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Interferon-induced retinopathy in A uniform regimen of natural interferon-alfa therapy for chronic hepatitis C
A1484 AASLD ABSTRACTS
6717 INTERFERON-INDUCED RETINOPATHY IN A UNIFORM REGIMEN OF NATURAL INTERFERON-ALFA THERAPY FOR CHRONIC HEPATITIS C. Hidetsugu Saito, Hirotoshi Ebinuma, Hiroshi Nagata, Yasutaka Inagaki, Kanji Wakabayashi, Tamako Takagi, Hiromasa Ishii, Keio Univ, Tokyo, Japan; Nihon Kohkan Hosp, Kawasaki, Japan. Background/Aims: The development of retinal lesions induced by a sixmonth-course uniform regimen of interferon-alfa therapy for chronic hepatitis C was prospectively investigated. Methods: Eighty-one patients with serologically and histologically proven chronic active hepatitis C received 6 mega units of natural interferon-alfa (Sumiferon, Sumitomo Pharmaceutical Co., Osaka, Japan) intramuscularly daily for 2 weeks and then 3 times a week for 22 weeks. The total dose of natural interferon-alfa administered was uniformly 478 mega units per patient during 24 weeks. Retinal lesions were prospectively examined by two experts of ophthalmologists before, during and after the therapy. Results: Retinopathy was not found in any of the patients before interferon treatment and totally 34.6% (28/81) of the patients revealed cotton-wool spots or minor retinal hemorrhage or both lesions during therapy, but these lesions were reversed during or after 6-month interferon therapy. The occurrence rate of cotton-wool spots alone, retinal hemorrhage alone and both legions were 13.6% (\1/81), 6.2% (5/81), and 14.8% (\2/81), respectively. Appearance of retinopathy did not correlate with patients' background including viral loads, serotypes and response to the therapy, but was more frequently found in older patients (p=0.04) and patients complicated with hypertension and/or diabetes mellitus in whom disappearance of retinopathy was more prolonged than in patients without these complications. Almost all the lesions appeared between 2-4 months after the start of the therapy and the severity of the lesion did not differ between patients with and without hypertension and/or diabetes mellitus. Other side effects than retinopathy were also observed and all of them recovered during or after the therapy except for one case of hyperthyroidism in which case interferon therapy was discontinued. Conclusion: Altough it is not clear if interferon-associated retinopathy occurs in a dose-dependent manner, the present study shows a standard pattern of the occurrence of retinopathy in patients with chronic hepatitis C receiving a uniform dosage of natural interferon-alfa. Examination of optic fundi in patients with chronic hepatitis C especially complicated with hypertension and/or diabetes mellitus should be regularly performed in interferon treatment.
6718 PROPRANOLOL AMELIORATES HYPERSPLENISM IN PATIENTS WITH CIRRHOSIS. Kenji Sakai, Tadashi Iwao, Kazuhiko Oho, Ryohichi Nakano, Masahiro Sato, Yasuo Miyamoto, Masafumi Kumamoto, Michio Sata, Atsushi Toyonaga, Kurume Univ Sch of Medicine, Kurume, Japan; Iwao Hosp, Hita, Japan. Background/aims: Propranolol causes splanchnic arterial vasoconstriction due to unopposed alpha vasoconstriction resulting from blockade of beta-2 adrenoceptors. lt is therefore hypothesized that this drug may cause vasoconstriction on the splenic arterial circulation and thus modify hypersplenism such as thrombocytopenia. The aim of the present study was to test this hypothesis. Methods: Fifteen patients with cirrhosis and thrombocytopenia (less than 8 x I 04/mm3) were included. All subjects were studied in the morning after an overnight fast. To evaluate splenic arterial hemodynamics, pulsatility index and resistive index were measured by means of Doppler ultrasonography. These splenic Doppler impedance indices were obtained at the main branches of the splenic artery near the hilum. Platelet count and platelet-associated immunoglobulin G were also recorded. Subjects were then randomized to receive propranolol (n = 8) or placebo (n = 7). The measurements were repeated one-week after propranolol or placebo administration. The dose of propranolol was determined by the achievement of a 15-20% reduction in heart rate. Results: Placebo administration had no significant effect on platelet count (from 4.6 ::!: 0.3 to 4.4 ::!: 0.5 x 104/mm3, P = 0.51) and other parameters. In contrast, propranolol administration (mean dose 34 mg) significantly increased platelet count (from 4.4 :':: 0.3 to 6.0 :':: 0.8 x 104/mm3, P < 0.05). This drug also caused a significant increase in pulsatility index (from 1.07 :':: 0.06 to 1.26 :':: 0.07, P < 0.05) and resistive index (from 0.64 :':: 0.02 to 0.70 :':: 0.02, P < 0.05) of the splenic artery. However, the level of platelet-associated immunoglobulin G was not modified during the experiment (from 298 :':: 123 to 272 :':: 100 ng/l07 platelets, P = 0.50). Conclusions: Propranolol ameliorates thrombocytopenia in patients with cirrhosis. This effect may be mainly due to hemodynamic changes in the splenic artery rather than immunological mechanisms.
