GASTROENTEROLOGY
BRIEF
1990;99:1332-1833
REPORTS
Fulminant Hepatitis After Lisinopril Administration DOMINIQUE LARREY, GERARD BABANY, JACQUES BERNUAU, JACQUES ANDRIEUX, CLAUDE DEGOTT, BENHAMOU DOMINIQUE PESSAYRE, and JEAN-PIERRE Unite de Recherches de Physiopathologie HBpatique (INSERM U-24). Service d’HBpatologie and Service d’Anatomie et de Cytologie Pathologiques. Hapital Beaujon, Clichy; and Service de MBdecine Interne, HBpital M¬, Le Chesnay, France
A case of fulminant hepatitis in a patient taking lisinopril for 5 weeks for arterial hypertension is reported. Jaundice, fever, myalgia, and marked increase in serum aminotransferase activities occurred after z weeks of treatment. Continuation of lisinopril administration for 3 weeks after the onset of jaundice was associated with the development of grade III encephalopathy and a marked decrease in prothrombin and proaccelerin levels. This case strongly suggests that lisinopril may induce acute hepatitis and that continuation of the treatment after the onset of jaundice can lead to life-threatening hepatic failure.
I
nhibitors of angiotensin-converting enzyme are used widely in the treatment of arterial hypertension and congestive heart failure. Usually, these drugs are tolerated well and side effects, if any, are mild. Uncommonly, however, captopril and enalapril can induce acute hepatitis (l-4). To our knowledge, liver injury has not been reported with lisinopril, a new inhibitor of angiotensin-converting enzyme marketed worldwide since 1988 (5). This case report involves a patient affected by fulminant hepatitis within 5 weeks after the beginning of lisinopril administration for arterial hypertension. Case Report A 55-year-old man was admitted for acute hepatitis on October 10,1988. He had no history of disease of the liver or biliary tract, blood transfusion, surgery, drug addiction, or alcohol abuse. He started taking enalapril for arterial hypertension in December 1986. Furosemide and bisoprolol were added to enalapril in October 1987 and April 1988, respectively. These drugs were well tolerated but failed to reduce arterial pressure to normal value. The administration of enalapril was discontinued on September 7, 1988, and was replaced by that of lisinopril, 20 mg daily. On September 15, fever and myalgia developed. On September 19, the patient
was jaundiced. Initial clinical examination was normal except for jaundice. Serum aminotransferase activities were markedly increased and prothrombin time was normal (Table 1). Blood cell counts were normal: in particular, eosinophil count was 1Wmm”. On September 20, administration of furosemide was withdrawn, whereas administration of lisinopril and bisoprolol was continued. On October 10, the patient was admitted because of the worsening of jaundice and the development of ascites. Lisinopril and bisoprolol were withdrawn immediately. Serum aminotransferase levels had further increased; prothrombin and proaccelerin counts had markedly diminished (Table 1).Serum gammaglobulin count was 1.3 g/dL (13 g/L) and serum albumin 3.4 g/dL (34 g/L]. Immunoglobulin M antibody to hepatitis A virus, hepatitis B surface antigen, antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen were absent. Results of serological tests for infection by hepatitis C virus were negative. Results of serological tests were also negative for recent infection with cytomegalovirus, Epstein-Barr virus, herpes simplex viruses, rickettsiae, human immunodeficiency virus, and spirochestes. Serological tests were slightly positive (1:lOO) for antibodies to smooth muscle and were negative for antibodies to nuclei, mitochondria, and microsomes. The serum levels of copper, ceruloplasmin, and a,-antitrypsin were normal. Ultrasonography and computed tomography (CT) showed ascites, normal liver, and normal biliary tract. The injection of contrast medium for dynamic CT was followed by acute renal failure. On October 18, ascites level had increased and was associated with leg edema; confusion and coma developed. On October 20, hepatic vein catheterization was performed: the gradient between wedged and free hepatic venous pressures was 22 mm Hg, a value consistent with portal hypertension (normal, 2-4). Histological examination of a liver tissue specimen taken by transvenous biopsy showed extensive hepatocyte necrosis predominating in centrilobular area, cholestasis, associated with infiltration with polymorphonuclear and mononuclear cells. Inflammatory cells were
@ 1~10by the American GastroenterologicaI Association 0019-5095/90/$3.00
December 1990
LISINOPRIL AND FLJLMINANT HEPATITIS
1833
Table 2. Relationship Between Lisinopril Administration and Time Course of Liver Tests
Date
September zz October 11 October 19
November 7 November 26 Normal values
Serum bilirubin (fimoVL1
Serum ALT (U/L)
Serum AST (U/L)
Prothrombin (% of normal)
Proaccelerin (% of normal]
316 689 640 1200
2510 2561 520 97
1470 2360 263 94
90 20 30 42
30 27 68
239
BRIEF
1990;99:1332-1833
REPORTS
Fulminant Hepatitis After Lisinopril Administration DOMINIQUE LARREY, GERARD BABANY, JACQUES BERNUAU, JACQUES ANDRIEUX, CLAUDE DEGOTT, BENHAMOU DOMINIQUE PESSAYRE, and JEAN-PIERRE Unite de Recherches de Physiopathologie HBpatique (INSERM U-24). Service d’HBpatologie and Service d’Anatomie et de Cytologie Pathologiques. Hapital Beaujon, Clichy; and Service de MBdecine Interne, HBpital M¬, Le Chesnay, France
A case of fulminant hepatitis in a patient taking lisinopril for 5 weeks for arterial hypertension is reported. Jaundice, fever, myalgia, and marked increase in serum aminotransferase activities occurred after z weeks of treatment. Continuation of lisinopril administration for 3 weeks after the onset of jaundice was associated with the development of grade III encephalopathy and a marked decrease in prothrombin and proaccelerin levels. This case strongly suggests that lisinopril may induce acute hepatitis and that continuation of the treatment after the onset of jaundice can lead to life-threatening hepatic failure.
