4/6/99

Pathology II

 

Hepatitis A (HAV)—"infectious hepatitis"

·        Benign, self limited disease w/incubation period of 2-6 wks

·        Shed in stools for 2-3 wks before and 1 wk after onset of jaundice

·        Lack of carrier state

·        Antibodies in blood—life long immunity

·        Concern in flood areas contaminating the water

 

Hepatitis B—"serum hepatitis"

·        Occupational hazard

1.      acute hepatitis

2.      chronic nonprogressive hepatitis

3.      progressive chronic disease leading to cirrhosis

4.      fulminate hepatitis w/massive liver necrosis

5.      asymptomatic carrier state (w/ or w/o progressive subclinical disease)

6.      important role in development of hepatocellular carcinoma

·        transmitted by blood and body fluids—also w/semen, saliva, sweat, tears, breast milk, and pathologic effusions

·        primary risk categories for HBV infection:

·        transfusion

·        blood products

·        dialysis

·        needle stick accidents

·        intravenous drug use

·        male-to-male sexual activity

·        Long asymptomatic incubation period (4-26 wks, average is 6-8 wks).  Acute disease may lasts many weeks to months

 

Hepatitis C

·        major transmission routes—inoculations and blood transfusions—low sexual risk

·        HVC thought to be most important cause of transfusion—associated hepatitis, being responsible for 90% to 95% of cases

·        High rate of progression to chronic disease and eventual cirrhosis, exceeding 50%

·        HVC may be the leading cause of chronic liver disease in the Western world

·        Characteristic feature is episodic elevations of serum transaminase levels, even in absence of clinical symptoms.  Reflects recurrent bouts of hepatocellular necrosis

·        Cirrhosis may be present at time of diagnosis or may develop over 5-10yrs

 

Clinical

·        Not all of hepatic viruses will provoke each syndrome

1.      carrier state

·        W/ or w/o subclinical disease but can transmit to others.  IN infected early in life (childbirth) Carrier State occurs 90-95%.  If adult infection only 1-10% cause carrier.  Individuals w/impaired immunity.

2.      asymptomatic infection—ID incidentally by minimally elevated serum transaminases or by presence of antiviral ab

3.       acute hepatitis (w/ or w/o jaundice)

·        four phases of the disease process:

a.       incubation period

b.      symptomatic preicteric (before jaundice appears) phase

c.       symptomatic icteric phase (jaundice, scleral icterus)

d.      convalescence

4.      Chronic hepatitis—symptomatic, biochemical, or serologic evidence of continuing or relapsing hepatic disease for more than months, w/histologically documented inflammation and necrosis.  Course is variable

5.      Fulminant—leads to liver failure that progresses from onset of symptoms to hepatic encephalopathy (increased ammonia levels affect the brain) w/in 2-3 wks.  Overall mortality ranges from 25-90% in the absence of liver transplantation

 

Primary Carcinoma of the Liver

·        Hepatocellular carcinoma (HCC) is most common type

·        Relatively uncommon in North America (0.5%-2% of all cancers).  Incidence is 3-7 cases per 100,000

·        Countries around Mediterranean are higher w/20 cases per 100,000

·        Taiwan, Mozambique, Southeast China may have 150 cases per 100,000

·        High incidence regions are characterized by HBV a carrier state in infancy, after infection from mother.  Confers a 200-fold increased risk

·        Metastasis if very common due to large blood supply

·        Western World—more common risk is cirrhosis—found in 85%-90% of HCC cases (alcohol route)

·        3 major etiologic associations

1. HBV infection—increasing evidence of HCV too.  Repeated cycles of cell death and regeneration.  Leads to possibilities of mutations
2. Hepatocarcinogens in food (1° aflatoxins)—derived from Aspergillus flavus—moldy grains and peanuts—highly carcinogenic toxins seem to bind to DNA and cause mutations (p53).  Carcinogenesis occurs only when liver is mitotically active as in chronic hepatitis w/recurrent bouts of injury and regeneration
3. Chronic liver disease—cirrhosis seems to be an important contributor.

·        Clinical features

·        Generally appears in individuals already presenting w/symptoms of liver disease

·        Rapid increase in liver size, sudden worsening of ascites, fever or pain may signal the development of a tumor

·        90% will have elevation in serum a-fetoprotein.  Not specific to liver tumor, but very high levels are rarely encountered except w/HCC

·        prognosis is grim—death w/in 6 months of diagnosis

·        tumors tend to occur after surgical resection, even after transplantation

 

Gall Bladder

·        95% of biliary tract disease is due to gallstones (cholelithiasis) or gall bladder inflammation (cholecystitis)

·        Cholelithiasis

·        Affect 10%-20% of adults in developed countries

·        Most gallstones (>80%) are silent—most will not have pain or stone complications

·        80% of stones are composed of cholesterol

·        remainder are predominantly bilirubin calcium salts—termed pigment stones

·        cholesterol is water insoluble and requires aggregation w/bile salts and lecithin to become soluble.  When bile becomes supersaturated w/cholesterol, it nucleates into solid cholesterol monohydrate crystals and forms stones

·        risk factors:

1. age and gender—increases w/age (5-6% for >40yrs)—25-30% >80yrs—white women 2x higher than men
2. ethnic and geographic

·        75% in Native Americans:  Pima, Hopi, Navajos—cholesterol stones only

·        industrialized societies—rare in underdeveloped countries

3. Environment

·        Estrogenic influences—pregnancy, oral contraceptives increase cholesterol uptake

·        Obesity and rapid weight loss—same mechanism

      4.  Acquired disorders