Viral and Non-viral Liver Disease Flashcards
Cirrhosis
Scarred liver
End point to many chronic liver diseases
Compensated:
Functional
Decompensated:
Failing functions
-diffuse fibrous septation that divides liver parenchyma into nodules
Result of chronic recurring death of hepatocytes, deposition of extracellular matrix, and architectural and vascular reorganization
Liver has high
functional reserve and regenerative capacity
Liver functions
Lipid, carb, prot metab Coagulation factor produc Detox stores vit/glycogen Reticuloendothelial system Bile processing and secretion Albumin production
Bile flows in ___ direction of blood in liver
opposite
Portal tracts/triads
PV
HA
BD
Acute vs chronic injury
acute injury usually resolves
Chronic injury–> cirrhosis (scarred down)–> liver failure
Liver failure signs/sx
Jaundice (bilirubin buildup in tissues)
Ascites, peripheral edema (from hypoalbuminemia)
smell (sulfur metabolites)
spider angiomata (estrogen problem)
Palmar erythema
Hypogonadism and gynecomastia in men
Coagulapathy
Encephalopathy (derangements in consciousness, accum of ammonia in blood)
Hepatorenal syndrome (vascular perfusion abnormalities)
gross failed liver
Massive necrosis (death of most of liver: gray; yellow/green is alive)
**Cirrhosis: nodular, shrunken, scarred liver
Dysfunction without cirrhosis or necrosis (looks normal)
Cirrhotic liver gross
septation
parenchymal nodularity
Portal hypertension
Increase blood pressure in portal system
Result of vascular reorganization in liver
Increase in sinusoidal pressure (increased vascular resistance)
- abnormal portal- systemic shunts (large connections) Ex: esophageal varices; hemorrhoids; periumbilical caput medusae
- hepatic encephalopathy,
Jaundice and cholestasis
Bilirubin production > Bilirubin clearance
Excessive extrahepatic bilirubin production Reduced hepatocyte uptake Impaired conjugation Decreased hepatocellular excretion Impaired bile flow**
Most common chronic liver diseases in US adults
Viral hepatitis C Alcohol induced liver disease Non-alc fatty liver disease Viral hep B Other
Hepatitis
Necroinflammatory injury to hepatocytes
Inflammatory injury and death of hepatocytes
etiologies: Steatohepatitities: (Alcohol or not) Viral Common cause of chronic liver disease
Hepatitis on histology
swelling/degen apoptosis/lobular apo/interface bridging necrosis geographic coagulative necrosis
**look @ pics
Inflammation in hepatitis
Lymphocytes – many hepatitides; common in viral
Neutrophils – common in steatohepatitis (assoc w/ fat)
Eosinophils – common in drug injury
Plasma cells – common in autoimmune hepatitis
Acute hepatitis
New onset (
Chronic hepatitis
Long-standing, on-going hepatocyte injury and inflammation (>6 months)
Common causes: chronic viral hepatitis, autoimmune hepatitis, drug injury
Microscopic findings: less prominent inflammation and injury, preponderance of portal tract-based inflammation, fibrosis; looks “less severe” than acute; Spotty
General features of liver injury
Cytoplasmic accumulations
Degeneration, necrosis, and apoptosis
Inflammation
Regeneration, fibrosis, and cirrhosis
Cytoplasmic accumulation
*may be cause of disease or just seen due to disease
Fat – Steatosis
Bile – Cholestasis
Iron – Hemosiderosis/ genetic hemochromatosis
Copper – Wilson Disease / chronic cholestasis
Viral particles – Viral hepatitis
Histology of viral inclusion
“ground glass inclusion”
-cells filled with virions
Regeneration and fibrosis
- cycles of inj/regen
- activated stellate cells deposit collagen
- architectural and vascular reorganization
- leads to cirrhosis
Fibrosis histology
type I collagen (blue) (normally just in portal tract)
- lines wrapping around hepatocytes
- pericellular fibrosis
Portal fibrosis: larger, rounder portal tracts
Periportal fibrosis: stellate appearance of portal tracts
bridging fibrosis: connections of collagen (portal tract to tract or to central v.)
well defined septa w/ nodules: cirrhosis
what can you use to track chronic hepatitis?
