Viral Hepatitis Flashcards
1
Q
Within liver anatomy, during hepatitis, where does the inflammation occur?
A
-around the portal triads
2
Q
Numerous viruses can infect the liver; however, the term viral hepatitis is reserved for those viruses that ___________.
A
- target the liver specifically
- they are hepatotropic
3
Q
T/F: Hepatitis A-E is caused by related viruses.
A
- false- not related to eachother
- while all hepatitis viruses cause hepatitis, the viruses themselves are quite different and the severity of their symptoms can vary in important ways
4
Q
What is the mechanism of acute hepatitis?
A
-immune-mediated damage to infected hepatocytes
5
Q
What are the symptoms of acute hepatitis (ranging from less specific to more specific)?
A
- fever, fatigue, malaise, nausea, vomiting
- abdominal pain
- right upper quadrant abdominal pain
- hepatomegaly
- jaundice (icteric phase)
- fulminant hepatitis
6
Q
What is fulminant hepatitis?
A
- massive hepatic necrosis leading to death
- rare outcome of acute hepatitis
7
Q
Describe common manifestations of jaundice. What is jaundice?
A
- yellow discoloration of skin, sclera, and mucus membranes due to systemic retention of pigmented bilirubin in tissues
1. dark urine, pale stools
2. pruritus (itchy skin)
3. scleral icterus: white of eyes are yellow
8
Q
What causes jaundice to be yellow?
A
-systemic retention of pigmented bilirubin in tissues
9
Q
Describe the breakdown of heme
A
- RBCs are degraded in spleen and bone marrow, releasing Hb, which is degraded to heme
- heme is converted into unconjugated bilirubin in macrophages of the spleen and BM, bound to plasma albumin and transported to the liver
- there it is conjugated to glucuronic acid, making it soluble for excretion
10
Q
What 2 forms of bilirubin occur in the blood and tissues? Together these two forms add to make the total bilirubin.
A
- conjugated:direct
2. unconjugated: indirect
11
Q
Conjugated bilirubin is excreted from the liver into the bile and passed into the intestine where it is further metabolized to stercobilin; what is stercobilin responsible for?
A
-colors feces brown
12
Q
Which forms of bilirubin are soluble and insoluble.
A
- unconjugated is not soluble (hence why it is transferred to liver by albumin)
- conjugated form (occurs in liver) improves solubility
13
Q
Which forms of bilirubin are considered direct and indirect?
A
- direct: conjugated
- indirect: unconjugated
14
Q
Jaundice can result from increased production, decreased excretion, or both of bilirubin. Give 3 mechanisms that result in elevated unconjugated (indirect) bilirubin. Give 2 to cause elevated conjugated bilirubin.
A
- Unconjugated: increased bilirubin production (hemolytic anemias like malaria); reduced hepatocellular uptake (drug interferences with transport systems); impaired conjugation (diffuse hepatocellular disease like hepatitis)
- Conjugated: decreased hepatocellular excretion (Dubin-Johnson syndrome); impaired bile flow (biliary obstruction)
15
Q
In addition to measuring bilirubin levels, what else can one measure to determine severity of hepatitis?
A
- Liver Function Tests
- death of hepatocytes releases various enzymes that LFT measure
16
Q
4 enzymes measures in LFT and their specificity
A
- ALT (alanine aminotransferase): more specific for liver abnormalities than other enzyme tests
- AST: Aspartate aminotransferase: less specific since its also found in muscle and other tissues
- AP (alkaline phosphatase): less specific, but indicative of bile duct injury
- GT (gamma glutamyl transpeptidase): often elevated in those who use alcohol or other liver toxic substances to excess
17
Q
When measuring bilirubin and LFTs, if patient was merely suffering from just hemolytic anemia, what results would you expect?
A
-high bilirubin but normal LFTs
18
Q
T/F: Chronic Hepatitis can be caused by HAV or HAC.
A
- False
- only hep B or Hep C
19
Q
If the acute infection is not cleared, patient may develop chronic hepatitis; what forms of hepatitis viruses cause this, describe generally if symptoms occur, and what it can lead to?
A
- Hep B or Hep C with variable frequency
- can be asymptomatic (chronic persistent hepatitis)
- can be symptomatic (chronic active hepatitis; CAH)
- can lead to cirrhosis or hepatocellular carcinoma
20
Q
What does cirrhosis refer to?
