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Effect of a low iron diet in chronic hepatitis C
patients who did not use alcohol and did not have previous gastric surgery (8 male and 15 female, 62+/-10 years old); and compared to 63 patients not on a special diet (41 male and 22 female, 52 +/-9 years old). Individual patient consulted their nutritional status for 6 months. By face to face interview patients were asked to change iron-rich food to another one. We measured serum ALT and ferritin levels, albumin (ALB), hemoglobin (Hgb), and red blood cell count (RBC). RESULTS. 36.3% of the 215 HCV patients had high serum ferritin levels (347.9 +/-263.2ng/m[). Serum ALT levels were significantly higher in patients with high serum ferritin levels compared to those with normal ferritin levels. After 6 months of a low iron diet, serum ferritin levels decreased from 347.9 +/-263.2ng/ml to 280.0+/177.2ng/ml (p<0.05), and serum ALT levels improved from 136.8 +/-89.8U/L to 85.2+/50.0U/L (p<0.05). Sigraficant decrements in ALT occurred in 90.9% of patients with decreased serum ferritin levels. Nutritional parameters as measured by ALB, Hgb, and RBC were not significantly changed by the low iron diet. In patients on the non-iron restricted diet, there were no significant changes in ferritin or ALT levels. CONCLUSION. Serum ferritin levels are increased in patients with chronic hepatitis C, and those with higher serum ferritin levels had increased ALT levles. A low iron diet reduced serum ferritin and ALT levels, while maintaining normal nutritional parameters. A low iron diet appears to be safe and effective in patients with chronic hepatitis C, and may be an ahemative treatment option in patients who do not respond to or are not candidates for interferon therapy.
C (HCV) was tested by PCR in 7 studies; 4 used ELISA; 11 did not provide the information. 8 publications (59 patients) reported progression of NASH to cirrhosis (4 LS, 1 CCS, 1 CS, 2 CR). 90% of liver explants from CC patients were shown in 1 CCS to have histologic features of NASH. 5 studies (3 CCS, 1 CS, 1 CR) reported the dLsappearance of histologic features of NASH in a total of 6 patients upon the development of cirrhosis. The prevalence of NASH risk factors was higher in patients with CC compared to controls in 8 studies (1 Co, 3 LS, 4 CCS). Development of NASH post-transplant (OLT) in patients with NASH cirrhosis was described in 5 articles (1 LS, 1 CCS, 3 CR). The CCS reported this occurrence in 60% of patients with NASH cirrhosis compared to 5%, 15% and 15% of patients with cholestatic, alcohol, and HCV-related cirrhosis, respectively; P value and amount of immunosuppression received by each group were not reported. Development of NASH post-OLT in patients with CC was described in 4 studies (1 Co, 1 LS, 2 CCS); the LS did not have a control group. The amount of immunosuppression received by each group was described and considered a potential confounding variable in all 4 studies; in only 1 of 4 studies (CCS) was the cumulative steroid dose associated with steatosis in the allograft. Conclusions: Current evidence suggests that NASH leads to cirrhosis, that features of NASH disappear with the development of cirrhosis, that there is an increased prevalence of NASH risk factors in CC, and that NASH recurs post-OLT in patients with NASH cirrhosis and in those with CC. There is, therefore, sufficient basis to believe that NASH is a contributing factor in the development of CC. Limitations of the available evidence include the retrospective design of most studies, and the lack of documentation of HCV status and definition of signficant alcohol use in half the studies.
