LETTERS
270
TO THE EDITOR
HEPAT 01111
Enoxacin acute liver injury [ 1-ethyld-fluoro-1,4-dihydro-7-( l-piperazinyl)Enoxacin 1,8-naphthiridine-3-carboxylic acid] is a broad-spectrum antibiotic belongiilg to the quinolone group. It is used in bacterial infections, particularly those of the respiratory and urinary tracts (1). Although mild elevations in liver enzymes have been reported in patients taking quinolones (2), clinically overt hepatitis induced by enoxacin has never been described. We should like to present the case of a patient with acute liver damage caused by this drug. A 27-year-old woman was admitted to our hospital in January 1991 complaining of jaundice, itching, dark urine, and pale stools which had started 17 days before. She had never had fever or abdominal pain. There was no history of chronic liver disease or allergies. Recent alcohol abuse, blood transfusions or surgery were excluded. Nine days before admission the patient had a flu-like syndrome and took enoxacin 400 mg t.i.d. orally. After the second dose the patient began to itch. On examination she looked well, but showed scratch marks and an enlarged liver with no palpable spleen. No other signs of chronic liver disease were seen. Biochemical investigations showed: total bilirubin, 119 pmol/l (conjugated 68 pmol/l); albumin, 3.8 ~1; AST, 140 (normal up to 25) IUII; ALT, 201 (normal up to 29) IU/l; alkaline phosphatase, 430 (normal up to 207) IV/l; GGT, 28 (normal up to 38) Iv/l; LDH, 400 (normal up to 320) Iv/l; prothrombin time, normal; gammaglobulin, 0.9 g/l. Renal function tests and full blood count were normal. HBSAg, IgM anti-HBcAg, IgM anti-HAV, anti-HCV, IgM anticytomegalovirus, and autoantibodies (ANA, AMA, SMA) were all negative. Liver ultrasonography confirmed hepatomegaly, with normal biliary tract; the gallbladder was normal with no
References 1 Maple P, Bmmfitt W, Hamilton-Miller JM. A review of the antimicrobialactivityof the fluoroquinolones. J Chemother 1990;
Bil. tmol/L
AUTU.Ia A
168 ’ 141
0
2
--Au
\
/
-Bil,
\
4
6
8
18
12
313
14
Meek Fig. 1. Total bilirubin and AST trend.
gallstones. Retrograde endoscopic cholangiopancreatography showed a normal biliary tree. One month after the onset of the symptoms, bilirubin reached 374 pmol/l while aminotransferase decreased to 1.5 the upper limit of the normal range. The patient was treated conservatively because of the possibility of druginduced liver damage, jaundice regressed gradually. All liver function tests were within the normal range in 10 weeks time (Fig. 1) and were repeately confirmed to be normal after 6 months of follow-up. The clinical course of the illness suggests a cholestatic liver injury caused by enoxacin according to the criteria currently in use (3). To our knowledge, this is the first report of enoxacin acute liver injury. Lucia Amitranoa, Tullio Gigliotti”, Maria Anna Guardascioneb and Antonio Ascioneb “Divisione di Gastroenterologia and bServizio di Fisiopntologia Epatica, Ospedale A. Cardarelli, Naples, Ztafy
2 Halkin H. Adverse effects of the Ruoroquinolones. Rev Infect Dis 1988; 10 (Suppl 1): S258-61. 3 Criteria of drug-induced liver disorders. Report of an International Consensus Meeting. J Hepatol 1990; 11: 272-6.
2: 280-94.
HEPAT 01127
Portal pressure response to propranolol We read the article ‘Propranolol and haemodynamic response in cirrhosis’ with interest (1). We have also used
in portal h.y
propranolol in children with portal hypertension due to cirrhosis, chronic active hepatitis, idiopathic portal hy
LETTERS
TO THE EDITOR
271
pertension, extra-hepatic portal hypertension or congenital hepatic fibrosis (2). In our patients kigher propranolo1 doses (2.1-6.3 mg/kg) were required for longer periods (9-28 days) than the single dose used by the authors to achieve a 25% decrease in heart rate. Splenic pulp and peripheral venous pressure were evaluated in our patients prior to propranolol and after reaching the required pulse decrease. Both were found to be markedly decreased by the drug (p c 0.01 for both). Although the authors said: ‘no difference in the effect of propranolol on portal pressure was observed between patients with or without ascites’, when hepatic blood was evaluated, a decrease in splenic pulp pressure was observed in all our cases without ascites, but in half with ascites. This was not related to the cause of portal hypertension when splenic pressure was taken into consideferences 1 Bendtsen F, Hem&en
JH, Stireusen TIA.
Propratlolol 2nd hae-
eration. There also seemed to be certain differences in decreases in peripheral venous pressure between these groups. Further studies might determine whetiler these differences are related to the age of the patients or to the etiology of portal hypertension. Since splenic pulp pressure decreases in most patients, we use propranolol to treat our patients with portal hypertension.
