Alexander McMillan1, 2
(1)
Department of Genitourinary Medicine, NHS Lothian, Edinburgh Royal Infirmary, Edinburgh, Uk
(2)
University of Edinburgh, Edinburgh, Uk
Alexander McMillanFormerly, Consultant Physician, part-time Senior Lecturer
Email: a.amcmm@btinternet.com
Abstract
Michael, a 19-year-old man, presents to his General Practitioner with a 7-day history of nausea, malaise, poor appetite, and discomfort in the right upper abdomen. Over the past few days he has noticed that his urine is darker than normal and that his stools are pale. His friends have told him that his skin looks yellowish. He drinks about 10 units of alcohol per week, but he does not use recreational drugs, and he is not receiving any medication. He has not traveled abroad in the past 2 years. He lives with his parents and a 16-year-old sister. For the past 3 months Michael has been in a regular sexual relationship with a 28-year-old man, but he has had no other partners in that time. He has insertive and receptive oral–genital, oral–anal, and peno-anal intercourse; condoms are used infrequently for anal intercourse and not at all for oral sex. What conditions may cause his symptoms?
Michael, a 19-year-old man, presents to his General Practitioner with a 7-day history of nausea, malaise, poor appetite, and discomfort in the right upper abdomen. Over the past few days he has noticed that his urine is darker than normal and that his stools are pale. His friends have told him that his skin looks yellowish. He drinks about 10 units of alcohol per week, but he does not use recreational drugs, and he is not receiving any medication. He has not traveled abroad in the past 2 years. He lives with his parents and a 16-year-old sister. For the past 3 months Michael has been in a regular sexual relationship with a 28-year-old man, but he has had no other partners in that time. He has insertive and receptive oral–genital, oral–anal, and peno-anal intercourse; condoms are used infrequently for anal intercourse and not at all for oral sex.
32.1 What Conditions May Cause His Symptoms?
The symptoms are strongly suggestive of acute hepatitis. The sexual transmission of hepatitis A and B viruses among men who have sex with men is well recognized, and infection with either virus must be considered in this case. Hepatitis C virus is also transmissible sexually but, with the exception of HIV-infected individuals, both the prevalence of infection among MSM and the risk of transmission are low. Less common causes of viral hepatitis include cytomegalovirus and Epstein–Barr virus infections. Hepatitis can also be a feature of secondary syphilis. Acute alcoholic hepatitis and drug-induced hepatitis can be excluded if the history is accurate. Rarer conditions such as Wilson’s disease and autoimmune hepatitis need to be considered if viral hepatitis is excluded.
Michael is not distressed. His sclerae and skin are yellow. His temperature is 37.1°C, and his pulse rate is 55 per minute. There is no significant superficial lymph node enlargement. The abdomen moves well with respiration. The liver is palpable 2 cm below the costal margin and is slightly tender; the spleen is not palpable. There are no other abnormal clinical findings. Table 32.1 shows the results of laboratory tests. How do you interpret these?
Table 32.1.
Results of laboratory tests.
|
Hematology: |
Clinical biochemistry: |
|
Hemoglobin: 146 g/L (130–180 g/L)a |
Bilirubin: 46 μmol/L (2–17 μmol) |
|
Mean corpuscular volume: 83 fL (78–98 fL) |
Alanine aminotransferase (ALT): 900 U/L (10–50 U/L) |
|
Leucocytes: 8.9 × 109/L (4.0–11.0 × 109/L) |
Alkaline phosphatase: 180 U/L (40–125 U/L) |
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Differential white cell count: • Neutrophil granulocytes: 3.2 × 109/L (2.0–7.5 × 109/L) |
Gamma glutamyl transferase: 92 U/L (5–55 U/L) |
|
• Lymphocytes: 4.9 × 109/L (1.5–4.0 × 109/L) |
Albumin: 36 g/L (35–50 g/L) |
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• Monocytes: 0.7 × 109/L (0.2–0.8 × 109/L) |
|
|
• Platelets: 148 × 109/L (150–350 × 109/L) |
|
|
• Prothrombin time: 13.5 s (8.0–10.5 s) |
a Reference values in parentheses.
