Hepatitis B Infection with Case

00:00 Welcome.

00:01 Today we'll talk about disorders of the liver, specifically hepatitis and acute liver failure.

00:09 So, before we begin, let's talk about how to interpret abnormal liver tests.

00:14 So, how do you generally approach a patient who has abnormal liver lab tests? First, you should always identify the pattern of injury and then look for underlying cause.

00:25 So what do we mean by the pattern of injury? There are two types of liver injury.

00:31 The first type is hepatocellular injury pattern where you have a predominant elevation in the aspartate transferase or the alanine transferase, or we read it as AST and ALT.

00:43 The second type of pattern is a cholestatic injury pattern where there is a predominant elevation in the alkaline phosphatase or ALP or GGT.

00:53 So if you remember these two key patterns in liver injury, you'll be able to interpret most liver tests.

01:01 So now let's go to a case.

01:03 A 48-year-old man is seen in clinic.

01:06 His past medical history is notable for IV drug use 8 years ago.

01:11 He has no family history of hepatitis.

01:13 He feels well and takes no medications.

01:16 He asks to be screened for hepatitis B, so his lab studies results as follows: So ALT is normal, hepatitis B surface antigen is negative, hepatitis B surface antibody is positive, his hepatitis B core antibody is positive and when tested for viral DNA, he has less than 20 copies.

01:38 So, how do we interpret his serologies? This is a difficult question so we'll break it down.

01:44 First, he has a history of intravenous drug use which places him at elevated risk of having a hepatitis B infection.

01:53 We first look at his ALT.

01:55 Because it's normal, this suggests to us that there is no active hepatitis currently.

02:02 He has both, however, a positive surface antibody and a positive core antibody.

02:09 So we'll talk about what that means next.

02:13 So, the big question is: Does he have an active infection or did he have a prior infection that was cleared? So, before we go into hepatitis B serologies, let's take a step back and talk about the various types of hepatitis.

02:30 This slide will summarize the relative transmission, the characteristics of each type of hepatitis and their potential for causing chronic disease.

02:39 So, I'm not gonna go into them in that much detail but you should know that hepatitis A is fecal-oral transmission, and does not have the ability to cause chronic disease.

02:49 Hepatitis B is transmitted by exposure to blood or body fluids.

02:55 Hepatitis C can be transmitted by exposure to blood from an infected person.

03:00 Hepatitis D only occurs as a coinfection with hepatitis B since it depends on hepatitis B to replicate.

03:08 And lastly, hepatitis E like A, is a fecal-oral transmission.

03:14 The important distinguishment here to point out is that both hepatitis A and E do not have the potential to cause chronic disease.

03:24 So, all types of viral hepatitis presents similarly.

03:28 Patients may come in with fatigue, a general lack of appetite, they may develop jaundice, bleeding or bruising, nausea or vomiting and they may have dark urine.

03:42 If we talk specifically about hepatitis B, as a quick review, it is transmitted from exposure to blood or body fluids from an infected person.

03:52 It can also be transmitted vertically from mother to child when acquired at birth, this is most likely to cause chronic infection.

04:01 In most cases, about 90% of those who acquire an acute infection will resolve and only 10% will then go on to develop chronic hepatitis B.

04:13 So, to summarize its natural progression of disease, you'd first begin with acute infection.

04:20 90% of adults will develop a cure, and 10% of them will then go on to develop chronic inflammation.

04:27 Note here that in children, to acquire hepatitis B from vertical transmission, their disease is very different and over 90% of them will actually develop chronic hepatitis B.

04:40 To go back to adults, however, chronic inflammation then leads to fibrosis which can then lead to the end stage of cirrhosis of the liver.

04:49 and that may lead in turn to cancer or hepatocellular carcinoma.

04:55 Hepatitis B, however, is unique and that you do not need to develop fibrosis or cirrhosis to develop cancer.

05:02 So you can go straight from chronic infection or chronic inflammation to cancer.

05:10 So now, let's get to the hepatitis B serologies.

05:14 We'll go through first each serology test and how to interpret it and then we'll go and then we'll go through some common scenarios you may encounter since this is quite a challenging topic.

05:24 So the first test is the hep B surface antigen.

05:29 Its presence indicates that the person is infected in general.

05:34 The second test is a surface antibody.

05:37 When this is present, it indicates that the person has developed immunity.

05:41 Either they have been vaccinated or they had a prior infection.

