Viral, autoimmune and metabolic hepatitis — formative SAQs

SAQ 1 — The perinatally infected school-age child with chronic hepatitis B (20 marks, ~15 minutes)

A ten-year-old boy is referred because his mother, who is hepatitis B surface antigen positive, has just been diagnosed. The boy is well and growing normally. His serology shows a positive hepatitis B surface antigen, a positive e antigen, an HBV DNA of two hundred million international units per millilitre, and persistently normal alanine aminotransferase. [2]

Questions

1. Give the diagnosis, the phase of chronic hepatitis B, and the clinical reasoning that distinguishes it. (5 marks) [3]
2. Outline the management and explain why antiviral treatment is not started at this point. (5 marks) [3]
3. Describe the perinatal prevention that should have been offered and why perinatal chronicity is so high. (4 marks) [3]
4. Explain the hepatocellular carcinoma surveillance the child now needs. (3 marks) [2]
5. Describe the trigger that would change the management to active treatment. (3 marks) [3]

Model answer (must-hit)

1. The diagnosis is chronic hepatitis B acquired perinatally. The phase is the immune-tolerant phase, defined by the positive surface antigen and e antigen, the very high HBV DNA and the persistently normal alanine aminotransferase, which shows that the immune system is not yet attacking the infected hepatocytes. The low inflammation despite the high viral load is the hallmark that separates it from the immune-active phase. [2] [3]
2. The management is surveillance without antiviral treatment, because the immune-tolerant phase carries minimal histological inflammation and the risk of treatment is not justified by the benefit; treating here risks antiviral resistance without halting meaningful disease. The child is monitored with six-monthly transaminases and liver function, and hepatocellular carcinoma surveillance is begun. [3]
3. Perinatal prevention is the hepatitis B vaccine plus hepatitis B immunoglobulin given within twelve hours of birth, followed by the full vaccine course, with post-vaccination serology at nine to twelve months. For a mother with a high viral load, maternal tenofovir prophylaxis from twenty-eight weeks further reduces the residual risk. Perinatal chronicity is around ninety per cent without immunoprophylaxis, because the immature neonatal immune system tolerates rather than clears the virus. [3]
4. The child needs six-monthly abdominal ultrasound with alpha-fetoprotein for hepatocellular carcinoma surveillance, because chronic hepatitis B carries a risk of hepatocellular carcinoma that begins in childhood and is independent of cirrhosis. [2]
5. The trigger for active treatment is the transition to the immune-active phase, signalled by a persistently rising alanine aminotransferase with active inflammation, at which point a nucleoside analogue such as entecavir or tenofovir is started to suppress replication. [3]

SAQ 2 — The adolescent girl with autoimmune hepatitis (20 marks, ~15 minutes)

A thirteen-year-old girl presents with three months of fatigue, jaundice, acne, amenorrhoea and arthralgia. Her immunoglobulin G is twenty-five grams per litre, her antinuclear antibody is positive at one in six hundred forty, and viral hepatitis serology is negative. Liver biopsy shows interface hepatitis with a dense plasma-cell infiltrate. [8]

Questions

1. Give the diagnosis and the type, and apply the simplified International Autoimmune Hepatitis Group score. (6 marks) [9]
2. Outline the induction treatment with doses and the safety check before the steroid-sparing agent. (5 marks) [8]
3. Explain why the disease is described as a loss of self-tolerance and the histological correlate. (3 marks) [8]
4. Describe the monitoring and the likely duration of treatment. (3 marks) [8]
5. Name the condition to exclude by cholangiography and the association that makes it likely. (3 marks) [8]

Model answer (must-hit)

1. The diagnosis is type 1 autoimmune hepatitis, given the raised immunoglobulin G and the positive antinuclear antibody. The simplified score is eight out of eight: two for the high-titre antinuclear antibody at one in six hundred forty, two for the immunoglobulin G above one point one times the upper limit of normal, two for the typical interface hepatitis with plasma cells, and two for the absence of viral hepatitis. A score of seven or more defines definite autoimmune hepatitis. [9]
2. The induction is oral prednisolone at one to two milligrams per kilogram per day, to a maximum of around sixty milligrams per day, combined with azathioprine at one to two milligrams per kilogram per day. The safety check is thiopurine methyltransferase activity before the full azathioprine dose, because deficiency causes fatal myelosuppression; the steroid is tapered over weeks to months as the transaminases and immunoglobulin G fall. [8]
3. Autoimmune hepatitis is a loss of tolerance to liver antigens at the portal limiting plate, where an antigen-presenting cell presents a liver autoantigen on a disease-associated HLA class 2 molecule to CD4 T-helper cells, which drive the inflammatory cascade and recruit the plasma cells. The histological correlate is interface hepatitis, the inflammation spilling across the limiting plate into the lobule. [8]
4. The monitoring is the clinical response, the transaminases and the immunoglobulin G to confirm biochemical remission, the full blood count and liver function for the azathioprine, and the weight, height, bone density, blood pressure and glucose for the steroid toxicity. The maintenance continues for years, often into adulthood, because relapse off treatment is the rule. [8]
5. The condition to exclude by magnetic-resonance cholangiopancreatography is autoimmune sclerosing cholangitis, which shares the autoantibodies and the interface hepatitis but adds bile-duct injury, and its strong association with inflammatory bowel disease makes a colonoscopy part of the workup. [8]