A
-the way the liver scars due to damage
21
Q
What forms of Hepatitis viruses can cause Hepatocellular Carcinoma?
A
- Hep B or C, but NEVER A
- this makes sense since this is associated with chronic hepatitis, which A does not cause
22
Q
3 general outcomes of infection with a hepatitis virus
A
- asymptomatic carrier
- acute hepatitis
- chronic hepatitis
23
Q
What is hepatitis referred to in a chronically infected individual who is asymptomatic vs. symptomatic?
A
- asymptomatic: chronic persistent hepatitis
- symptomatic: chronic active hepatitis
24
Q
Describe a cirrhotic liver compared to a normal liver and what are the major causes of cirrhosis in the US? What is microscopically seen in a cirrhotic liver?
A
- shrunken, micronodular, and very firm to touch
- bridging fibrosis seen microscopically; connect portal triads
- chronic alcohol abuse, hepatitis C, hepatitis B
25
T/F: If a liver is cirrhotic, all signs point to hepatitis virus.
-false; cirrhosis can have many causes, it truly is insightful into something being chronic, beyond that it is not helpful in diagnosing
26
Why is fibrosis in the liver during cirrhosis called bridging cirrhosis?
- it connects portal triads
| - due to anything cause chronic hepatic necrosis
27
Cirrhosis is essentially a rigid, non-compliant liver that is harder for blood to flow through. What are consequences of this?
- portal hypertensin leads to increased venous pressure throughout and leads to fluid transudation (ascites)
1. esophageal varices due to gastric vein backup
2. splenomegaly due to splenic vein backup
3. Hemorrhoids due to superior rectal backup
4. ascites due to backup in superior mesenteric vein and periumbilical vein
28
Physical consequences of cirrhosis lead to ascites and varices/splenomegaly. Are there any other consequences?
- metabolic consequences
| - jaundice and hepatic encephalopathy; coagulopathy, hypoglycemia, and increased ammonia (hepatic encephalopathy)
29
What causes hepatic encephalopathy?
- increased ammonia due to cirrhosis
| - metabolic consequence of cirrhosis
30
Describe the structure and infection type caused by Hepatitis A virus.
- RNA picornavirus
- pico=small (30nm diameter)
- RNA + strand genome
- nonenveloped and thus stable outside of the body
- causes acute disease and asymptomatic infection ONLY (NO CHRONIC)
- NOT cytopathic;
31
What are the symptoms of Hepatitis A virus due to?
- immune-mediated destruction of virus-infected cells
- the virus itself is not cytopathic which makes sense in an acute infection because you cannot kill host before you have change to replicate
32
Describe pathogenesis of Hepatitis A virus
- enters bloodstream through oropharynx, replicates in GI tract then viremia spreads to liver
- virus produced and released into bile, and then shed into stool for about 10 days BEFORE symptoms appear
- replicates slowly in liver and is not cytopathic; instead immune response causes liver pathology and symptoms
33
Describe transmission of Hepatitis A virus
- enteric transmission
- spread person to person via fecal-oral route
- acquired from contaminated food and water
- stable in fresh and salt water for long periods
* *shellfish is common source**
34
How many serotypes exist of HAV?
-1
35
Describe HAV outbreaks
- usually originate from point source like daycare center, water supply, restaurant)
- spreads readily because infected people are contagious before symptomatic
- infection typically confers immunity
36
What kind of hepatitis should you associated with HAV?
-acute
37
2 mechanisms are recognized for foodborne spread of HAV. What are they?
1. clean food is contaminated by incubating handler
| 2. food may be contaminated at its source, such as shellfish harvested from contaminated waters
38
HAV infection rates have decreased in US by _______ in recent years, why?
- >90%
| - due to vaccine, especially in children since they are often asymptomatic
39
Describe clinical symptoms of HAV infection, being sure to mention children vs. adults
- acute, self-limited illness with no chronic infection and no association with cancer
- >80% of adults are asymptomatic while rarely symptomatic n children
- symptoms occur abruptly 15-50 days post-exposure, intensify for 4-6 days before icteric (jaundice) phase
- hepatomegaly in 80%; jaundice in 70% adults and 15% in children
- less commonly see splenomegaly and rash
- FULMINANT HEP rareL 1-3 in 1000
40
Diagnosis of Hepatitis A virus infection
-Laboratory findingsL=: increased LFTs and bilirubin
-Detect: serum HAV IgM immunoassay*** gold standard
-
41
Why is IgM gold-standard for diagnosing acute infection rather than IgG?
