Viral hepatitis: Clinical practice
AssessmentsViral hepatitis: Clinical practice
USMLE® Step 2 style questions USMLE
A 26-year-old woman comes to emergency department with right upper quadrant pain and fever. For the past two weeks, after returning from a trip to India, she has been exhausted and "itchy all over". On physical exam, she has marked jaundice with tenderness to palpation in the epigastric region and right upper quadrant. Laboratory results are remarkable for elevated aminotransferases and bilirubin. If a liver biopsy were performed, what would the acidophilic bodies seen on biopsy represent?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Pauline Rowsome, BSc (Hons), Anca-Elena Stefan, MD
Viral hepatitis is liver inflammation caused by a viral infection and it can either be acute or chronic, and five important causes are hepatitis A, B, C, D and E.
Acute viral hepatitis lasts for less than six months and the individual has nausea, vomiting, and right upper quadrant pain. Sometimes if there’s a high total bilirubin, it can lead to jaundice, pruritus, dark urine, and clay- colored stools.
Chronic viral hepatitis lasts for more than six months and the individual can sometimes be asymptomatic. Other times, chronic viral hepatitis can cause fever, fatigue, and loss of appetite, as well as extrahepatic symptoms like arthralgias and skin rashes.
On the physical examination, with acute hepatitis, there’s typically hepatomegaly, but with chronic hepatitis, the liver may feel normal on palpation, and if there’s cirrhosis, the lower margin of the liver can feel irregular.
A diagnostic workup for viral hepatitis includes a CBC, AST, ALT, total bilirubin and unconjugated bilirubin, alkaline phosphatase, and PT, PTT, INR.
Thrombocytopenia, prolonged PT and prolonged PTT as well as an elevated INR can be present in both acute and chronic hepatitis.
In acute hepatitis, levels of AST, ALT are over 100 international units per liter and sometimes the alkaline phosphatase and total bilirubin are elevated as well. If the total bilirubin is above 2 milligrams per deciliter, then an individual can appear jaundiced.
With chronic hepatitis, elevation of AST and ALT persists for more than six months but levels don’t usually rise above 400 international units per liter. In addition, total bilirubin and alkaline phosphatase levels can also be elevated.
During viral hepatitis, medications that are metabolized by the liver, like aspirin, or medications that can damage the liver, like acetaminophen, should be used with caution, because they can further damage the liver.
Okay, now let’s start with hepatitis A which only causes acute hepatitis. It’s caused by contaminated food and water and often affects travelers.
In hepatitis A, serum anti-hepatitis A virus IgM antibodies are elevated for about 6 weeks , and anti-hepatitis A IgG antibodies begin to rise a couple weeks after IgM antibodies and usually persist for life.
So, if there are IgG antibodies and no IgM antibodies, that means that the person was vaccinated for hepatitis A or had a prior infection and developed immunity.
Hepatitis A usually resolves within a few weeks, and the main treatment is giving fluids in case of dehydration.
Hepatitis A can be prevented by vaccinating children, as well as adults that are about to travel in countries with a high rate of hepatitis A infection. Two doses of the vaccine are given 6 months apart.
Next up is Hepatitis E - which typically causes acute hepatitis, but can also cause chronic hepatitis in immunocompromised individuals.
Like hepatitis A, it’s also caused by contaminated food and water, but it can also be transmitted from mother to child during birth. Usually the symptoms are mild, but if it develops in pregnancy, it can be severe and lead to acute liver failure.
In acute hepatitis E, anti-hepatitis E virus IgM are elevated for about 2 months and IgG antibodies begin to rise around the same time as IgM antibodies, but they don’t persist for more than a few years. HEV RNA - which is a marker of virus replication- is also checked in the stool or in the serum to confirm the infection and levels are usually high.
With chronic hepatitis E, HEV RNA is detected in the serum or in the stool for more than six months.
Acute hepatitis E usually resolves within a few weeks, and the main treatment is giving fluids in case of dehydration. However, in acute liver failure, a liver transplant may be needed.
In immunocompromised individuals with chronic hepatitis E, treatment involves lowering the doses of immunosuppressants and giving ribavirin for 12 weeks.
Next is hepatitis B which can cause acute hepatitis and chronic hepatitis. It’s caused by contact with blood - like sharing needles or syringes, and contact with body fluids - like unprotected sex and during passing from mother to child during labor and delivery.
Testing for hepatitis B requires sending serology.
First, there’s HBsAg and Anti-Hbs, which is the antibody to Hepatitis B surface antigen. Usually, if one is positive, the other’s negative, sort of like yin and yang. One exception is if an individual has never been exposed to the hepatitis B virus or vaccine in their life - in which case they’re both negative.
