Changing from NAFLD to MASLD: Similar prognosis of unresectable extrahepatic gastrointestinal cancer under chemotherapy between NAFLD and MASLD
Authors: Hiroyuki Suzuki, Toshimitsu Tanaka, Shotaro Yamaguchi, Keisuke Miwa, Takumi Kawaguchi
Journal: Journal of Hepatology (2023)

A multisociety Delphi consensus statement on new fatty liver disease nomenclatureJournal of HepatologyVol. 79Issue 6PreviewThe principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. Full-Text PDF Open Access A multi-society consensus group redefined the nomenclature of non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) in 2023.[1]Rinella M.E. Lazarus J.V. Ratziu V. et al.A multisociety Delphi consensus statement on new fatty liver disease nomenclature.J Hepatol. 2023 Dec; 79: 1542-1556Abstract Full Text Full Text PDF PubMed Scopus (237) Google Scholar This revision enables us to better capture the underlying etiologic pathways of the disease and eliminate potential stigmatization.[1]Rinella M.E. Lazarus J.V. Ratziu V. et al.A multisociety Delphi consensus statement on new fatty liver disease nomenclature.J Hepatol. 2023 Dec; 79: 1542-1556Abstract Full Text Full Text PDF PubMed Scopus (237) Google Scholar,[2]Younossi Z.M. AlQahtani S.A. Alswat K. et al.Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.J Hepatol. 2023 Nov 18; (05279-0): S0168-S8278Google Scholar As such modifications often yield considerable confusion from numerous perspectives, it is likely that we will encounter obstacles for some time. In particular, in order to avoid wasting valuable research resources, it is important to extend previous research on NAFLD to MASLD, and several reports have already provided evidence supporting this transition.[3]Hagström H. Vessby J. Ekstedt M. Shang Y. 99% of patients with NAFLD meet MASLD criteria and natural history is therefore identical.J Hepatol. 2023 Sep 9; S0168–8278: 5080-5088Google Scholar,[4]Song S.J. Lai J.C. Wong G.L. Wong V.W. Yip T.C. Can we use old NAFLD data under the new MASLD definition?.J Hepatol. 2023 Aug 2; S0168–8278 (6): 5000Google Scholar The growing burden of NAFLD has resulted in an alarming rise in NAFLD-related cancer deaths, which have become a major public health issue worldwide.[5]Devarbhavi H. Asrani S.K. Arab J.P. Nartey Y.A. Pose E. Kamath P.S. Global burden of liver disease: 2023 update.J Hepatol. 2023 Aug; 79: 516-537Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar,[6]Tan D.J.H. Ng C.H. Muthiah M. et al.Rising global burden of cancer attributable to high BMI from 2010 to 2019.Metabolism. 2023 Nov 27; 155744Abstract Full Text Full Text PDF Google Scholar Although NAFLD, particularly the severity of hepatic fibrosis, is widely known as a significant risk factor for primary liver cancer, it is also recognized as a risk factor for the development of extrahepatic gastrointestinal (GI) cancers, with a two-fold increase in risk, particularly colorectal and pancreatic cancers.[7]Mantovani A. Petracca G. Beatrice G. et al.Non-alcoholic fatty liver disease and increased risk of incident extrahepatic cancers: a meta-analysis of observational cohort studies.Gut. 2022 Apr; 71: 778-788Crossref PubMed Scopus (116) Google Scholar GI cancers have frequently been linked to aging and lifestyle-related factors, such as poor eating habits, exercise, and metabolic dysfunction, which are also strongly correlated with the presence of NAFLD.[8]Ulrich C.M. Himbert C. Holowatyj A.N. Hursting S.D. Energy balance and gastrointestinal cancer: risk, interventions, outcomes and mechanisms.Nat Rev Gastroenterol Hepatol. 