-IgG can be due to prior exposure or vaccine and not signify a real-time infection
42
Treatment and prevention of HAV
- Tx: supportive since Dz is self-limited and most have full recovery in 3 months
- Prevent: maintenance of sanitary conditions (handwashing, cooked foods, avoid impure water) and HAV vaccine
43
What type of vaccine is the HAV vaccine and who should get it?
- inactivated vaccine
- indications: travel, chronic liver disease
- recommended for children as part of routine immunization schedules
44
Describe HBV genome and structure
- partially dsDNA genome that makes new DNA from viral RNA by using reverse transcriptase
- genome is covered by core antigen (HBcAg), which is surrounded by a lipid envelope and surface antigen (HBsAg)
45
What is unique about HBV HBsAg?
-it can assemble into subviral particles that are not infectious, but are more common than virus in the blood of infected people!!!
46
In addition to the virus itself, and HBsAg, what else is detected in infected patient sera?
-another viral protein, called the E antigen, HBeAg
47
What is the Dane particle?
-the real HBV virus in patients that is infectious, in contrast to the subparticles
48
What forms the basis of the HBV vaccine?
-HBsAg
49
HBV transmission
- parenteral transmission: IV drug use, sexual transmission
| - healthcare workers at risk
50
Why are rates of HBV infection so high?
-chronic, asymptomatic infections, esp. in children
51
Compare the natural history of HBV in adults vs. children
- Adults: 95% of acute cases are resolved; 5-10% become chronic. Once chronic, can lead to hepatocellular carcinoma (with 30 years time) or cirrhosis (20%)
- Children: same progression, except 95% become chronic and only 5-10% of acute are resolved
52
What factors can accelerate the progression of chronic HBV infections to cirrhosis?
-alcohol, HIV, HCVm abd HDV may accelerase fibrosis
53
Clinical manifestations of acute and chronic HBV
- Acute: 70% with subclinical hepatitis unlike hep A; longer incubation period than Hep A; symptoms improve after 1-3 mos
- Chronic: many asymptomatic for years; fatigue is most common symptom; hepatomegaly early in course; persistence depends on age at infection; major cause of hepatocellular carcinoma
54
80% of all HCC are attributable to chronic HBV infection, which increases one's chances by more than ______ times. Give 2 mechanisms HBV may induce HCC.
- 100x
- indirectly: HBV promotes continues liver repair and cell growth in response to tissue damage
- directly: integration and expression of some viral proteins may also promote tumor development directly!!
55
How many one detect or become suspicious of HBV infection in someone?
-observing increased LFTs in an asymptomatic person
56
How do you tell if a patient is HBV infected? What do you measure and what do they tell you?
- HBV serologies
1. HBsAg: HBV surface antigen; if positive, then patient is acutely or chronically infected
2. Anti-HBsAg IgG: if positive, either vaccinated, infected in past, or chronically infected if HBsAg is also positive
3. Anti-HBcAg: IgG means patient has been infected in past because HBcAg is NOT in vaccine; IgM means acute infection!!
4. HBeAg: if detected, suggests high virus levels
57
A diagnosis of HBV can be made on basis of what in serum?
-HBcAg IgM
58
Treatment of HBV
1. no treatment for acute infection
2. pegylated alpha-interferon for chronic infection
3. replication blockers for chronic infections
59
Role of pegylated alpha-interferon for chronic HBV infection: what does it do, who gets it, and are there side effects?
- suppresses HBV replication
- activates monocytes and macrophages
- induces antiviral state in uninfected cells
- used in younger patients, without HIV, HCV+, and certain genotypes
- significant side effects like flu and psychiatric side effects
60
Role of replication blockers for chronic HBV infection: what does it do, who gets it, any issues?
