Viral Hepatitis: Viral Hepatitis: Acute Hepatitis A and E

0:00Welcome to Board Pearls. This is episode one of three of the Viral Hepatitis chapter, in the Liver Disease module. This episode covers acute viral hepatitis and the two enteric viruses, hepatitis A and E. A man with jaundice and a viral panel that looks negative shows why symptoms can't tell the viruses apart, which panel goes out first, why a negative antibody can miss the diagnosis, and which acute infections get treated. A woman with acute hepatitis B and a man with a flare of chronic disease show the two readings of the same antibody. A man labeled with drug injury turns out to have hepatitis E, and the two women after him show who gets chronic infection and how it's treated, and why it's so dangerous in pregnancy. Then a man with hepatitis A shows its unusual courses, who should be vaccinated, and how prophylaxis after an exposure depends on who was exposed.

0:52Here's the first patient. A thirty-one-year-old man who injects drugs has had malaise, nausea, and loss of appetite for a week, then dark urine, and now yellow eyes. His alanine aminotransferase, ALT, is one thousand four hundred, and his bilirubin is six, mostly conjugated. His hepatitis B surface antigen and core immunoglobulin M, IgM, are negative. His hepatitis A IgM is negative. His hepatitis C antibody is negative. He asks whether that means it isn't a virus.

1:24A prodrome, then dark urine and jaundice, with an ALT in the thousands and a conjugated bilirubin, is acute hepatitis, and in a man who injects drugs it's viral until proven otherwise. His negative tests don't settle which virus, and his symptoms can't either, because acute viral hepatitis follows the same course whatever the virus. So the serologic panel, not the history, identifies it.

1:51The course has three phases. After enteric or parenteral exposure, the virus replicates in hepatocytes during a silent incubation, around twenty-eight days for hepatitis A, two to three months for hepatitis B, and two to twelve weeks for hepatitis C, and then the immune response produces the illness. The prodrome is malaise, anorexia, nausea, mild right upper quadrant discomfort, and a flu-like illness. Some patients have a prodrome like serum sickness, with rash, hives, or joint pain, which is most classic for hepatitis B and comes from circulating immune complexes that contain surface antigen.

2:30The icteric phase brings dark urine, pale stools, scleral icterus, and jaundice, with aminotransferases in the hundreds to thousands and a conjugated hyperbilirubinemia. Recovery follows, with the aminotransferases normalizing over weeks and the bilirubin trailing behind. Thirty to fifty percent of immunocompetent adults with acute hepatitis B become jaundiced, while most other acute viral infections in adults are anicteric, so even jaundice doesn't identify the virus.

2:59The first panel is hepatitis B surface antigen, hepatitis B core IgM, hepatitis C antibody with a reflex to hepatitis C virus, HCV, ribonucleic acid, RNA, and hepatitis A IgM. Hepatitis E IgM is added for a traveler returning from South Asia or Africa, for someone who eats a lot of pork or game, and for an unexplained acute hepatitis when the conventional panel is negative.

3:27Each result has a fixed reading. Surface antigen with core IgM is acute hepatitis B, and surface antigen with total core antibody but no core IgM is chronic hepatitis B. Hepatitis A IgM is acute hepatitis A, essentially diagnostic, because hepatitis A doesn't become chronic. Hepatitis E IgM supports acute hepatitis E, and hepatitis E virus, HEV, RNA adds value in immunocompromised patients, whose antibody response is blunted. A positive hepatitis C antibody with a positive RNA means infection, acute or chronic, and the antibody alone can't say which.

4:07His negative antibody doesn't rule out hepatitis C. The antibody can be negative for the first one to three months, because seroconversion lags behind the viremia. HCV RNA confirms acute hepatitis C when the antibody is negative or indeterminate, and he's exactly the patient for it: injection drug use, acute hepatitis, and an otherwise negative panel. His HCV RNA is two million international units, so he has acute hepatitis C.

