1
Q
What type of virus is Hep A?
A
RNA hepatovirus from the picornavirus family
2
Q
How is HAV transmitted?
A
Fecal-oral transmission
Most commonly in crowded areas with poor sanitation
Excreted from feces for 2 weeks BEFORE sx!!!
3
Q
What are risk factors for contracting HAV?
A
- Traveling to area with poor sanitation (contaminated water)
- Unwashed produce or food
- Personal contact with infected person (clean-up, daycare)
- Sexual contact (oral to anal contact)
BUT, in up to 55% of infections, no identified risk factor!
4
Q
How long is the incubation period for HAV?
A
2-6 weeks
5
Q
What is the HAV timeline?
A
- Viral infection for about 5 weeks
- HAV present in stool from 1-5 weeks
- Clinical illness at about 2.5 weeks to 8 weeks that coincides with peaks in ALT and IgM
- IgG starts to rise at about 2.5 weeks
6
Q
What are the prodromal symptoms of HAV?
A
Malaise Myalgia Arthralgia Easy fatigability Anorexia
7
Q
What are the s/sx of HAV?
A
-Anorexa, N/V, low grade fever
-Jaundice: typically after 5-10 days of prodrome
-Abdominal RUQ pain
-Hepatomegaly in >50%
-Splenomegaly
-Enlarged lymph nodes
(kids typically asymptomatic)
8
Q
What are the laboratory findings in HAV?
A
- EXTREME elevations in AST/ALT
- Elevated bilirubin and Alk Phos
- Proteinuria and bilirubinuria that precedes jaundice
- Hep A antibody:
- IgM anti-HAV in 1st week of symptoms to confirm diagnosis
- IgG anti-HAV rises after 1 month
9
Q
What is the resolution of HAV?
A
A self-limiting virus!
Symptoms last less than 2 months
Does NOT cause chronic liver disease
10
Q
What are complications from HAV?
A
Most common in ages >50
- Can have a relapse infection w/in 6 mos
- Fulminant hepatitis (UNCOMMON): risk is increased in those with chronic liver disease
- Acute renal failure, acute pericarditis, arthritis, acute pancreatitis, hemolytic anemia (all SUPER rare)
11
Q
What is the treatment of HAV?
A
Bed rest
Oral/IV hydration with 10% glucose if N/V
Food (as tolerated)
No medications needed (also meds can be hepatotoxic)
Avoid physical exertion/activity because of splenomegaly
12
Q
How to prevent HAV?
A
HAND WASHING!!!
If unvaccinated and exposed, post-exposure prophylaxis with HAV vaccine or immunoglobulin
Vaccination: inactivated vaccine given to children between 1-2 and/or international travelers
13
Q
What type of virus is Hep B?
A
DNA hepadenavirus with inner core protein and outer surface coat
Subtypes (A-H)
14
Q
How is HBV transmitted?
A
Transmitted via blood, blood products, or body fluids
Present in saliva, semen, vaginal secretions
HIGHLY transmittable because of high viral loads in fluid
15
Q
What are the risk factors for contracting HBV?
A
- Mother to child transmission: ~90% transmission
- Injection drug use
- Any sexual contact with vaginal/seminal fluid
- Contact with infected person’s fluid (utensils, etc.)
- Hemodialysis
16
Q
Who is at increased risk for contracting HBV?
A
- Healthcare providers (clinicians, dentists, nurses, people in labs, blood banks, etc.)
- Incarcerated or formerly incarcerated
- People with hx of STIs
17
Q
What is the incubation period for HBV?
A
6 weeks to 6 months
18
Q
What is the HBV timeline?
A
Incubation: 6 weeks to 6 months
Acute infection: 2 weeks to 3 months
Early recovery: 3 to 8 months
Recovery: 6 to 12 months
15-20% of adults will become chronic
19
Q
What are s/sx during the prodromal period of HBV?
A
- A/N/V, malaise, aversion to smoking
- Can be mostly asymptomatic
20
Q
What are s/sx during the acute icteric period of HBV?
