Liver Pathology II Flashcards by Kevin N

What is the mode of transmission of Hepatitis A?

Fecal-oral due to poor hygiene

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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

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What is the mode of transmission of Hep B?

Perinatal - SE Asia

Sexual - primary in US

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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

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What is Hep B associated with?

Increased risk of Hepatocellular Cancer

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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.

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What are ground glass hepatocytes indicative of?

Hepatitis B

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What type of virus is Hep B?

DNA Virus

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What type of virus is Hep C?

Single stranded RNA Virus - does NOT incorporate into the human genome

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What are the clinical manifestations of Hep C?

Most cases are asymptomatic

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What is Hep C associated with?

Increased risk of Hepatocellular Cancer

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What is the main risk for transmission of Hep C?

IV drug use

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What is Hep D associated with?

Increased risk of Hepatocellular Cancer

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What population is Hep D found in with coinfection?

Around 5% of HBV patients are coinfected with Hep D

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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

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What will be seen on serology of a superinfected individual with HBV and HDV?

IgM and IgG anti-HDV

- HBsAG

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What are most cases of HDV infection known as?

Superinfection. An HBV carrier gets infected with HDV

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What is the route of transmission of Hep E?

Fecal-oral route of transmission – Contaminated water supply

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What is a major risk for fulminant hepatitis in Hep E?

Pregnancy

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Is there a carrier state for Hep E?

Is there an increased risk of hepatocellular carcinoma with Hep E?

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

3. 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