M1619 Hispanics with Chronic Hepatitis C Have More Fibrosis and Cirrhosis Victor L. Carlo, Esther A. Tortes, Priscilla Magno, Maria Vazquez, Carmen GonzalezKeelan
M1616 The A 3 2 Mutation of the Chemokine-receptor 5 Gene is Neither Correlated with Chronic Hepatitis C nor Does it Predict Response to Therapy with Interferon-~ and Ribavirin Juergen Glas, Helga-Paula Torok, Christian Simperl, August Koenig, Katja Martin, Folkhard Schmidt, Martin Schaefer, Christian Folwaczny
Aims: 1. Determine prevalence of cirrhosis and fibrosis progression in Hispanics with chronic hepatitis C. 2. Describe associations between METAVIR score, fibrosis progression (FP) and gender, alcohol use, blood transfusions (BT) and illicit drug use. Methods: Records of patients with chronic hepatitis C seen at the UPR GI Research Unit from 1990 to 2001 who had an elevated ALT and liver biopsy available for interpretation were reviewed. Demographics, alcohol use, and risk factors were collected. Liver biopsies were reviewed by a single pathologist using the METAVIR scoring system for level of activity and fibrosis. EP was determined by the ratio of fibrosis score and the time-interval between earliest known risk exposure and the liver biopsy and correlated with medical data. Statistical analysis was performed with EPI Info v 6.0. Results: Two hundred patients out of 332 were included; 125 were male; mean age 43 -+ 11.9. Seventy-one (35.5%) had received BT. Alcohol use was recorded in 94/200 (47.2%) and 1VDUin 67/200 (33.5%). No risk factors were identified in 12 (6.0%) patients. Chronic hepatitis C with minimal activity (A1) was present in 83 (41.5%, 53M: 301=) and moderate activity (A2) in 69 (34.5%, 42M: 27F). Thirty-three percem (65/200, 43M: 22F) presented portal fibrosis without septa (F 1), twenty-eight percent (55/200, 36M: 19F) portal fibrosis with some septa (F2), seventeen percent (33/200, 21M: 12F) portal fibrosis with septa (F3), and twenty-two percent (43/200, 22M: 21F) with cirrhosis (1=4). Fifty-three percent (23/43) of cirrhosis, thirty-one percent (48/153) of fibrosis (F1-F3) had received BT. The mean rote of FP in 104 patients was 0.167 _+0.159 units. Conclusions: The percentage of patients presenting with fibrosis (76.5%) and cirrhosis (21.5%) in our population was higher than reported in other ethnic groups. The mean rate of FP per year was not different from those reported in Japanese (0.12 _+0.15) and European (0.133) studies. No risk factors or gender were associated with an increased rate of FP. Blood transfusion correlated sigulficantly with higher incidence of fibrosis and cirrhosis (p < 0.008). Higher ALT levels correlated significantly with worse scores for both activity and fibrosis (p < 0.05). Genetic factors may play a role in influencing the severity of disease. Further studies in this area are warranted to clarify ethnic differences in the presentation of chronic hepatitis C.
BACKGROUND: As opposed to patients infected with HIV, homozygosity for a 32 bp deletion (A32) of the chemokine-receptor 5 (CCR5) gene was recently described in increased frequency in patients with chronic hepatitis C. Thus, it was speculated that this mutation might be relevant for disease susceptibility and influence the response to antiviral therapy. While a protective effect of this homozygous mutation against HIV infection is widely accepted, its role in hepatitis C is not yet clear. AIM: The present study sought to confirm the association between chronic hepatitis C and the A32 mutation of the CCR5 gene and to correlate it with the response to therapy with interferon-a-2a and rihavirm. METHODS: 62 patients with chronic hepatitis C and 119 healthy unrelated controls were genotyped for the A32 mutation by PCR and agarose gel electrophoresis. For the correlation between the A32 mutation and response to therapy only patients (n = 59) who completed six months of combination therapy as part of a prospective study were evaluated. RESULTS: The A32 mutation was not observed in increased frequency in chronic hepatitis C. Furthermore, a significant difference concerning the viral load or aminotmnsferase values was not observed in carriers versus ~n-carriers of the A32 mutation. After stratification for potentially confounding factors such as gender or HCV-genotype a sigmficant difference was also not detected with respect to treatment outcome. CONCLUSIONS: These observations argue strongly against a role of CCR5 for susceptibility to chronic infection with HCV or response to combination therapy with interferon-a-2a and ribavirin.
