What Is the Risk of Developing Hepatotoxicity From Statin Therapy in Hyperlipide

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From Medscape Gastroenterology

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Articles

Viewpoint: What Is the Risk of Developing Hepatotoxicity From Statin Therapy

in Hyperlipidemic Patients With Hepatitis C?

Posted

A. , MD, FACG, FACP

Incidence of Statin Hepatotoxicity in Patients With Hepatitis C

Khorashadi S, Hasson NK, Cheung RC

Clin Gastroenterol Hepatol. 2006;4:902-907

Summary

Drug-related hepatotoxicity refers to an injury associated with impairment

of liver function caused by exposure to a medication. Overall, drug-related

hepatotoxicity is relatively uncommon, with an incidence ranging between

1/10,000 and 1/100,000.[1]

The statin class of medications — drugs used to treat hyperlipidemia — has

been associated with a spectrum of liver injury, ranging from increased

aminotransferase levels (0.2% to 2.7%) to rare reports of fatal hepatic

failure. Usually, the hepatic enzyme elevation occurs early in the course of

therapy — typically within the first 3-12 months of initiation of the

medication. Most of these elevations are asymptomatic and associated with

higher doses of drug.

This well-recognized association between statins and liver injury, albeit

relatively rare, has led to recommendations by the pharmaceutical

manufacturers as well as expert physician advisory panels for routine

monitoring of liver enzyme levels in patients receiving statin medication

and avoidance of statins in patients with active or chronic liver disease.

However, there has been recent challenge to these recommendations, given

data suggesting that at least in normal-risk patients, there was no

difference in statin- and placebo-related hepatic enzyme elevation.[2]

Indeed, the most recent clinical guidelines on the use of statins in

patients with diabetes mellitus did not even recommend hepatic enzyme

monitoring unless the baseline values were elevated.[3]

However, the clinical assessment of statin use in patients with chronic

liver disease is less clear. The aim of this study by Khorashadi and

colleagues was to assess the use of this class of medication in 3 cohorts:

166 patients with hepatitis C on statin therapy, 332 patients with hepatitis

C not on statin therapy, and 332 patients on statin therapy but without

hepatitis C.

The 3 study cohorts were appropriately matched for age, sex, and body mass

index. For patients in the first cohort (hepatitis C, statin therapy), they

found a higher incidence of mild-to-moderate elevations in aminotransferase

levels compared with those not on statin therapy (22.9% vs 13.3%; P = .009),

but a lower incidence of severe increases in liver biochemistry (1.2% vs

6.6%; P = .015). Overall, for patients on statin therapy there were no

significant differences between the hepatitis C-positive or -negative

cohorts, with regard to mild-to-moderate aminotransferase increases, severe

increases in aminotransferases, or the need to discontinue statins as a

result of hepatotoxicity. Therefore, statin therapy was not associated with

a higher risk for severe hepatotoxicity.

Viewpoint

Drug-related hepatotoxicity cannot be viewed as a single disease. Many

different mechanisms lead to hepatotoxicity, which may be predictable or

unpredictable. In the case of statin-related injury, it seems to be an

idiosyncratic reaction that is not predictable. Additionally, the evidence

would support that no relation exists between the type of statin used and

the occurrence of liver abnormalities. On the basis of these study findings,

it also appears that in patients with hepatitis C and well-compensated liver

disease, these agents can be used in a manner that is comparable to that in

patients without chronic liver disease.

These findings are very much supported by a recent liver expert panel

recommendation to the National Lipid Association.[4] This panel that (1)

asymptomatic increases in aminotransferases represent a class effect

associated with statin use and do not necessarily indicate liver

dysfunction; (2) fulminant liver disease associated with statins is very

rare; (3) routine monitoring of liver biochemistries is not warranted for

patients receiving statin therapy; (4) well-compensated chronic liver

disease and Child's A cirrhosis are not contraindications to statin use; and

(5) statins can be used in patients with nonalcoholic fatty liver disease

and steatohepatitis.

Appropriate use of statins in an expanded population of eligible patients

should hopefully lead to improvement in the cardiovascular health of

appropriately selected at-risk patients. Additionally, these agents may

improve the hepatic disease — especially in those patients with

hyperlipidemic-related nonalcoholic steatohepatitis.

Abstract:

http://www.medscape.com/medline/abstract/http://www.medscape.com/medline/abstrac\

t/16697272

References

Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med.

2006;354:731-739. Abstract

de Denus S, Spinler SA, K, AM. Statins and liver toxicity: a

meta-analysis. Pharmacotherapy. 2004;24:584-591. Abstract

Snow V, Aronson MD, Hornbake ER, et al. Lipid control in the management of

type 2 diabetes mellitus: a clinical practice guideline from the American

College of Physicians. Ann Intern Med. 2004;140:644-649. Abstract

Cohen DE, Anania FA, Chalasani N, et al. An assessment of statin safety by

hepatologists. Am J Cardiol. 2006;97:77C-81C. Abstract

A. , MD, FACG, FACP, Professor of Medicine; Chief of

Gastroenterology, Eastern Virginia School of Medicine, Norfolk, Virginia

Disclosure: A. , MD, FACG, FACP, has disclosed that he has

received grants for clinical research from AstraZeneca, TAP, Wyeth,

Novartis, and Abbott, and grants for educational activities from AstraZeneca

and Novartis. Dr. has also disclosed that he has served as an

advisor or consultant to AstraZeneca, TAP, and Novartis.

Medscape Gastroenterology.

