THE CONSULTANT'S CHOICE Based on the liver biopsy results, the best choice here is B. A biopsy provides 2 pieces of information that are key to establishing a prognosis and making therapeutic decisions: the grade of inflammation and the stage of fibrosis. Because morbidity and mortality in HCV infection are largely the result of cirrhosis, the extent of fibrosis is invaluable in estimating prognosis.¹ The grade of necroinflammatory activity is determined by 2 parameters: the severity of periportal inflammation and the degree of parenchymal necrosis (Table 1). There is a 1.2% annual risk that cirrhosis will develop in patients with mild inflammation. In those with moderate inflammation, this risk rises to 4.6% annually, and to 90% within 20 years of biopsy.² Cirrhosis develops within 10 years in nearly all patients with severe inflammation.²

Table 1 — Histologic grading of chronic hepatitis C Grade   Histologic description 0   Inflammation is absent 1   Inflammation is confined to the portal tract 2   Both periportal (interface) inflammation and parenchymal injury are mild Data from Rosenberg PM. Clin Infect Dis. 2001.1

The stage of fibrosis is determined by Masson trichrome stain (Table 2). On average, the condition progresses 1 stage every 4 years in patients with HCV infection. ³ Those with HCV infection and compensated cirrhosis have a good prognosis (a 10-year survival rate over 80%⁴); once complications of cirrhosis develop, however, the 5-year survival rate falls below 50%.⁵ It may be reasonable to observe patients with mild inflammation and no fibrosis. This can be done by checking aminotransferase levels regularly and repeating liver biopsy in 3 to 5 years.^6,7 However, our patient has moderate inflammation and bridging fibrosis. There is a high likelihood that his disease will progress to cirrhosis in the next decade. Thus, it is appropriate to recommend therapy with interferon and ribavirin(Drug information on ribavirin). Unless contraindicated, treatment is recommended for all patients in whom biopsy reveals at least grade 2 inflammation and stage 1 fibrosis. However, patients with decompensated cirrhosis should not be treated.^1,8,9 (Treatment may be of benefit to some patients with subclinical cirrhosis.)

Table 2 — Histologic staging of chronic hepatitis C Stage   Histologic description 0   No fibrosis 1   Fibrous portal tract expansion 2   Periportal fibrosis 3   Bridging or septal fibrosis 4   Cirrhosis Data from Rosenberg PM. Clin Infect Dis. 2001.1

Hepatocellular carcinoma develops almost exclusively in patients with cirrhosis—and at a rate of 1% to 4% per year.¹⁰ Consequently, periodic screening with serum alpha-fetoprotein measurements and ultrasonography of the liver every 6 to 12 months has been advocated in patients with HCV cirrhosis— despite the lack of long-term studies showing costeffectiveness. ¹¹ However, our patient’s disease has not yet progressed to cirrhosis, making such screening unnecessary. The patient inquired about nonprescription therapies for HCV infection. Silymarin(Drug information on silymarin) (milk thistle) is reported to possess antioxidant properties and is commonly used by patients with HCV infection. Although theoretically beneficial in preventing fibrosis, long-term data are limited.¹² Vitamin E(Drug information on vitamin e) may improve fibrinogenesis and decrease serum transaminase levels.^13,14 However, there is far too little supportive evidence to recommend either of these as sole therapy for a patient with serious liver disease.