M1617 Clinical Examination of Osteoporosis in the Chronic Liver Disease Kazutomo Suzuki, Hiroshi Takada, Hajime Kuwayama
TaMe 1: RiskFactorvs. Fibrosis Risk Factor BT IVDA EtOH
AIM. Osteoporosis is often present in patients with chronic hver disease. However, the frequency of signdicant osteoporosis m Japanese patients with chronic liver disease, and whether there are differences in different disease etiologies, is not well defined. We therefore evaluated the frequency of osteoporosis in patients with primary bihary cirrhosis (PBC), liver cirrhosis (LC), chronic active hepatitis (CAH), and autoimmune hepatitis (AIH). METHODS. The subjects were 75 patients with chronic liver disease (13 PBC, 23 LC, 27 CAH, and 12 AIH). Bone mineral density (BMD) was measured in lumbar spine (SPINE) and femoral neck (FEMUR), using dual energy X-ray absorptiometry (DXA). Osteoporosis is defined as a T-score of -2.5 standard deviations(SDs) or greater. RESULTS. 1. Osteoporosis was found in 60% (45/75) of patients with chronic liver disease - 76.9 %(10/13) in PBC, 65.2%(15/32) in LC, 48.1(13/27) in CAH, and 58.0%(7/12) in AIH. 2. T-score of SPINE was -2.21 with PBC, -1.55 with LC, -1.55 with CAH, and -1.55 with AIH. T-score was significantly lower in PBC than CAH (p<0.05). 3. T-score of FEMUR was -2.08 with PBC, 2.28 with LC, -1.54 with CAH, and -1.55 with A1H, but not sigmficantly different among groups. 4. In 8 patients (10%), osteoporosis was found by a T-seore that was low in FEMUR but not in SPINE. CONCLUSION. Osteoporusis as measured by decreased BMD is frequent in chronic liver disease, and appears to have similar frequency in PBC, cirrhosis, CAH, and AIH. In patients with chronic liver disease, BMD should be measured to detect osteoporosis, and BMD should be measured in both SPINE and FEMUR.
Ft 20 24 32
F2 14 23 25
F3 14 6 17
F4 23 12 18
p-value 0.008 0.151 0.792
M1620 Nf-Kappa B Activation and Decreased CD 194- B-Cell Apoptosis Are Key Mechanisms in Hepatitis C Virus Infection Induced Lymphomagenesis? Beata Gasztonyi, Katahn Kiss, Alajos Par, Laszlo Szereday, Laszlo Kereskai, Gabiella Par, Gyula Mozsik Background: Hepatitis C virus (HCV) is hepatotropic and lymphotropic agent, infects not only hepatocytes, but monocytes-macrophages, and lymphoid cells, all which may play a role in the persistence of infection and in development of extrahepatic manifestations such as B-cell proliferation and non-Hodgkins lymphoma (NHL). Antiapoptotic effect of the HCV may display via activation of nuclear factor kappa B (NF-kappa B) and can lead to development of hepatocellular carcinoma (HCC) and even B-cell NHL Aims: 1. Activated NF-kappa B was examined in lymphocytes of patients with HCV infection and NHL 2. NF-kappa B was detected in liver biopsies of patients with HCC and in lymp nodes of patients with NHL. 3. CD 19+ B-cell apoptosis was studied in lymphocytes of patients with HCV infection and with B-cell NHL. Patients and methods: 1. Total 56 patients with chronic hepatitis C, 21 patients with B-cell NHL and 2 HCC patients were studied. We examined the activity of NF-kappa B using electrophoretic mobility shift assay, immunohistocbemistry was performed in liver and lymph nodes biopsies. Fhiorescein labelled Annexin V flow cytometry was used for the evaluation of apoptosis. Results: 1. NF-kappa B activation was found in the lymphocyte extracts from all patients with chronic HCV infection and in 10/13 (76,92%) patients with B-cell NHL 2. NF-kappa B was detectable in 7/8 cases in liver biopsies from HCV positive patients. Strong reaction was detected in nuclei in HCV positive HCC and NHL patients (no reaction in HCV negative biopsies). 3. Decreased B-cell apoptosis was detected in 31/38 (81,57%) HCV patients and in 6/6 (100%) NHL patients. Conclusions: NF-kappa B activation together with decreased CD 19 + B-cell apoptosis, mechanisms by
M1618 Effect of a Low Iron Diet in Chronic Hepatitis C Tomoko Katoh, Kazutomo Suzuki, Hiroshi Takada, Gordon Luk, Hajime Kuwayama BACKGROUND AND AIMS. Excessive hepatic iron deposition contributes to the progression of liver disease in hemochromatosis; and plasmapheresis or iron chelation are the mainstay of therapy. It is unclear whether excessive iron deposition may also contribute to progression of other chronic liver diseases, such as hepatitis C, and whether a low iron diet alone may be therapeutic. We therefore investigated the effect nf a low iron diet in chronic hepatitis C. METHODS. We measured serum alanine transaminase (ALT) and ferritin levels in 215 patients with chronic hepatitis C. The effect of a low iron diet was studied in 23 of these
