Predicting liver-related events in NAFLD: A predictive model.

BACKGROUND AND AIMS: Management of NAFLD involves noninvasive prediction of fibrosis, which is a surrogate for patient outcomes. We aimed to develop and validate a model predictive of liver-related events (LREs) of decompensation and/or HCC and compare its accuracy with fibrosis models. APPROACH AND RESULTS: Patients with NAFLD from Australia and Spain who were followed for up to 28 years formed derivation (n = 584) and validation (n = 477) cohorts. Competing risk regression and information criteria were used for model development. Accuracy was compared with fibrosis models using time-dependent AUC analysis. During follow-up, LREs occurred in 52 (9%) and 11 (2.3%) patients in derivation and validation cohorts, respectively. Age, type 2 diabetes, albumin, bilirubin, platelet count, and international normalized ratio were independent predictors of LRE and were combined into a model [NAFLD outcomes score (NOS)]. The NOS model calibrated well [calibration slope, 0.99 (derivation), 0.98 (validation)] with excellent overall performance [integrated Brier score, 0.07 (derivation) and 0.01 (validation)]. A cutoff ≥1.3 identified subjects at a higher risk of LRE, (sub-HR 24.6, p < 0.001, 5-year cumulative incidence 38% vs 1.0%, respectively). The predictive accuracy at 5 and 10 years was excellent in both derivation (time-dependent AUC,0.92 and 0.90, respectively) and validation cohorts (time-dependent AUC,0.80 and 0.82, respectively). The NOS was more accurate than the fibrosis-4 or NAFLD fibrosis score for predicting LREs at 5 and 10 years ( p < 0.001). CONCLUSIONS: The NOS model consists of readily available measures and has greater accuracy in predicting outcomes in patients with NAFLD than existing fibrosis models.

FIB-4 score as predictor of COVID-19-related severity in hospitalized patients.

AIM: To determine the impact of liver fibrosis on the prognosis of COVID and the liver injury associated with the infection. METHODS: Retrospective multicenter study including 575 patients requiring admission for COVID-19 between January and June 2020. FIB-4 was calculated within 6 months prior to infection and at 6 months post-infection. RESULTS: Baseline FIB-4 was increased in patients who died (1.91±0.95 vs. 1.43±0.85; p<0.001). In addition, the 17.1% (32/187) of patients with baseline FIB-4<1.45 died versus 52.9% (9/17) if FIB-4>3.25 (p<0.001). In the adjusted multivariate analysis, baseline FIB-4 (OR 1.61 (95%CI 1.19-2.18); p=0.002) was independently associated with mortality. Parameters associated with liver injury, including AST (28±10 vs. 45±56IU/L; p<0.001) and ALT (20±12 vs. 38±48IU/L; p<0.001) were significantly higher at admission compared to baseline. Also, FIB-4 was increased from baseline to the time of admission (1.53±0.88 vs. 2.55±1.91; p<0.001), and up to 6.9% (10/145) of patients with FIB-4<1.45 at admission died versus 47.5% if FIB-4>3.25 (58/122) (p<0.001). In the adjusted multivariate analysis, FIB-4 at admission (OR 1.14 (95%CI 1.03-1.27); p=0.015) was independently associated with mortality. Also, AST (42±38 vs. 22±17IU/L; p<0.001) and ALT (40±50 vs. 20±19 IU/L; p<0.001) were significantly reduced at 6 months after the resolution of infection. Accordingly, FIB-4 decreased significantly (2.12±1.25 vs. 1.32±0.57; p<0.001) six months after the infection. CONCLUSION: Increased FIB-4, either at baseline or at the time of admission, was related to the severity and mortality related to SARS-CoV-2 infection. However, the liver damage expressed by elevated transaminases and FIB-4 was reversible in most of patients.

[Wilson's disease: overview]. / Enfermedad de Wilson.

Wilson's disease (WD) is an uncommon hereditary disorder caused by a deficiency in the ATP7B transporter. The protein codified by this gene facilitates the incorporation of the copper into ceruloplasmin. Therefore, WD accumulates copper primary in the liver and secondary in other organs, such as the central nervous system. It represents a wide spectrum of disease, ranging from being asymptomatic in some patients to promote an acute liver failure in others. The diagnosis requires a combination of clinical signs and symptoms, as well as some diagnostic tests such as the measurement of serum ceruloplasmin, the urinary excretion of copper, the liver biopsy or the genetic testing. The treatment must be maintained lifelong and includes some drugs such as chelating agents (penicillamine and trientine) and inhibitors of the copper absorption (zinc salts). Lastly, the liver transplant should be an option for patients with end-stage liver disease.

Wilson's disease: Revisiting an old friend.

Wilson's disease (WD) is a rare condition caused by copper accumulation primarily in the liver and secondly in other organs, such as the central nervous system. It is a hereditary autosomal recessive disease caused by a deficiency in the ATP7B transporter. This protein facilitates the incorporation of copper into ceruloplasmin. More than 800 mutations associated with WD have been described. The onset of the disease frequently includes manifestations related to the liver (as chronic liver disease or acute liver failure) and neurological symptoms, although it can sometimes be asymptomatic. Despite it being more frequent in young people, WD has been described in all life stages. Due to its fatal prognosis, WD should be suspected in all patients with unexplained biochemical liver abnormalities or neurological or psychiatric symptoms. The diagnosis is established with a combination of clinical signs and tests, including the measurement of ceruloplasmin, urinary copper excretion, copper quantification in liver biopsy, or genetic assessment. The pharmacological therapies include chelating drugs, such as D-penicillamine or trientine, and zinc salts, which are able to change the natural history of the disease, increasing the survival of these patients. In some cases of end-stage liver disease or acute liver failure, liver transplantation must be an option to increase survival. In this narrative review, we offer an overview of WD, focusing on the importance of clinical suspicion, the correct diagnosis, and treatment.

Impact of COVID-19 on liver disease: From the experimental to the clinic perspective.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic unprecedented in over a century. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a predominantly respiratory infection, various degrees of liver function abnormalities have been reported. Pre-existing liver disease in patients with SARS-CoV-2 infection has not been comprehensively evaluated in most studies, but it can critically compromise survival and trigger hepatic decompensation. The collapse of the healthcare services has negatively impacted the diagnosis, monitoring, and treatment of liver diseases in non-COVID-19 patients. In this review, we aim to discuss the impact of COVID-19 on liver disease from the experimental to the clinic perspective.