Hepatitis Flashcards
What is viral hepatitis?
Systemic diseases are caused by viral agents whose primary tissue tropism is the liver (hepatocytes are inflamed, damaged, and are unable to carry out their function)
- There are 5-well recognized hepatotropic viruses including:
1) Hepatitis A
2) Hepatitis B
3) Hepatitis C
4) Hepatitis D
5) Hepatitis E
- These five different viruses differ in their outcome
How are hepatitis A and E transmitted?
Via the feco-oral route
What are hepatitis B, C, & D transmitted?
Through body fluid (sexually transmitted)
What are the types of hepatitis that are transmitted via the faeco-oral route?
Hepatitis A & E
What are the types of hepatitis that is transmitted via bodily fluids?
Hepatitis B, C & D
What is hepatitis A?
- It is the infectious hepatitis “epidemic hepatitis”
- It is a non-enveloped RNA virus, which is difficult to grow in cell culture
- Transmitted via contaminated food and water (infected food handlers, raw shellfish, sexual contact, saliva)
- It is inactivated by boiling it for 1 minute and it can survive prolonged storage at 4 degrees or below
Which type of hepatitis is known as epidemic hepatitis/infectious hepatitis?
Hepatitis A
Describe the pathogenesis of Hepatitis A
- It has an incubation period of 2-6 weeks
1) It replicates in the alimentary tract and spreads to the liver, where it multiplies in the hepatocytes (it resists denaturation by the gastric acid)
2) Causes transient viremia
- It can be asymptomatic typically in children and severe typically in adult pregnant women (Acute in adults, and Asymptomatic in children)
- A and E cause only acute hepatitis while B, C, & D might become chronic
What are the phases of hepatitis A infection?
1) Prodromal/preicteric phase: before the appearance of jaundice, where the symptoms range from fatigue, joint and abdominal pain, malaise, vomiting, lack of appetite, and hepatomegaly
2) Icteric phase: Jaundice appears, where the skin, sclera, and mucus membrane have an elevated level of bilirubin and thus jaundice which could also result in bilirubinuria (dark urine and pale stool)
How to diagnose hepatitis A?
1) Signs and symptoms
2) Elevated liver enzyme (LFTs)
3) Anti-HAV IgM antibodies (golden standard), which appear early and persist for 4-16 weeks
4) Anti-HAV IgG in 1//3 of the patients who develop symptoms (turn over of IgM for long-term immunity)
What are the antibodies that are associated with the serology of hepatitis A?
1) Anti-HAV IgG and IgM
What is the gold standard diagnostic for hepatitis A?
Anti-HAV IgG
- They can stay elevated for up to 4 months and then get replaced by IgG antibodies for long-term immunity
How to prevent hepatitis A?
- By taking the killed HAV vaccine given for:
1) 2 years old and above
2) Travelers (to endemic areas) and adults who are at high risk
3) People who take care of food
What type of vaccine is used to prevent hepatitis A?
Killed vaccine
What is hepatitis B?
- AKA: Serum hepatitis/Post-transfusion hepatitis
- It is a small enveloped DNA virus that is circular, and “partially” double-stranded from the hepadnavirus group
- It encodes via reverse transcriptase enzyme and replicates through an RNA intermediate
- It cannot be grown in culture
What are the characteristics of hepatitis B?
It is serum hepatitis, post-transfusion hepatitis (if someone develops jaundice after transfusion, then most probably it is Hep-B)
What are the antigens of the HBV?
1) HBsAg (surface/coat protein), is the characteristic antigen for hepatitis B (used in serology)
2) HBcAg (Inner core protein “it is not detectable)
3) HBeAg (secreted protein that has an unknown function)
How is hepatitis B transmitted?
- The virus is present in the blood, semen, saliva, and vaginal fluids (mainly via blood, The max concentration of the virus is in semen and blood)
1) Sexual transmission
2) Perinatal (vertical) transmission from the mother HBeAg+ to the fetus during labor
3) Parentral transmission (IV drugs, health worker)
What is the antigen transmitted from the mother of a HBV to the infant?
HBeAg+
What are the clinical features of hepatitis B?
- It ranges from asymptomatic (infants below 5 years, and immunosuppressed adults with a new acquired HBV) infection to a fulminant hepatitis (results in liver failure <1% of cases)
- The average incubation period is 60 days
- Signs and symptoms include (nausea, vomiting, abdominal pain, fever, dark urine, changes in stool color, hepatomegaly, splenomegaly, and jaundice)
- The acute illness (jaundice) occurs mainly in people who are above 5 years with a fatality rate of 0.5-1%, while chronic occurs mainly in people who are below five years (30-90%)
- HBV is usually associated with primary hepatocellular carcinoma (PHC, occurs in chronic active hepatitis along with cirrhosis)
What are the extrahepatic manifestations of HBV?
1) Skin rash
2) Arthralgia
3) Arthritis
- Occurs in both, chronic persistent and active hepatitis
What are the different diagnostic measures for hepatitis B?
1) Signs and symptoms
2) Elevated LFTs
3) Serological tests
4) PCR to detect the infectious virion and estimate the viral load
What are the different serological tests of hepatitis B?