AGA Abstracts
F0 0 2 2
A-384
C (HCV) was tested by PCR in 7 studies; 4 used ELISA; 11 did not provide the information. 8 publications (59 patients) reported progression of NASH to cirrhosis (4 LS, 1 CCS, 1 CS, 2 CR). 90% of liver explants from CC patients were shown in 1 CCS to have histologic features of NASH. 5 studies (3 CCS, 1 CS, 1 CR) reported the dLsappearance of histologic features of NASH in a total of 6 patients upon the development of cirrhosis. The prevalence of NASH risk factors was higher in patients with CC compared to controls in 8 studies (1 Co, 3 LS, 4 CCS). Development of NASH post-transplant (OLT) in patients with NASH cirrhosis was described in 5 articles (1 LS, 1 CCS, 3 CR). The CCS reported this occurrence in 60% of patients with NASH cirrhosis compared to 5%, 15% and 15% of patients with cholestatic, alcohol, and HCV-related cirrhosis, respectively; P value and amount of immunosuppression received by each group were not reported. Development of NASH post-OLT in patients with CC was described in 4 studies (1 Co, 1 LS, 2 CCS); the LS did not have a control group. The amount of immunosuppression received by each group was described and considered a potential confounding variable in all 4 studies; in only 1 of 4 studies (CCS) was the cumulative steroid dose associated with steatosis in the allograft. Conclusions: Current evidence suggests that NASH leads to cirrhosis, that features of NASH disappear with the development of cirrhosis, that there is an increased prevalence of NASH risk factors in CC, and that NASH recurs post-OLT in patients with NASH cirrhosis and in those with CC. There is, therefore, sufficient basis to believe that NASH is a contributing factor in the development of CC. Limitations of the available evidence include the retrospective design of most studies, and the lack of documentation of HCV status and definition of signficant alcohol use in half the studies.
M1619 Hispanics with Chronic Hepatitis C Have More Fibrosis and Cirrhosis Victor L. Carlo, Esther A. Tortes, Priscilla Magno, Maria Vazquez, Carmen GonzalezKeelan
M1616 The A 3 2 Mutation of the Chemokine-receptor 5 Gene is Neither Correlated with Chronic Hepatitis C nor Does it Predict Response to Therapy with Interferon-~ and Ribavirin Juergen Glas, Helga-Paula Torok, Christian Simperl, August Koenig, Katja Martin, Folkhard Schmidt, Martin Schaefer, Christian Folwaczny
Aims: 1. Determine prevalence of cirrhosis and fibrosis progression in Hispanics with chronic hepatitis C. 2. Describe associations between METAVIR score, fibrosis progression (FP) and gender, alcohol use, blood transfusions (BT) and illicit drug use. Methods: Records of patients with chronic hepatitis C seen at the UPR GI Research Unit from 1990 to 2001 who had an elevated ALT and liver biopsy available for interpretation were reviewed. Demographics, alcohol use, and risk factors were collected. Liver biopsies were reviewed by a single pathologist using the METAVIR scoring system for level of activity and fibrosis. EP was determined by the ratio of fibrosis score and the time-interval between earliest known risk exposure and the liver biopsy and correlated with medical data. Statistical analysis was performed with EPI Info v 6.0. Results: Two hundred patients out of 332 were included; 125 were male; mean age 43 -+ 11.9. Seventy-one (35.5%) had received BT. Alcohol use was recorded in 94/200 (47.2%) and 1VDUin 67/200 (33.5%). No risk factors were identified in 12 (6.0%) patients. Chronic hepatitis C with minimal activity (A1) was present in 83 (41.5%, 53M: 301=) and moderate activity (A2) in 69 (34.5%, 42M: 27F). Thirty-three percem (65/200, 43M: 22F) presented portal fibrosis without septa (F 1), twenty-eight percent (55/200, 36M: 19F) portal fibrosis with some septa (F2), seventeen percent (33/200, 21M: 12F) portal fibrosis with septa (F3), and twenty-two percent (43/200, 22M: 21F) with cirrhosis (1=4). Fifty-three percent (23/43) of cirrhosis, thirty-one percent (48/153) of fibrosis (F1-F3) had received BT. The mean rote of FP in 104 patients was 0.167 _+0.159 units. Conclusions: The percentage of patients presenting with fibrosis (76.5%) and cirrhosis (21.5%) in our population was higher than reported in other ethnic groups. The mean rate of FP per year was not different from those reported in Japanese (0.12 _+0.15) and European (0.133) studies. No risk factors or gender were associated with an increased rate of FP. Blood transfusion correlated sigulficantly with higher incidence of fibrosis and cirrhosis (p < 0.008). Higher ALT levels correlated significantly with worse scores for both activity and fibrosis (p < 0.05). Genetic factors may play a role in influencing the severity of disease. Further studies in this area are warranted to clarify ethnic differences in the presentation of chronic hepatitis C.
BACKGROUND: As opposed to patients infected with HIV, homozygosity for a 32 bp deletion (A32) of the chemokine-receptor 5 (CCR5) gene was recently described in increased frequency in patients with chronic hepatitis C. Thus, it was speculated that this mutation might be relevant for disease susceptibility and influence the response to antiviral therapy. While a protective effect of this homozygous mutation against HIV infection is widely accepted, its role in hepatitis C is not yet clear. AIM: The present study sought to confirm the association between chronic hepatitis C and the A32 mutation of the CCR5 gene and to correlate it with the response to therapy with interferon-a-2a and rihavirm. METHODS: 62 patients with chronic hepatitis C and 119 healthy unrelated controls were genotyped for the A32 mutation by PCR and agarose gel electrophoresis. For the correlation between the A32 mutation and response to therapy only patients (n = 59) who completed six months of combination therapy as part of a prospective study were evaluated. RESULTS: The A32 mutation was not observed in increased frequency in chronic hepatitis C. Furthermore, a significant difference concerning the viral load or aminotmnsferase values was not observed in carriers versus ~n-carriers of the A32 mutation. After stratification for potentially confounding factors such as gender or HCV-genotype a sigmficant difference was also not detected with respect to treatment outcome. CONCLUSIONS: These observations argue strongly against a role of CCR5 for susceptibility to chronic infection with HCV or response to combination therapy with interferon-a-2a and ribavirin.
M1617 Clinical Examination of Osteoporosis in the Chronic Liver Disease Kazutomo Suzuki, Hiroshi Takada, Hajime Kuwayama
TaMe 1: RiskFactorvs. Fibrosis Risk Factor BT IVDA EtOH
AIM. Osteoporosis is often present in patients with chronic hver disease. However, the frequency of signdicant osteoporosis m Japanese patients with chronic liver disease, and whether there are differences in different disease etiologies, is not well defined. We therefore evaluated the frequency of osteoporosis in patients with primary bihary cirrhosis (PBC), liver cirrhosis (LC), chronic active hepatitis (CAH), and autoimmune hepatitis (AIH). METHODS. The subjects were 75 patients with chronic liver disease (13 PBC, 23 LC, 27 CAH, and 12 AIH). Bone mineral density (BMD) was measured in lumbar spine (SPINE) and femoral neck (FEMUR), using dual energy X-ray absorptiometry (DXA). Osteoporosis is defined as a T-score of -2.5 standard deviations(SDs) or greater. RESULTS. 1. Osteoporosis was found in 60% (45/75) of patients with chronic liver disease - 76.9 %(10/13) in PBC, 65.2%(15/32) in LC, 48.1(13/27) in CAH, and 58.0%(7/12) in AIH. 2. T-score of SPINE was -2.21 with PBC, -1.55 with LC, -1.55 with CAH, and -1.55 with AIH. T-score was significantly lower in PBC than CAH (p<0.05). 3. T-score of FEMUR was -2.08 with PBC, 2.28 with LC, -1.54 with CAH, and -1.55 with A1H, but not sigmficantly different among groups. 4. In 8 patients (10%), osteoporosis was found by a T-seore that was low in FEMUR but not in SPINE. CONCLUSION. Osteoporusis as measured by decreased BMD is frequent in chronic liver disease, and appears to have similar frequency in PBC, cirrhosis, CAH, and AIH. In patients with chronic liver disease, BMD should be measured to detect osteoporosis, and BMD should be measured in both SPINE and FEMUR.
