Hepatitis C virus carriers with persistently normal ALT levels: biological peculiarities and update of the natural history of liver disease at 10 years

Abstract

Some chronic hepatitis C (CHC) patients exhibit persistently normal alanine aminotransferase (ALT) levels (PNAL). Patients with PNAL experience significantly milder disease. In order to understand the differences between CHC patients with elevated ALT levels compared with those with PNAL better, we compared epidemiological, immunological and histological findings, in particular, the value of proliferating hepatocyte activity (PCNA) between the two groups of patients. We studied 40 chronic hepatitis C virus (HCV) carriers with increased ALT who underwent liver biopsy for histological diagnosis and determination of clinical prognosis, and 24 PNAL patients under follow-up for 10 years. Immunological response to different HCV genomic epitopes was tested in both the control group and in PNAL subjects. PCNA values from liver specimens of all patients as well as liver biopsies of PNAL patients at time points 0 and 5 years were calculated according to Hall et al.Age, sex and body mass index (BMI) were not significantly different between the two groups. The median liver histology stage was significantly higher in HCV carriers vs the PNAL group (2.5, range = 2-6 vs 1.5, range = 1-2; P < 0.01). Among PNAL patients, histological stage was not statistically different at the three time points considered. Interferon (IFN)-gamma production was comparable in the two groups. PCNA was significantly higher in the group with elevated ALT levels vs the PNAL group (8%, range = 4-15%vs 5% range = 3-8%; P < 0.05) and no statistically significant differences were found in PNAL patients at time points 0, 5 and 10 years. This study confirms that progression to cirrhosis is slow or absent in PNAL patients after 10 years of follow-up. Accordingly, the hepatic proliferative activity index is low and seems to be stable over time.

Serum miR-122 as a Biomarker of Necroinflammation in Patients With Chronic Hepatitis C Virus Infection

“…CHC patients with persistently normal ALT serum levels show milder disease activity and lower hepatic proliferative activity index (29,30). Analyses of the patients with CHC and persistently normal serum ALT activity for miR-122 serum levels revealed that the miR-122 concentration in these patients were undistinguishable from those in healthy controls.…”

Clinical significance of alanine aminotransferase levels and the effect of ursodeoxycholic acid in hemodialysis patients with chronic hepatitis C

“…HCV carriers with persistently normal ALT (PNALT) are more often females than chronic hepatitis C patients with abnormal ALT [40]. This distinction is likely due to lifestyle differences such as alcohol consumption [40], hormonal factors [41] or lower serum iron levels [42]. Although the normal range of ALT in HD patients with HCV may be different compared to the range in HCV carriers with normal renal function, our study demonstrated that females are more likely to have lower ALT levels, even in HD patients (Table 4).…”

Hepatitis C Infection With Normal Liver Chemistry Tests

“…In a study of 24 patients with PNALT who underwent serial liver biopsies over a ten-year follow-up period, fibrosis stage remained stable 5 . In aggregate, these data support the favorable natural history of HCV with PNALT, but the potential still exists for progression to advanced liver disease.…”