A 70-year-old woman has had worsening fatigue with nausea and a 3 kg weight loss over the past year. On examination she is afebrile. Her heart rate is regular. There is no abdominal tenderness. The neurologic examination is unremarkable.

Laboratory studies show Hgb 11.8 g/dL, Hct 35.3%, MCV 85 fL, WBC count 5950/microliter, platelet count 229,300/microliter, sodium 141 mmol/L, potassium 4.0 mmol/L, chloride 104 mmol/L, HCO3 24 mmol/L, glucose 72 mg/dL, creatinine 0.7 mg/dL, total protein 5.6 g/dL, albumin 3.4 g/dL, LDH 510 U/L, alkaline phosphatase 61 U/L, AST 281 U/L, ALT 307 U/L, total bilirubin 4.8 mg/dL, and direct bilirubin 3.0 mg/dL.

Questions:

2.1 What is suggested by these findings?

Hepatocellular injury.

2.2 What additional laboratory tests are indicated?

Additional laboratory studies show:

2.3 What do these findings indicate?

She has had past infection with hepatitis A. She either had past infection with hepatitis B or received a hepatitis B vaccination. Her major problem is hepatitis C infection.

2.4 Explain the pathophysiology of the liver function tests.

Viral hepatitis leads to apoptosis of hepatocytes, mediated via cytotoxic CD8 lymphocytes. Dying and dead hepatocytes release intracellular enzymes, including AST and ALT. Virally infected cells have less capacity to function, so they are going to have diminished capacity to process bilirubin. Both the clearance from the blood and glucuronidation (elevated indirect bilirubin) and excretion into the bile (elevated direct bilirubin) are affected.

2.5 How should she be treated?

• HCV genotype 1: ribavirin for 48 weeks with a standard dosage (1000 or 1200 mg qd); ribavirin with pegylated interferon alfa-2b (12 kD) is 800 mg qd.

• HCV genotype 2 or 3: ribavirin for 24 weeks at 800 mg qd with peginterferon alfa-2a (40 kD); when using pegylated interferon alfa-2b (12 kD) in patients infected with HCV genotype 2 or in patients infected with genotype 3 and hepatitis C virus RNA <600,000 IU/mL, the duration of treatment should be 24 weeks. When the viral load exceeds 600,000 IU/mL, the duration of treatment may need to be longer and the dose of ribavirin greater.

2.6 What dietary modifications may be useful for this patient if hepatic function worsens?

Decreasing the amount of protein in the diet may help reduce the nitrogen load and reduce the risk for hepatic encephalopathy. An increasing blood ammonia suggests greater risk for hepatic encephalopathy. The non-absorbable disaccharide lactulose will diminish ammonia absorption from the bowel.