By John Gever, Deputy Managing Editor, MedPage Today
Published: April 29, 2013
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania
AMSTERDAM -- High levels of hemoglobin may be dangerous in patients with nonalcoholic fatty liver disease (NAFLD), with bleeding a potential remedy, researchers said here.
NAFLD patients undergoing periodic phlebotomy for 2 years in an open-label, randomized trial showed significant declines in alanine and aspartate aminotransferase (ALT, AST) levels and improvements in liver tissue histology relative to an untreated control group, according to Luca Valenti, MD, of the University of Milan in Italy, and colleagues.
And, in a separate study led by Angela Peltec, MD, of the University of Medicine and Pharmacy in Kishinev, Moldova, NAFLD patients in the highest quartile of hemoglobin (more than 152 g/L) had significantly poorer cardiovascular risk profiles than those in the lowest (less than 128.5 g/L).
The Moldovan group found that patients in the highest hemoglobin quintile had a mean 10-year probability of a major cardiovascular event of 28% according to the Framingham equation, compared with 4% in the lowest quartile (P<0.05).
Both studies were reported at the European Association for the Study of the Liver's annual meeting.
Previous studies have found that NAFLD patients are prone to show a degree of iron overload, Valenti and colleagues noted. Some research has linked hemoglobin levels to the level of liver damage in NAFLD patients, as well as suggesting that excess iron may be overtly hepatotoxic -- that is, not just an epiphenomenon in NAFLD.
A pilot clinical study led by Valenti in 2011 found that phlebotomy reduced serum transaminase levels, prompting the group to conduct a larger, randomized trial.
The Italian researchers recruited 38 patients with iron overload, defined as serum ferritin higher than 250 mg/mL or on the basis of liver histological analysis and blood hemoglobin of more than 11 g/dL. They were randomized either to no iron-directed treatment or to phlebotomy every 2 weeks, with 350 mL of blood taken at each session, until serum ferritin declined to less than 100 mg/mL and transferrin saturation was in the range of 40% to 50%.
All patients also underwent lifestyle counseling as usually provided to NAFLD patients in the Milan clinic.
Heavy drinkers, the severely obese, and patients with hereditary hemochromatosis or non-NAFLD liver diseases were excluded.
Control patients showed slight average declines from baseline in serum ferritin and transferrin saturation, whereas those undergoing phlebotomy had markedly steeper reductions.
At the 2-year evaluation, mean ferritin levels stood at about 600 mg/mL in the control group compared with less than 200 mg/mL in the phlebotomy arm (P<0.005). Similarly, mean transferrin saturation was about 38% in controls versus 28% in the phlebotomy group after 2 years (P<0.05); at baseline, both groups had averages close to 40%.
Both groups had dips in mean ALT and AST levels at the 6-month mark, but levels plateaued or increased in the control group at subsequent evaluations, whereas they continued to decline in the phlebotomy group.
At the 2-year measurement, mean ALT and AST levels in controls were 37 and 28 IU/mL, respectively, compared with 24 and 21 IU/mL in the phlebotomy group (both P<0.05 relative to control), Valenti and colleagues reported.
Also, histologic analysis of liver biopsy samples indicated that 33% of the phlebotomy patients and 11% of the controls (P<0.05) had improvements from baseline during the study period.
There were no significant differences between groups in weight loss or changes in waist circumference.
The Moldovan study was a cross-sectional analysis of 117 NAFLD patients, with data collected for cardiovascular risk prediction according to the Framingham system as well as measurements of blood hemoglobin content.
After adjusting for known cardiovascular risk factors, the odds ratio for having a Framingham risk rated as high (greater than 20%) was 3.45 for the highest versus lowest quartile (95% CI 1.12 to 10.70). For patients in the third quartile (hemoglobin of 140 to 152 g/L), the adjusted odds ratio for high cardiovascular risk was 2.07 (95% CI 1.68 to 10.97) versus the lowest quartile.
High hemoglobin levels were associated with younger patient age, higher blood lipid levels, and increased ALT and AST, Peltec and colleagues reported. But the prevalence of hypertension and type 2 diabetes did not correlate significantly with hemoglobin, nor did body mass index values.
Peltec and colleagues concluded that hemoglobin measurement could be helpful in gauging cardiovascular risk in NAFLD patients, in addition to traditional risk factors.
The Moldovan study was limited by its cross-sectional nature and relatively small enrollment. The study by Valenti and colleagues also had relatively few patients. Neither study used actual clinical outcomes.
Neither study had commercial funding.
Valenti and Peltec reported that they had no relevant financial interests.
Primary source: European Association for the Study of the Liver
Source reference:
Valenti L, et al "Effect of iron depletion on liver damage in nonalcoholic fatty liver disease: preliminary results of a randomized controlled trial" EASL 2013; Abstract 1373.
Additional source: European Association for the Study of the Liver
Source reference:
Peltec A, et al "May hemoglobin be a mediator of increased cardiovascular risk in NAFLD?" EASL 2013; Abstract 1357.
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