A young woman with jaundice

Published on 10/04/2015 by admin

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Problem 36 A young woman with jaundice

A 25-year-old woman presents with a 2-week history of general malaise. She had developed a sore throat and fever followed by nausea and diarrhoea. She has vomited and has been eating little. Yesterday, a friend noticed that her eyes had turned yellow. Her urine has turned dark brown but she has not noticed what colour her bowel motions are.

She is thin, jaundiced and looks unwell. She has tattoos, puncture marks in her antecubital fossae and tracks along the lines of her veins in her forearms. She has no lymphadenopathy. Cardiovascular and respiratory examinations are normal. Her abdomen is soft without ascites. Her liver is palpable 4 cm below the costal margin and is smooth and tender. The spleen is not palpable. There are no stigmata of chronic liver disease. She is not encephalopathic. Her urine is positive for ketones and bilirubin.

Q.1

What extra questions would you like to ask this young woman?

She is admitted and admits that she has used intravenous drugs for 2 years. She claims that she has only ever shared needles with her current boyfriend of 4 months.

Q.2

What preliminary investigations would you perform on this patient?

The results of some initial investigations are as follows:

Investigation 36.1 Initial laboratory investigations

Q.3

Interpret these blood results. What other investigations should be performed?

The following results become available:

Investigation 36.2 Ultrasound of liver

• Enlarged liver with heterogenous echotexture with normal contours.

• Thin-walled gallbladder with no gallstones seen.

• Normal calibre to common bile duct and intrahepatic ducts.

• Spleen at the upper limit of normal.

Investigation 36.3 Department of virology

Anti-hepatitis A IgM:	Negative
Hepatitis B surface antigen:	Positive
Anti-hepatitis B core IgM:	Positive
Anti-hepatitis C IgG:	Negative
Hepatitis C antibody:	Positive
Hepatitis C viral PCR:	Negative
HIV antibody:	Negative

Q.4

What is the diagnosis (A, B, C, D or E)?

A Previous infection with hepatitis B (HBV)?

C Acute hepatitis C (HCV)?

Liver synthetic function remains normal. She remains nauseated and finds it difficult to eat.

Q.5

How would you further manage this woman (A, B, C, D or E)?

A Commence antiviral medications?

B Start an infusion of N-acetylcysteine?

C Start HBV immunoglobulin?

D Consider interferon therapy?

E Ensure good hydration and nutrition?

A few days later her boyfriend visits her with a 4-year-old boy. The boy is the patient’s son by another man. They agree to blood tests from the man and the child. The results are as follows:

Investigation 36.4 Boyfriend’s test results

Investigation 36.5 Son’s test results

Virology
Hepatitis B surface antigen:	Negative
Anti-hepatitis B surface IgG:	Negative
Anti-hepatitis B core IgG:	Negative
Anti-hepatitis C IgG:	Negative

Q.6

How would you interpret these results?

Answers

A.1 The history is extremely important. It is essential in making the final diagnosis. Her Intravenous drug use (IDU) is a major risk factor in acquiring a blood-borne hepatitis virus (B, C, D). Ascertain if she has shared needles, and when, for clues as to the likelihood and possible length of infection. HBV is more readily transmitted by sex than HCV. Risk of blood transfusion transmission is now rare since blood in developed countries is screened for blood-borne viruses. Tattoos are low risk if done professionally. She could have a faeco-orally transmitted viral hepatitis (hepatitis A or E), but HBV or HCV seem more likely. However, other possibilities should not be dismissed (Table 36.1).

Table 36.1 Risk factors for hepatitis in the acutely jaundiced patient

Diagnosis	Important Points in History
Hepatitis A	Contacts, foreign travel, recent diarrhoeal illness, dietary risk factors, e.g. shellfish ingestion, recreational risk factors, e.g. swimming and surfing, esp. urban beaches
Hepatitis B	Close contacts, sexual history, blood transfusion, IDU, foreign travel, tattoos, body piercing
Hepatitis E	As for hepatitis A
Other viruses, e.g. EBV	Contacts, sore throat, age
Drug-induced hepatitis	Recent medications, although do not get caught out as can be as long as 1–2 months since offending drug was taken – detailed drug history is important; frequently antibiotics, especially flucloxacillin and co-amoxiclav; over-the-counter drugs (especially NSAIDs); complimentary therapies; Chinese medicines; recreational drugs; Ecstasy use
Alcohol-related hepatitis	Alcohol history
Autoimmune hepatitis	Age, female sex, history of other autoimmune disease, e.g. thyroid

A.2 Initial blood tests should include liver and renal profiles. Jaundice of any cause can lead to dehydration and renal failure. A full blood count must be performed along with a clotting profile. The prothrombin time (or INR) is an essential indicator of liver function.

Here, a diagnosis of viral hepatitis is likely. You should specify the tests that you require. Too often, a blanket request for ‘hepatitis virology’ is misinterpreted by the laboratory and the wrong investigations are provided.

Blood should be taken for hepatitis A IgM and HBV. A positive hepatitis A IgG is a measure of past, not current, infection. The standard screening test for acute HBV is to measure surface antigen. However, if suspicion is high, a HBV core IgM should also be requested.

HCV rarely causes a severe acute hepatitis; most cases are asymptomatic. In view of her history, evidence of this infection should be sought. Chronic HCV is diagnosed by the presence of HCV IgG antibodies. A PCR (polymerase chain reaction) will confirm the presence of circulating virus. This latter test should only be requested if there is a high suspicion of acute HCV.