4:34The reverse pattern means something else. A positive antibody with a negative RNA is a resolved infection or a false-positive antibody. Spontaneous clearance occurs in fifteen to fifty percent, more often after a symptomatic illness, in women, in younger patients, and with the favorable IL28B CC genotype.

4:55Before treatment, each test in his workup has a reason. He's tested for human immunodeficiency virus, HIV, because injection drug use is a shared risk. He gets hepatitis B serology, surface antigen, surface antibody, and core antibody, because hepatitis B reactivation has been reported during direct-acting antiviral therapy in patients positive for surface antigen. His fibrosis is assessed. And a woman of childbearing age would get a pregnancy test. His hepatitis B serology shows neither infection nor immunity, so he's vaccinated against hepatitis B, and against hepatitis A too, since people who use drugs are a recommended group.

5:37Whether acute hepatitis is treated depends on the virus, and his is treated. Acute hepatitis C is treated promptly with a direct-acting antiviral regimen once viremia is documented, because fifty to eighty-five percent of acute infections become chronic, and waiting for spontaneous clearance trades cures for chronic disease. It uses the same regimens and durations as chronic hepatitis C, covered in episode three. He starts sofosbuvir-velpatasvir for twelve weeks. Cure is a sustained virologic response, an undetectable HCV RNA twelve weeks after treatment ends, and because he still injects, he's tested for HCV every year.

6:17The other acute viruses are mostly supportive. Acute hepatitis A is supportive. Acute hepatitis E is supportive in an immunocompetent host, with ribavirin reserved for immunocompromised patients who don't clear it. Acute hepatitis D, in coinfection or superinfection, is supportive in the acute phase.

6:36Acute hepatitis B is different, and the second patient shows how it's handled. A forty-four-year-old woman with an acute hepatitis has a positive surface antigen and core IgM, which is acute hepatitis B. She's observed, and she'd be treated with entecavir, tenofovir disoproxil, or tenofovir alafenamide only if her disease became fulminant, or protracted and severe, with a rising international normalized ratio, INR, and deep jaundice persisting beyond about four weeks. Peginterferon is contraindicated in this setting, and most adults recover without an antiviral. Her INR and bilirubin are followed, her INR stays normal, and she's rechecked to confirm that her surface antigen clears.

7:18Liver failure is rare but not evenly spread. Fewer than one percent of cases of acute hepatitis A and B in healthy adults progress to acute liver failure, but the rate is materially higher with hepatitis B and D coinfection, with hepatitis E in pregnancy, and with any acute virus on top of chronic liver disease. Chapter nineteen covers acute liver failure.

7:40The third patient shows that some flares only look like a new infection. A fifty-two-year-old man with known chronic hepatitis B has a sudden ALT of nine hundred and a positive core IgM. Core IgM can reappear during a reactivation flare, so this could be reactivation, hepatitis D superinfection, a flare related to immunosuppression, or another virus on top. His workup mirrors the acute panel, plus hepatitis D testing. Episode two covers reactivation and hepatitis D.

8:12A negative conventional panel is where hepatitis E hides, and the fourth patient shows it. A sixty-one-year-old man started a new statin two months ago and now has an ALT of nine hundred and jaundice. He's been labeled with drug-induced liver injury, and the statin has been stopped. His hepatitis A, B, and C tests are negative. He doesn't travel, but he hunts, and his family eats a lot of wild boar and venison.

8:37His diet raises the possibility that this isn't drug injury but hepatitis E. Three to thirteen percent of cases first labeled as drug-induced liver injury are reclassified as hepatitis E after testing, so hepatitis E IgM is sent whenever an apparent drug injury doesn't quite fit.

8:55The two kinds of hepatitis E are almost two diseases. Genotypes one and two spread fecal-orally through contaminated water in endemic regions of Asia and Africa and cause epidemic and sporadic acute hepatitis like hepatitis A. Genotype three, and less often four, is zoonotic, coming from undercooked pork, deer, wild boar, sheep, and shellfish. Genotype three dominates in the United States and Europe, causing acute and occasionally chronic hepatitis, and about six to nine percent of the United States population has antibody evidence of past exposure.

