Liver and Hepatobiliary Viral and Bacterial Infections Flashcards

1
Q

Liver Disease - Systemic Symptoms

A
  • fever, malaise, nausea and vomiting
  • Although many patients with acute viral hepatitis have a low-grade fever, a high fever can be seen in those with acute HAV (Hepatitis A Virus) as well as alcoholic hepatitis and obstructive jaundice
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2
Q

Liver Disease - Jaundice

A

•Jaundice can result from intrinsic liver disease or hepatobiliary disease and workup should be designed to distinguish these possibilities.

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3
Q

Liver DIsease - Coagulopathy

A
  • All clotting factors other than factor VIII are made by hepatocytes.
  • Coagulation disorders resulting from liver dysfunction and inadequate production of liverdependent coagulation factors will result in elevated prothrombin (PT) and partial thromboplastin (PTT) times.
  • This is typically found in the setting of severe chronic liver disease, but can result from acute hepatic failure.
  • In addition, splenomegaly is frequently found in chronic liver disease and can result in thrombocytopenia.
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4
Q

Liver Disease - Ascites

A
  • Ascites most commonly results from one of the three salt retaining states (heart, liver, or kidney failure).
  • In the patient with liver disease, ascites develops in the face of portal hypertension seen most commonly with cirrhosis.
  • As the liver disease worsens, the ascites becomes more difficult to treat and renal failure may develop late during the illness.
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5
Q

Liver Disease - Portal Hypertension

A
  • The portal vein begins in the capillaries of the intestine and ends in the hepatic sinusoids. A blockage anywhere in its drainage leads to a rise in pressure.
  • Most commonly cirrhosis increases the resistance to flow in the portal vein leading to the development of varices and ascites.
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6
Q

Liver Disease - Liver Enzymes

A

•Incidental discovery of abnormal liver enzymes – Chronic hepatitis C or B and other liver diseases such as primary biliary cirrhosis and commonly identified in this way, typically with mild elevations of aminotransferases.

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7
Q

Hepatitis or Some Other Illness? - Aminotransferases

A

•ALT; SGPT

  • ALT = alanine aminotransferase
  • SGPT = serum glutamic pyruvic transaminase

•AST; SGOT

  • AST = aspartate aminotransferase aka
  • SGOT = serum glutamic-oxaloacetic transaminase
  • The aminotransferases are present in highest concentrations in liver (ALT > AST) and muscle (AST > ALT).
  • With injury to the hepatocytes or myocytes the enzymes are released into the blood where their increase in concentration is measured.
  • Small elevations (up to twice the upper limit of normal) are nonspecific, although those lower elevations may be the sole manifestation of chronic hepatitis.
  • Acute hepatitis typically presents with markedly elevated AST and ALT.

-Greater than 10-fold elevations are typically seen with acute hepatitis and ALT is usually greater than AST.

•The major exception to this result is alcoholic liver disease in which the AST is more than 2-fold greater than ALT.

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8
Q

Hepatitis or Some Other Illness? - Alkaline Phosphatase

A
  • Alkaline phosphatase (AP) is located primarily on the canalicular membrane.
  • With liver injury, it is relocated to the plasma membrane where it is released into the blood.
  • Elevations reflect bile duct injury or infiltrative disease of the liver.
  • Confirmation that the source of increased AP levels is the liver relies on finding increased levels of other enzymes such as gamma glutamyltranspeptidase (GGTP)
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9
Q

Hepatitis or Some Other Illness? - Bilirubin

A
  • Bilirubin with fractionation
  • Bilirubin is a breakdown product of heme.
  • Unconjugated bilirubin (indirect reacting form) is cleared by the liver and conjugated in the hepatocytes (direct reacting form).
  • Elevated bilirubin results in visible jaundice at levels of approximately 3-4 mg/dl and is usually an indication of liver disease.
  • However, bilirubin levels can be moderately elevated from RBC breakdown (hemolytic anemia). In this case, bilirubin fractionation can be useful.
  • Typically, in the presence of liver or biliary disease, the measured bilirubin is a combination of conjugated and unconjugated bilirubin but where the major problem is overproduction, it will be predominately unconjugated.
  • Another common cause of jaundice due to unconjugated hyperbilirubinemia is the common metabolic disorder, Gilbert’s syndrome.
  • Failure to conjugate bilirubin as is seen with Crigler-Najjar or physiologic jaundice of the newborn are also causes of indirect hyperbilirubinemia.

•Pure conjugated hyperbilirubinemia is seen with Rotor’s and Dubin’s syndromes in which there is an inherited defect in the export of conjugated bilirubin.