Serology for hepatitis E could be sent if the patient is thought to be at risk. This virus, transmitted by the faecal–oral route, is endemic in India, the Middle East, South East Asia and Latin America and Africa. It is also found in Western nations, e.g. the UK. Other viruses can cause an acute hepatitis (e.g. Epstein–Barr virus and cytomegalovirus).

This may not be acute viral hepatitis. The possibility of autoimmune liver disease means that an autoantibody screen and immunoglobulins should be done (positive liver-specific antibodies, such as anti-smooth muscle antibodies, and a raised IgG fraction is in favour of autoimmune disease). Ultrasound is an important test for any patient with jaundice to exclude biliary dilatation and vascular thromboses and allow planning of further investigations. It may help demonstrate features to suggest chronic liver disease (e.g. irregular shrunken liver (cirrhosis) or features of portal hypertension, splenomegaly, etc.).

A.3 These tests suggest a ‘hepatitic’ cause for her jaundice with predominant elevation of her transaminases (ALT and AST). The only true markers of liver function are the bilirubin, prothrombin time (or INR) and albumin.

She has a thrombocytosis which is likely to represent an acute-phase reaction. Lymphocytosis and the presence of atypical lymphocytes raise the possibility of viral infection

A.4 The diagnosis is acute HBV. This is shown by the presence of both hepatitis B surface antigen and core antibody (IgM).

She is at increased risk of other parenterally transmitted viruses. Hepatitis D (delta agent) serology is a ‘defective’ RNA virus requiring co-infection with hepatitis B to replicate successfully. Superinfection with the delta agent in a patient with pre-existing chronic hepatitis B may cause an acute hepatitis.

Prevalence of HCV in intravenous drug users is very high (up to 90%). The presence of a positive antibody and negative PCR test mean she has had HCV in the past but has cleared the virus without treatment (spontaneous resolution). This happens infrequently (10% of cases of HCV).

Consent should be sought to test for HIV.

A.5 The correct response is E.

Management is supportive with hydration and nutrition. Most clear the virus completely and develop lifelong immunity (>95% in adults) and will improve enough to be discharged home relatively early. A very small proportion (0.1–0.5%) may develop acute liver failure. Therefore close monitoring is important with regular blood testing. Worrying features include hepatic encephalopathy and coagulopathy. If any of these occurred then she would need transfer to a liver unit. Antiviral drugs in acute HBV do not affect the course or outcome. The main indication for N-acetylcysteine is in paracetamol overdose. It is sometimes used in non-paracetamol related acute liver failure, but should only be used in the liver unit setting. Interferon therapy has no role.

Contact tracing is extremely important. Public health or health protection agencies should be informed. There are robust systems to ensure contact tracing. Support for her drug addiction should be offered.

A.6 Her boyfriend is positive for surface antigen and therefore has HBV. The positive IgG antibody and negative core IgM suggest chronic infection. The presence of the e-antigen and absence of anti-e antibodies indicate viral replication. Further tests such as HBV DNA levels and liver biopsy may be required.

Prevent her boyfriend infecting others. HBV can be transmitted to intimate non-sexual contacts, for example by sharing of shaving equipment or toothbrushes. Her son is currently negative for HBV but should be immunized along with close contacts. She needs follow-up in approximately 6 months to check viral clearance with a negative hepatitis B surface antigen.

Revision Points

Hepatitis B Virus

Epidemiology

• In excess of 300 million HBV carriers worldwide.

• Prevalence of chronic HBV between 0.1% and 2% in the developing world to 20% in sub-Saharan Africa.

Clinical Features

Incubation period: 1–6 months.

Acute hepatitis with jaundice presents similarly to our case. Prodromal symptoms are common. Seventy per cent of patients will develop subclinical disease without jaundice.

Interpretation of hepatitis B serology is approached with trepidation by undergraduates and postgraduates alike. Its really quite simple (Table 36.2).

Table 36.2 Understanding hepatitis B serology

Treatment and Course

Some with chronic infection will develop cirrhosis, especially if the virus goes undetected and untreated. There is a significantly increased risk of hepatocellular carcinoma.

Treatment has revolutionized over the last 10 years with the use of interferon and with the advent of powerful oral antiviral medications. Newer drugs (e.g. entecavir, tenofovir) deliver rapid viral suppression with minimal side-effects and are helping to overcome the rising resistance to older antivirals such as lamivudine. In some cases of cirrhosis liver transplantation may be required.

Prevention

HBV is a massive public health problem worldwide. Vaccination of all those at risk, e.g. health workers, high-risk intravenous drug users, children born in highly enedemic areas, results in falls in the prevalence of the disease. Ideally, anyone with HBV should be seen by a qualified doctor and given access to antiviral drugs and surveillance programmes if appropriate. Unfortunately, in areas of the world with the highest prevalence rates, this is too often wishful thinking.

Issues to Consider

• The A to G of viral hepatitis.

• The risk of HBV transmission in healthcare workers.

• What other health problems do you foresee for intravenous drug users? What issues may be problematic for health professionals involved in their care?

• The role of the immune system in the pathogenesis and subsequent clearance of acute HBV.

• How do antiviral drugs work? How can a virus adapt to develop immunity?

Further Information

, www.britishlivertrust.org.uk.

, www.digestive.niddk.nih.gov/ddiseases/pubs/hepb_ez.

, www.hepb.org.uk.

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