Cirrhosis: Pathology review

At the family medicine clinic, a 52- year- old male immigrant from Africa, named Jamar, came in for a checkup for the first time in a decade. On questioning, he admits to an extensive history of alcohol abuse. Physical examination reveals gynecomastia, palmar erythema and spider angiomata, as well as a palpable spleen.

Next, a 70- year- old Caucasian female, named Eleanor, with a history of chronic hepatitis C infection, is brought to the emergency department by paramedics due to altered mental status. She is completely disoriented and unable to provide an adequate history. Neurologic examination also reveals asterixis.

Lab tests of both show increased aspartate aminotransferase, or AST, and alanine aminotransferase or ALT. There’s also decreased albumin and increased prothrombin time. The difference is that Jamar has an AST level twice as high as ALT, in contrast with Eleanor, who has an ALT higher than AST. Eleanor, in particular, also has high serum levels of ammonia.

Both Jamar and Eleanor have cirrhosis. This is when chronic inflammation damages the liver causing it to become fibrotic. Normally, the liver is highly regenerative but scar tissue can replace liver cells which prevents regeneration and when this goes on for too long, it reaches the point where the damage is no longer reversible. If enough of the liver is replaced by scar tissue in advanced cirrhosis, a liver transplant might be needed. . Now, if we zoom into a hepatic lobule, we can see that it’s made of sheets of hepatocytes with sinusoids between them. The sinusoids are made of branches of the portal vein and hepatic artery, and together with the bile duct, form the portal triad which runs towards the central vein.

Now, there’s a space around each sinusoid, called the perisinusoidal space which contains stellate cells. When the hepatocytes are injured, they cluster together and form regenerative nodules. Here, they secrete paracrine factors that activate the stellate cells, which then proliferate, and start secreting transforming growth factor beta1, or TGF-beta. This causes them to produce collagen. The collagen builds up around the nodules and helps form scar tissue, leading to fibrosis.