Rod S Taylor1, Rebecca J Taylor2, Sue Bayliss3, Hannes Hagström4, Patrik Nasr5, Jorn M Schattenberg6, Masatoshi Ishigami7, Hidenori Toyoda8, Vincent Wai-Sun Wong9, Noam Peleg10, Amir Shlomai11, Giada Sebastiani12, Yuya Seko13, Neeraj Bhala14, Zobair M Younossi15, Quentin M Anstee16, Stuart McPherson17, Philip N Newsome18. 1. Institute of Health and Well Being, University of Glasgow, United Kingdom. Electronic address: rod.taylor@glasgow.ac.uk. 2. R(2) Consultancy, Glasgow, United Kingdom. 3. Institute of Applied Health Research, University of Birmingham, United Kingdom. 4. Unit of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden. 5. Department of Gastroenterology and Hepatology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. 6. University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany. 7. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan. 8. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan. 9. Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. 10. Department of Gastroenterology and Hepatology, Rabin Medical Center, Beilinson Hospital, Petach-Tikva Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Medicine D, Rabin Medical Center, Beilinson hospital, Petach-Tikva. 11. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 12. Department of Medicine, McGill University Health Centre, Montréal, Quebec, Canada. 13. Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan. 14. Institute of Applied Health Research, University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, United Kingdom. 15. Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia. 16. Institute of Clinical and Translational Research, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Newcastle National Institute of Health Research Biomedical Research Centre and Liver Transplant Unit, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, United Kingdom. 17. Liver Transplant Unit, The Newcastle upon Tyne Hospitals NHS Foundation Trust; Institute of Clinical and Translational Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Newcastle National Institute of Health Research Biomedical Research Centre, Newcastle-upon-Tyne, United Kingdom. 18. National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, United Kingdom; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, United Kingdom; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
Abstract
BACKGROUND & AIMS: Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with nonalcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint. METHODS: We searched the MEDLINE, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all cause and liver related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage-specific relative risk (RR) and 95% confidence interval (CI) values for mortality and morbidities. We performed fixed-effect and random-effect model meta-analyses. Metaregression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow-up (in years). RESULTS: Our meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared with no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4): all-cause mortality RR, 3.42 (95% CI, 2.63-4.46); liver-related mortality RR, 11.13 (95% CI, 4.15-29.84); liver transplant RR, 5.42 (95% CI, 1.05-27.89); and liver-related events RR, 12.78 (95% CI, 6.85-23.85). The magnitude of RR did not differ significantly after adjustment for confounders, including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings. CONCLUSIONS: In a systematic review and meta-analysis, we found biopsy-confirmed fibrosis to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials.
BACKGROUND & AIMS: Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with nonalcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint. METHODS: We searched the MEDLINE, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all cause and liver related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage-specific relative risk (RR) and 95% confidence interval (CI) values for mortality and morbidities. We performed fixed-effect and random-effect model meta-analyses. Metaregression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow-up (in years). RESULTS: Our meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared with no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4): all-cause mortality RR, 3.42 (95% CI, 2.63-4.46); liver-related mortality RR, 11.13 (95% CI, 4.15-29.84); liver transplant RR, 5.42 (95% CI, 1.05-27.89); and liver-related events RR, 12.78 (95% CI, 6.85-23.85). The magnitude of RR did not differ significantly after adjustment for confounders, including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings. CONCLUSIONS: In a systematic review and meta-analysis, we found biopsy-confirmed fibrosis to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials.
Authors: Manuel Romero-Gómez; Jörn M Schattenberg; Jeffrey V Lazarus; Quentin M Anstee; Hannes Hagström; Kenneth Cusi; Helena Cortez-Pinto; Henry E Mark; Michael Roden; Emmanuel A Tsochatzis; Vincent Wai-Sun Wong; Zobair M Younossi; Shira Zelber-Sagi Journal: Nat Rev Gastroenterol Hepatol Date: 2021-06-25 Impact factor: 46.802
Authors: Andrew D Schreiner; Sherry Livingston; Jingwen Zhang; Mulugeta Gebregziabher; Justin Marsden; David G Koch; Chelsey A Petz; Valerie L Durkalski-Mauldin; Patrick D Mauldin; William P Moran Journal: J Clin Gastroenterol Date: 2021-07-22 Impact factor: 3.062
Authors: Stefan Traussnigg; Emina Halilbasic; Harald Hofer; Petra Munda; Tatjana Stojakovic; Günter Fauler; Karl Kashofer; Martin Krssak; Michael Wolzt; Michael Trauner Journal: Wien Klin Wochenschr Date: 2020-09-15 Impact factor: 1.704