!jinasi ijzsoylu, dzbag
Nurten Kolak,
Aysel Yiice, and Elif
Faculty of Medicine, Departments of Pediatrics and Gastroenterology, Faculty of Medicine, Hacettepe iJniversi:!l and Hacettepe Children’s Hospital, Ankara, Turkey.
modynamic response in cirrhosis. 9 Hepatol 1991; 13: 1&I-S. 2 CizsoyluS, Kqak N. Yiice A. Propranolol therapy for hypertensian in children. J Rdiatr 1985: 106: 317-21.
HEPAT 01128
Several uncrontrolled studies have reported that dialytic ultraiiltration of ascitic fluid associated with peritoneal reinfusion of the concentrate can be a safe and effective therapy for refractory ascites (1,2). The aim of this study was to compare dialytic ultrafiltration of ascitic fluid with large paracentesis in cirrhotic patients. The preliminary results of this study are as follows: Patients with massive intractable ascites were included. Exclusion criteria were recent gastrointestinal bleeding, porto-systemic encephalopatL, sepsis, cardiac failure, serum creatinine over 200 pmol/l, and hepatocellular car+nma. Eigh? courses of dialytic ultrafiltr!inon and 10 large ,paracenteses were performed in 5 patients. Four patients had alcoholic cirrhosis. The techniqine used was randomized at each session. Dialytic ultrafiltration was performed using a multiperforated sterile catheter inserted into the peritoneal cavity. Ascitic fluid passed through an hemofilter (Biospal, SCU CAVH) by gravity. Concentrated fluid was collected in a 2000~ml sterile bag, then placed 150 cm above the patient’s bed and refiltered. Concentrated fiuid
was reinfused by gravity into the peritoneal cavity us.ing the same catheter. This procedure was repeated to obtain either complete evacuation of ascites or the collection of 8 liters of ultrafiltrate. During large paracentesis, 8 liters of ascitic fluid were collected or complete evacuation was achieved using the same type of catheter as in the preceding technique. Clinical and biorhcmical monitoring were performed before each procedure, 24 h later and at the fourth and seventh days after the procedure. Albumin (20 g/l00 ml) was infused when serum ceeatinine levels increased abore 150 @mol. Effects ot dialytic ultrafiltration and large paracentesis are shown in Tables 1 and 2. The volume of ultrafiltered or removed ascitcs was 8.1 2 0.7 vs. 8.8 + 0.6 (n.s.) respectively. No change in hemetocrit, serum or urinary electrolytes or plasmatic Mood volume was observed after either procedure. However, dialytic ultrafiltration &Iduced a significant increase in serum aFbumin and ascitic protein concentrations that lasted less rhan 7 days (Tabie 2) and a transient increase in daily urin~j c&put @ : 0.02) (Table 1). The number of procedures requiring
270
TO THE EDITOR
HEPAT 01111
Enoxacin acute liver injury [ 1-ethyld-fluoro-1,4-dihydro-7-( l-piperazinyl)Enoxacin 1,8-naphthiridine-3-carboxylic acid] is a broad-spectrum antibiotic belongiilg to the quinolone group. It is used in bacterial infections, particularly those of the respiratory and urinary tracts (1). Although mild elevations in liver enzymes have been reported in patients taking quinolones (2), clinically overt hepatitis induced by enoxacin has never been described. We should like to present the case of a patient with acute liver damage caused by this drug. A 27-year-old woman was admitted to our hospital in January 1991 complaining of jaundice, itching, dark urine, and pale stools which had started 17 days before. She had never had fever or abdominal pain. There was no history of chronic liver disease or allergies. Recent alcohol abuse, blood transfusions or surgery were excluded. Nine days before admission the patient had a flu-like syndrome and took enoxacin 400 mg t.i.d. orally. After the second dose the patient began to itch. On examination she looked well, but showed scratch marks and an enlarged liver with no palpable spleen. No other signs of chronic liver disease were seen. Biochemical investigations showed: total bilirubin, 119 pmol/l (conjugated 68 pmol/l); albumin, 3.8 ~1; AST, 140 (normal up to 25) IUII; ALT, 201 (normal up to 29) IU/l; alkaline phosphatase, 430 (normal up to 207) IV/l; GGT, 28 (normal up to 38) Iv/l; LDH, 400 (normal up to 320) Iv/l; prothrombin time, normal; gammaglobulin, 0.9 g/l. Renal function tests and full blood count were normal. HBSAg, IgM anti-HBcAg, IgM anti-HAV, anti-HCV, IgM anticytomegalovirus, and autoantibodies (ANA, AMA, SMA) were all negative. Liver ultrasonography confirmed hepatomegaly, with normal biliary tract; the gallbladder was normal with no
References 1 Maple P, Bmmfitt W, Hamilton-Miller JM. A review of the antimicrobialactivityof the fluoroquinolones. J Chemother 1990;
Bil. tmol/L
AUTU.Ia A
168 ’ 141
0
2
--Au
\
/
-Bil,
\
4
6
8
18
12
313
14
Meek Fig. 1. Total bilirubin and AST trend.
