Open-label pilot study of folic acid in patients with nonalcoholic steatohepatitis

Phunchai Charatcharoenwitthaya, Cynthia Levy, Paul Angulo, Jill Keach, Roberta Jorgensen, Keith D. Lindor

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background/Aims: Folate deficiency disturbs hepatic methionine metabolism and promotes the development of steatohepatitis in animal models. Our aims were (1) to determine the safety and efficacy of folic acid treatment in patients with nonalcoholic steatohepatitis (NASH) on changes in liver biochemistries, and (2) to investigate the presence of subclinical folate deficiency in this population. Methods: Patients with biopsy-proven NASH were treated with folic acid 1 mg/day for 6 months. Liver enzymes and adverse events were monitored every 3 months until completion. Results: Ten patients (one male and nine females) with a median age of 54 years were enrolled in this study. At baseline, the median steatosis grade was 2 (range 1-3), the median necroinflammatory grade was 1 (1-3), and the median fibrosis stage was 2 (0-4). The median level of red cell folate was 526 ng/ml (range 99-708); the normal level was 268-616 ng/ml. One compensated cirrhotic patient had folate deficiency. No serious adverse events occurred. After 6 months of therapy, no significant reductions in serum aspartate and alanine aminotransferase levels (60±25 vs. 54±29, P = 0.5 and 86±29 vs. 83±42, P = 0.6, respectively), were observed. Serum levels of bilirubin, alkaline phosphatase, albumin, and prothrombin time remained in the normal range during treatment in all patients. Conclusion: Six months of therapy with folic acid at a dose of 1 mg/day, although safe and well tolerated, does not lead to a significant biochemical improvement in patients with NASH. In a small number of patients, folate deficiency was present in only a cirrhotic patient.

Original languageEnglish
Pages (from-to)220-226
Number of pages7
JournalLiver International
Volume27
Issue number2
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Fingerprint

Folic Acid
Liver
Non-alcoholic Fatty Liver Disease
Prothrombin Time
Fatty Liver
Therapeutics
Aspartate Aminotransferases
Serum
Alanine Transaminase
Bilirubin
Methionine
Biochemistry
Alkaline Phosphatase
Albumins
Reference Values
Fibrosis
Animal Models
Biopsy
Safety
Enzymes

Keywords

  • Clinical trial
  • Folate
  • Folic acid
  • Homocysteine
  • Nonalcoholic steatohepatitis
  • Therapy

ASJC Scopus subject areas

  • Hepatology

Cite this

Charatcharoenwitthaya, P., Levy, C., Angulo, P., Keach, J., Jorgensen, R., & Lindor, K. D. (2007). Open-label pilot study of folic acid in patients with nonalcoholic steatohepatitis. Liver International, 27(2), 220-226. https://doi.org/10.1111/j.1478-3231.2006.01404.x

Open-label pilot study of folic acid in patients with nonalcoholic steatohepatitis. / Charatcharoenwitthaya, Phunchai; Levy, Cynthia; Angulo, Paul; Keach, Jill; Jorgensen, Roberta; Lindor, Keith D.

In: Liver International, Vol. 27, No. 2, 01.03.2007, p. 220-226.

Research output: Contribution to journalArticle

Charatcharoenwitthaya, P, Levy, C, Angulo, P, Keach, J, Jorgensen, R & Lindor, KD 2007, 'Open-label pilot study of folic acid in patients with nonalcoholic steatohepatitis', Liver International, vol. 27, no. 2, pp. 220-226. https://doi.org/10.1111/j.1478-3231.2006.01404.x
Charatcharoenwitthaya, Phunchai ; Levy, Cynthia ; Angulo, Paul ; Keach, Jill ; Jorgensen, Roberta ; Lindor, Keith D. / Open-label pilot study of folic acid in patients with nonalcoholic steatohepatitis. In: Liver International. 2007 ; Vol. 27, No. 2. pp. 220-226.
@article{02827ff50e7a498b9090dcc47d6495ce,
title = "Open-label pilot study of folic acid in patients with nonalcoholic steatohepatitis",
abstract = "Background/Aims: Folate deficiency disturbs hepatic methionine metabolism and promotes the development of steatohepatitis in animal models. Our aims were (1) to determine the safety and efficacy of folic acid treatment in patients with nonalcoholic steatohepatitis (NASH) on changes in liver biochemistries, and (2) to investigate the presence of subclinical folate deficiency in this population. Methods: Patients with biopsy-proven NASH were treated with folic acid 1 mg/day for 6 months. Liver enzymes and adverse events were monitored every 3 months until completion. Results: Ten patients (one male and nine females) with a median age of 54 years were enrolled in this study. At baseline, the median steatosis grade was 2 (range 1-3), the median necroinflammatory grade was 1 (1-3), and the median fibrosis stage was 2 (0-4). The median level of red cell folate was 526 ng/ml (range 99-708); the normal level was 268-616 ng/ml. One compensated cirrhotic patient had folate deficiency. No serious adverse events occurred. After 6 months of therapy, no significant reductions in serum aspartate and alanine aminotransferase levels (60±25 vs. 54±29, P = 0.5 and 86±29 vs. 83±42, P = 0.6, respectively), were observed. Serum levels of bilirubin, alkaline phosphatase, albumin, and prothrombin time remained in the normal range during treatment in all patients. Conclusion: Six months of therapy with folic acid at a dose of 1 mg/day, although safe and well tolerated, does not lead to a significant biochemical improvement in patients with NASH. In a small number of patients, folate deficiency was present in only a cirrhotic patient.",
keywords = "Clinical trial, Folate, Folic acid, Homocysteine, Nonalcoholic steatohepatitis, Therapy",
author = "Phunchai Charatcharoenwitthaya and Cynthia Levy and Paul Angulo and Jill Keach and Roberta Jorgensen and Lindor, {Keith D.}",
year = "2007",
month = "3",
day = "1",
doi = "10.1111/j.1478-3231.2006.01404.x",
language = "English",
volume = "27",
pages = "220--226",
journal = "Liver International",
issn = "1478-3223",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Open-label pilot study of folic acid in patients with nonalcoholic steatohepatitis

