Viral and metabolic factors influencing alanine aminotransferase activity in patients with chronic hepatitis C.
OBJECTIVE
In chronic hepatitis C, disease progression and clinical manifestations are heterogenous. To clarify the role and interactions of viral and host factors in inducing liver cell injury, we examined the associations of several virological and metabolic variables with serum alanine aminotransferase levels.


METHODS
Patients with chronic hepatitis C enrolled in three phase III clinical trials of peginterferon alfa-2a (40KD) plus ribavirin (two studies analysing 'elevated' and one persistently 'normal' alanine aminotransferase) were included.


RESULTS
Multivariate analyses of 2,881 patients before treatment and of 1,403 patients with a sustained virological response indicated that gender, viral factors (genotype, HCV RNA titer) and indicators of metabolic syndrome (body mass index, blood pressure, blood glucose, cholesterol and triglyceride concentration) were associated with alanine aminotransferase levels. In addition, hepatitis C virus infection influenced serum lipids concentration according to a genotype-specific effect.


CONCLUSIONS
Heterogeneity in alanine aminotransferase levels in patients with chronic hepatitis C partially depends on the degree of derangement of fat and carbohydrate metabolism. As this is the result of an interaction of chronic hepatitis C infection with the patient's individual characteristics, treatment decisions should not be based on alanine aminotransferase level alone but rather on global evaluation of the patient.
Prati
Daniele
D
Ospedale A. Manzoni, Lecco and IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Milan, Italy. d.prati@ospedale.lecco.it
Shiffman
Mitchell L
ML
Diago
Moisés
M
Gane
Edward
E
Rajender Reddy
K
K
Pockros
Paul
P
Farci
Patrizia
P
O'Brien
Christopher B
CB
Lardelli
Pilar
P
Blotner
Steven
S
Zeuzem
Stefan
S
D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D016014:Linear Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000503:physiopathology; D008660:Metabolism / Q000502:physiology*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012016:Reference Values; D012254:Ribavirin / Q000627:therapeutic use; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood
D000998:Antiviral Agents; D001786:Blood Glucose; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D014280:Triglycerides; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a