biopsy surveillance (serial liver biopsies)
grade: amount of inflammation and injury
“Stage” = amount of fibrous tissue deposition
viral hepatitides
Hepatotropic viruses = hepatocyte is primary target
Hepatitis C Hepatitis B Hepatitis D Hepatitis A Hepatitis E
Other viruses also uncommonly cause hepatitis
Hep B
partially dsDNA (all others hep viruses are RNA viruses)
freq of chronic liver disease 10%
fecal oral hep virus transmission
Hep A, E: and NEVER go on to chronic liver disease (acute)
(BCD parenteral)
Parenteral hep virus transmission
B: 10% go on to chronic liver disease
C: 80%
D: 5%
*look at rest of table 10/26 9am
Hep C virus infection
Major cause of chronic liver disease in the United States
Genetically unstable = multiple genotypes and subtypes
(Anti-HCV antibodies made, but antibodies are not neutralizing)
Transmission mostly by blood and body fluids
Range of clinical outcomes/presentations
(Most common is a chronic hepatitis (~85%))
HCV Risk factors
IV drug abuse multiple sexual partners recent surgery needle stick injury HCV infected person contact employment in med/dental fields
Acute infections of HCV
always asymptomatic!!!
- 15-20% clear virus after infec
- rare:fulminant hepatitis
80% w/ chronic hep go to stable disease, 20% go to cirrhosis
Chronic hepatitis histology
spotty
can see lymphoid aggregate
Hep B virus infection
Major cause of chronic liver disease worldwide
Can integrate into genome
Transmission by blood and body fluids; also vertical transmission is important
Range of clinical outcomes and presentations
(Most recover; only ~5% progress to chronic hepatitis)
Hep B acute hepatitis
70% subclinical disease
30% icteric disease (sx)
Most adults (>90%) will clear virus on own 5-10% go to chronic hep, then either clear infec, healthy carrier state (most), 12-20% cirrhosis, and some (6-15%) w/ cirrhosis go to hepatocellular carcinoma.
Hep B w/ recovery
incubation: 8 weeks
Sx: jaundice, pain, fatigue
HBeAg, HBV-DNA, HBsAg signify active disease/viral rep
IgM to IgG Ab confer immunity
Hep B chronic carrier
incubation, infection
HBeAg, HBV-DNA, HBsAg remain present due to ineffective immune response against virus
Hep B histology
ground glass hepatocytes (Hep B virions)
Sanded nucleus (O shape)
Hep D virus
Replication incompetent, completely dependent on HBV coinfection
Potentiates effects of HBV: increased risk of fulminant hepatitis, increased activity, and faster progression to end stage liver disease
Intravenous drug abuse**
Hep A
fecal oral
causes acute hepatitis only
(weeks to months)
jaundice, pain, fatigue
Hep E
acute hep only
fecal oral
higher mortality in pregnant women
Autoimmune liver disease
Autoimmune Hepatitis
Primary Biliary Cirrhosis
Primary Sclerosing Cholangitis
Autoimmune Hepatitis
Immune-mediated attack directed at hepatocytes
Clinical Presentation:
F> M (78% ))
Often present in association with other autoimmune diseases.
Has a variable course: indolent to severe
Serology:
Autoantibodies (ANA, ASMA (anti smooth muscle ab), Anti-LKMB) (80%)
Elevated IgG
Histology:
Spotty interface hepatitis
Plasma cell rich
Primary Biliary Cirrhosis
Immune-mediated attack of intrahepatic small caliber bile ducts
Clinical Presentation:
Insidious onset with pruritus often before jaundice
**Middle aged women most commonly affected
Cholestatic liver function testing (elevated ALP, GGT, bilirubin)
Serology:
Anti-mitochondrial antibody (90%)
Elevated IgM
Prognosis:
25% with liver failure at 10 years
*all pts with PBC do NOT necessarily have cirrhosis at that time
Histology: “active stage” bile ducts damaged by lymphocytes; granulomatous duct destruction
Later: absence of bile ducts, minimal inflamm
PSC
Primary sclerosing cholangitis
Presumed immune-mediated obliterative fibrosis of intrahepatic and extrahepatic bile ducts (LARGE caliber bile ducts)
Clinical Presentation:
Men > women; 70% of patients have ulcerative colitis
Asymptomatic with persistent alkaline phosphatase elevation
Progressive fatigue, pruritus, and jaundice
Diagnosis:
Cholangiography = alternating biliary strictures and dilation
No specific serologic findings!!