_________________________________________________________________

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[Guest guest]

From Medscape Gastroenterology

http://www.medscape.com/viewarticle/542993?src=mp

Articles

Viewpoint: What Is the Risk of Developing Hepatotoxicity From Statin Therapy

in Hyperlipidemic Patients With Hepatitis C?

Posted

A. , MD, FACG, FACP

Incidence of Statin Hepatotoxicity in Patients With Hepatitis C

Khorashadi S, Hasson NK, Cheung RC

Clin Gastroenterol Hepatol. 2006;4:902-907

Summary

Drug-related hepatotoxicity refers to an injury associated with impairment

of liver function caused by exposure to a medication. Overall, drug-related

hepatotoxicity is relatively uncommon, with an incidence ranging between

1/10,000 and 1/100,000.[1]

The statin class of medications — drugs used to treat hyperlipidemia — has

been associated with a spectrum of liver injury, ranging from increased

aminotransferase levels (0.2% to 2.7%) to rare reports of fatal hepatic

failure. Usually, the hepatic enzyme elevation occurs early in the course of

therapy — typically within the first 3-12 months of initiation of the

medication. Most of these elevations are asymptomatic and associated with

higher doses of drug.

This well-recognized association between statins and liver injury, albeit

relatively rare, has led to recommendations by the pharmaceutical

manufacturers as well as expert physician advisory panels for routine

monitoring of liver enzyme levels in patients receiving statin medication

and avoidance of statins in patients with active or chronic liver disease.

However, there has been recent challenge to these recommendations, given

data suggesting that at least in normal-risk patients, there was no

difference in statin- and placebo-related hepatic enzyme elevation.[2]

Indeed, the most recent clinical guidelines on the use of statins in

patients with diabetes mellitus did not even recommend hepatic enzyme

monitoring unless the baseline values were elevated.[3]

However, the clinical assessment of statin use in patients with chronic

liver disease is less clear. The aim of this study by Khorashadi and

colleagues was to assess the use of this class of medication in 3 cohorts:

166 patients with hepatitis C on statin therapy, 332 patients with hepatitis

C not on statin therapy, and 332 patients on statin therapy but without

hepatitis C.

The 3 study cohorts were appropriately matched for age, sex, and body mass

index. For patients in the first cohort (hepatitis C, statin therapy), they

found a higher incidence of mild-to-moderate elevations in aminotransferase

levels compared with those not on statin therapy (22.9% vs 13.3%; P = .009),

but a lower incidence of severe increases in liver biochemistry (1.2% vs

6.6%; P = .015). Overall, for patients on statin therapy there were no

significant differences between the hepatitis C-positive or -negative

cohorts, with regard to mild-to-moderate aminotransferase increases, severe

increases in aminotransferases, or the need to discontinue statins as a

result of hepatotoxicity. Therefore, statin therapy was not associated with

a higher risk for severe hepatotoxicity.

Viewpoint

Drug-related hepatotoxicity cannot be viewed as a single disease. Many

different mechanisms lead to hepatotoxicity, which may be predictable or

unpredictable. In the case of statin-related injury, it seems to be an

idiosyncratic reaction that is not predictable. Additionally, the evidence

would support that no relation exists between the type of statin used and

the occurrence of liver abnormalities. On the basis of these study findings,

it also appears that in patients with hepatitis C and well-compensated liver

disease, these agents can be used in a manner that is comparable to that in

patients without chronic liver disease.

These findings are very much supported by a recent liver expert panel

recommendation to the National Lipid Association.[4] This panel that (1)

asymptomatic increases in aminotransferases represent a class effect

associated with statin use and do not necessarily indicate liver

dysfunction; (2) fulminant liver disease associated with statins is very

rare; (3) routine monitoring of liver biochemistries is not warranted for

patients receiving statin therapy; (4) well-compensated chronic liver

disease and Child's A cirrhosis are not contraindications to statin use; and

(5) statins can be used in patients with nonalcoholic fatty liver disease

and steatohepatitis.

Appropriate use of statins in an expanded population of eligible patients

should hopefully lead to improvement in the cardiovascular health of

appropriately selected at-risk patients. Additionally, these agents may

improve the hepatic disease — especially in those patients with

hyperlipidemic-related nonalcoholic steatohepatitis.

Abstract:

http://www.medscape.com/medline/abstract/http://www.medscape.com/medline/abstrac\

t/16697272

References

Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med.

2006;354:731-739. Abstract

de Denus S, Spinler SA, K, AM. Statins and liver toxicity: a

meta-analysis. Pharmacotherapy. 2004;24:584-591. Abstract

Snow V, Aronson MD, Hornbake ER, et al. Lipid control in the management of

type 2 diabetes mellitus: a clinical practice guideline from the American

College of Physicians. Ann Intern Med. 2004;140:644-649. Abstract

Cohen DE, Anania FA, Chalasani N, et al. An assessment of statin safety by

hepatologists. Am J Cardiol. 2006;97:77C-81C. Abstract

A. , MD, FACG, FACP, Professor of Medicine; Chief of

Gastroenterology, Eastern Virginia School of Medicine, Norfolk, Virginia

Disclosure: A. , MD, FACG, FACP, has disclosed that he has

received grants for clinical research from AstraZeneca, TAP, Wyeth,

Novartis, and Abbott, and grants for educational activities from AstraZeneca

and Novartis. Dr. has also disclosed that he has served as an

advisor or consultant to AstraZeneca, TAP, and Novartis.

Medscape Gastroenterology.

_________________________________________________________________

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