I
nhibitors of angiotensin-converting enzyme are used widely in the treatment of arterial hypertension and congestive heart failure. Usually, these drugs are tolerated well and side effects, if any, are mild. Uncommonly, however, captopril and enalapril can induce acute hepatitis (l-4). To our knowledge, liver injury has not been reported with lisinopril, a new inhibitor of angiotensin-converting enzyme marketed worldwide since 1988 (5). This case report involves a patient affected by fulminant hepatitis within 5 weeks after the beginning of lisinopril administration for arterial hypertension. Case Report A 55-year-old man was admitted for acute hepatitis on October 10,1988. He had no history of disease of the liver or biliary tract, blood transfusion, surgery, drug addiction, or alcohol abuse. He started taking enalapril for arterial hypertension in December 1986. Furosemide and bisoprolol were added to enalapril in October 1987 and April 1988, respectively. These drugs were well tolerated but failed to reduce arterial pressure to normal value. The administration of enalapril was discontinued on September 7, 1988, and was replaced by that of lisinopril, 20 mg daily. On September 15, fever and myalgia developed. On September 19, the patient
was jaundiced. Initial clinical examination was normal except for jaundice. Serum aminotransferase activities were markedly increased and prothrombin time was normal (Table 1). Blood cell counts were normal: in particular, eosinophil count was 1Wmm”. On September 20, administration of furosemide was withdrawn, whereas administration of lisinopril and bisoprolol was continued. On October 10, the patient was admitted because of the worsening of jaundice and the development of ascites. Lisinopril and bisoprolol were withdrawn immediately. Serum aminotransferase levels had further increased; prothrombin and proaccelerin counts had markedly diminished (Table 1).Serum gammaglobulin count was 1.3 g/dL (13 g/L) and serum albumin 3.4 g/dL (34 g/L]. Immunoglobulin M antibody to hepatitis A virus, hepatitis B surface antigen, antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen were absent. Results of serological tests for infection by hepatitis C virus were negative. Results of serological tests were also negative for recent infection with cytomegalovirus, Epstein-Barr virus, herpes simplex viruses, rickettsiae, human immunodeficiency virus, and spirochestes. Serological tests were slightly positive (1:lOO) for antibodies to smooth muscle and were negative for antibodies to nuclei, mitochondria, and microsomes. The serum levels of copper, ceruloplasmin, and a,-antitrypsin were normal. Ultrasonography and computed tomography (CT) showed ascites, normal liver, and normal biliary tract. The injection of contrast medium for dynamic CT was followed by acute renal failure. On October 18, ascites level had increased and was associated with leg edema; confusion and coma developed. On October 20, hepatic vein catheterization was performed: the gradient between wedged and free hepatic venous pressures was 22 mm Hg, a value consistent with portal hypertension (normal, 2-4). Histological examination of a liver tissue specimen taken by transvenous biopsy showed extensive hepatocyte necrosis predominating in centrilobular area, cholestasis, associated with infiltration with polymorphonuclear and mononuclear cells. Inflammatory cells were
@ 1~10by the American GastroenterologicaI Association 0019-5095/90/$3.00
December 1990
LISINOPRIL AND FLJLMINANT HEPATITIS
1833
Table 2. Relationship Between Lisinopril Administration and Time Course of Liver Tests
Date
September zz October 11 October 19
November 7 November 26 Normal values
Serum bilirubin (fimoVL1
Serum ALT (U/L)
Serum AST (U/L)
Prothrombin (% of normal)
Proaccelerin (% of normal]
316 689 640 1200
2510 2561 520 97
1470 2360 263 94
90 20 30 42
30 27 68
239
