{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:39:11Z","timestamp":1790627951648,"version":"4.1.0"},"reference-count":91,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero della Salute, Ricerca Corrente 2022, Fondazione IRCCS C\u00e0 Granda, Ospedale Maggiore Policlinico."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease worldwide affecting both adults and children. Nowadays, no therapeutic strategies have been approved for NAFLD management, and hepatic biopsy remains the gold standard procedure for its diagnosis. NAFLD is a multifactorial disease whose pathogenesis is affected by environmental and genetic factors, and it covers a spectrum of conditions ranging from simple steatosis up to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Several studies underlined the urgent need to develop an NAFLD risk prediction model based on genetics, biochemical indicators, and metabolic disorders. The loss of mitochondrial dynamics represents a typical feature of progressive NAFLD. The imbalance of mitochondrial lifecycle together with the impairment of mitochondrial biomass and function trigger oxidative stress, which in turn damages mitochondrial DNA (mtDNA). We recently demonstrated that the main genetic predictors of NAFLD led to mitochondrial dysfunction. Moreover, emerging evidence shows that variations in the displacement loop (D-loop) region impair mtDNA replication, and they have been associated with advanced NAFLD. Finally, lower levels of mitophagy foster the overload of damaged mitochondria, resulting in the release of cell-free circulating mitochondrial DNA (mt-ccf) that exacerbates liver injury. Thus, in this review we summarized what is known about D-loop region alterations and mt-ccf content during NAFLD to propose them as novel non-invasive biomarkers.<\/jats:p>","DOI":"10.3390\/ijms24032331","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T03:53:18Z","timestamp":1674618798000},"page":"2331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Non-Invasive Assessment of Circulating D-Loop and mt-ccf Levels Opens an Intriguing Spyhole into Novel Approaches for the Tricky Diagnosis of NASH"],"prefix":"10.3390","volume":"24","author":[{"given":"Erika","family":"Paolini","sequence":"first","affiliation":[{"name":"General Medicine and Metabolic Diseases, Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"},{"name":"Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9433-3492","authenticated-orcid":false,"given":"Miriam","family":"Longo","sequence":"additional","affiliation":[{"name":"General Medicine and Metabolic Diseases, Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"},{"name":"Department of Clinical Sciences and Community Health, Universit\u00e0 degli Studi di Milano, 20122 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9912-9482","authenticated-orcid":false,"given":"Alberto","family":"Corsini","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences, Universit\u00e0 degli Studi di Milano, 20133 Milano, Italy"},{"name":"IRCCS Multimedica, 20099 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4343-7213","authenticated-orcid":false,"given":"Paola","family":"Dongiovanni","sequence":"additional","affiliation":[{"name":"General Medicine and Metabolic Diseases, Fondazione IRCCS C\u00e0 Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/TP.0000000000002484","article-title":"Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver Transplantation","volume":"103","author":"Younossi","year":"2019","journal-title":"Transplantation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e13519","DOI":"10.1111\/eci.13519","article-title":"Nonalcoholic fatty liver disease or metabolic dysfunction-associated fatty liver disease diagnoses and cardiovascular diseases: From epidemiology to drug approaches","volume":"51","author":"Dongiovanni","year":"2021","journal-title":"Eur. 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