- Lamivudine (can be used for HIV too; nucleoside analog)
- Adefovir ( not used for HIV; nucleoside analog)
- older patients; HIV+; HCV-; low viral DNA
- drug resistance may arise
61
4 indications, as listed by NIH, for HBV treatment
1. acute liver failure
2. cirrhosis and clinical complications
3. cirrhosis or advanced fibrosis and HBV DNA in serum
4. patients who will be receiving cancer chemotherapy or immunosuppressive therapy
62
HBV prevention
- subunit vaccine based on HBsAg
- produced in yeast engineered to express HBaAg
- 3 doses needed
- injected IM
- highly effective
- make Ab to surface antigen
63
Describe structure of HCV
- member of flaviviruses
- + strand RNA genome
- lipid envelop
- 6 genotypes worldwide
- high replication rates with lots of errors leading to diversity
- does NOT integrate unlike Hep B
64
Transmission of HCV
-parenteral transmission like HBV: transfusion of blood products and IV drug use; sexual transmission is LESS common as with HBV
65
How many HCV genotypes are there and why does this matter?
- 6
| - makes a difference for treatment
66
HCV is the leading cause of what 4 things?
1. chronic liver disease (85% of new infections become chronic--only 5-10% in HBV)
2. cirrhosis
3. liver cancer
4. liver transplantation
67
What cohort in US likely encompasses most HCV infections?
- baby boomers
| - males twice as likely to be infected
68
HCV clinical manifestations
1. Acute symptoms are rare: malaise, nausea, vomiting, abdominal pain, jaundice is less than 10%, fuliminant hepatitis rare
2. Symptoms of chronic HCV non-specific: fatigue, intermittent nausea, vague diffuse or RUQ abdominal pain, myalgias, arthralgias
3. extrahepatic manifestations: immune complexes like glomerulonephritis and vasculitis
69
2 major clinical differences between HBV and HCV
- HCV is much more likely to cause chronic infection
| - HCV only increases risk of HCC 17x compared to HBC 100x
70
How does one screen and monitor treatment for HCV in the lab
1. HCV antibody for screening via enzyme immunoassay that tests for core and non-structural proteins
2. HCV viral load in monitoring treatment by PCR techniques
* *HCV genotype needed via sequences for proper treatment**
71
What must you be wearing of when screening for HCV antibody?
- takes 4-10 weeks of infection to detect Abs
| - False - in immunocompromised patients
72
Qualitative vs. Quantitative PCR for determining HCV load and what load predicts.
- Quantitative: predict response to treatment, monitor
- Qualitative: detects as low as 100 copies/mL
- virus load does NOT predict disease progression
73
Hep C chronic treatment
1. no vaccine
2. liver biopsy used to determine is tx should be started
3. old standard= PEG-interferon + ribavirin, a nucleoside analogue for 6-12 months
74
What is pegylation?
- covalent attachment of polyethelene glycol to peptide
- inceases hydrodynamic size
- prolonged circulation, delayed renal clearance
* *gives better pharmacokinetics so less frequence injections needed**
75
What are the side effects of PEG-IFN/Ribavirin?
- depression ranging from mild to suicidal
- irritability, aggressive behavior
- worsening of mania
- fatigue
- insomnia
- myalgias, fever, flu-like symptoms
- hair loss
- cytopenias
76
What may be the new gold standard for HCV chronic treatment? What are they active against?
- antivirals that target viral NS3 protease used in combo with PEG-IFN and RBV
- active against genotype 1 only!!
- Boceprevir and telaprevir
77
Hepatitis D virus other name and its structure
- aka delta agent
- small RNA genome that produces only 1 protein
- requires HBsAg to package its genome bc it does not have its own sAg
78
When can HDV establish an infection? What are the usual outcomes?
- in people who are already HBV+
| - most recover, but superinfection with HDV greatly increases risk of fulminant hep and HCC
79
HEV structure and prevalence; how is it spread?
- non-enveloped RNA virus that is rare in the US but endemic in other parts of the world
- spread fecal-oral (non-enveloped!!)
80
Typical infection of HEV and any important concerns to be aware of
- causes acute, self-limited viral hepatitis
- does NOT lead to chronic infection
- low mortality rates, but still higher than HAV
- HEV INFECTION IN A PREGNANT WOMAN CARRIES WITH IT A 20% MORTALITY OF FETUS!!!!
81
What other hepatitis virus is HEV most like clinically?
-HAV
