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Page 14 of 22                                                                              Ballestri et al. Metab Target Organ Damage 2023;3:1     https://dx.doi.org/10.20517/mtod.2022.23



                                       Longitudinal
                                 [103]
                          Liu et al.   4282 consecutive patients with  26    51.4% (CAP ≥  20% advanced LF        1.6% incident CVE      LSM predicted liver-related events but not CVEs.  Age, sex, platelet count, serum
                                       suspected liver disease (1697   months  248 dB/m)   (VCTE LSM ≥10 kPa)                            Subgroup analyses of viral hepatitis and NAFLD   albumin, creatinine, cardiometabolic
                                       chronic viral hepatitis; 1542   median                                                            patients revealed similar results           risk factors, diabetes-related
                                       NAFLD), 56.7% men, median                                                                                                                     variables
                                       age 57 years
                          Shili-       2251 consecutive NAFLD       27       100% (US)     13% advanced fibrosis   6.7% incident CVE     LSM independently predicted overall survival   Age, gender, BMI, MetS, diabetes,
                          Masmoudi     patients, men 53%, median    months                 (VCTE LSM > 12 kPa)                           (HR 2.85, 95%CI: 1.65-4.92). Patients with   hypertension, abdominal obesity,
                              [104]
                          et al.       (IQR) age 59 (51-66) years   median                                                               elevated LSM presented significantly more CVEs  low HDL-C, high TG
                                                                                                                                         and liver events but not cancers
                                                                                                                                         LSM was as accurate as a clinical model to
                                                                                                                                         predict overall survival and CVEs
                          Mikolasevic  238 T2D outpatients without a  7.6    76% (CAP ≥  34% significant LF       23.9% incident AMI,    Elevated CAP (HR 2.34) and elevated LSM (HR   Traditional CV risk factors and
                              [105]
                          et al.       prior history of AMI/CVI/CKD,  years   238 dB/m)    (VCTE LSM ≥ 7.0/6.2    7.9% incident          2.84), independently of each other, were    diabetes-related variables
                                       52.9% men, median (IQR) age  median                 kPa by M/XL probe)     CVI, 42.4% incident    associated with a higher risk of developing the
                                       57 (47-64) years                                                           CKD                    composite outcome (AMI, CVI, or CKD), as well
                                                                                                                                         as incident AMI or CKD alone
                          Cardoso      400 T2D with NAFLD, 64%      5.5      100% severe  15% advanced LF         17% incident CVE       An increasing LSM was a risk marker for total   Age, sex, smoking, cardiometabolic
                              [106]
                          et al.       women, 64.4 ± 9.9 years      years    steatosis     (VCTE LSM > 9.6 kPa)   21% died (47% from     CVEs (HR 1.05) and all-cause mortality (HR:   risk factors, diabetes-related
                                                                    median   (CAP > 296                           CVD)                   1.04). If LSM > 9.6 kPa: HR 2.66 for total CVEs,   variables, ASCVD, microvascular
                                                                             or > 330                                                    3.03 for MCVEs, 1.7 for all-cause mortality, and   complications at baseline, use of
                                                                             dB/m)                                                       2.46 for CV mortality                       statins and aspirin
                          Grgurevic    454 T2D patients, 52% men,   2 years  77.8% had     9.9% advanced LF       11% incident CVE 3.7%   Age and platelet count (but not FIB-4, LSM, and  -
                              [107]
                          et al.       mean age of 62.5 ± 12 years  median   fatty liver   (VCTE LSM ≥ 9.6 kPa)   died                   CAP) independently predicted poor outcomes.
                                                                             (CAP > 248                                                  This study found that no liver-related
                                                                             dB/m)                                                       morbidity/mortality may virtually mirror a low
                                                                                                                                         prevalence of advanced LF, probably overrated
                                                                                                                                         by using a 9.6 LSM cut-off
                          Petta        1039 consecutive NAFLD       35       100%          100% advanced LF       -                      In 533 patients with available LSMs during the   Age, gender, BMI, presence of Child-
                              [108]
                          et al.       patients with compensated    months                 (histological F3-F4                           follow-up period, change in LSM was         Pugh A6, platelets and baseline LSM
                                       advanced chronic             median                 fibrosis and/or VCTE                          independently associated with overall mortality
                                       liver disease, 56.3% of men,                        LSMs > 10 kPa),                               (HR 1.73) and liver-related mortality (HR 1.96).
                                       mean age of 60.3 ± 10.7 years                       baseline median LSM =                         LSM did not predict extra-hepatic events
                                                                                           17.6 kPa                                      occurrence at univariate analysis

                          AF: atrial fibrillation; AMI: acute myocardial infarction; ASCVD: atherosclerotic cardiovascular diseases; BMI: body mass index; CAC: coronary artery calcium; CHD: coronary heart disease; CKD: chronic kidney
                          disease; CTA: computed tomography angiography; CV: cardiovascular; CVD: cardiovascular disease; CVE: cardiovascular event; CVI: cerebrovascular insult (i.e. ischemic stroke or transient ischemic attack); F-up:
                          follow-up; FRS: framingham risk score; HbA1C: glycosylated hemoglobin; HDL-C: high-density lipoprotein cholesterol; HR: hazard ratio; IQR: interquartile range; IS: ischemic stroke; kPa: kilopascal; LDL-C: low-density
                          lipoprotein cholesterol; LSM: liver stiffness measurement; MI: myocardial infarction; MRE: magnetic resonance elastography; MRI-PDFF: Magnetic Resonance Imaging Proton Density Fat Fraction; MVA: multivariate
                          analysis: NAFLD: nonalcoholic fatty liver disease; NHANES: National Health and Nutrition Examination Survey; SBP: systolic blood pressure; 2DSWE-SSI: two-dimensional point shear wave elastography-SuperSonic
                          Imagine; T2D: type 2 diabetes; TG: triglycerides; US: ultrasonography; VCTE: vibration-controlled transient elastography; -: not applicable/available.




                          Current NAFLD guidelines suggest VCTE and MRE (but not SWE techniques) for LSM because no NAFLD follow-up studies have used SWE; moreover,
                          VCTE and MRE can evaluate liver fibrosis and steatosis quantitively .
                                                                                                          [80]
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