Pathophysiology
P-II-6. Liver disease, Case 3
肝疾患 症例3
A 21-year-old student as she arrived home from university noticed that her sclera turned yellow, therefore she went to see her GP immediately. A few days ago she observed that her skin was yellowish; however she attributed this sign to her allergies. She reported no complaints other than a strong itching on the back of her hand. Her GP requested a laboratory test.
Physical examination:
- height: 171 cm
- weight: 58 kg
- icterus
- excoriation on the back of the hand
- soft, palpable abdomen, no abnormality or tenderness
Laboratory test — Blood:
- total bilirubin: 143 μmol/L
- direct bilirubin: 130 μmol/L
- ASAT: 714 U/L
- ALAT: 960 U/L
- GGT: 201 U
- albumin 36 g/L
- PTT: 36.7 s (21.5-34.0 s)
Urine:
- UBG: elevated
- bilirubin: positive
Abdominal ultrasound: no abnormalities
On further history taking, the patient confirmed that in the previous weeks she had no sex life, did not use drugs, did not travel abroad, did not change her diet and only consumed minimal amount of alcohol. She reported a very healthy and active life.
Liver biopsy: Lymphocytic infiltration, eosinophils and plasma cells in portal regions, inflammatory cells in sinusoids. Hepatocyte necrosis with fibrosis can also be seen sporadically, which might refer to the progression of the disease.
Serology:
- CMV: negative
- EBV: negative
- HAV: negative
- HBV: negative
- HCV: negative
- ANA (antinuclear antibody) 1:160 (higher than 80 is abnormal)
Key Quotes & What They Tell Us
| Quote / Value | Interpretation |
|---|---|
| ASAT 714, ALAT 960 U/L | Markedly raised transaminases → a hepatocellular (hepatitic) pattern of injury |
| Total bilirubin 143, direct 130 µmol/L; urine bilirubin positive, UBG elevated | Predominantly conjugated hyperbilirubinaemia of hepatocellular origin |
| ANA 1:160 (abnormal) | Positive autoantibody → points to autoimmune hepatitis |
| CMV, EBV, HAV, HBV, HCV all negative | Excludes viral hepatitis as the cause |
| “no sex life, did not use drugs, did not travel … minimal alcohol” | Excludes infectious, toxic, and alcoholic causes |
| Biopsy: “lymphocytic infiltration, eosinophils and plasma cells in portal regions” | Interface hepatitis with plasma cells — the histological hallmark of autoimmune hepatitis |
| “Hepatocyte necrosis with fibrosis”, with PTT 36.7 s (mildly prolonged) | Ongoing injury already progressing toward fibrosis with early synthetic impact |
Key Points
- Diagnosis: Autoimmune hepatitis.
- Pattern: Hepatocellular injury (very high transaminases) with conjugated hyperbilirubinaemia.
- Supporting evidence: Positive ANA, plasma-cell–rich interface hepatitis on biopsy, and negative viral serology.
- Exclusion-based reasoning: Lifestyle history and serology rule out viral, toxic, and alcoholic hepatitis.
- Pathophysiology: T-cell–mediated autoimmune attack on hepatocytes → chronic inflammation → necrosis and progressive fibrosis if untreated.
- Demographic clue: Young woman with another atopic/autoimmune tendency (allergies) fits the typical profile.
一問一答
▶What is the diagnosis in a 21-year-old woman with jaundice, very high transaminases, positive ANA, and negative viral serology?
Autoimmune hepatitis.
▶What pattern of liver injury is shown by ALAT 960 and ASAT 714 U/L?
A hepatocellular (hepatitic) pattern of injury.
▶Which autoantibody supports the diagnosis of autoimmune hepatitis here?
Antinuclear antibody (ANA), positive at 1:160.
▶What is the histological hallmark of autoimmune hepatitis on biopsy?
Interface hepatitis with a plasma-cell–rich lymphocytic infiltrate in the portal regions.
▶How is viral hepatitis excluded in this case?
Negative CMV, EBV, HAV, HBV, and HCV serology.
▶Why does the lifestyle history help in this diagnosis?
No drugs, no travel, minimal alcohol, and no sexual exposure exclude toxic, infectious, and alcoholic causes.
▶What is the underlying pathophysiology of autoimmune hepatitis?
A T-cell–mediated autoimmune attack on hepatocytes causing chronic inflammation, necrosis, and progressive fibrosis.
▶Why is the bilirubin predominantly conjugated in autoimmune hepatitis?
Damaged hepatocytes can still conjugate bilirubin but cannot excrete it properly, so conjugated bilirubin regurgitates into blood and urine.
▶What does the mildly prolonged PTT (36.7 s) indicate here?
Early impairment of hepatic synthetic function as injury progresses toward fibrosis.
▶Why are both urine bilirubin positive and urobilinogen elevated in hepatocellular jaundice?
Conjugated bilirubin spills into urine, and impaired hepatic re-uptake of urobilinogen raises its urinary level.
▶What is the typical demographic for autoimmune hepatitis?
Often young women, frequently with other autoimmune/atopic tendencies.
▶Why is liver biopsy useful in suspected autoimmune hepatitis?
It shows characteristic interface hepatitis with plasma cells and assesses the degree of necrosis/fibrosis.
▶What is the first-line treatment principle for autoimmune hepatitis?
Immunosuppression (corticosteroids, often with azathioprine) to suppress the autoimmune attack.
▶What does a normal abdominal ultrasound contribute to the diagnosis?
It excludes biliary obstruction, supporting an intrahepatic (hepatocellular) cause of jaundice.
▶Why does autoimmune hepatitis cause pruritus?
Impaired bile excretion leads to bile-salt retention that irritates the skin.
▶What does sporadic hepatocyte necrosis with fibrosis on biopsy imply about disease course?
The disease is progressing and, if untreated, can advance to cirrhosis.
▶Why is a high ANA titre considered abnormal here?
Titres above 1:80 are abnormal; 1:160 indicates a clinically significant autoantibody response.
▶What is the significance of eosinophils and plasma cells in the portal infiltrate?
They reflect an immune-mediated (autoimmune) inflammatory process rather than a viral or toxic one.
▶Why is albumin still relatively preserved (36 g/L) in this patient?
Synthetic function is only mildly affected early; albumin drops more in advanced/chronic disease.
▶What general diagnostic strategy confirms autoimmune hepatitis?
Demonstrating hepatocellular injury plus autoantibodies and compatible biopsy, while excluding viral, toxic, and alcoholic causes.