Another exception is when a person has actually cleared the hepatitis B infection so the HBsAg is gone, but levels of Anti-Hbs still haven’t risen high enough to be detected, so it appears to be negative, even though technically there is Anti-Hbs floating around. That’s called the “window period”.
But most of the time, if HBsAg is positive and Anti-Hbs is negative, that means - there’s an acute or chronic hepatitis B infection.
And if HBsAg is negative and Anti-Hbs is positive, that means that an individual has been immunized or has recovered from a natural infection - either way, they’re protected from hepatitis B.
After looking at HBsAg and Anti-Hbs, the next step is to look at antibodies made against HBcAg, which is hepatitis B core antigen.
There’s IgM-anti-HBc, which is IgM antibodies against hepatitis B core antigen, and there’s total anti-HBc, which is total antibodies against hepatitis B core antigen, mostly made up of IgG antibodies. Neither of these rises with the vaccine.
Now, in acute hepatitis, both the IgM-anti-HBc and the total anti-HBc become positive. But as weeks go by, the IgM-anti-HBc becomes negative, while the total anti-HBc remains positive. That happens if the person clears the hepatitis B infection, or if there’s chronic hepatitis - so it really tells you about the passage of time.
Finally there’s HBeAg, which is hepatitis B e antigen - try saying that 3 times quickly. If it’s positive then the virus is actively replicating, and that means that the person is highly infectious. If it’s negative, it could be because the virus isn’t actively replicating or because there’s no virus around at all.
There’s also HBV DNA PCR, or Hepatitis B virus DNA PCR that can be sent, and it usually mirrors HBeAg but gives even more information.
High HBV DNA levels mean that the virus is actively replicating and highly infectious low HBV DNA levels mean that the virus is around but not actively replicating, and having no detectable HBV DNA means that there’s no virus.
Now let’s put these Hepatitis B serological markers into a table and go through some scenarios. In someone that’s susceptible to hepatitis B and hasn’t been immunized, HBsAg, Anti-Hbs, IgM-anti-HBc, total anti-HBc, HBeAg, and HBV DNA are all negative.
In someone that is immunized, Anti-Hbs becomes positive, while HBsAg is negative, and the rest remain negative as well.
Now in someone with acute hepatitis B infection, HBsAg is positive and Anti-Hbs is negative, and because it’s acute - IgM-anti-HBc and total anti-HBc are positive. Typically the virus is actively replicating at this stage so HBeAg and HBV DNA levels are elevated as well.
After a number of weeks later, IgM-anti-HBc becomes negative, while total anti-HBc remains positive for life.
Finally, if the infection gets brought under control to the point where the virus is no longer actively replicating, then the HBeAg becomes negative and the HBV DNA levels fall, and anti-HBe antibodies appear.
Finally there’s chronic hepatitis B infection, which has a few phases. The immune-tolerant phase usually develops in individuals that were infected during birth, and it can last a few decades. There’s minimal liver inflammation, so the ALT and AST may be normal or slightly elevated.
During this phase, HBsAg is positive and Anti-Hbs is negative, and because it’s chronic - IgM-anti-HBc is negative, while total anti-HBc remains positive.
Typically the virus is actively replicating at this stage so HBeAg and HBV DNA levels are elevated as well.
Then there’s the immune-active phase with positive HBeAg- which is when there’s more liver inflammation so ALT and AST are elevated, and as a result the HBV DNA levels start to fall a bit, but in other ways the labs are the same.
HBsAg is positive, Anti-Hbs is negative, IgM-anti-HBc is negative, and total anti-HBc remains positive.
And the virus is still actively replicating so HBeAg is positive.
Next there’s, immune-active phase with negative HBeAg- which is when the ALT and AST remain elevated, but the HBV DNA levels fall even lower, and the HBeAg becomes negative - meaning that the individual is less infectious.
In other ways the other labs are the same. HBsAg is positive, Anti-Hbs is negative, IgM-anti-HBc is negative, and total anti-HBc remains positive.
Next there’s the inactive chronic HBV phase- which is when the ALT and AST normalize and HBV DNA levels fall even lower, and the HBeAg remains negative.
And as before the other labs are the same. HBsAg is positive, Anti-Hbs is negative, IgM-anti-HBc is negative, and total anti-HBc remains positive.
Finally, when someone successfully clears the infection, Anti-Hbs becomes positive, while HBsAg is negative, total anti-HBc remains positive as well, and the IgM-anti-HBc, HBeAg, and HBV DNA are negative.