6719 EFFECT OF BRANCHED-CHAIN AMINO ACID GRANULES (BCAA-G) ON 99MTC-GSA LIVER SCINTIGRAPHY AND BRANCHED-CHAIN AMINO ACID TYROSINE MOLE RATIO (BTR) IN CIRRHOTIC PATIENTS. Motonari Sakai, Masaharu Ohta, Takashi Mori, Naoki Hori, Takayoshi Horii, Torn Ohishi, Hiroyuki Fujino, Kanji Yamaguchi, Yasuharu Inada, Saiseikai kyotofu Hosp, Kyoto, Japan. We investigated the effect of oral supplementation of branched-chain amino acid granules (BCAA-G) on functional reserve capacity of the liver
GASTROENTEROLOGY Vol. 118, No.4
by 99mTc-GSA liver scintigraphy and branched-chain amino acid tyrosine mole ratio (BTR) values in cirrhotic patients. BCAA-G was given at the dose of 14.22g/day for 12 weeks to 21 cirrhotic patients. 99mTc-GSA liver scintigraphy, BTR values and usual liver function tests were analyzed before and at 12 weeks after administration of BCAA-G; and the following results were obtained. The administration of BCAA-G significantly improved serum albumin level, RBC, cholinesterase value and prothrombin time, respectively (p<0.05). The BTR value was also increased from 2.92:'::1.14 to 3.66:':: 1.51, although there was no statistical significance (p
RBC (x 10'(111) Platelets (x 10'/111) ACE (7·25 U/I) Prothrombin time(60·130 %) Acidphosphatase (4-11 UII) Gaucher cellsin bone marrow
Before lx.
6 months
12months
262 5.4 899 54 142 3%
322 56 48.1 60 50.2 1%
332 102 436 69 355 0.1 %
6721 AGE AND CHRONIC NECROINFLAMMATORY CHANGES DETERMINE SEVERITY OF FIBROSIS IN HEPATITIS C. Arun Samanta, Thomas Chen, Lynn Schellhase, VA Med Ctr AND NEW JERSEY Med Sch, East Orange, NJ; VA Med Ctr, East Orange, NJ. Liver injury resulting from chronic hepatitis C produces a spectrum of changes namely portal inflammation and lymphoid aggregate, bile duct injury, hepatocyte steatosis, periportal inflammation and necrosis, focal lobular inflammation and necrosis, and perivenular sclerosis. Whereas distribution of fibrosis in chronic hepatitis C is seen preferentially in areas of predominant hepatocellular injury, relative importance of each of these lesions on the evolution and severity of fibrosis is not clear. AIM: Present study was undertaken to study the importance of different lesions seen in chronic hepatitis C in the pathogenesis and severity of fibrosis. METHODS: Fifty-three patients with HCV-RNA positive chronic hepatitis C were studied. Median age of the patients was 48 years (range 37 to 65 years) Patients were negative for HIV and hepatitis B. All the liver biopsies were obtained prior to treatment. Degree of necrosis, inflammation and fibrosis was scored using Knodell s criteria. Bile duct injury was categorized (absent, mild: occasional duct damage, moderate: consistent duct damage, severe: duct damage with dense periductal inflammation) and
6717 INTERFERON-INDUCED RETINOPATHY IN A UNIFORM REGIMEN OF NATURAL INTERFERON-ALFA THERAPY FOR CHRONIC HEPATITIS C. Hidetsugu Saito, Hirotoshi Ebinuma, Hiroshi Nagata, Yasutaka Inagaki, Kanji Wakabayashi, Tamako Takagi, Hiromasa Ishii, Keio Univ, Tokyo, Japan; Nihon Kohkan Hosp, Kawasaki, Japan. Background/Aims: The development of retinal lesions induced by a sixmonth-course uniform regimen of interferon-alfa therapy for chronic hepatitis C was prospectively investigated. Methods: Eighty-one patients with serologically and histologically proven chronic active hepatitis C received 6 mega units of natural interferon-alfa (Sumiferon, Sumitomo Pharmaceutical Co., Osaka, Japan) intramuscularly daily for 2 weeks and then 3 times a week for 22 weeks. The total dose of natural interferon-alfa administered was uniformly 478 mega units per patient during 24 weeks. Retinal lesions were prospectively examined by two experts of ophthalmologists before, during and after the therapy. Results: Retinopathy was not found in any of the patients before interferon treatment and totally 