptoms like weakness, fatigue, nausea, vomiting, muscle cramps, anorexia, and upper abdominal discomfort may be present.

1. Spider naevi (spider telangectasia ,spider angioma ,arterial spiders)
   
   It consists of a central arteriole from which small vessels radiate peripherally.
   It occurs as a result of an increase in estradiol in the peripheral circulation.
    
2. Palmar erythema /liver palm:
   It occurs as a result of an increase in peripheral blood flow. However, it can also in other cases with hyperdynamic circulation like pregnancy.
   Main sites involved: Thenar and Hypothenar eminence.
    
3. Diminished body hair and loss of hair :
   Seen commonly in males and is due to hyperestrogenism.
   Causes: Androstenedione (precursor of estrogen and progesterone) is usually cleared in the liver. As a result of cirrhosis, there is decreased clearance.  
   Effects in males: Gynecomastia, testicular atrophy. 
   Effects in females: Amenorrhea, irregular menses, breast atrophy
    
4. Ascites:
   It can occur as a result of portal hypertension occurring as a complication leading to increased hydrostatic pressure. 
   Hypoalbuminemia is due to decreased production of albumin by the liver. 
    
5. Hepatomegaly:
   In the early stages, the liver is enlarged, and in later stages, it decreases in size due to fibrosis.
    
6. Jaundice :
   It can occur as a result of defective bilirubin excretion, intrahepatic cholestasis, and also because of hemolysis due to hypersplenism.

Spider Nevi

Other features

• Generalized skin hyperpigmentation – due to melanin deposition.
• Hemorrhagic manifestation – due to decreased production of coagulation factors by the liver.
• Dupuytrens contracture – fibrosis of palmar aponeurois.
• Clubbing and cyanosis – due to pulmonary arteriovenous shunts.
• Nail changes –white chalky, brittle nails.
• Muehrckes nails – white transverse lines that disappear on pressure.

Complications

Portal hypertension: It develops as a result of pressure on the portal vein. It is a common complication, and it can be treated by band ligation, sclerotherapy, and it aims to prevent bleeding from occurring as a result.

Hepatic encephalopathy: Generally, toxins in the blood, like the gut-derived toxins, are metabolized in the liver. In cirrhosis, these toxins are not metabolized, and it enters the brain, disturbing its functions, producing the manifestations of the Nervous system damage.

Renal failure: Due to cirrhosis, there is peripheral vasoconstriction, which reduces the blood volume, and as a response to this, there is rennin–aldosterone (RAAS) activation. 

Activation of RAAS further leads to vasoconstriction, finally resulting in a reduction in the GFR, ultimately leading to renal failure.

Extrahepatic Manifestations

• Pleural effusion: As a result of hypoalbuminemia, there is decreased colloidal osmotic pressure, which ultimately pushes the fluids into the third space(pleural space), leading to pleural effusion.
• Hepatopulmonary syndrome: This usually occurs due to hypoxemia that arises as a result of peripheral vasodilation.
• Hepatic osteodystrophy: Osteomalacia and Osteoporosis

Investigations

Liver function test

• Serum protein levels may show:
  - Hypoalbuminemia (due to defective synthesis).
  - Hyperglobulinemia (due to stimulation of the reticuloendothelial system).
• Prothrombin time: May be elevated due to defective synthesis of coagulation factors.
• Transaminases: ALT, AST, alkaline phosphate are increased

Haematological

• Leukopenia and thrombocytopenia may occur due to hypersplenism because they are destroyed in the liver.
• Anemia: Can occur due to variceal bleeding, emerging as a result of portal hypertension.

Biochemical markers

• Decrease in levels of sodium as a result of excessive use of diuretics for ascites
• Increased levels of ammonia can suggest hepatic encephalopathy as a complication. It occurs as a result of decreased clearance by the liver.

USG examination

It may reveal a change in the liver’s size and shape and may exhibit nodularity, sometimes may detect ascites and hepatocellular carcinoma.

CT Scan - Abdomen 

To detect the hepatosplenomegaly as well as to rule out any other gross pathology in the liver.

Endoscopy and barium enema to rule out variceal bleeding as a result of portal hypertension.

Measurement of serum iron and α1 antitrypsin to rule out Wilson’s disease and α1-antitrypsin deficiency, respectively, as a cause of cirrhosis.

Management

To date, there is no treatment available to arrest or reverse the cirrhotic change. However, when deemed necessary and feasible, in end-stage liver disease, the treatment of choice is liver transplantation. 

As with every other disease in liver cirrhosis, prevention is always better than cure.

The primary method to prevent liver cirrhosis is the removal of the cause:

• Withholding hepatotoxic drugs like aspirin and other NSAIDs
• Abstinence from drinking
• Weight loss for patients suffering from non-alcoholic steatohepatitis has been shown to produce some improvement.

Regular follow-up is a vital part of managing such patients as they have a high risk of developing hepatocellular carcinoma. Thus, regular USD examinations and measurement of serum αFP levels are crucial.

References:

1. Davidson's Practice of Medicine, 23^rd edition, Page no. 866-867
2. https://www.uptodate.com/contents/cirrhosis-in-adults-etiologies-clinical-manifestations-and-diagnosis

Author's Footnote

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