N-ACETYLCYSTEINE AND/OR URSODEOXYCHOLIC ACID ASSOCIATED WITH METFORMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL MULTICENTER RANDOMIZED CONTROLLED TRIAL
ABSTRACT BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenes...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia (IBEPEGE)
|
| Series: | Arquivos de Gastroenterologia |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-28032019000200184&lng=en&tlng=en |
| _version_ | 1818601092136566784 |
|---|---|
| author | Claudia P OLIVEIRA Helma P COTRIM Jose Tadeu STEFANO Ana Cristina G SIQUEIRA Ana Lucia Azevedo SALGADO Edison Roberto PARISE |
| author_facet | Claudia P OLIVEIRA Helma P COTRIM Jose Tadeu STEFANO Ana Cristina G SIQUEIRA Ana Lucia Azevedo SALGADO Edison Roberto PARISE |
| author_sort | Claudia P OLIVEIRA |
| collection | DOAJ |
| description | ABSTRACT BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS: Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS: A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION: This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients. |
| first_indexed | 2024-12-16T12:45:53Z |
| format | Article |
| id | doaj.art-d856298d9a9e4b53bd45186e7bf3a417 |
| institution | Directory Open Access Journal |
| issn | 1678-4219 |
| language | English |
| last_indexed | 2024-12-16T12:45:53Z |
| publisher | Instituto Brasileiro de Estudos e Pesquisas de Gastroenterologia (IBEPEGE) |
| record_format | Article |
| series | Arquivos de Gastroenterologia |
| spelling | doaj.art-d856298d9a9e4b53bd45186e7bf3a4172022-12-21T22:31:18ZengInstituto Brasileiro de Estudos e Pesquisas de Gastroenterologia (IBEPEGE)Arquivos de Gastroenterologia1678-421956218419010.1590/s0004-2803.201900000-36S0004-28032019000200184N-ACETYLCYSTEINE AND/OR URSODEOXYCHOLIC ACID ASSOCIATED WITH METFORMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL MULTICENTER RANDOMIZED CONTROLLED TRIALClaudia P OLIVEIRAHelma P COTRIMJose Tadeu STEFANOAna Cristina G SIQUEIRAAna Lucia Azevedo SALGADOEdison Roberto PARISEABSTRACT BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS: Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS: A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION: This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-28032019000200184&lng=en&tlng=enHepatopatia gordurosa não alcoólicaAcetilcisteínaÁcido ursodesoxicólicoMetformina |
| spellingShingle | Claudia P OLIVEIRA Helma P COTRIM Jose Tadeu STEFANO Ana Cristina G SIQUEIRA Ana Lucia Azevedo SALGADO Edison Roberto PARISE N-ACETYLCYSTEINE AND/OR URSODEOXYCHOLIC ACID ASSOCIATED WITH METFORMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL MULTICENTER RANDOMIZED CONTROLLED TRIAL Arquivos de Gastroenterologia Hepatopatia gordurosa não alcoólica Acetilcisteína Ácido ursodesoxicólico Metformina |
| title | N-ACETYLCYSTEINE AND/OR URSODEOXYCHOLIC ACID ASSOCIATED WITH METFORMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL MULTICENTER RANDOMIZED CONTROLLED TRIAL |
| title_full | N-ACETYLCYSTEINE AND/OR URSODEOXYCHOLIC ACID ASSOCIATED WITH METFORMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL MULTICENTER RANDOMIZED CONTROLLED TRIAL |
| title_fullStr | N-ACETYLCYSTEINE AND/OR URSODEOXYCHOLIC ACID ASSOCIATED WITH METFORMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL MULTICENTER RANDOMIZED CONTROLLED TRIAL |
| title_full_unstemmed | N-ACETYLCYSTEINE AND/OR URSODEOXYCHOLIC ACID ASSOCIATED WITH METFORMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL MULTICENTER RANDOMIZED CONTROLLED TRIAL |
| title_short | N-ACETYLCYSTEINE AND/OR URSODEOXYCHOLIC ACID ASSOCIATED WITH METFORMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL MULTICENTER RANDOMIZED CONTROLLED TRIAL |
| title_sort | n acetylcysteine and or ursodeoxycholic acid associated with metformin in non alcoholic steatohepatitis an open label multicenter randomized controlled trial |
| topic | Hepatopatia gordurosa não alcoólica Acetilcisteína Ácido ursodesoxicólico Metformina |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-28032019000200184&lng=en&tlng=en |
| work_keys_str_mv | AT claudiapoliveira nacetylcysteineandorursodeoxycholicacidassociatedwithmetformininnonalcoholicsteatohepatitisanopenlabelmulticenterrandomizedcontrolledtrial AT helmapcotrim nacetylcysteineandorursodeoxycholicacidassociatedwithmetformininnonalcoholicsteatohepatitisanopenlabelmulticenterrandomizedcontrolledtrial AT josetadeustefano nacetylcysteineandorursodeoxycholicacidassociatedwithmetformininnonalcoholicsteatohepatitisanopenlabelmulticenterrandomizedcontrolledtrial AT anacristinagsiqueira nacetylcysteineandorursodeoxycholicacidassociatedwithmetformininnonalcoholicsteatohepatitisanopenlabelmulticenterrandomizedcontrolledtrial AT analuciaazevedosalgado nacetylcysteineandorursodeoxycholicacidassociatedwithmetformininnonalcoholicsteatohepatitisanopenlabelmulticenterrandomizedcontrolledtrial AT edisonrobertoparise nacetylcysteineandorursodeoxycholicacidassociatedwithmetformininnonalcoholicsteatohepatitisanopenlabelmulticenterrandomizedcontrolledtrial |