34.6% (28/81) of the patients revealed cotton-wool spots or minor retinal hemorrhage or both lesions during therapy, but these lesions were reversed during or after 6-month interferon therapy. The occurrence rate of cotton-wool spots alone, retinal hemorrhage alone and both legions were 13.6% (\1/81), 6.2% (5/81), and 14.8% (\2/81), respectively. Appearance of retinopathy did not correlate with patients' background including viral loads, serotypes and response to the therapy, but was more frequently found in older patients (p=0.04) and patients complicated with hypertension and/or diabetes mellitus in whom disappearance of retinopathy was more prolonged than in patients without these complications. Almost all the lesions appeared between 2-4 months after the start of the therapy and the severity of the lesion did not differ between patients with and without hypertension and/or diabetes mellitus. Other side effects than retinopathy were also observed and all of them recovered during or after the therapy except for one case of hyperthyroidism in which case interferon therapy was discontinued. Conclusion: Altough it is not clear if interferon-associated retinopathy occurs in a dose-dependent manner, the present study shows a standard pattern of the occurrence of retinopathy in patients with chronic hepatitis C receiving a uniform dosage of natural interferon-alfa. Examination of optic fundi in patients with chronic hepatitis C especially complicated with hypertension and/or diabetes mellitus should be regularly performed in interferon treatment.
6718 PROPRANOLOL AMELIORATES HYPERSPLENISM IN PATIENTS WITH CIRRHOSIS. Kenji Sakai, Tadashi Iwao, Kazuhiko Oho, Ryohichi Nakano, Masahiro Sato, Yasuo Miyamoto, Masafumi Kumamoto, Michio Sata, Atsushi Toyonaga, Kurume Univ Sch of Medicine, Kurume, Japan; Iwao Hosp, Hita, Japan. Background/aims: Propranolol causes splanchnic arterial vasoconstriction due to unopposed alpha vasoconstriction resulting from blockade of beta-2 adrenoceptors. lt is therefore hypothesized that this drug may cause vasoconstriction on the splenic arterial circulation and thus modify hypersplenism such as thrombocytopenia. The aim of the present study was to test this hypothesis. Methods: Fifteen patients with cirrhosis and thrombocytopenia (less than 8 x I 04/mm3) were included. All subjects were studied in the morning after an overnight fast. To evaluate splenic arterial hemodynamics, pulsatility index and resistive index were measured by means of Doppler ultrasonography. These splenic Doppler impedance indices were obtained at the main branches of the splenic artery near the hilum. Platelet count and platelet-associated immunoglobulin G were also recorded. Subjects were then randomized to receive propranolol (n = 8) or placebo (n = 7). The measurements were repeated one-week after propranolol or placebo administration. The dose of propranolol was determined by the achievement of a 15-20% reduction in heart rate. Results: Placebo administration had no significant effect on platelet count (from 4.6 ::!: 0.3 to 4.4 ::!: 0.5 x 104/mm3, P = 0.51) and other parameters. In contrast, propranolol administration (mean dose 34 mg) significantly increased platelet count (from 4.4 :':: 0.3 to 6.0 :':: 0.8 x 104/mm3, P < 0.05). This drug also caused a significant increase in pulsatility index (from 1.07 :':: 0.06 to 1.26 :':: 0.07, P < 0.05) and resistive index (from 0.64 :':: 0.02 to 0.70 :':: 0.02, P < 0.05) of the splenic artery. However, the level of platelet-associated immunoglobulin G was not modified during the experiment (from 298 :':: 123 to 272 :':: 100 ng/l07 platelets, P = 0.50). Conclusions: Propranolol ameliorates thrombocytopenia in patients with cirrhosis. This effect may be mainly due to hemodynamic changes in the splenic artery rather than immunological mechanisms.