A
Lasts for 2-4 weeks
-Jaundice
-Fulminant disease, liver failure in 1% of patients
(Check PLT and INR to see if liver is beginning to fail…may need transplant!)
21
Q
What are laboratory findings in HBV?
A
- Similar to HAV, but significantly HIGHER ALT/AST
- Can have elevated INR, which is a sign of increased mortality (liver failure)
- HBV serology patterns (lots…)
22
Q
How do you interpret HBV serology?
A
Check HBsAg, HBsAb, HBcAb, HBeAg, and HBeAb
Helps you determine if it is acute or chronic HBV, if there is active viral replication and how much virus is being replicated, if the patient has been vaccinated, and if the patient has recovered from previous HBV
If you see surface antibodies (HBsAb) indicates pt has been vaccinated against HBV
23
Q
How do you treat HBV?
A
- Rest, aggressive hydration (oral or IV if needed)
- If any indication of liver failure (encephalopathy, coagulopathy) HOSPITALIZE pt and evaluate for liver transplant
- Antivirals are only warranted in fulminant disease
24
Q
How do you prevent HBV?
A
- VACCINATE!! Recommended for infants
- Careful handling of items from infected people
- Practice safe sex with HBV-infected people
- No utensil sharing in houses with positive person
- Hep B immunoglobulins w/in 7 days of exposure
25
What is the incidence of chronic Hep B?
1-2% of acute infections progress to chronic infection
(in acute immunocompromised pts, 10-15% progress)
Higher incidence in males than females
Commonly seen in all family members in endemic countries
Highest in Africa, Middle East, South America (parts)
26
What is the "Immune Tolerant Phase" of chronic Hep B?
- HBeAg and HBV DNA are present
- Normal to slightly elevated LFTs with little liver inflammation
- Common in infants and children
27
What is the "Immune Clearance Phase" of chronic Hep B?
- Elevated LFTs and liver inflammation
- Progression to cirrhosis and risk of HCC is >2% per year
- HBV DNA (lower levels) and HBeAg may be positive OR NEGATIVE! (May see HBeAb positive)
28
What is the "Inactive HBsAg Carrier" phase of chronic Hep B?
- Low or no detectable HBV DNA levels (<100,000 copies)
- HBeAg is negative, HBeAb positive
- Low risk of cirrhosis and/or HCC
29
What is the "Reactivated Chronic Hep B" phase?
- Infection by pre-core mutant or spontaneous mutation of genome
- Elevated HBV DNA and possible progression to cirrhosis
- Can have HBeAg negative chronic Hep B
- Most common in old age, males, HBV genotype C
30
What is the INITIAL medical assessment of chronic Hep B?
Ongoing assessment of additional risk factors:
- Co-infections? (HCV, HDV, HIV)
- Alcohol intake? Tylenol intake?
- Family history of liver disease or liver cancer?
31
What is the INITIAL laboratory assessment of chronic Hep B?
- HBV serology panel (including HBeAg and HBV DNA)
- LFT assessment
- HBV genotyping (only indicated if they don't clear the virus)
Note: HBV viral loads may take a long time to drop/clear
32
What are INITIAL imaging/fibrosis staging considerations in chronic Hep B?
Liver biopsy/fibroscan that can assess for the degree of damage
33
What are the ONGOING lab assessments of chronic Hep B?
- HBeAg to assess if positive or negative every 6-12 months
- HBV DNA PCR: cutoff for treatment is 20,000 units
- ALT every 3-6 months
34
What is the ONGOING recommendation for fibrosis staging in Hep B?
No definitive timeline...
| But liver biopsy/fibroscan may be done every 2-5 years
35
What is the ONGOING recommendation for HCC surveillance in Hep B?
Liver ultrasound with doppler flow every 6 months for HCC monitoring
Chronic HBV patients can get HCC even if they are not cirrhotic!!
36
What is the treatment of Chronic Hep B?