9:31The tests read differently. Hepatitis E IgM indicates acute or recent infection, total antibody indicates past exposure, and HEV RNA indicates active infection. The RNA matters most in immunosuppressed patients, in whom a negative antibody doesn't exclude infection.

9:51His hepatitis E IgM is positive, so he has acute genotype three hepatitis E, not statin injury. Acute hepatitis E in an immunocompetent patient is supportive, and he recovers over six weeks. His statin was never the culprit, so it can be restarted.

10:09The same genotype can persist in the wrong host, and the fifth patient shows it. A fifty-three-year-old woman two years after a kidney transplant, on tacrolimus, has had a mildly raised ALT for eight months, and her HEV RNA is positive. She has chronic hepatitis E, defined as HEV RNA persisting beyond three to six months. It occurs almost exclusively in solid organ and stem cell transplant recipients, in people with HIV and a low cluster of differentiation four, CD4, count, and in others on heavy immunosuppression. It produces progressive fibrosis and can lead to cirrhosis within years.

10:47Her treatment starts with her immunosuppression. Reducing it, when that's feasible, clears the virus in roughly a third of patients. If the virus persists, ribavirin six hundred to twelve hundred milligrams daily for three months gives a virologic response above ninety-five percent and a sustained cure in about eighty percent. Pegylated interferon is second-line in selected liver transplant recipients, but it's avoided after heart, lung, and kidney transplants because of the risk of rejection. Her tacrolimus is lowered, her HEV RNA persists, and three months of ribavirin cures her.

11:23Pregnancy is the third host, and the most dangerous. A twenty-five-year-old woman in her third trimester has just returned from South Asia with acute hepatitis and is becoming confused. Acute hepatitis in a pregnant traveler returning from South Asia raises hepatitis E, which is at its most dangerous here. In genotype one and two disease, infection in the third trimester carries an acute liver failure mortality of twenty to thirty percent, far above the rate outside pregnancy, along with low birth weight and fetal death. The mechanism appears to involve altered cellular immunity in pregnancy, hormonal effects on viral replication, and reduced hepatic regeneration.

12:00Her treatment is supportive. There's no antiviral approved in pregnancy, so management is supportive, and when acute liver failure develops, the management of delivery dominates. A recombinant hepatitis E vaccine is licensed in China but not in the United States or Europe. Her confusion means acute liver failure, and she's moved immediately to a center that can manage it, along with her obstetric team. Chapters nineteen and thirty-five cover acute liver failure and pregnancy.

12:28So genotype and host decide the outcome. A healthy man with genotype three recovers, a transplant recipient with genotype three can't clear it, and a pregnant woman with genotype one or two can die of it.

12:41The other enteric virus is preventable, and the last patient shows why vaccination matters more than treatment. A thirty-four-year-old man who has sex with men develops malaise, anorexia, and right upper quadrant discomfort, then jaundice, with an ALT in the thousands, and his hepatitis A IgM is positive. Hepatitis A is a fecal-oral picornavirus with an incubation averaging twenty-eight days. In most adults the prodrome eases once the jaundice appears. Its risk factors are travel to endemic areas, men who have sex with men, food workers, people experiencing homelessness, injection drug use, and outbreaks from contaminated produce or shellfish. Fulminant failure is rare and concentrated in people over fifty and those with chronic liver disease.

13:28His course runs longer than usual. About five percent of patients develop a prolonged cholestatic variant lasting up to six months, with persistent jaundice, itching, and a high alkaline phosphatase, and a smaller fraction have a relapsing course, with virus reappearing in the stool over weeks to months. Both are managed supportively. His jaundice and itching last four months and then resolve, which is the cholestatic variant, not a new disease. Rarely, hepatitis A triggers autoimmune hepatitis weeks to months later, which is treated as autoimmune hepatitis, as chapter twenty covers.