gallstones. Retrograde endoscopic cholangiopancreatography showed a normal biliary tree. One month after the onset of the symptoms, bilirubin reached 374 pmol/l while aminotransferase decreased to 1.5 the upper limit of the normal range. The patient was treated conservatively because of the possibility of druginduced liver damage, jaundice regressed gradually. All liver function tests were within the normal range in 10 weeks time (Fig. 1) and were repeately confirmed to be normal after 6 months of follow-up. The clinical course of the illness suggests a cholestatic liver injury caused by enoxacin according to the criteria currently in use (3). To our knowledge, this is the first report of enoxacin acute liver injury. Lucia Amitranoa, Tullio Gigliotti”, Maria Anna Guardascioneb and Antonio Ascioneb “Divisione di Gastroenterologia and bServizio di Fisiopntologia Epatica, Ospedale A. Cardarelli, Naples, Ztafy
2 Halkin H. Adverse effects of the Ruoroquinolones. Rev Infect Dis 1988; 10 (Suppl 1): S258-61. 3 Criteria of drug-induced liver disorders. Report of an International Consensus Meeting. J Hepatol 1990; 11: 272-6.
2: 280-94.
HEPAT 01127
Portal pressure response to propranolol We read the article ‘Propranolol and haemodynamic response in cirrhosis’ with interest (1). We have also used
in portal h.y
propranolol in children with portal hypertension due to cirrhosis, chronic active hepatitis, idiopathic portal hy
LETTERS
TO THE EDITOR
271
pertension, extra-hepatic portal hypertension or congenital hepatic fibrosis (2). In our patients kigher propranolo1 doses (2.1-6.3 mg/kg) were required for longer periods (9-28 days) than the single dose used by the authors to achieve a 25% decrease in heart rate. Splenic pulp and peripheral venous pressure were evaluated in our patients prior to propranolol and after reaching the required pulse decrease. Both were found to be markedly decreased by the drug (p c 0.01 for both). Although the authors said: ‘no difference in the effect of propranolol on portal pressure was observed between patients with or without ascites’, when hepatic blood was evaluated, a decrease in splenic pulp pressure was observed in all our cases without ascites, but in half with ascites. This was not related to the cause of portal hypertension when splenic pressure was taken into consideferences 1 Bendtsen F, Hem&en
JH, Stireusen TIA.
Propratlolol 2nd hae-
eration. There also seemed to be certain differences in decreases in peripheral venous pressure between these groups. Further studies might determine whetiler these differences are related to the age of the patients or to the etiology of portal hypertension. Since splenic pulp pressure decreases in most patients, we use propranolol to treat our patients with portal hypertension.
!jinasi ijzsoylu, dzbag
Nurten Kolak,
Aysel Yiice, and Elif
Faculty of Medicine, Departments of Pediatrics and Gastroenterology, Faculty of Medicine, Hacettepe iJniversi:!l and Hacettepe Children’s Hospital, Ankara, Turkey.
modynamic response in cirrhosis. 9 Hepatol 1991; 13: 1&I-S. 2 CizsoyluS, Kqak N. Yiice A. Propranolol therapy for hypertensian in children. J Rdiatr 1985: 106: 317-21.
HEPAT 01128
Several uncrontrolled studies have reported that dialytic ultraiiltration of ascitic fluid associated with peritoneal reinfusion of the concentrate can be a safe and effective therapy for refractory ascites (1,2). The aim of this study was to compare dialytic ultrafiltration of ascitic fluid with large paracentesis in cirrhotic patients. The preliminary results of this study are as follows: Patients with massive intractable ascites were included. Exclusion criteria were recent gastrointestinal bleeding, porto-systemic encephalopatL, sepsis, cardiac failure, serum creatinine over 200 pmol/l, and hepatocellular car+nma. Eigh? courses of dialytic ultrafiltr!inon and 10 large ,paracenteses were performed in 5 patients. Four patients had alcoholic cirrhosis. The techniqine used was randomized at each session. Dialytic ultrafiltration was performed using a multiperforated sterile catheter inserted into the peritoneal cavity. Ascitic fluid passed through an hemofilter (Biospal, SCU CAVH) by gravity. Concentrated fluid was collected in a 2000~ml sterile bag, then placed 150 cm above the patient’s bed and refiltered. Concentrated fiuid
was reinfused by gravity into the peritoneal cavity us.ing the same catheter. This procedure was repeated to obtain either complete evacuation of ascites or the collection of 8 liters of ultrafiltrate. During large paracentesis, 8 liters of ascitic fluid were collected or complete evacuation was achieved using the same type of catheter as in the preceding technique. Clinical and biorhcmical monitoring were performed before each procedure, 24 h later and at the fourth and seventh days after the procedure. Albumin (20 g/l00 ml) was infused when serum ceeatinine levels increased abore 150 @mol. Effects ot dialytic ultrafiltration and large paracentesis are shown in Tables 1 and 2. The volume of ultrafiltered or removed ascitcs was 8.1 2 0.7 vs. 8.8 + 0.6 (n.s.) respectively. No change in hemetocrit, serum or urinary electrolytes or plasmatic Mood volume was observed after either procedure. However, dialytic ultrafiltration &Iduced a significant increase in serum aFbumin and ascitic protein concentrations that lasted less rhan 7 days (Tabie 2) and a transient increase in daily urin~j c&put @ : 0.02) (Table 1). The number of procedures requiring
