Pathophysiology
P-II-7. Liver disease, Case 4
肝疾患 症例4
A 52-year-old, otherwise healthy woman consulted her doctor because of cramping pain in her right rib cage for 3 weeks. She reported vomiting bile, and she also had jaundice. She had no history of transfusion but changed partners frequently. The patient is an occasional drinker (1-2 beers per week) and has been an intravenous drug user for 3 years, for which she has been in rehabilitation several times.
Physical examination:
- height: 174 cm
- weight: 63 kg
- yellow sclera
- The right lower quadrant of the abdomen is sensitive, without resistance or muscular defense. The liver is not palpable.
Lab results:
- total bilirubin: 270.18 µmol/L
- direct bilirubin: 205 µmol/L
- ALAT: 1316 U/L
- ASAT: 2749 U/L
- PTT: 15.9 s
- INR: 1.49
- ferritin: 5351 pm/L (33.7-449.4 pmol/L)
- transferrin saturation: 88% (14%-50%)
- Fe2+: 211 μg/dL (50-150 μg/dL)
- acetaminophen: negative
- HAV, HBV, HCV, and HIV tests were taken three weeks earlier, all negative
Abdominal ultrasound: Cholestasis without cholecystitis.
An autoimmune panel test was done with negative results. HAV, HBV, and HCV antibody tests were repeated, which confirmed HCV infection: 20 739 524 IU/mL viral load and genotype 1.
Liver biopsy: Severe active-chronic hepatitis, ballooning and hyaline degeneration of hepatocytes. Prominent Kupffer cells and councilman bodies were described without iron deposits.
Key Quotes & What They Tell Us
| Quote / Value | Interpretation |
|---|---|
| “intravenous drug user for 3 years”; “changed partners frequently” | Parenteral and sexual exposure → high risk for blood-borne viral hepatitis |
| ALAT 1316, ASAT 2749 U/L | Very high transaminases → severe acute hepatocellular injury |
| “confirmed HCV infection: 20 739 524 IU/mL viral load, genotype 1” | Establishes hepatitis C as the cause |
| Total bilirubin 270, direct 205 µmol/L; INR 1.49 | Conjugated hyperbilirubinaemia with early coagulopathy → significant hepatic dysfunction |
| Ferritin 5351, transferrin sat 88%, Fe high — but biopsy “without iron deposits” | Iron markers are reactive (acute-phase) from hepatic inflammation, NOT haemochromatosis (no tissue iron) |
| Acetaminophen negative; autoimmune panel negative; initial viral tests negative | Excludes paracetamol toxicity and autoimmune hepatitis; early seronegativity reflects the window period |
| Biopsy: “ballooning … hyaline degeneration … Kupffer cells and councilman bodies” | Apoptotic hepatocytes (Councilman bodies) and activated macrophages → active viral hepatitis |
Key Points
- Diagnosis: Viral hepatitis C (confirmed by high viral load, genotype 1), with severe active hepatitis.
- Pattern: Marked hepatocellular injury (very high ALAT/ASAT) with conjugated hyperbilirubinaemia and coagulopathy.
- Key trap: High ferritin/transferrin saturation suggests iron overload, but the absence of iron on biopsy shows these are acute-phase reactants — NOT hereditary haemochromatosis.
- Risk factors: IV drug use and multiple sexual partners (blood-borne transmission).
- Exclusions: Negative paracetamol level and autoimmune panel rule out major alternatives; window-period explains initial negative serology.
一問一答
▶Why are ferritin and transferrin saturation high despite no iron deposits on biopsy?
Ferritin is an acute-phase reactant raised by hepatic inflammation; the absence of tissue iron excludes haemochromatosis.
▶What are the main risk factors for hepatitis C transmission in this case?
Intravenous drug use and frequent change of sexual partners (blood-borne/parenteral exposure).
▶What is the diagnosis in a 52-year-old IV drug user with very high transaminases and a confirmed positive HCV viral load?
Acute/active viral hepatitis C.
▶Why might initial HCV serology be negative even when infection is present?
The window period — antibodies have not yet developed; repeat testing/viral load confirms infection.
▶What does ALAT 1316 and ASAT 2749 U/L indicate?
Severe acute hepatocellular injury.
▶What are Councilman bodies and what do they indicate?
Apoptotic (dying) hepatocytes; they indicate active hepatocellular injury, as in viral hepatitis.
▶What does an INR of 1.49 in acute hepatitis indicate?
Early coagulopathy from significant hepatic dysfunction (impaired clotting-factor synthesis).
▶Why is a negative autoimmune panel relevant in this case?
It excludes autoimmune hepatitis as the cause of the severe hepatitic picture.
▶Why is a negative acetaminophen level important here?
It excludes paracetamol toxicity, a common cause of very high transaminases.
▶What type of hyperbilirubinaemia is seen (total 270, direct 205 µmol/L)?
Predominantly conjugated hyperbilirubinaemia of hepatocellular origin.
▶What is hepatocyte ballooning degeneration?
Swelling of injured hepatocytes with rarefied cytoplasm, a sign of cell injury in active hepatitis.
▶What are Kupffer cells and why are they prominent here?
Resident hepatic macrophages; they become prominent/activated when clearing debris during active hepatitis.
▶Why does hepatitis C tend to become chronic?
HCV evades immune clearance (high mutation rate), so most infections persist as chronic hepatitis.
▶What long-term complications can chronic hepatitis C cause?
Cirrhosis and hepatocellular carcinoma.
▶What confirms active HCV infection rather than just past exposure?
A detectable HCV viral load (HCV RNA) — here over 20 million IU/mL, genotype 1.
▶What does 'cholestasis without cholecystitis' on ultrasound tell us?
There is impaired bile flow but no gallbladder inflammation/obstructing stone, consistent with hepatocellular disease.
▶Why is the iron-overload misinterpretation a classic trap in acute hepatitis?
Inflammation raises ferritin and transferrin saturation as acute-phase markers, mimicking haemochromatosis without true tissue iron.
▶How is hepatitis C treated today?
Direct-acting antiviral (DAA) drugs, which cure most patients.
▶What does 'active-chronic hepatitis' on biopsy mean?
There is ongoing active inflammation/necrosis superimposed on a chronic (long-standing) hepatitic process.
▶What is the systematic approach to a hepatitic picture with very high transaminases?
Exclude paracetamol/toxins, ischaemia, autoimmune, and viral causes — here repeat serology and viral load identify HCV.