Clinical, histological, and virological features of hepatitis C virus carriers with persistently normal or abnormal alanine transaminase levels

Abstract

This study was aimed to evaluate demographic, clinical, histological, and virological characteristics of 46 hepatitis C virus (HCV) carriers with persistently normal alanine transaminase (ALT) levels and to compare the results with those obtained in a group of 52 HCV-RNA-positive patients with elevated ALT levels. Subjects with normal ALT were more often females (P < .001), were more likely to be asymptomatic (P < .001), and have a lower incidence of risk factors for HCV transmission (P < .01). All patients with normal ALT had significant histological liver damage. The mean grading and staging did not differ between patients with normal and those with raised ALT concentrations. Moderate to severe hepatitis was more frequently found among subjects with normal than with elevated ALT. HCV genotype 2a was far more common in subjects with normal (43%) than with abnormal ALT levels (6%; P < .002), genotype 1b being more frequent in these latter (50% vs. 17%; P < .001). Patients with normal ALT levels had similar serum HCV-RNA titers than subjects with raised ALT. Neither HCV genotype distribution nor viral load correlated with the severity of liver damage. We conclude that significant liver disease may occur irrespective of clinical symptoms, ALT levels, HCV genotypes, and viral load.

Clinical features of hepatitis C-infected patients with persistently normal alanine transaminase levels in the southwestern United States

“…Contrary to previous reports, 16,27 our study shows no sex difference between the persistently normal and abnormal ALT groups, which might be a limitation of our study. However, based on multivariate analysis, sex was not found to be a confounding variable for fibrosis progression.…”

“…Using the revised scoring system we have shown significantly less severe portal inflammation, piecemeal necrosis, and lobular inflammation as well as degree of fibrosis, and incidence of cirrhosis in patients with persistently normal ALT compared with patients with abnormal ALT. Similar results were reported by other investigators, 14,15 which are in contrast to the findings of at least 1 study 16 showing moderate to severe disease in persistently normal ALT patients.…”

“…Controversies still exist regarding the severity of disease on liver biopsy in these patients. [14][15][16] A clear understanding of these features is important in making rational therapeutic decisions regarding the care of these patients. A crucial aspect of this study is our definition of persistently normal ALT, which is at least 4 consecutive, normal ALT values within a period of 12 months and at least 3 values within 6 months.…”

Detection of apoptotic caspase activation in sera from patients with chronic HCV infection is associated with fibrotic liver injury

“…This observation could be of clinical relevance, because presently the questions of (1) whether or not patients with persistently normal aminotransferases should undergo liver biopsy and (2) the therapeutic management of these patients are hotly debated. 47,48 Most of the patients with normal aminotransferase levels have mild degrees of inflammation with mild or no fibrosis. However, recent large-scale case studies have shown that a considerable percentage of patients with normal ALT levels have stage 3 or 4 liver fibrosis (reviewed by Bacon 49 ).…”

Should chronic HBV infected patients with normal ALT treated: debate

“…The extent of liver cell necrosis and degree of elevated ALT level do not always correlate, and ALT measurements may fail to identify patients with necro-inflammatory activity or fibrosis, as seen in hepatitis C [12,13]. In addition, the ALT activity may vary with body mass index, sex, abnormal lipid and carbohydrate metabolism as well as the time of the day [14,15].…”