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
- ****Entecavir****
- Lamivudine
- Telbivudine
Nucleotide Reverse Transcriptase Inhibitors (NtRTIs)
- ****Tenofovir****
- Adefovir
Pegylated Interferon
-Peginterferon alfa-2a or peginterferon alfa-2b
37
What is the goal of treating Chronic Hep B?
Suppress HBV DNA and HBeAg to HBeAb seroconversion
38
Hepatitis D Virus Info
- Only occurs in association with HBV when HBsAg is present
- Defective RNA virus
- Only detectable by antibody test (HDsAb)
- May co-infect with HBV or super-infect with HBV
- Co-infection occurs with acute HBV with same severity as HBV alone
- Super-infection can occur with chronic HBV and causes worse short-term prognosis, fulminant disease, rapid cirrhosis
- Only seen in endemic areas to HBV
39
What type of virus is HCV?
```
RNA hepacivirus, similar to flavivirus
6 genotypes (1-6) with multiple sub-types (a-f)
```
40
How is HCV transmitted?
Transmitted via blood and discovered in 1992
Transmission prior to 1992:
-Blood transfusions, tattoos, IVDU, dental/medical equipment, occupational exposure
Transmission post 1992:
-IVDU, sexual behaviors involving blood, occupational exposure
41
What are the risk factors for contracting HCV?
- IVDU (even once in past)
- Receiving blood products before 1992
- Receiving clotting factors before 1987
- Incarceration >24 hrs
- Receiving tattoos or piercings
- Employed in a medical or dental field
- Needle stick
- Contact with known positive (what type of contact?)
- Long term hemodialysis
- MSM
- HIV+
- Baby boomers (born between 1945-1965)
Yearly screening recommended in people who continue to have these risk factors
42
What is the incubation of HCV?
6-7 weeks (on average)
43
What are the clinical findings in acute HCV?
- Much milder compared to HAV and HBV
- Can be completely asymptomatic (more common in pts who do not clear the virus)
- Jaundice, fatigue, anorexia, tea-colored urine
- The more sx you have, the more likely you are to clear/cure the virus
44
What are laboratory findings in acute HCV?
- ALT high (>AST)
- Detectable HCV RNA PCR
- HCV-Ab may be negative in early infection (can take 2-3 months), so check RNA PCR if you are suspicious for acute HCV
45
Does acute HCV resolve?
About 15-25% of pts will spontaneously resolve!
- Defined as negative HCV RNA PCR w/in 1 year of infection
- Will always be HCV Ab+ (this is NOT immunity!!!)
46
What happens with acute HCV progressing to chronic?
75-85% of cases will progress to chronic HCV
- Defined as having detectable HCV RNA PCR 1 year after infection
- LFTs normalize (or may be slightly elevated)
47
What is the HCV disease progression impact on the liver?
HCV infection...
75-85% progress to chronic HCV...
20-30% progress to cirrhosis...
2-7% per year progress to HCC and ESLD
48
What are extra-hepatic manifestations of HCV?
- Mixed cryoglobinemia
- Lichen planus
- Porphyria cutanea tarda
- DM
- Renal disease
- Non-Hodgkin's Lymphoma
49
What are the screening guidelines for HCV?
- Age-based testing: anyone born between 1945-1964
- Risk-based testing: anyone with ongoing risk factors
- Sx-based testing: anyone with elevated LFTs of unknown etiology
50
How do you screen for HCV?
HCV Antibody tests
- Serum test
- Rapid (20 min) finger stick test
51
How do you handle the results of HCV screening?
Anti-HCV antibody test:
Negative? --> no further testing
Positive? --> get HCV RNA test
HCV RNA negative? --> no active disease, spontaneous resolution; may test with HCV RNA if ongoing risk
HCV RNA positive? --> pt has ACTIVE DISEASE; genotype, liver fibrosis stagin, linkage to care
52
How do you assess for progression and stage the liver disease in chronic Hep C?