6719 EFFECT OF BRANCHED-CHAIN AMINO ACID GRANULES (BCAA-G) ON 99MTC-GSA LIVER SCINTIGRAPHY AND BRANCHED-CHAIN AMINO ACID TYROSINE MOLE RATIO (BTR) IN CIRRHOTIC PATIENTS. Motonari Sakai, Masaharu Ohta, Takashi Mori, Naoki Hori, Takayoshi Horii, Torn Ohishi, Hiroyuki Fujino, Kanji Yamaguchi, Yasuharu Inada, Saiseikai kyotofu Hosp, Kyoto, Japan. We investigated the effect of oral supplementation of branched-chain amino acid granules (BCAA-G) on functional reserve capacity of the liver
GASTROENTEROLOGY Vol. 118, No.4
by 99mTc-GSA liver scintigraphy and branched-chain amino acid tyrosine mole ratio (BTR) values in cirrhotic patients. BCAA-G was given at the dose of 14.22g/day for 12 weeks to 21 cirrhotic patients. 99mTc-GSA liver scintigraphy, BTR values and usual liver function tests were analyzed before and at 12 weeks after administration of BCAA-G; and the following results were obtained. The administration of BCAA-G significantly improved serum albumin level, RBC, cholinesterase value and prothrombin time, respectively (p<0.05). The BTR value was also increased from 2.92:'::1.14 to 3.66:':: 1.51, although there was no statistical significance (p
RBC (x 10'(111) Platelets (x 10'/111) ACE (7·25 U/I) Prothrombin time(60·130 %) Acidphosphatase (4-11 UII) Gaucher cellsin bone marrow
Before lx.
6 months
12months
262 5.4 899 54 142 3%
322 56 48.1 60 50.2 1%
332 102 436 69 355 0.1 %
6721 AGE AND CHRONIC NECROINFLAMMATORY CHANGES DETERMINE SEVERITY OF FIBROSIS IN HEPATITIS C. Arun Samanta, Thomas Chen, Lynn Schellhase, VA Med Ctr AND NEW JERSEY Med Sch, East Orange, NJ; VA Med Ctr, East Orange, NJ. Liver injury resulting from chronic hepatitis C produces a spectrum of changes namely portal inflammation and lymphoid aggregate, bile duct injury, hepatocyte steatosis, periportal inflammation and necrosis, focal lobular inflammation and necrosis, and perivenular sclerosis. Whereas distribution of fibrosis in chronic hepatitis C is seen preferentially in areas of predominant hepatocellular injury, relative importance of each of these lesions on the evolution and severity of fibrosis is not clear. AIM: Present study was undertaken to study the importance of different lesions seen in chronic hepatitis C in the pathogenesis and severity of fibrosis. METHODS: Fifty-three patients with HCV-RNA positive chronic hepatitis C were studied. Median age of the patients was 48 years (range 37 to 65 years) Patients were negative for HIV and hepatitis B. All the liver biopsies were obtained prior to treatment. Degree of necrosis, inflammation and fibrosis was scored using Knodell s criteria. Bile duct injury was categorized (absent, mild: occasional duct damage, moderate: consistent duct damage, severe: duct damage with dense periductal inflammation) and