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10
Q

Etiology of Acute or Chronic Hepatitis

A

•Viral

  • Hep A
  • Hep B
  • Hep C
  • Hep D
  • Hep E

•Other Viruses that cause hepatitis

  • Cytomegalovirus (CMV) - Seen most commonly in immunocompromised patients with increased liver enzyme levels.
  • Epstein-Barr virus (EBV) - The agent of acute mononucleosis causes lymphadenopathy and malaise with prolonged illness and may include liver involvement.
  • Herpes simplex (HSV) - May cause an acute severe and frequently fatal hepatitis in immunocompromised or pregnant patients.
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11
Q

Hepatitis Definition

A

•a disease characterized by inflammation of the liver

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12
Q

Serologic Testing for Hepatitis A

A

•Antibody (AB)

  • IgM – acute infection
  • IgG – resolved infection or immunized
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13
Q

Serologic Testing for Hepatitis - Hepatitis B

A
  • The results of testing of individuals infected with HBV depend on the type of infection they have.
  • They may have an acute infection or previous infection that has resolved.
  • In addition, with the carrier state there are two types of infection, replicative and nonreplicative.
  • High levels of virus are seen in the replicative and much lower levels in the non-replicative phase. The vaccine contains only HBsAg.
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14
Q

HBsAg

A
  • Acute +
  • Carrier State +
  • Resolved Infection -
  • Immunization -
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15
Q

HBsAB

A
  • Acute -
  • Carrier State -
  • Resolved Infection +/-
  • Immunization +
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16
Q

HBcAB, IgM, Total

A

IgM

  • Acute +
  • Carrier State -
  • Resolved Infection -
  • Immunization -

Total

  • Acute +
  • Carrier State +
  • Resolved Infection +
  • Immunization -
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17
Q

HbeAg

A
  • Acute +/-
  • Carrier State

+replicative

  • nonreplicative
  • Resolved Infection -
  • Immunization -
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18
Q

HBV DNA

A
  • Acute +
  • Carrier State
  • replicative + high titers
  • nonreplicative + low titers
  • Resolved Infection -
  • Immunization -
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19
Q

Serology Testing for Hepatitis C

A
  • HCVAB-positive in carriers and past infection
  • HCV RNA-positive in chronic carriers-no correlation with disease activity
  • HCV genotype- 6 different genotypes and have different responses to treatment
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20
Q

Serology Testing for Hepatitis D (HDV - delta)

A

•HDVAB

  • IgM positive acute
  • IgG positive chronic or past
  • HDV RNA positive chronic
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21
Q

Serology Testing for Hepatitis E

A

•HEVAB positive in acute and past infection

22
Q

Treatment for Hepatitis

A
  • HAV-supportive care. No effective antivirals
  • HBV-Interferon alpha or nucleoside analogs
  • HCV- protease inhibitors
  • HDV-Interferon alpha
  • HEV-supportive care. No effective antivirals
23
Q

Other Diseases Causing Illness Like Viral Hepatitis

A
  • Drugs such as acetaminophen/INH
  • Autoimmune hepatitis
  • Shock
  • Heart failure
  • Chronic Hepatitis
24
Q

Chronic Hepatitis

A
  • Autoimmune hepatitis/sclerosing cholangitis/primary biliary cirrhosis
  • Alcoholic liver disease
  • Drugs such as alpha-methyldopa
25
Q

Bacterial Infections of the Liver

A

•In general, bacterial infections of the liver involve the biliary tree or are pyogenic abscesses. During sepsis the liver rarely becomes infected.

26
Q

Biliary Tract Diseases

A
  • Stones within the biliary tree are the most common cause of cholangitis.
  • The stones interfere with the flow of bile and when the bile becomes contaminated infection occurs.
  • Other disorders of the biliary tree such as sclerosing cholangitis can also be associated with infection.
27
Q

Biliary Tract Disease - Jaundice

A
  • Jaundice may be the presenting symptom/sign of hepatobiliary infection (or other hepatobiliary disease) and by itself will not distinguish hepatobiliary from hepatocellular disease.
  • Accompanying aspects of the history, exam and laboratory will be required.
28
Q

Biliary Tract Disease - Fever

A

•Patients with cholangitis present with hectic fevers and commonly have true rigors.

