Liver Pathology Flashcards
What is the most common primary malignancy of hepatocytes?
- Hepatocellular carcinoma
Why is incidence of hepatocellular rising in western countries?
- HCV and metabolic syndrome
What are some important underlying factors of hepatocellular carcinoma?
- Alpha1 AT
- Hemochromatosis
- NAFLD/metabolic syndrome
- Wilson disease
- Precursor lesions (adenomas)
How can a fungus cause hepatocellular carcinoma?
- Aflatoxins which are a family of toxins produced by certain fungi (aspergillus) that are found on agricultural crops
What is most often seen with HCCs?
- Chronic liver disease with cirrhosis
What is a distinctive variant of HCC?
- Fibrolamellar carcinoma
What is fibrolamellar carcinoma?
- 85% occur under the age of 35 years and without gender predilection or identifiable predisposing conditions.
- Usually presents as single large, hard “scirrhous” tumor with fibrous bands coursing through it
What is the best treatment for HCC tumors in non-cirrhotic livers and cirrhotic livers with adequate function?
- Surgical resection when possible
What is done for unresectable tumors?
- Image-guided ablation with alcohol or radiofrequency waves
Where does HCC metastasize?
- Hematogenous metastases, especially to the lung
Why are outcomes in HCC poor?
- Due to underlying liver disease and the intrinsic resistance of HCC to conventional chemotherapy
What type if virus is Hep A?
- ssRNA
What is the route of transmission for Hep A?
- Fecal-Oral (contaminated food or water)
What is the mean incubation period for Hep A?
- 2-6 weeks
What is the frequency of chronic liver disease in Hep A?
- Never
How is the diagnosis made in Hep A?
- Serum IgM antibodies
What type of virus is Hep B?
- Partially dsDNA
What is the route of transmission of Hep B?
- Parental, sexual contact, perinatal
What is the mean incubation period for Hep B?
- 2-26 weeks
What is the frequency of chronic liver disease in Hep B?
- 5-10%
How is the diagnosis made in Hep B?
- HBsAg
- HBcAg antibodies
- PCR for HBV DNA
What type of virus is Hep C?
- ssRNA
What is the route of transmission of Hep C?
- Parenteral; intranasal cocaine use
What is the mean incubation period for Hep C?
- 4-26 weeks
What is the frequency of chronic liver disease in Hep C?
- > 80%
How is the diagnosis made in Hep C?
- ELISA for HCV antibodies
- PCR for HCV RNA
What are the symptoms of Hep A?
- Nonspecific
- Fatigue
- Loss of appetite
- Often jaundice
What are some extrahepatic manifestations of Hep A?
- Rash
- Arthralgia
- Immune complex mediated complications like leukocytoclastic vasculitis, glomerulonephritis, and cryoglobulinemia
What are the four different clinical presentations of Hep B?
- Acute hepatitis followed by recovery and clearance of the virus
- Acute hepatitis failure with massive liver necrosis
- Chronic hepatitis with or without progression to cirrhosis
- An asymptomatic, “healthy” carrier state
What is the clinical presentation of an acute Hep C infection?
- Asymptomatic in about 85% of individuals
What are the hallmarks of a HCV infection?
- Persistent infection and chronic hepatitis despite the generally asymptomatic nature of the acute illness
What are some diseases that result in chronic liver failure/cirrhosis?
- Chronic hep B and C
- Nonalcoholic fatty liver disease
- Alcoholic liver disease
What are some symptoms of chronic liver failure?
- 40% are asymptomatic until advanced stages
- Non specific early symptoms are anorexia, weight loss, and weakness
- Palmar erythema
- Spider angiomata
- Hypogonadism
- Gynecomastia
What is a1-antitrypsin deficiency?
- A disorder of protein folding marked by low levels of circulating a1-antitrypsin
What does a1-antitrypsin deficiency lead to?
- Development of pulmonary emphysema
Why does a1-antitrypsin lead to pulmonary emphysema?
- The activity of destructive proteases is not inhibited
What is the major function of a1-antitrypsin?
- Inhibition of proteases, particularly elastase, cathepsin G, and proteinase 3, which are normally released from neutrophils at sites of inflammation
What is the most common clinically significant mutation in a1-antitrypsin deficiency?
- PiZ
- PiZZ (homozygous) have circulating levels around 10% of normal –> these people are at high risk for developing clinical disease
What is the heterozygous genotype in a1-antitrypsin deficiency?
- PiMZ
What is the mutation for a1-antitrypsin deficiency?
