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Metabolic Factors and Inflammatory Changes Are Responsible for Increased Gamma-Glutamyltranspeptidase Level in Chronic Hepatitis C
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Reported by Jules Levin
DDW, May 17-22, 2008, San Diego
Federica Benini1, Marie Graciella Pigozzi1, Luisa Bercich2, Alessandro Reggiani3, Bruno M Cesana4, Stefania S Bertolazzi1, Alessandra Mora1, Alessandro Pozzi1, Francesco Lanzarotto1, Chiara Ricci1, Alberto Lanzini1
1. Medicine, University-Spedali Civili Brescia, Brescia, Italy, 2. Histopathology, University-Spedali Civili Brescia, Brescia, Italy, 3. Medicine, Hospital, Cremona, Italy, 4. Biostatistics, University, Brescia, Italy
Serum gamma-glutamyltranspeptidase (_GT) is frequently increased in chronic hepatitis C. The mechanism involved is unclear. Environmental (alcohol or drugs) and metabolic factors may be important as suggested by studies in health.
The aim of our study was to identify factors associated with increased serum _GT activity in chronic hepatitis C by carefully selecting patients with no alcohol or drugs consumption . Consecutive patients with chronic hepatitis C and absent past or present alcohol consumption and/or chronic treatment with drugs have been prospectively enrolled in a multicentre study.
Anthropometric, virological, histological, and biochemical parameters including insulinemia, insulin resistance (HOMA-IR) and C peptide have been recorded and analyzed by multiple linear regression analysis and by multivariate logistic regression analysis. 71 patients (M 47, F 24, mean age ± SD 48 ± 12 years) entered the study.
Thirty nine patients had elevated _GT levels and they had significantly higher BMI than patients with normal serum _GT (n=31) (26.2 ± 3.9 vs 24.5 ± 3.7, respectively, p=0.04), insulinemia (14.4 ± 14.2 vs 8.6 ± 4.5, p=0.01), HOMA-IR score (3.4 ± 3.3 vs 1.8 ± 1.1, p=0.008), C peptide (3.1 ± 1.6 vs 2.1 ± 0.9, p=0.01).
Piecemeal necrosis score => 3 was present in 36% of patients with elevated _GT vs 10% in patients with normal _GT (p=0.01), and the corresponding values for hepatic fibrosis score => 2 was 41% vs 19%, respectively (p=0.01), and for hepatic steatosis score => 1 was 67% vs 34%, respectively (p=0.007). At multiple linear regression analysis serum _GT level was influenced by C peptide level, HOMA-IR and histopathologic grading .
At multiple logistic regression analysis, C peptide (OR=2.13) and piecemeal necrosis score =>3 (OR=4.59) were the only factors independently associated to elevated serum _GT.
Serum _GT levels are influenced by metabolic factors in patients with chronic hepatitic C abstinent from alcohol and drugs. Abnormal _GT level is present in the majority of patients, and C peptide and hepatic inflammation are the main factors independently involved in this phenomenon.
The GGT test helps to detect liver and bile duct injury. While some doctors use it in all people they suspect of having liver disease, others use it only to help explain the cause of other changes or if they suspect alcohol abuse. For example, both ALP and GGT are elevated in disease of the bile ducts and in some liver diseases, but only ALP will be elevated in bone disease. If the GGT level is normal in a person with a high ALP, the cause is most likely bone disease. GGT can also be used to screen for chronic alcohol abuse (it will be elevated in about 75% of chronic drinkers).
A doctor usually orders GGT along with other tests to evaluate a person who has signs or symptoms that suggest liver disease. Some of the symptoms of liver injury include jaundice, nausea, vomiting, abdominal swelling, abdominal pain, pruritus (severe itching), and fatigue.
GGT is increased in most diseases that cause acute damage to the liver or bile ducts, but is usually not helpful in distinguishing between different causes of liver damage. For this reason, use of GGT is controversial, and guidelines published by the National Academy of Clinical Biochemistry and the American Association for the Study of Liver Diseases do not recommend routine use of GGT. These guidelines suggest that it can be useful in determining the cause of a high ALP. In persons with a history of alcohol abuse who have completed alcohol treatment, GGT may be used to monitor compliance with the treatment program.
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