14:02His infection could have been prevented. Hepatitis A vaccine is two doses six months apart, with the second given at six to twelve or six to eighteen months depending on the product, and it protects more than ninety-seven percent of healthy recipients. It's indicated for international travelers, men who have sex with men, people who use injection or non-injection drugs, people with chronic liver disease of any cause, people experiencing homelessness, people with occupational risk such as research laboratory work or primate handling, close contacts of international adoptees, and recipients of clotting factor concentrates.

14:35His household shows how prophylaxis after an exposure works. It's given within two weeks of exposure, and the product depends on who was exposed. Healthy people from twelve months to forty years get a single dose of vaccine. Healthy adults over forty get vaccine, with immune globulin, zero point one milliliters per kilogram, added by risk assessment. Immunocompromised people and those with chronic liver disease get both vaccine and immune globulin, at separate sites. Infants under twelve months get immune globulin alone. Immune globulin is added when the person can't be counted on to mount a rapid antibody response, so his partner, who has cirrhosis, gets vaccine and immune globulin.

15:16Hepatitis A in pregnancy is milder than hepatitis E. It doesn't raise maternal mortality, vertical transmission is low, and both vaccine and immune globulin are safe in pregnancy. If a mother develops hepatitis A within two weeks of delivery, her infant gets immune globulin.

15:32Here are the traps the boards set in these patients. Symptoms don't identify the virus. A negative hepatitis C antibody doesn't rule out acute infection in someone at high risk. Acute hepatitis C isn't left to clear on its own. A direct-acting antiviral doesn't start without hepatitis B serology. A patient without hepatitis A and B immunity is vaccinated. Acute hepatitis B isn't always treated, and never with interferon. Core IgM in a known carrier isn't necessarily a new infection, and hepatitis D is tested for in a hepatitis B flare.

16:08The hepatitis E traps follow. Drug injury isn't diagnosed without testing for hepatitis E, which doesn't only come from travel. Antibody alone isn't enough in an immunosuppressed patient. Chronic hepatitis E in a transplant recipient is treated by reducing immunosuppression first, and peginterferon isn't used after a kidney transplant. And hepatitis E in the third trimester is a medical emergency.

16:33The hepatitis A traps close the list. A prolonged cholestatic course isn't a new disease. An exposed patient with cirrhosis needs immune globulin as well as vaccine. And an exposed infant under twelve months gets immune globulin, not vaccine.

16:48So, start to finish. Acute viral hepatitis looks the same whatever the virus, so the panel decides: surface antigen, core IgM, hepatitis C antibody with reflex RNA, and hepatitis A IgM, with hepatitis E IgM for travelers, pork or game eaters, or a negative panel. Core IgM means acute hepatitis B but can reappear in a chronic flare. Hepatitis C antibody lags the viremia by one to three months, so check RNA when suspicion is high.

17:22Treat acute hepatitis C promptly with a direct-acting antiviral. Treat acute hepatitis B only if it's fulminant or protracted, and never with interferon. Support acute hepatitis A and E.

17:35Hepatitis E genotypes one and two come from water and kill twenty to thirty percent of infected women in the third trimester. Genotype three comes from pork and game, mimics drug injury, and becomes chronic in transplant recipients, where it's treated by reducing immunosuppression and then with ribavirin for three months.

17:54Hepatitis A is self-limited but can run a prolonged cholestatic or relapsing course. Vaccinate the groups at risk. After an exposure, within two weeks, give vaccine from twelve months to forty years, consider immune globulin over forty, give both to the immunocompromised and those with chronic liver disease, and give immune globulin alone under twelve months.

18:16Episode two is hepatitis B, from serology and phases through treatment, reactivation, pregnancy, and hepatitis D.

18:25For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode one of three of chapter eighteen, and I'll see you in the next one.