1) HBsAg (surface antigen)
2) anti-HBsAg (antibody to the surface antigen)
3) Anti-HBcAg (Antibody to the core antigen)
4) HBeAg (E antigen)
5) ANTI-HBeAB (ANTIBODY TO e ANTIGEN)
6) IgM anti-HBc
7) IgG anti-HBc
What are the serological markers of acute HBV?
1) HBsAg (4-weeks)
2) IgM-anti-HBc (marker of acute infection)
3) HBeAg (detectable in people with acute infection, correlates with greater infectivity)
4) anti-HBe (virus no longer replicating but it is persistent)
5) Total antibody (IgM + IgG “IgG is a marker of past infection”)
- FYI: Acute hepatitis = IgM anti-HBc, in addition to that anti-HBsAg indicate immunity from past infection
- Months after the infection (no more antigens):
1) Total anti-HBc
2) Anti-HBe
What are the serological markers of chronic HBV?
- HBsAg for more than 6- months
- HBsAg and IgG anti-HBc remain persistently detectable (for life)
- FYI: Chronic hepatitis = negative IgM anti-HBc + HBsAg positive
What are the clinical syndromes of HBV?
1) Acute infection: detection of both HBsAg, IgM Anti-HBc, and HBeAg
2) Chronic hepatitis: Presence of HBsAg > 6 months and HBcAB total (IgM and IgG)
3) Chronic infection: occurs in 80-90% of infected pnt
4) Hepatocellular carcinoma
What is the serological test of a person with a natural immunity to HBV?
1) Positive Anti-HBc (IgG)
2) Positive Anti-HBs
What is the serological test of a person with immunity to HBV due to HB vaccination??
1) Positive Anti-HBs
What is the serological test of a person with acute HBV infection?
1) Positive HBsAg
2) Positive IgM anti-HBc
3) Positive Anti-HBs
4) Positive/Negative IgG anti-HBc
What is the serological test of a person with chronic HBV infection?
1) Positive HBsAg (>6 months)
2) Positive IgG Anti-HBc
What are the treatment options for hepatitis?
- Used together
1) Interferons
- Drugs like conventional IFN-a, and Peg-IFN a-2a “PEGASYS”
- They have a combined antiviral and immunomodulatory effect
2) Nucleoside/Nucleotide analogs
- Drugs like (Lamivudine, adefovir, entecavir, telbivudine, and tenofovir)
- which all have a direct antiviral effect
What are the preventative measures of hepatitis B?
1) Hepatitis B vaccination (the main HBV prevention, pre-exposure for active immunity)
2) Educating the people about needles, sex, and universal precautions
3) HBIG (for passive immunity and post-exposure)
What is the pre-exposure prevention of HBV?
HB vaccination, which provides active immunity
What is the post-exposure vaccination of HB?
HBIG, provides passive immunity
What is the hepatitis B vaccine?
- The first HB vaccine consisted of a plasma-derived HBsAg and recombinant HepB vaccines which contained yeast-derived HBsAg
- Vaccines like (Recombivax-HE or Engerix-B)
- Given in three doses (day-0, day-30, and in 6-months)
- If antibody-HBsAg is more than 10mlU/mL then okay if not then give a booster (typically after 10 years)
When to give post-exposure HBIG?
- Not given to vaccinated individuals
- When the antiHBs are less than 10mlU/mL and the patient is HBsAg positive
- Then we give antibodies in 2 doses one month apart
What is hepatitis C?
- Remember C = Chronicity
1) Positive strand RNA enveloped virus
2) Endemic, with high incidence in Japan, Italy , and Spain
- Classified into 6 types
3) types 1-4 have a poorer prognosis and respond to interferon therapy
4) Transmitted similar to HBV (parenterally)
5) Usually asymptomatic and chronic is very common (70%)
- No vaccines available for HCV
What are the complications of HCV?
1) Chronic liver disease
2) Hepatocellular carcinoma
Describe the HCV infection
1) 15% recovery and clearance
2) 15% cirrhosis with a rapid onset
3) 70% Persistent infection
- If someone acquired the persistent infection:
1) 40% ASYMPTOMATIC
2) 60% Chronic hepatitis
- If someone acquired chronic hepatitis then:
1) 6% liver failure
2) 20% cirrhosis
3) 4% Hepatocellular carcinoma
How to diagnose HCV?
1) HCV antibody (after 4 weeks at least)
2) HCV-RNA (using PCR or branched DNA)
3) HCV-antigen (EIA technique)
What are the preventative measures of HCV?
1) Screening of blood, organ, or tissue donors
2) Blood and body fluid precautions
3) Education (blood> sex > perinatal)
What is the treatment of HCV?
1) Rabivarin +INF-a (50% recovery)
- Ribavirin (Guanosine analog – inhibit nucleoside synthesis/RNA synthesis)
- INF α or pegylated interferon - enhances rabivarin lifetime
2) Sovaldi, Harvoni
Which hepatitis virus has the highest incubation period?
Hepatitis C (140-180 days)