AU - Charatcharoenwitthaya, Phunchai

AU - Levy, Cynthia

AU - Angulo, Paul

AU - Keach, Jill

AU - Jorgensen, Roberta

AU - Lindor, Keith D.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - Background/Aims: Folate deficiency disturbs hepatic methionine metabolism and promotes the development of steatohepatitis in animal models. Our aims were (1) to determine the safety and efficacy of folic acid treatment in patients with nonalcoholic steatohepatitis (NASH) on changes in liver biochemistries, and (2) to investigate the presence of subclinical folate deficiency in this population. Methods: Patients with biopsy-proven NASH were treated with folic acid 1 mg/day for 6 months. Liver enzymes and adverse events were monitored every 3 months until completion. Results: Ten patients (one male and nine females) with a median age of 54 years were enrolled in this study. At baseline, the median steatosis grade was 2 (range 1-3), the median necroinflammatory grade was 1 (1-3), and the median fibrosis stage was 2 (0-4). The median level of red cell folate was 526 ng/ml (range 99-708); the normal level was 268-616 ng/ml. One compensated cirrhotic patient had folate deficiency. No serious adverse events occurred. After 6 months of therapy, no significant reductions in serum aspartate and alanine aminotransferase levels (60±25 vs. 54±29, P = 0.5 and 86±29 vs. 83±42, P = 0.6, respectively), were observed. Serum levels of bilirubin, alkaline phosphatase, albumin, and prothrombin time remained in the normal range during treatment in all patients. Conclusion: Six months of therapy with folic acid at a dose of 1 mg/day, although safe and well tolerated, does not lead to a significant biochemical improvement in patients with NASH. In a small number of patients, folate deficiency was present in only a cirrhotic patient.

AB - Background/Aims: Folate deficiency disturbs hepatic methionine metabolism and promotes the development of steatohepatitis in animal models. Our aims were (1) to determine the safety and efficacy of folic acid treatment in patients with nonalcoholic steatohepatitis (NASH) on changes in liver biochemistries, and (2) to investigate the presence of subclinical folate deficiency in this population. Methods: Patients with biopsy-proven NASH were treated with folic acid 1 mg/day for 6 months. Liver enzymes and adverse events were monitored every 3 months until completion. Results: Ten patients (one male and nine females) with a median age of 54 years were enrolled in this study. At baseline, the median steatosis grade was 2 (range 1-3), the median necroinflammatory grade was 1 (1-3), and the median fibrosis stage was 2 (0-4). The median level of red cell folate was 526 ng/ml (range 99-708); the normal level was 268-616 ng/ml. One compensated cirrhotic patient had folate deficiency. No serious adverse events occurred. After 6 months of therapy, no significant reductions in serum aspartate and alanine aminotransferase levels (60±25 vs. 54±29, P = 0.5 and 86±29 vs. 83±42, P = 0.6, respectively), were observed. Serum levels of bilirubin, alkaline phosphatase, albumin, and prothrombin time remained in the normal range during treatment in all patients. Conclusion: Six months of therapy with folic acid at a dose of 1 mg/day, although safe and well tolerated, does not lead to a significant biochemical improvement in patients with NASH. In a small number of patients, folate deficiency was present in only a cirrhotic patient.

KW - Clinical trial

KW - Folate

KW - Folic acid

KW - Homocysteine

KW - Nonalcoholic steatohepatitis

KW - Therapy

UR - http://www.scopus.com/inward/record.url?scp=34247635191&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247635191&partnerID=8YFLogxK

U2 - 10.1111/j.1478-3231.2006.01404.x

DO - 10.1111/j.1478-3231.2006.01404.x

M3 - Article

C2 - 17311617

AN - SCOPUS:34247635191

VL - 27

SP - 220

EP - 226

JO - Liver International

JF - Liver International

SN - 1478-3223

IS - 2

ER -