-Can also see “onion skin” fibrosis (concentric rings) around bile duct on biopsy
Prognosis:
Variable clinical course; increased risk for cholangiocarcinoma
Drug induced liver injury
common
Many patterns of injury (mimics other diseases):
Necrosis, cholestasis, bile ducts, autoimmune-like hepatitis, steatosis, steatohepatitis, acute hepatitis, or chronic hepatitis
Intrinsic or idiosyncratic:
Intrinsic (often dose related) (e.g. acetaminophen)
Idiosyncratic (unpredictable)
Acetaminophen
Major cause of ACUTE liver failure that leads to liver transplant in United States
Intrinsic hepatotoxin
Centrilobular necrosis (zone 3)
Metabolic liver diseases
Steatosis/Steatohepatitis:
Alcohol-related
Non Alcoholic
Hereditary Hemochromatosis
Wilson Disease
Alpha-1-antitrypsin deficiency
Steatosis
Accumulation of fat in hepatocytes
Metabolic derangement of hepatocytes
Many causes: metabolic syndrome, alcohol, drug effect, Wilson disease, viral infection
lipid influx> lipid clearance
fat enters via: chylomicrons (diet), from periphery (lipolysis), carbs–> lipogenesis. Removal by beta oxidation (CO2, ketones( or into VLDL
Steatohepatitis
Hepatocellular injury in association with steatosis:
+/- overt inflammation
Causes: alcohol, metabolic syndrome, drug injury
Not all causes of steatosis also cause steatohepatitis
Often chronic and can lead to fibrosis and cirrhosis
histology
swelling, fat, neutrophils
pericentral/pericellular fibrosis
Alcohol steatosis
Alcohol steatosis: carb load short circuits feedback control of lipogenesis— so accum of lots of hepatic lipid; also stim of lipolysis from periphery; modification of oxidative state of hepatocyte– Beta oxidation impeded; packaging abnormalities in VLDL
-leads to injury
Histology
see injured hepatocytes, neutrophilic infiltrate, fat
**Mallory bodies (ropy inclusions w/in hepatocytes)
Non-alcholic steatosis/ steatohepatitis
Fatty liver disease associated with:
Obesity, diabetes type II, hypertriglyceridemia
Increasing prevalence in US
-**lipolysis: increase in delivery from peripheral sources to liver (endocrine abnormalities)
-minor: dietary delivery of fats and certain types of carbs
–>increased hepatic lipid,
changes in B ox, VLDL formation
Hereditary hemochromatosis
Genetic iron overload disease:
Manifests as liver disease, diabetes, heart failure
AR inheritance
5/1000 (Northern European descent)
-HFE gene mutations (C282Y and H63D)
Abnormal regulation of iron absorption (don’t turn off iron absorption)
histology:
iron deposits in hepatocytes (blue w/ Prussian blue stain)
Wilson Disease
Cu overload thru body -Liver disease, neuropsych problems -Mut: ATP7B gene AR inheritance 1/30,000 Transporter involved in bile excretion of Cu (remains in hepatocyte)
Alpha-1-Antitrypsin deficiency
Genetic decreased production of alpha-1-antitrypsin
Alpha-1-antitrypsin is a protease inhibitor
AR inheritance
PiMM is normal; PiZZ is common disease genotype
Protease inhibitor levels less than 10% normal in PiZZ
In PiZZ…
…most have pulmonary emphysema
…10% develop liver disease
Histology: PASD stain (pink globules) A-1-A
Abnorm of blood flow
Problems with blood entering liver (obstruction) intrahepatic causes (not getting thru liver-- often cirrhosis) post hepatic obstruction (hepatic v thrombosis)
Malignant liver masses in adults
heptaocellular carcinoma
cholangiocarcinoma
Benign liver masses in adults
Hemangioma
Focal Nodular Hyperplasia
Hepatocellular Adenoma
Hepatocellular carcinoma
Malignant neoplasm of hepatocytes
Most common PRIMARY malignant liver tumor (most common are mets)
Occurs mostly in patients with chronic liver disease (HCV, HBV, alcohol) and cirrhosis
dismal long-term survival
Cholangiocarcinoma
Malignant neoplasm of bile ducts
May be intrahepatic or extrahepatic
RF: primary sclerosing cholangitis
dismal long-term survival
gross: fibrotic mass
histology: gland forming, malignant, w. abnormal fibrosis or desmoplasia
Hemangioma
Benign neoplasm of dilated vascular spaces
Most common primary hepatic tumor (~2%)
More common in women (1:4)
Usually small and asymptomatic; Larger ones may require resection
Vague RUQ pain, early satiety, nausea, vomiting
Histology: dilated vascular spaces
Focal nodular hyperplasia
Benign mass-like proliferation of hepatocytes
Arises due to a local vascular flow anomaly
Old term = “focal cirrhosis”
Second most common primary hepatic mass
More common in F:M 4:1
Usually asymptomatic
Histology: septation, nodularity, **central stellate scar w/ large thickened arteriole
Hepatocellular adenoma
Benign neoplasm of hepatocytes
mostly in women of child-bearing age
Associated with oral contraceptive use
Usually no underlying chronic liver disease
Asymptomatic or RUQ abdominal pain
Risk is of rupture into abdomen with hemorrhage
***Extremely low risk of malignant transformation
Histology: prolif of hepatocytes