The results show a predominantly hepatocellular jaundice: the alanine aminotransferase is disproportionately elevated compared with the alkaline phosphatase and gamma glutamyl transferase (GGT). 1 A relative lymphocytosis is common in viral hepatitis, and the only mildly prolonged prothrombin time indicates mild liver damage.
Table 32.2 shows the results of the serological tests that his GP undertook. How do you interpret these?
Table 32.2.
Results of serological tests for viral hepatitis, syphilis, and HIV.
|
Viral infection tested for: |
Results |
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Hepatitis A |
Anti-HAV IgM: NEGATIVE Anti-HAV IgG: POSITIVE |
|
Hepatitis B |
HBsAg: POSITIVE Anti-HBc IgG: POSITIVE Anti-HBc IgM: POSITIVE HBe antigen: POSITIVE Anti-HBe: NEGATIVE Anti-HBs: NEGATIVE |
|
Hepatitis C |
Anti-HCV: NEGATIVE |
|
Cytomegalovirus |
Anti-HCMV IgG: POSITIVE Anti-HCMV IgM: NEGATIVE |
|
Epstein–Barr virus |
Anti-EBV IgG: POSITIVE Anti-VCA IgM: NEGATIVE |
|
Syphilis |
Anti-treponemal EIA: NEGATIVE |
|
HIV |
Anti-HIV EIA: NEGATIVE |
Key to abbreviations:
Anti-HAV: antibody against hepatitis A virus.
HBsAg: hepatitis B surface antigen.
Anti-HBc: antibody against hepatitis B core antigen.
Anti-HBs: antibody against hepatitis B surface antigen.
Anti-HCV: antibody against hepatitis C virus.
Anti-HCMV: antibody against human cytomegalovirus.
Anti-EBV: antibody against Epstein–Barr virus
Anti-VCA: antibody against Epstein–Barr virus capsid antigens.
EIA: Enzyme immunoassay.
There is clear evidence of acute hepatitis B infection: HBsAg is present in the plasma, and the IgM antibody response to hepatitis B core antigen is characteristic of acute infection. Although anti-HBc is found in chronic hepatitis B, it is of the IgG class, and not IgM. During the course of acute infection, antibody against hepatitis B surface antigen only becomes detectable during convalescence (Fig. 32.1 ).
Figure 32.1.
Serological events observed during acute hepatitis B virus infection.
The finding of IgG antibody against hepatitis A virus, cytomegalovirus, and Epstein–Barr virus indicates previous exposure to these agents; acute infection elicits an IgM response.
The negative screening test (anti-treponemal EIA) excludes a diagnosis of secondary syphilis.
32.2 How Is Hepatitis B Transmitted?
Hepatitis B virus (HBV) is transmitted parenterally, and, for example, may be transmitted as a result of inoculation of minute quantities of blood as may occur during intravenous drug use, if care is not taken to sterilize the needles or other equipment. For some time it has been known that MSM are at risk of HBV infection. Practices likely to result in mucosal trauma, including genital–anal and oral–anal intercourse and rectal douching, correlate with the presence of HBV serological markers. Vaccination should therefore be offered to all sexually active MSM who are not known to be immune to the infection (serum anti-HBs negative) (see Case 3).
32.3 What Clinical Features May Be Associated with Acute Hepatitis B Virus Infection?
Many cases of hepatitis B are symptomless and detectable only by biochemical tests for hepatocellular damage. In those who develop clinical manifestations of the disease, following an incubation period of 40–160 days, there is a pre-icteric stage (prodrome) during which the symptoms of the disease develop. The patient complains of nausea, malaise, anorexia, and discomfort in the upper right abdomen. Tender enlargement of the liver is found in most cases, and in about 20% of patients the spleen is also enlarged. Other, less common clinical features include erythematous, maculopapular or urticarial skin rash, and arthralgia.
32.4 Although Not the Causes of the Hepatitis in this Case, How are Hepatitis A, Cytomegalovirus and Epstein–Barr Virus Transmitted?
