Liver disease progression in hepatitis C virus carriers with normal alanine aminotransferase levels

Abstract

We read with great enthusiasm the article of Wiese et al.1 that, in our opinion, has a paramount relevance to understanding the natural history of hepatitis C virus (HCV) infection. In particular, this article does greatly in helping us to evaluate the progression to more severe liver damage of the so-called healthy HCV carriers (i.e., viremic persons with normal alanine aminotransferase [ALT] levels and liver histology). It is known that up to 30%-40% of patients with chronic HCV infection have persistently normal ALT levels,2 with many of them showing normal liver histology or minimal fibrosis. The natural course of HCV infection in these patients is not well known. Whereas some studies showed that HCV carriers with normal ALT have mild and stable disease, others reported a significant progression of fibrosis in approximately 20%-30% of such patients.3 In their first study4 describing the 20-year follow-up of over 1,000 women infected in East Germany in January 1979 by contaminated anti-D immune globulin, the researchers reported that 26 patients should be considered as true healthy carriers (i.e., normal liver, normal ALT, and persistent HCV viremia). At 25-year follow-up,5 only 11 women had remained in a healthy state, whereas the others had progressed to chronic hepatitis C (CHC). However, in this third evaluation after 35-year follow-up,1 no mention has been made about the histological and clinical status of these otherwise healthy, HCV-infected women. Thus, we wonder how many of these carriers had remained in a true healthy state 35 years after contamination and how many further carriers had progressed to CHC. Furthermore, the degree of liver damage was more or less severe in the carriers progressing to CHC with respect to other patients; were differences observed in virological response between the two groups of patients? Indeed, whether healthy HCV carriers should be offered antiviral treatment in clinical practice has been the subject of an ongoing debate.6 Introduction of the combination therapy of pegylated interferon plus ribavirin results in higher response rates,7 with a favorable risk/benefit ratio also in patients with mild or no fibrosis.8, 9 The important data of the East Germany HCV Study Group might give an answer to this unmet issue: What should we treat, the infection or the disease?10 Claudio Puoti, M.D.1 Lia Bellis, M.D.1 Olga Mitidieri Costanza, M.D.2 Maria Giuseppa Elmo, M.D.3 1Department of Internal Medicine and Liver Unit Marino General Hospital Rome, Italy 2Molecular Biology Unit Marino General Hospital Rome, Italy 3Department of Mental Health, Local Health Center Rome, Italy