05:47 The next test is a core antibody.

05:50 In general, when we refer to the total core antibody, we're referring to the IgG antibody.

05:56 This appears initially during the first infection and then its presence later on indicates a prior or ongoing infection.

06:05 The next test is the core IgM antibody.

06:09 So this appears during a acute infection, so when it's present, it indicates a recent infection less than 6 months ago.

06:19 The last thing you may see is a hep B e-antigen.

06:23 This simply indicates that there's active viral replication going on.

06:29 So now that we've covered that long list of different types of serologies, let's go through some common scenarios that you might encounter on a test or in a patient.

06:41 Before we do that, let's talk a bit about what these antibodies and antigens look like over the course of the disease.

06:47 So here, you can see a graphical depiction of the various antigens and antibodies that are present during disease.

06:54 I'll first point to weeks 4 to 24, which is when you have the initial infection.

07:01 As you can see, the hepatitis B surface antigen or HBsAg becomes positive with acute infection overtime then you develop an IgM anti core antibody which then disappears overtime and then you'll also develop this green curve which is the total core antibody.

07:22 This is the IgG that develops after infection and remains positive for the rest of that person's lifetime.

07:30 Over time after the acute initial infection, the core IgM antibody and the surface antigen will resolve.

07:39 Then, after a period of time, at about weeks 32 after exposure, the person will then develop a surface antibody.

07:48 The surface antibody's presence indicates that they have then built an immunity to the prior infection.

07:56 Note that there is a small period in time between weeks 24 and 32 where you may have an IgM core antibody that stays positive.

08:05 That's the pink line here.

08:07 So, that's a particular type of clinical picture that can be very confusing and we'll talk about that soon.

08:14 So now let's get to our various scenarios.

08:17 The first scenario you may encounter is a positive surface antigen with a positive core antibody - that's an IgM antibody.

08:26 This indicates that you have an acute infection because the only way to have a positive surface antigen is to be exposed to the virus.

08:36 On the other hand, if you have a positive surface antigen with a positive IgG core antibody, this means that you have now progressed to the chronic state of infection.

08:49 Our next scenario is a negative surface antigen with a positive surface antibody and a positive core antibody.

08:57 So, for this one, you should remember that a surface antibody only appears when the person has built an immunity to the infection.

09:07 In this case, because the core antibody is also positive, you know this person has been infected at some point and they now have a resolved infection because they've built up immunity.

09:19 Our next scenario is one you may commonly encounter in real life.

09:24 So you may have a negative surface antigen, a positive surface antibody and a negative core antibody.

09:30 This means that the person has been vaccinated or immunized against hepatitis B.

09:35 This is the only way in which you have a positive surface antibody and that is the only thing that is positive.

09:44 Our next scenario is where you have negative test all across the board.

09:49 This indicates that this person has never been exposed to the virus and they've never been vaccinated, as you can tell from the surface antibody also being negative.

09:58 So this person is what we call susceptible to developing infection.

10:03 Lastly, we mentioned that window period where you may have an isolated core antibody.

10:10 This can be many different things.

10:12 It can either be that window period between acute and chronic infection that we discussed earlier.

10:18 It can mean that the person has recovered.

10:20 It can be a latent or dormant phase of the virus or it could be a false positive.

10:26 So since there are very many scenarios that could appear with this particular test scenario, you will often not be tested on this because it's so difficult to interpret.

10:38 So, who to treat with hepatitis B is a very complicated decision but we take into account several different factors including pregnancy, whether they've developed cirrhosis, do they have an elevated ALT, a high level of DNA replication, acute liver failure, are they immunosupressed or planning to become immunosuppressed on various medications, or do they have a coinfection with hepatitis C.

11:04 Also, you should remember that hepatitis B is entirely preventable.

11:08 So anyone who is at risk of the disease or who asks about a vaccination should be offered the vaccine.

11:17 Treatment options include nucleoside analogs like tenofovir or entecavir or pegylated interferon.

11:28 So now, we can return to our case.

11:30 Our 48-year-old man with a history of IV drug use which puts him at risk for hepatitis B.

11:36 He has a normal ALT which suggests no active hepatitis currently.

11:41 His surface antibody and core antibody are positive which we now know indicates that he has had prior infection and has now developed immunity.

11:51 So, how do we interpret this? He most likely has a prior infection, has developed immunity and he should be reassured and counseled to avoid future exposure.