Man With Elevated ALT and History of Blood Transfusion

A 43-year-old fireman comes to your office after a routine blood test revealedthat his serum alanine transferase (ALT) level was elevated to approximatelytwice the normal value. The level was confirmed by repeated testing.HISTORY
The patient is otherwise healthy and is physically fit. He denies havingrashes or arthritis symptoms. He has sustained job-related trauma severaltimes; in 1988, he required blood transfusions for multiple traumatic injuries.He does not smoke but occasionally drinks beer.PHYSICAL EXAMINATION
Vital signs, heart, and lungs are normal. There is no evidence of scleralicterus, adenopathy, abdominal masses, enlargement of the liver or spleen,ascites, arthritis, rash, or spider angiomata.LABORATORY FINDINGS
Hemogram and routine chemistry panel are normal. Bilirubin level is1.2 mg/dL; aspartate aminotransferase level, 75 U/L; and ALT level,200 U/L. INR is 1. Initial enzyme immunoassay reveals hepatitis C virus (HCV)infection.Which of the following is the most appropriate next step?A. Monitor the patient clinically and with biannual ALT measurements;initiate therapy when the level rises to 4 times the normal value. B. Initiate therapy with peginterferon and ribavirin. C. Evaluate the patient for elective liver transplantation. D. Order a polymerase chain reaction test to assess viral load andgenotype. E. Order a liver biopsy to evaluate and stage HCV-related liver disease. CORRECT ANSWER: EThis patient has well-documented HCV infection. Theblood transfusion he received before 1990 placed him athigh risk for the disease. (In fact, until recently, bloodtransfusion before 1990 was the major risk factor in developingcountries.) His presentation-no obvious symptomsfor a prolonged period after infection-is typical. The elevatedALT level is a clinical clue that liver disease is present.Finally, the enzyme immunoassay was positive forHCV infection.Because the patient has a significant risk factor, confirmationby recombinant immunoblot assay is not necessary.Reserve confirmatory testing for patients withoutrisk factors or without clinical or laboratory evidence ofliver disease.The issue here is, What is the best initial evaluationfor an asymptomatic patient with newly diagnosed HCVinfection who has an elevated ALT level? There has beenan explosion in methods of characterizing HCV infectionand measuring viral load. Assays based on molecular detectionof HCV RNA can quantitate the presence and degreeof viremia. The results of such assays are relevant tothe outcome of and response to anti-HCV therapy, butthey do not always correlate with either the extent of liverdamage or the likelihood of disease progression. Viralgenotyping can be performed in conjunction with viralload studies and can aid in selecting therapy and predictingoutcome. However, the need for therapy has not yetbeen determined in this patient. Thus, these studies(choice D) are not the best option at this time.Although ALT measurement is an excellent, inexpensivestudy for identifying liver disease, levels fluctuategreatly in patients with HCV infection. Consequently, thisstudy cannot rule out active infection, assess progressionof liver disease, or indicate success of therapy.¹ At a timewhen so many more effective means of measuring diseaseactivity (quantification of viral load, liver biopsy) and oftreating disease (antiviral therapy, liver transplantation)are available, few if any authorities would monitor a newlydiagnosed patient only with ALT levels. Thus, choice A isnot appropriate.The "gold standard" for determining viral activity anddegree of liver damage remains biopsy. Tissue sampling isalso the only reliable means of establishing a prognosisand determining the likelihood of HCV-related progressionof liver disease.² Liver biopsy can detect the degreeand extent of active inflammation, as well as the presenceof bridging fibrosis and cirrhosis. Therefore, liver biopsy(choice E) is currently recommended for initial assessmentof patients with chronic HCV infection.^2-4There are currently insufficient data to make a decisionabout therapy for this patient. He has no severe immunecomplex findings (ie, mixed cryoglobulins with vasculitis,arthritis, and rash), which on their own can be anindication for therapy. Treatment with interferon/ribavirinregimens (choice B) is usually reserved for patients withdocumented HCV titers, persistently elevated ALT levels,and a liver biopsy that shows significant necrosis and inflammationand/or fibrosis.Hepatitis C is now the most common indication forliver transplantation (choice C), but the procedure is indicatedfor patients with decompensated cirrhosis. This patienthas no clinical stigmata for cirrhosis, let alone decompensatedliver failure. Although transplantation maybe an option in the future, it is not at this time.

References:

REFERENCES:

1.

National Institutes of Health Consensus Development Conference Panelstatement: management of hepatitis C. Hepatology. 1997;26(suppl 11):2S-10S.

2.

Yano M, Kumada H, Kage M, et al. The long-term pathological evolutionof chronic hepatitis C. Hepatology. 1996;23:1334-1340.

3.

Alter MJ, Kruszon-Moran D, Nainan DV, et al. The prevalence of hepatitis Cvirus infection in the United States, 1988-1994. N Engl J Med. 1999;341:556-562.4. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001;345:41-52.