Regeneration and repair processes

Question 1

cirrhosis

Answer 1

hepatocytes surrounded by fibrous tissue

not necessarily irreversible

Question 2

alpha1 anti-trypsin

Answer 2

linked to fibrosis in people with high alcohol consumption

Question 3

liver morbidity and mortality

Answer 3

liver pathology only cause that is still increasing in the uk

Question 4

NAFLD

Answer 4

can be seen on USS, confirmed by biopsy
includes:
simple steatosis - liver response to injury, causes fat to be stored. no inflammation, no injury to liver. reversible
non alcoholic steatohepatitis (NASH) - fat with inflammation and injury
10-30% of patients with NAFLD will have NASH
diabetic patients with metabolic syndrome are at highest risk

Question 5

biopsy

Answer 5

fatty liver: 70-90%
NASH: 10-30%
cirrhosis: ~1%

can also show how close patient is to end stage liver disease

Question 6

blood tests

Answer 6

AST/ALT ratio: <0.8 excludes advanced fibrosis with negative predictive value >90%
positive predictive value however is only 44%, so only useful for ruling out diagnosis

nothing is as good as a biopsy

Question 7

serum markers for fibrosis

Answer 7

fibrotest: alpha2-macroglobulin, GGT, bilirubin, haptoglobin, apolipoproteinA1

enhanced liver fibrosis tests (ELF): TIMP-1, HA, P3NP

Question 8

serum markers for fibrosis

Answer 8

fibrotest: alpha2-macroglobulin, GGT, bilirubin, haptoglobin, apolipoproteinA1

enhanced liver fibrosis tests (ELF): TIMP-1, HA, P3NP

Question 9

hepatocellular carcinoma

Answer 9

(nearly) always happens in fibrotic patients

Question 10

grading vs staging

Answer 10

grading: how bad something is now
staging: prognostic

Question 11

fibrosis

Answer 11

inflammation following insult leading to fibrosis, which will eventually lead to cancer
long standing damage
can be:
alcohol
inherited disease
viruses
autoimmune

Question 12

patterns of fibrosis

Answer 12

histologically fibrosis differs by cause:
autoimmune: portal-central vein bridging
viral hep: portal-central vein bridging
acute alcohol hep: chicken wire pattern
nonalcoholic steatohepatitis: macrovesicular steatosis and pericellular fibrosis
biliary cirrhosis: portal-portal fibrotic septa, ductular proliferation

Question 13

cell biology

Answer 13

hepatic stellate cells in the space of disse are crucial cells in fibrosis
produce hepatic myofibroblasts which move through the liver, generating matrix, and stop clearing matrix
if hepatic myofibroblasts cells are apoptosed, the process can be reversed. will normally happen in some conditions e.g hep A

Question 14

ACE inhibitors

Answer 14

can be used to disrupt the pathway and induce apoptosis in hepatic myofibroblasts

Question 15

serotonin

Answer 15

plays a role in liver disease
platelet derived serotonin essential for hepatocyte regeneration (2a receptors)
by acting on the 2b receptors, serotonin causes fibrosis. therefore blocking the 2b receptor will aid liver repair