Increased liver enzmyes

Question

Dear expert team,
at a control of a blood sample, increased liver enzymes have been detected.
SGOT/AST in the serum was increased by a factor of 2 of the laboratory reference range,
SGPT/ALT in the serum was increased by a factor of 3 of the laboratory reference range,
ALP in the serum was increased by a factor of 2 of the laboratory reference range,
GGT in the serum was increased by a factor of 4 of the laboratory reference range.
Ultrasound investigation of the upper abdominal region was without pathological finding in April 2012, except for a suspicion of steatosis grade I.
After 3 weeks the values were controlled. ALT/AST and GGT are decreasing but still elevated. The ALP slightly further increased.
I am CF patient, I take azithromycin for 2 days as a long-term therapy and had now in november additionally a therapy with moxifloxacin for 14 days. Due to an increased blood chloesterol level I am taking 10mg ezetimib in the mornings and 80mg fluvastatin in the evenings. Could it also be possible that the increased liver enzymes have a correlation with this?

Thank you very much for your work and that you run this website.
S.

Answer

Hello,
you report that at a routine investigation an increase of the liver enzymes SGOT, SGPT, ALP and GGT has been detected. With that, SGPT and GGT had been elevated by a factor of 3 resp. 4 of the normal range. Three weeks after the first blood test the values of SGOT, SGPT and GGT decreased, while the ALP increased slightly. You report furhter that in April a steatosis grade I had been detected by ultrasound of the abdomen.
Furthermore, you report that you receive a therapy with ezetimib 10mg (cholesterole uptake inhibitor) in the mornings and fluvastatin 80 mg (chloesterol lowering drug) in the evenings due to an increased cholesterol blood level. In addition, you receive a long-term therapy with azithromycin and had in november additionally for 14 days a therapy with moxifloxacin.
You ask, if the increased liver enzymes could probably have a connection to the therapy with ezetimib and fluvastatin or what other explanation there might be.

Several factors are coming into question causing the elevation of liver enzymes in your case. The elevation could be due to the underlying disease (CF). You report an ultrasound in april. In case there had not been another control later, this should be initiated immediately in order to exclude e.g. the existance of gallstones or only simply thickened gall secretions in the gallbladder (sludge). Furthermore, viral infections have to be excluded via investigation of blood.

On the other hand, all drugs you have taken and you are still taking come into question as a reason. As you are taking azithromycin for a longer time, this drug does not seem to be the causing agent of the increased liver enzymes, even if slight elevations of liver enzymes are seen under azithromycin therapy. With the intake of moxifloxacin elevation of liver enzymes is reported quite frequently. Due to this known side effect and especially due to side effects concering the heart, moxifloxacin should only be used under strict indication in case of severe infections if there is no alternative therapy available.

On the other hand, the drugs ezetimib and fluvastatin- each of it on its own- can cause elevation of liver enzymes. Only in vary rare cases an elevation of more than the factor 3 of the normal range has been reported under a monotherapy with fluvastatin. A monotherapy with ezetimib can also lead to an elevation of liver enzymes. In case of a combination therapy with ezetimib with a so-called statin like e.g. fluvastatin, the risk of an elevation of liver enzymes is increased.

From the complicated issue the following advice results:
First of all it has to be excluded for sure that there are no gallstones at the moment.
Before a change of the long term therapy, one should await further laboratory results of another control investigation with a larger distance of time to the end of the therapy with moxifloxacin. In case the liver enzymes should not normalize, then one should discuss a change in the therapy with the cholesterol lowering drugs.
Furthermore, a therapeutic attempt with ursodeoxycholic acid has to be discussed.
We hope to have helped you a bit with this information.

Yours sincerely,
Dr. H.-G. Posselt

24.01.2013