Hepatitis A virus (HAV) is transmitted by the fecal–oral route. The virus is excreted in the feces and infection is usually acquired orally under conditions of poor hygiene and sanitation. Most studies have shown that the prevalence of antibody against HAV is significantly higher in the sera of homosexual men than in heterosexual men who attend STD clinics. The occurrence of outbreaks of hepatitis A among MSM also supports the conclusion that such men are at increased risk of infection. The acquisition of hepatitis A correlates with a large number of sexual partners and frequent oral–anal sexual contact. Vaccination is therefore routinely offered to sexually active MSM who have no serological evidence of prior infection (serum anti-HAV IgG negative).
The majority of infections with HAV are symptomless. When symptomatic, the clinical and biochemical features of hepatitis A are similar to those of any other viral hepatitis (see above). The incubation period of hepatitis A varies between 30 and 50 days. In general the course of the illness is shorter and less severe than that of hepatitis B, with resolution of both clinical and biochemical abnormalities within 1 month of onset of the illness.
Human cytomegalovirus (HCMV) is usually acquired in early childhood probably from contact with infected secretions from infected children. Mother-to-child transmission is important as congenital infection can lead to considerable morbidity. The virus is found in semen, and there is good evidence for sexual transmission of. The prevalence of HCMV antibodies is higher among MSM than among men who have sex with women. Transmission via blood or blood products or transplanted tissues is also possible.
Although most infections with EBV are acquired through kissing, the virus can be transmitted sexually, possibly by oral–genital contact, but perhaps also from the male genital tract. There is no evidence that EBV infection is more prevalent among MSM than the general population.
32.5 What Is the Course of Acute Hepatitis B, and How Would You Manage This Man?
With the development of jaundice, the patient’s condition improves and within 2–4 weeks most infections have resolved. Uncommonly (<1% of cases), acute liver failure develops within 4 weeks of the onset of symptoms. The mortality rate of acute hepatitis B is less than 1%. Individuals who have symptomatic acute hepatitis B are likely to clear the virus, the risk of developing chronic hepatitis being <10%; this risk, however, is increased if the person is HIV infected.
In most cases, acute hepatitis B virus infection is a self-limiting condition, and there is no specific therapy. The development of hepatic decompensation (somnolence or change of personality) necessitates admission to hospital and referral to a hepatologist for specialist management. Other than the avoidance of alcohol during the acute illness and convalescence, dietary restrictions are unnecessary. He should be advised about the risks of sexual transmission, and he should avoid unprotected sexual intercourse, oral–anal, and oral–genital contact until he has become HBsAg negative and anti-HBs positive, or his sexual partner(s) have been successfully vaccinated (anti-HBs >100 mIU/L).
Michael should be offered screening for other sexually transmitted infections (see Case 4).
He should be reviewed at 2-weekly intervals until the alanine (and aspartate) aminotransferase level is normal.
His parents and sister should be offered an accelerated course of recombinant hepatitis B vaccine (see Case 3), and Michael’s partner should be asked to attend for screening, and, if indicated, vaccination.
Michael’s partner, Sam, attends a sexual health clinic the day after Michael is told the diagnosis. He is symptomless, and he has never felt the need to attend such a clinic before because, until he met Michael, anal intercourse had always been protected. He has not been vaccinated against hepatitis B. Clinical examination is unremarkable; in particular there are no signs of chronic liver disease. Table 32.3 shows the results of serological testing for hepatitis B. His ALT is 72 U/L. An HIV antibody/antigen test is negative.
Table 32.3.
Results of serological tests for hepatitis B in the patient’s sexual partner.
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HBsAg: POSITIVE |
|
Anti-HBc IgG: POSITIVE |
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Anti-HBc IgM: NEGATIVE |
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HBeAg: POSITIVE |
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Anti-HBe: NEGATIVE |
|
Anti-HBs: NEGATIVE |
32.6 How Do You Interpret These Results?
The pattern of serological tests and the mildly elevated ALT suggest that he is a chronic carrier of HBV (immune active). As such patients are at high risk of disease progression with the development of cirrhosis and hepatocellular carcinoma, referral to a hepatologist is recommended.
Footnotes
1
Disproportionately elevated alkaline phosphatase and GGT compared with alanine aminotransferase is seen when jaundice is caused by biliary obstruction.