Ft 20 24 32
F2 14 23 25
F3 14 6 17
F4 23 12 18
p-value 0.008 0.151 0.792
M1620 Nf-Kappa B Activation and Decreased CD 194- B-Cell Apoptosis Are Key Mechanisms in Hepatitis C Virus Infection Induced Lymphomagenesis? Beata Gasztonyi, Katahn Kiss, Alajos Par, Laszlo Szereday, Laszlo Kereskai, Gabiella Par, Gyula Mozsik Background: Hepatitis C virus (HCV) is hepatotropic and lymphotropic agent, infects not only hepatocytes, but monocytes-macrophages, and lymphoid cells, all which may play a role in the persistence of infection and in development of extrahepatic manifestations such as B-cell proliferation and non-Hodgkins lymphoma (NHL). Antiapoptotic effect of the HCV may display via activation of nuclear factor kappa B (NF-kappa B) and can lead to development of hepatocellular carcinoma (HCC) and even B-cell NHL Aims: 1. Activated NF-kappa B was examined in lymphocytes of patients with HCV infection and NHL 2. NF-kappa B was detected in liver biopsies of patients with HCC and in lymp nodes of patients with NHL. 3. CD 19+ B-cell apoptosis was studied in lymphocytes of patients with HCV infection and with B-cell NHL. Patients and methods: 1. Total 56 patients with chronic hepatitis C, 21 patients with B-cell NHL and 2 HCC patients were studied. We examined the activity of NF-kappa B using electrophoretic mobility shift assay, immunohistocbemistry was performed in liver and lymph nodes biopsies. Fhiorescein labelled Annexin V flow cytometry was used for the evaluation of apoptosis. Results: 1. NF-kappa B activation was found in the lymphocyte extracts from all patients with chronic HCV infection and in 10/13 (76,92%) patients with B-cell NHL 2. NF-kappa B was detectable in 7/8 cases in liver biopsies from HCV positive patients. Strong reaction was detected in nuclei in HCV positive HCC and NHL patients (no reaction in HCV negative biopsies). 3. Decreased B-cell apoptosis was detected in 31/38 (81,57%) HCV patients and in 6/6 (100%) NHL patients. Conclusions: NF-kappa B activation together with decreased CD 19 + B-cell apoptosis, mechanisms by
M1618 Effect of a Low Iron Diet in Chronic Hepatitis C Tomoko Katoh, Kazutomo Suzuki, Hiroshi Takada, Gordon Luk, Hajime Kuwayama BACKGROUND AND AIMS. Excessive hepatic iron deposition contributes to the progression of liver disease in hemochromatosis; and plasmapheresis or iron chelation are the mainstay of therapy. It is unclear whether excessive iron deposition may also contribute to progression of other chronic liver diseases, such as hepatitis C, and whether a low iron diet alone may be therapeutic. We therefore investigated the effect nf a low iron diet in chronic hepatitis C. METHODS. We measured serum alanine transaminase (ALT) and ferritin levels in 215 patients with chronic hepatitis C. The effect of a low iron diet was studied in 23 of these
AGA Abstracts
F0 0 2 2
A-384