Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD.

Background & Aims: Long-term studies of the prognosis of NAFLD are scarce. Here, we investigated the risk of major adverse liver outcomes (MALO) in a large cohort of patients with NAFLD. Methods: We conducted a cohort study with data from Swedish university hospitals. Patients (n = 1,260) with NAFLD without cirrhosis were diagnosed through biopsy or radiology, and had fibrosis estimated through vibration-controlled transient elastography, biopsy, or FIB-4 score between 1974 and 2020 and followed up through 2020. Each patient was matched on age, sex, and municipality with up to 10 reference individuals from the general population (n = 12,529). MALO were ascertained from Swedish national registers. The rate of events was estimated by Cox regression. Results: MALO occurred in 111 (8.8%, incidence rate = 5.9/1,000 person-years) patients with NAFLD and 197 (1.6%, incidence rate = 1.0/1,000 person-years) reference individuals during a median follow up of 13 years. The rate of MALO was higher in patients with NAFLD (hazard ratio = 6.6; 95% CI = 5.2-8.5). The risk of MALO was highly associated with the stage of fibrosis at diagnosis. In the biopsy subcohort (72% of total sample), there was no difference in risk between patients with and without non-alcoholic steatohepatitis. The 20-year cumulative incidences of MALO were 2% for the reference population, 3% for patients with F0, and 35% for F3. Prognostic information from biopsy was comparable to FIB-4 (C-indices around 0.73 vs. 0.72 at 10 years). Conclusions: This study provides updated information on the natural history of NAFLD, showing a high rate of progression to cirrhosis in F3 and a similar prognostic capacity of non-invasive tests to liver biopsy. Impact and implications: Several implications for clinical care and future research may be noted based on these results. First, the risk estimates for cirrhosis development are important when communicating risk to patients and deciding on clinical monitoring and treatment. Estimates can also be used in updated health-economic evaluations, and for regulatory agencies. Second, our results again highlight the low predictive information obtained from ascertaining NASHstatus by histology and call for more objective means by which to define NASH. Such methods may include artificial intelligence-supported digital pathology. We highlight that NASH is most likely the causal factor for fibrosis progression in NAFLD, but the subjective definition makes the prognostic value of a histological NASH diagnosis of limited value. Third, the finding that prognostic information from biopsy and the very simple Fibrosis-4 score were comparable is important as it may lead to fewer biopsies and further move the field towards non-invasive means by which to define fibrosis and, importantly, use non-invasive tests as outcomes in clinical trials. However, all modalities had modest discriminatory capacity and new risk stratification systems are needed in NAFLD. Repeated measures of non-invasive scores may be a potential solution.

Antenatal awareness and obstetric outcomes in large fetuses: A retrospective evaluation.

INTRODUCTION: There is currently no consensus on the management of large fetuses in order to minimize fetal complications. The aim of this study was to assess whether antenatal recognition of large-for-gestational age (LGA) reduced poor obstetric newborn outcomes in a hospital where expectant management was used. MATERIAL AND METHODS: A retrospective cohort study was made of two delivery units at Karolinska University Hospital, Stockholm, Sweden, using expectant management of LGA. All deliveries > 37+0 weeks of gestation during an 8-year period (2002-2009) were included. The main outcome was severe adverse outcome, a composite variable including neonatal trauma (brachial plexus birth palsy [BPBP] and fractures) and asphyxic sequelae (severe asphyxia, cerebral damage, and fetal/infant death). RESULTS: The study population consisted of 63,542 appropriate-for-gestational age (AGA) and 3,343 LGA pregnancies (of which 21 % were identified before delivery). Compared to AGA, LGA pregnancies showed a five-fold increased risk of neonatal trauma (OR 5.1, 95 % CI 4.0 - 6.4), but no differences were seen regarding asphyxic sequelae. LGA fetuses identified antenatally had adverse outcomes in 3.7 % of all cases, compared to 3.5 % where LGA was not identified (OR 1.07 95 % CI 0.7 - 1.7). When adjusted for newborn weight deviation, the OR was 0.96, 95 % CI 0.6 - 1.5. There was a three-fold higher risk (OR 3.0, 95 % CI 1.2 - 7.4) of neonatal trauma among non-identified LGA cases > 41+0 gestational weeks. A total of 81 % of those with LGA were identified after a week 41 routine ultrasound. Out of 68 cases with planned vaginal delivery and expected birth weight > 5000 g, 7.4 % suffered BPBP, representing a 31-fold increase in risk, compared to 0% BPBP among those delivered by elective caesarean section. CONCLUSION: Antenatal awareness of LGA did not lower the risk of severe adverse outcomes in a unit using expectant management, but those identified postdate were at a lower risk of neonatal trauma. For every 14 fetuses with an expected birth weight > 5000 g delivered by cesarean section, one case of BPBP could be avoided.