Stage the liver:
- Liver biopsy: gold standard, but no done anymore
- FibroScan: non-invasive elastography that assesses fibrosis
- APRI or Fib-4: uses liver markers (good on the extremes)
Assess for extra-hepatic manifestations
Assess for treatment options:
- Genotype
- Prior HCV tx history
- Liver staging
53
What is the goal of chronic HCV treatment?
- Sustained viral response = undetectable viral load 3 months after finishing treatment
- If unable to achieve sustained viral response, goal is to prevent/delay disease progression and improve liver scarring
54
What are treatments for chronic HCV?
You cannot be treated if you are drinking alcohol
HCV treatments:
Harvoni (GT 1 and 4): 2 meds in 1 pill/day regimen
Sovaldi (GT 1-6): 1 med in 1 pill
Daklinza (GT 1 and 3)
Zepatier (GT 1 and 4)
Vosevi (G1-6)
Mavyret (G1-6)
Epclusa (G1-6)
Ribavirin (in combo with some of the above)
55
How long is treatment of HCV?
- May be 8-24 weeks based on patient factors
| - Tx regimen is determined by genotype, treatment history, and degree of disease (fibrosis)
56
What impacts the patient's response to chronic HCV treatment?
- Genotype
- Liver condition (cirrhosis and/or steatosis)
- Alcohol use
- Ability to consistently take meds
Because of new treatments, patient's response is NO LONGER influenced by race/ethnicity, age, weight, HIV status, or HCV viral load!!
57
What is cirrhosis?
Scar tissue that damages the hepatocytes and structure and function of the liver
Diagnosis is only confirmed with imaging
58
What occurs as a result of liver cirrhosis?
- Liver cannot remove or neutralize poisons from the blood
- Stops producing immune agents to control infection
- Inhibits making proteins that regulate blood clotting (elevated INR, low albumin, low PLT)
- Inhibits production of bile to help absorb fats and fat-soluble vitamins
59
How do you diagnose cirrhosis?
- Synthetic function abnormalities (high INR, low albumin, low PLT)
- Histology (actual liver tissue biopsied)
- Fibroscan (elastography to see stiffness of liver)
- Imaging is REQUIRED to confirm diagnosis
60
What are screening recommendations in pt with chronic Hep C?
- HCC screening: every 6 months via liver imaging because early detection --> better outcomes (transplant list vs chemo/lesion removal/radiation)
- Esophageal Variceal screening: every 3 years if no varices and every year once varices seen; banding of varices can prevent rupture
- Liver decompensation management
61
What are the s/sx of liver cirrhosis?
```
Possibly none!
Fatigue
Exhaustion
Loss of appetite
Nausea
Weakness
Weight loss
Abdominal pain
Spider angiomas
Jaundice
```
62
What do you do for ascites and edema in decompensated cirrhosis?
```
(Liver not making enough albumin/proteins to remove fluid from body)
Treat with:
-Diuretics
-Sodium restriction
-Fluid restriction
-NO NSAIDS
-Paracentesis if needed
-TIPS (transjugular intrahepatic portosystemic shunt)
```
63
What do you do for hepatic encephalopathy in decompensated cirrhosis?
(Disordered CNS due to the inability to remove toxins)
- First sign: circadian sleep pattern flips
- Stages: mild confusion, drowsiness, stupor, coma
- Treatment: lactulose, rifaxamin
64
What do you do for hepatorenal syndrome in decompensated cirrhosis?
(AKI (Creat>1.5) in the absence of kidney disease)
- Oliguria, hyponatremia, low urinary sodium
- Most often 2/2 over diuretics and low cardiac output
- Treatment: stop diuretics, IV albumin, liver transplant
65
What do you do for esophageal variceal bleed in decompensated cirrhosis?
- Caused by portal HTN (backup of blood into the portal vein) and increased pressure can cause rupture
- Treatment: binding of varices, decreased pressure (non-selective BB)
66
When would you liver transplant?
- Liver decompensation or HCC
| - MELD Score (Model for End-Stage Liver Disease): higher the MELD the higher on transplant list
646 Test 2
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