- Point mutation of Glu342-Lys342
What are some clinical findings in neonates of a1-antitrypsin deficiency?
- Neonatal presentations tend to be associated with severe disease and rapid progression to cirrhosis
What are some clinical findings in adolescence of a1-antitrypsin deficiency?
- Hepatitis
- Cirrhosis
- Lung disease
What are some clinical findings in middle to late life of a1-antitrypsin deficiency?
- Cirrhosis +/- HCC
What is the most common cause of chronic liver disease in the US?
- NAFLD
What is non-alcoholic fatty liver disease (NAFLD)?
- The presence of hepatic steatosis in individuals who do not consume alcohol or do so in small quantities and who do not have another cause of secondary hepatic fat accumulation
What are the histological hallmarks of NAFLD?
- Commonly associated with metabolic syndrome
What is needed for the diagnosis of metabolic syndrome?
- One of the following: DM, impaired glucose tolerance, impaired fasting glucose, insulin resistance
- AND two of the following: BP> 140/90, Dyslipidemia, central obesity, microalbuminuria
What is important for the management of NAFLD?
- Extent of fibrosis
- Fibrosis develops like a web around the central vein
What does the progression of fibrosis manifest as in NAFLD?
- Periportal fibrosis followed by bridging fibrosis and cirrhosis
How does pediatric NAFLD differ from adult NAFLD?
- Children show more diffuse steatosis and portal fibrosis
- Ballooned hepatocytes may not be present`
What are the clinical features of NAFLD?
- Asymptomatic except for signs and symptoms of metabolic syndrome
What are the clinical features of NASH (non-alcoholic steatohepatitis)?
- Asymptomatic except for elevated LFT’s and non-specific complaints of malaise, RUQ fullness/discomfort
What is the cause of hemochromatosis?
- Excessive iron absorption
Where is most of the iron deposited?
- In parenchymal organs such as liver and pancreas
- Followed by heart, joints, and endocrine system
When does hemochromatosis manifest?
- After 20g of stored iron has accumulated
What are the mechanisms of liver injury in hemochromatosis?
- Lipid peroxidation via iron-catalyzed free radical reactions
- Stimulation of collagen formation by activation of hepatic stellate cells
- Interaction of ROS and iron itself with DNA, leading to lethal cell injury and predisposition to hepatocellular carcinoma
What is the main regulator of iron absorption?
- Hepcidin (encoded by the HAMP gene)
- Produced and secreted by liver
What causes the adult form of hemochromatosis?
- Mutations of the HFE gene
What are the clinical features of hemochromatosis?
- Hepatomegly
- Abdominal pain
- Abnormal skin pigmentation
- Deranged glucose homeostasis or DM
- Cardiac dysfunction
- Atypical arthritis
- Hypogonadism
How is hemochromatosis diagnosed?
- Screening involves demonstration of very high levels of serum iron and ferritin with exclusion of secondary causes
- Liver biopsy
- With new tech in genetic testing, quantitative assessment of tissue iron content is no longe
How does acetaminophen harm the liver?
- Acetaminophen does not directly harm the liver but a metabolite produced by the cytochrome P450 system does
- Harms zone 3
What is the acetaminophen cytotoxicity dependent on?
The cytochrome P450 system, which may be upregulated by other agents like alcohol or codeine
What is the median age for PBC and PSC?
- PBC: 50 years (30-70)
- PSC: 30 years
What is the gender preference for PBC and PSC?
- PBC: 90% female
- PSC: 70% male
What is the clinical course for PBC and PSC?
- PBC: progressive
- PSC: unpredictable but progressive
What are some associated conditions with PBC and PSC?
- PBC: Sjogren syndrome, scleroderma, thyroid disease
- PSC: IBD, pancreatitis, idiopathic fibrosing disease
What is the serology of PBC and PSC?
- PBC: 95% AMA-positive, 50% ANA-positive, 40% ANCA-positive
- PSC: 0-5% AMA-positive, 6% ANA-positive, 65% ANCA-positive
What does radiology look like for PBC and PSC?
- PBC: normal
- PSC: Strictures and beading of large bile ducts; pruning of smaller ducts
What do the duct lesions look like in PBC and PSC?
- PBC: Florid duct lesions and loss of small ducts only
- PSC: Inflammatory destruction of extrahepatic and large intrahepatic ducts; fibrotic obliteration of medium and small intrahepatic ducts
Which cholangitis is autoimmune?
- PBC
Which cholangitis has “beads on a string” on radiograph?
- PSC