Mr. F, age 26 years and of French Canadian descent, worked as a hospital phlebotomist. When his father died at age 48 of an MI, Mr. F became concerned about his own heart health. Although he had no acute medical complaints and was in relatively good health, a cholesterol panel done during an employee screening a few years earlier had revealed elevated values.

The patient’s past medical history was positive for hepatitis C virus (HCV) infection through percutaneous exposure from a needle stick several years ago. Records from his gastroenterologist revealed a positive enzyme-linked immunosorbent assay for anti-HCV antibody, which was confirmed by viral load testing. HIV testing was negative. Current medications included peginterferon alfa and ribavirin for the hepatitis and ibuprofen when needed for low-grade fever and/or muscle aches associated with the treatment injections. Mr. F had no known drug allergies. There was no history of drug or alcohol abuse, and he reported no exposure to hazardous materials. The surgical history was positive only for a liver biopsy that confirmed chronic hepatitis C with stage 1 fibrosis.

1. Examination

Mr. F’s vital signs were as follows: BP 122/72 mm Hg, pulse 72 beats per minute, respiratory rate 20 breaths per minute, and temperature 97.8°F. He weighed 168 lb and was 5 ft 9 in tall.

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The patient’s eyes, skin, and mucous membranes were normal, with no evidence of jaundice and no muscle wasting. There were no signs of Dupuytren’s contractures, palmar erythema, or spider angiomata, which are findings associated with liver disease. Liver palpation and percussion revealed nothing unusual; no fluid retention was detected. Cardiovascular and neurologic exams were also unremarkable.

A complete blood count was within normal limits. Other than an elevated alanine aminotransferase (ALT) (90 IU/L), results of a complete metabolic profile were normal. Thyroid-stimulating hormone was 2.83 mU/L. A lipid panel revealed total cholesterol 292 mg/dL, HDL 52 mg/dL, LDL 218 mg/dL, and triglycerides 112 mg/dL. Urinalysis was unremarkable.

2. Diagnosis

Mr. F was diagnosed with familial hypercholesterolemia (FH), an inherited condition that renders the body unable to effectively remove LDL and other forms of cholesterol from the bloodstream. This leads to an accumulation of excessive plaque and the associated high risk for premature cardiovascular disease (CVD). A diagnosis of FH is usually based on markedly elevated LDL and a family history of premature coronary disease (i.e., before age 50 years).1 The condition is more common in people of French Canadian descent (one in 250). A Cardiolite stress test showed evidence of mild myocardial ischemia, which would indicate an early CVD process. Although absent in Mr. F’s case, cholesterol deposits are sometimes found on the cornea, eyelid, or extensor tendons of patients with FH.2

Mr. F’s hepatitis C made the FH diagnosis and treatment more complicated. Statin therapy is the gold standard for treatment of FH, but its use is controversial with hepatitis and other diseases of the liver.

3. Treatment and outcome

The three major LDL-lowering agents available for treatment of FH are statins, ezetimibe (Zetia), and bile acid sequestrants or resins. A statin is the medication of choice. The efficacy and safety of statins and their established performance in preventing CVD has been amply demonstrated in primary and secondary prevention trials. However, the clinical assessment of statin use in patients with chronic liver disease is less clear. A review of the literature guided the treatment decision for this patient.

Khorashadi et al assessed the use of statins in three cohorts: 166 patients with hepatitis C on statin therapy; 332 patients with hepatitis C not on statin therapy; and 332 patients on statin therapy but without hepatitis C. For patients on statin therapy, there were no significant differences between the hepatitis C-positive and the hepatitis C-negative cohorts with regard to mild-to-moderate aminotransferase increases, severe increases in aminotransferases, or the need to discontinue statins as a result of hepatotoxicity.3 Therefore, statin therapy was not associated with a higher risk for severe hepatotoxicity.

Another study showed that statins can inhibit the replication of HCV and could replace ribavirin in combination therapy with interferon for treatment.4

Segarra-Newnham et al retrospectively reviewed 146 patients with HCV and hypercholesterolemia who were treated with statins between January 1995 and September 2003. Lipid profiles and aminotransferase levels were determined at baseline and three and six months after starting the statin, with a mean follow-up of 22 months. A significant decrease in LDL levels from their baseline values was seen with no significant increase in serum ALT levels. Only one patient discontinued the statin because an ALT value rose to more than three times the upper limit of normal.5

Finally, the first prospective, randomized, double-blind, placebo-controlled trial of statin use in patients with chronic liver disease provided strong evidence that this treatment is safe and effective. In fact, the study showed that statins may even be beneficial in improving liver chemistries.6