Fibrosis Progression in Initially Mild Chronic Hepatitis C
S. Boccato; R. Pistis; F. Noventa; M. Guido; L. Benvegnù; A. Alberti
J Viral Hepat.  2006;13(5):297-302.  ©2006 Blackwell Publishing
Posted 05/11/2006

[...] Summary
The natural history of chronic hepatitis C presenting with no/minimal
liver fibrosis is uncertain with controversies on risk of progression
and need for antiviral treatment. We studied rates and determinants of
fibrosis progression in initially mild chronic hepatitis C. One hundred
and six patients (mean age 41.65 ± 12.83 years) with chronic hepatitis C
virus infection and no/minimal fibrosis in the initial liver biopsy
(F0/F1 by METAVIR score) were followed prospectively while untreated
with repeated biopsy after 5 or more years (mean interval 7.8 ± 1.51
years). Patients showing fibrosis progression were compared with
nonprogressors for baseline and follow-up parameters. Sixty-four
patients (60.4%) showed fibrosis progression including 13 of 27 (49%)
with F0 and 51 of 79 (65%) with F1. Progression to F3 or cirrhosis was
seen in 36% of those with F1 initially. Fibrosis progression (?F/year)
was associated with age (P < 0.0001), baseline and follow-up alanine
aminotransferase (ALT) (P = 0.005), histological activity (P = 0.004)
and steatosis (P = 0.002) in the initial biopsy and use of alcohol (P =
0.008). Thus liver fibrosis progression occurs in two-thirds of patients
with initially mild chronic hepatitis C within 5–10 years and advanced
fibrosis/cirrhosis develops in one-third of those with F1 initially.
Fibrosis is facilitated by older age and alcohol and associated with
inflammatory activity and ALT levels. Antiviral therapy should be
considered in mild chronic hepatitis C.

[...] These results clearly indicate that chronic hepatitis C is a
progressive disease in many patients who initially present with
no/minimal fibrosis and that progression to advanced fibrosis does occur
in a significant number of cases within 5–10 years. [...] fibrosis
progression in initially mild chronic hepatitis C is significantly
influenced by patients age and by the ALT profile. Indeed, age at first
biopsy directly correlated with fibrosis progression during follow-up
confirming that HCV infection becomes more 'fibrogenic' with advancing
host age.[23] Considering the ?F/year observed in different age
subgroups, our data indicate that patients >50 years can be predicted to
develop cirrhosis from initially mild disease in half (15–20 years) the
time interval estimated for those <35 years (time to cirrhosis: 30–40
years or more), mean ?F/year being 0.20–0.25 in the former and <0.10 in
the latter (see Fig. 2). Our results fully confirmed that ALT levels are
strongly associated with fibrosis progression in hepatitis C,
particularly when several determinations rather than a single point are
considered. Accordingly to our finding, each doubling in ALT levels is
reflected in doubling ?F/year, i.e. in the speed of fibrosis
accumulation in the liver (see Fig. 4). Thus, ALT monitoring represent
an easy, and extremely useful tool to assess prognosis of initially mild
hepatitis C. Some progression of fibrosis was seen also in 29% of the
patients with persistently normal ALT, however, we cannot exclude that
some of these cases, that were evaluated only every 6–12 months, might
have had abnormal ALT if checked more frequently. Other parameters that
were independently associated with disease progression included liver
steatosis and alcohol intake, indicating that these metabolic cofactors,
already described to influence the course of chronic hepatitis C,[24,25]
are relevant also in the more specific setting of initially mild
disease. In conclusion, our results indicate that chronic hepatitis C
presenting with no/minimal fibrosis in liver biopsy should not be
considered as a benign, steadily nonprogressive form of hepatitis C.
[...]

Full text at http://www.medscape.com/viewarticle/530758

Thomas