2018 Nov; 15: 683-698Crossref PubMed Scopus (68) Google Scholar Thus, it is important to deeply comprehend the prognostic implications of NAFLD in patients with extrahepatic GI cancers in order to effectively manage and treat these individuals. However, the influence of NAFLD on prognosis is currently the subject of debate, as it is difficult to control for possible confounding factors and biases in patient selection. Furthermore, no studies have examined the relationship between NAFLD and MASLD in individuals with advanced GI cancer who have undergone chemotherapy. We aimed to compare the prognosis of unresectable extrahepatic GI cancer between patients with NAFLD and MASLD. This study included 675 consecutive patients with histopathologically confirmed GI cancer at our institution in Japan between January 2017 and June 2023. All the patients were of Asian origin. We excluded patients who only requested a second opinion from our hospital, had a poor general condition (Eastern Cooperative Oncology Group performance status >3), were anticipated to survive for less than 90 days, or refused to receive chemotherapy (n = 152). In total, 523 participants who received chemotherapy (164 with pancreatic cancer, 154 with gastric cancer, 153 with colorectal cancer, and 51 with biliary tract cancer) were analyzed. The most common cancer stage was stage IV (50.6%), followed by stage III (23.5%). Data on 523 patients (57.9% male; median age 69 years, median BMI: 21.9 kg/m2) were analyzed. The diagnosis of steatotic liver disease (SLD) was based on a high hepatic steatotic index, with a cut-off >36.[9]Lee J.H. Kim D. Kim H.J. et al.Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease.Dig Liver Dis. 2010 Jul; 42: 503-508Abstract Full Text Full Text PDF PubMed Scopus (837) Google Scholar NAFLD was diagnosed in 11.1% (58/523) of the patients, including two who did not fulfill the cardiometabolic criteria for MASLD (Fig. 1A). Of these, only two individuals were classified as having cryptogenic SLD and 96.6% of patients with NAFLD in the present study were also diagnosed with MASLD. Our results were in good agreement with the previous studies which reported more than 95% of patients with NAFLD meet the MASLD criteria.[3]Hagström H. Vessby J. Ekstedt M. Shang Y. 99% of patients with NAFLD meet MASLD criteria and natural history is therefore identical.J Hepatol. 2023 Sep 9; S0168–8278: 5080-5088Google Scholar,[10]Yoon E.L. Jun D.W. Waiting for the changes after the adoption of steatotic liver disease.Clin Mol Hepatol. 2023 Oct; 29: 844-850Crossref PubMed Scopus (3) Google Scholar Fig. 1B shows the Kaplan-Meier curve for overall survival. No significant difference was seen in overall survival between the NAFLD and MASLD groups (median overall survival in patients with NAFLD and MASLD was 793 days [95% CI 436–1,627 days] and 793 days [95% CI 375–1,236 days], respectively). The 1-year/3-year survival rates were 58.6%/15.5% in patients with NAFLD and 59.0%/14.3% in patients with MASLD, respectively. These results indicate that for patients with GI cancer, the prognosis is comparable in those with MASLD or NAFLD. In conclusion, data on GI cancers obtained using the term NAFLD can be extrapolated to MASLD. This research was supported by the Japan Agency for Medical Research and Development (AMED) under grant number JP23fk0210090. Takumi Kawaguchi received lecture fees from Janssen Pharmaceutical K.K., Taisho Pharmaceutical Co., Ltd., Kowa Company, Ltd., Otsuka Pharmaceutical Co., Ltd., Eisai Co., Ltd., ASKA Pharmaceutical Co., Ltd., AbbVie GK., and EA Pharma Co., Ltd. The other authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details. Hiroyuki Suzuki: study concept, design, and statistical analysis; Toshimitsu Tanaka: data extraction, interpretation of data, and critical revision of the manuscript; Shotaro Yamaguchi: interpretation of data, drafting, and critical revision of the manuscript; Keisuke Miwa: interpretation of data and critical revision of the manuscript; Takumi Kawaguchi: interpretation of data and critical revision of the manuscript. The following are the supplementary data to this article: Download .pdf (.35 MB) Help with pdf files Multimedia component 1