Liver Pathology II Flashcards
What is the mode of transmission of Hepatitis A?
Fecal-oral due to poor hygiene
What are the clinical manifestations of Hep A?
Mild or asymptomatic with few developing acute liver failure – Severity of illness increases with age and those with underlying chronic liver disease
NO CHRONIC STATE
What is the mode of transmission of Hep B?
Perinatal - SE Asia
Sexual - primary in US
What are the clinical manifestations of Hep B?
Can present as Acute or Chronic Hepatitis - rarely is fulminant but there can be acute stage reactivation
What is Hep B associated with?
Increased risk of Hepatocellular Cancer
How does Hep B cause cell injury?
It is NOT directly cytotoxic, rather, liver injury is caused by the immune response and cytotoxic T cells.
What are ground glass hepatocytes indicative of?
Hepatitis B
What type of virus is Hep B?
DNA Virus
What type of virus is Hep C?
Single stranded RNA Virus - does NOT incorporate into the human genome
What are the clinical manifestations of Hep C?
Most cases are asymptomatic
What is Hep C associated with?
Increased risk of Hepatocellular Cancer
What is the main risk for transmission of Hep C?
IV drug use
What is Hep D associated with?
Increased risk of Hepatocellular Cancer
What population is Hep D found in with coinfection?
Around 5% of HBV patients are coinfected with Hep D
What will be seen on serology of a recently coinfected individual with HBV and HDV who was previously healthy?
- IgM anti HDAg
- IgM anti HBcAg
What will be seen on serology of a superinfected individual with HBV and HDV?
- IgM and IgG anti-HDV
- HBsAG
What are most cases of HDV infection known as?
Superinfection. An HBV carrier gets infected with HDV
What is the route of transmission of Hep E?
Fecal-oral route of transmission – Contaminated water supply
What is a major risk for fulminant hepatitis in Hep E?
Pregnancy
Is there a carrier state for Hep E?
No
Is there an increased risk of hepatocellular carcinoma with Hep E?
No
What is the most common viral cause of fulminant hepatitis?
HBV
What are the common viral causes of chronic hepatitis?
HBV and HCV
What are some of the clinical findings of acute viral hepatitis?
- Hepatocyte injury / necrosis
- Fatty change (HCV)
- Bile duct reaction
- Kupffer cell hypertrophy
- Inflammatory cells
What does grade of hepatitis refer to?
Degree of inflammation
What does the stage of hepatitis refer to?
Degree of fibrosis
What are the most likely causes of fulminant hepatitis?
HBV or HAV - the rest are far less likely
What population will be more likely to have autoimmune hepatitis?
Females more than males
What are the Ab seen in autoimmune hepatitis?
– ANA (antinuclear antibodies)
– Anti SMA (anti-smooth muscle antibodies)
– Anti LKM-1 (anti-liver kidney microsome-1 antibodies)
What are the main inflammatory cells in autoimmune hepatitis?
Plasma cells
What is a classical sign of autoimmune hepatitis?
Interface hepatitis
Hepatic Steatosis
Alcohol fatty liver disease that is reversible and due to short term consumption of large amounts of alcohol from impaired assembly and secretion of lipoproteins
What is Mallory hyaline?
It is an acute reaction to alcohol
What type of fibrosis is seen with alcoholic hepatitis?
Pericellular fibrosis
What is the pathogenesis of alcoholic hepatitis?
Acetaldehyde is a metabolite of EtOH that induces generation of reactive O2 species and damages cells and reduces glutathione
A 42 yo gentleman presents with a 2 week history of progressive jaundice and abdominal distension.
• He has a long-standing history of alcohol use, but over the past 6 months he has significantly increased his alcohol intake due to a divorce. He is drinking a 12 pack of beer and a 1⁄2 pint of liquor daily.
• His AST is 356 and his ALT 157, T.bili 12.6, WBC 17.4, INR 2.3. A liver biopsy in this gentleman would most likely demonstrate which of the following:

1. Cirrhosis with nodule formation but no inflammation
2. Hepatic steatosis
3. Steatohepatitis with inflammation, mallory hyaline bodies, and pericellular fibrosis
4. Interface hepatitis with plasma cell infiltration
5. Groundglass hepatocytes
- Steatohepatitis with inflammation, mallory hyaline bodies, and pericellular fibrosis
Non-alcholoic Fatty Liver Disease
Identical to EtOH induced disease and is found most often in obese individuals with dyslipidemia, hyperinsulinemia and insulin resistance
What is the difference between non-alcoholic steatohepatitis and steatosis?
NASH is:
– Elevated transaminase
– Asymptomatic or fatigue, RUQ discomfort
– Associated with cardivascular disease and metabolic syndrome
Simple steatosis is:
– Elevated transaminases
– Asymptomatic
– Benign
A 52-year old woman is referred abnormal LFT’s. She is overweight and has non- insulin requiring diabetes. Physical exam is unremarkable. She may have one or two glasses of wine on the weekends, but denies other alcohol use. Lab results are as follows:
• Bilirubin 1.1, ALT 83, AST 77, Alk Phos 127 Hepatitis A IgG (+); Hepatitis A IgM (-)
• Hepatitis BsAg, BsAb, BcAb all (-)
Hepatitis C Antibody (+); Hepatitis C RNA (-)
• ANA 1:20 (Normal ≤ 1:20)
Anti-Smooth muscle Antibody (-)
Ceruloplasmin, Iron studies, alpha-1-antitrypsin are all normal
The most likely diagnosis is:
A. Non-alcoholic steatohepatitis
B. Hepatitis A
C. Hepatitis C
D. Autoimmune Hepatitis
A. Non-alcoholic steatohepatitis
Hemochromatosis
Disease of iron overload and can be genetic or due to transfusions - Iron deposition in parenchymal tissues
What are patients with cirrhosis and hemochromatosis simultaneously at increased risk for?
Hepatocellular Carcinoma
What is the gene mutation in hereditary hemochromatosis?
- HFE on Ch6 -> C282Y Homozygous (one of most common gene disorders)
They cause excessive absorption of dietary iron
What will be seen on liver biopsy of patient with hemochromatosis?
Liver biopsy with brown pigmented hepatocytes - iron stain will show BLUE
Wilson’s Disease
Copper accumulation in the liver and the brain
What is the gene mutation in Wilson’s disease?
Autosomal Recessive Disorder (ATP7B gene)
- Responsible for linking copper to ceruloplasmin for release into bloodstream
What are the signs of Wilson’s disease?
– Neuropsychiatric (copper deposition in brain)
– Kayser Fleischer rings (copper ring in eye)
– Liver Failure
– Hemolytic Anemia
How is the diagnosis of Wilson’s disease made?
- Low ceruloplasmin
- Liver biopsy
- Increased urine copper
Alpha 1 Antitrypsin Deficiency
Defective production of A1AT in the liver
• Errors in coding sequence prevent its export from the hepatocyte – Abnormal accumulation of the protein results in cell death, inflammation, fibrosis, and cirrhosis
What is the gene mutation in A1AT deficiency?
Autosomal Recessive - PiZZ on Ch14