29
Q

Biliary Tract Disease - Pain

A
  • Colic pain associated with biliary tract disease is intermittent in nature and tends to be relieved by walking, ‘I tried to walk the pain off’.
  • In the presence of cholangitis, the pain becomes constant and the patient tries to remain still.
  • If the gallbladder has been removed, the pain may focus in the epigastrium.
30
Q

Biliary Tract Disease - Liver Tests

A
  • The results of liver tests are variable.
  • Alkaline phosphatase is generally elevated and with cholangitis may be increased 5-10-fold.
  • Similarly, the AST and ALT may be normal to mildly elevated with stones without infection but with infection are increased by usually not more than 5-fold.
  • The levels of bilirubin can be normal (no obstruction) to high.
31
Q

Biliary Tract Disease - Treatment

A
  • -Drainage of the infected bile either surgically or by Endoscopic Retrograde Cholangio-
  • Pancreatography (ERCP) leads to rapid resolution of the infection in concert with antibiotics.
32
Q

Liver Abscesses

A
  • -Pyogenic liver abscesses are becoming less common.
  • They previously were seen in association with intra-abdominal infections, such as a ruptured appendix or diverticulitis.
  • With more effective treatment of those conditions, the incidence of liver abscess has declined.
  • Currently in the US, more than half of pyogenic liver abscesses are idiopathic.
  • The abscesses are frequently polymicrobial with both anaerobes and aerobes present.
33
Q

Liver Abscesses - Fever

A
  • This is the most common way that pyogenic liver abscesses present, i.e. fever that is chronic.
  • Patients do not present with signs of sepsis, as this is a subacute illness except in the presence of a biliary infection.
  • They may or may not have RUQ abdominal pain.
34
Q

Liver Abscesses - Liver Tests

A

•These are in general normal or the alkaline phosphatase is increased unless there is co-existent biliary tract disease.

35
Q

Liver Abscesses - Diagnosis

A
  • This is made by imaging, either ultrasound, CT or MRI.
  • The diagnosis is confirmed by aspiration and culturing of the abscesses material.
  • Blood cultures may also be positive.
  • Treatment is with antibiotics that cover both anaerobes and aerobes (gram-negative enterics) with or without drainage.
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41
Q

Hepatitis A

A
  • RNA
  • Incubation: 15-45 days
  • Symptoms: 1/3 of patients
  • Onset: Abrupt
  • Transmission: fecal oral
  • Carrier state: none
  • Mortality 0.1-0.2%
  • Vaccine yes
42
Q

HAV Relapse

A
  • Incidence 3-20%
  • Usually single, rarely multiple
  • Occurs early (< 3 weeks)
  • Less severe than initial illness
  • Cholestasis
  • Immune phenomena common
  • Still shedding virus
43
Q

HAV Vaccine Targets

A
  • Travel to high risk countries
  • Providers of child care and children
  • Institutionalized children and adults
  • HCV and HBV carriers
  • Persons with other forms chronic liver disease
44
Q

Hepatitis E

A
  • RNA
  • Incubation: 14-270 days
  • Symptoms: 1/3 of patients
  • Onset: Abrupt
  • Transmission: fecal oral
  • Carrier state: none
  • Mortality: .01-0.2 10-20% pregnant
  • Vaccine: none
45
Q

Acute Hepatitis B

A
  • DNA
  • Incubation: 30 - 120 days
  • Symptoms: 1/2 patients
  • Onset: insidious
  • Transmission: sex/blood/vertical
  • Carrier state: yes
  • Mortality: 0.5-2%
  • Vaccine: yes (HBsAg)
46
Q

Acute Hepatitis C

A
  • Incubation: 15-75 days
  • Symptoms: rare
  • Onset: insidious
  • Transmission: bllod
  • Carrier state: yes
  • Mortality: not a cause of AHF
  • Vaccine: no
47
Q

Causes of chronic viral hepatitis and risk

A

• Hepatitis B

– Infants- 90%

– Children-50%

– Adults-5%

– Cirrhosis-yes

– HCC-yes

• Hepatitis C

– Infants-5%

– Children?

– Young women-30-40%

– Older patients 80%

– Cirrhosis-yes

– HCC-yes

48
Q

Chronic HBV - 2 Phases

A

• Replicative

– HBV DNA high

– HBeAg +

– ALT increased

• Non-replicative

– HBV DNA low

– HBeAg

– HBeAb ±

– ALT normal

• Pre-core mutant

– HBV DNA high

– HBeAg -

49
Q

Acute Autoimmune Hepatitis

A
  • May be jaundiced
  • AST/ALT > 1,000
  • Prolonged PT
  • Increased globulin
  • Increased IgG
    • ANA, ASMA
50
Q

Drug Induced Hepatitis

A
  • Acetaminophen
  • INH
  • Troglitazone
  • Mushroom poisoning

Clue is high LDH.

51
Q

Ischemic Hepatitis

A

• Setting

– Severe cardiac disease with forward and backward failure

– With chronic heart disease may be no clear evidence of shock

– Hemorrhagic shock

  • Rapid rise and fall of AST/ALT/LDH
  • Outcome determined by underlying disease
52
Q

Chronic Autoimmune Hepatitis

A
  • 70% women
  • Increased globulin
    • ANA, ASMA
  • Increased IgG
  • Increase in ALT variable
  • If overlap with PBC may have increased AP
  • Liver biopsy-lobular inflammation with plasma cells