Background & Aims
Non‐alcoholic fatty liver disease (NAFLD) has become a major public health problem, but the prevalence of fibrosis associated with non‐alcoholic steatohepatitis (NASH) is largely ...unknown in the general population. This study aimed to provide an updated estimation of the prevalence of NASH fibrosis in Spain.
Methods
This was an observational, retrospective, cross‐sectional, population‐based study with merged data from two Spanish datasets: a large (N = 12 246) population‐based cohort (ETHON), including transient elastography (TE) data, and a contemporary multi‐centric biopsy‐proven NASH cohort with paired TE data from tertiary centres (N = 501). Prevalence for each NASH fibrosis stage was estimated by crossing TE data from ETHON dataset with histology data from the biopsy‐proven cohort.
Results
From the patients with valid TE in ETHON dataset (N = 11 440), 5.61% (95% confidence interval 95% CI: 2.53‐11.97) had a liver stiffness measurement (LSM) ≥ 8 kPa. The proportion attributable to NAFLD (using clinical variables and Controlled Attenuation Parameter) was 57.3% and thus, the estimated prevalence of population with LSM ≥ 8 kPa because of NAFLD was 3.21% (95% CI 1.13–8.75). In the biopsy‐proven NASH cohort, 389 patients had LSM ≥ 8 kPa. Among these, 37% did not have significant fibrosis (F2‐4). The estimated prevalence of NASH F2‐3 and cirrhosis in Spain's adult population were 1.33% (95% CI 0.29–5.98) and 0.70% (95% CI 0.10–4.95) respectively.
Conclusions
These estimations provide an accurate picture of the current prevalence of NASH‐related fibrosis in Spain and can serve as reference point for dimensioning the therapeutic efforts that will be required as NASH therapies become available.
In non-alcoholic steatohepatitis (NASH), decreased nitric oxide and increased endothelin-1 (ET-1, also known as EDN1) released by sinusoidal endothelial cells (LSEC) induce hepatic stellate cell ...(HSC) contraction and contribute to portal hypertension (PH). Statins improve LSEC function, and ambrisentan is a selective endothelin-receptor-A antagonist. We aimed to analyse the combined effects of atorvastatin and ambrisentan on liver histopathology and hemodynamics, together with assessing the underlying mechanism in a rat NASH model. Diet-induced NASH rats were treated with atorvastatin (10 mg/kg/day), ambrisentan (30 mg/kg/day or 2 mg/kg/day) or a combination of both for 2 weeks. Hemodynamic parameters were registered and liver histology and serum biochemical determinations analysed. Expression of proteins were studied by immunoblotting. Conditioned media experiments were performed with LSEC. HSCs were characterized by RT-PCR, and a collagen lattice contraction assay was performed. Atorvastatin and ambrisentan act synergistically in combination to completely normalize liver hemodynamics and reverse histological NASH by 75%. Atorvastatin reversed the sinusoidal contractile phenotype, thus improving endothelial function, whereas ambrisentan prevented the contractile response in HSCs by blocking ET-1 response. Additionally, ambrisentan also increased eNOS (also known as Nos3) phosphorylation levels in LSEC, via facilitating the stimulation of endothelin-receptor-B in these cells. Furthermore, the serum alanine aminotransferase of the combined treatment group decreased to normal levels, and this group exhibited a restoration of the HSC quiescent phenotype. The combination of atorvastatin and ambrisentan remarkably improves liver histology and PH in a diet-induced NASH model. By recovering LSEC function, together with inhibiting the activation and contraction of HSC, this combined treatment may be an effective treatment for NASH patients.
Background
We aimed to investigate the early changes in liver and spleen stiffness measurement
(LSM, SSM) in hepatitis C virus (HCV) patients with compensated advanced chronic liver
disease (cACLD) ...treated with new antivirals (DAA) to elucidate factors determining the
initial change in stiffness and its implications for the long-term follow up of
HCV-cured patients.
Methods:
A total of 41 patients with cACLD who started DAA therapy underwent LSM and SSM at
baseline, week 4, end of treatment (EOT), 24 and 48 weeks of follow up using transient
elastography.
Results:
LSM improved rapidly during the first 4 weeks of treatment (baseline: 20.8kPa; week 4:
17.5kPa, p = 0.002), with no significant changes between week 4 and EOT
(18.3kPa, p = 0.444) and between EOT and 48-week follow up (14.3kPa,
p = 0.148). Likewise, SSM improved rapidly (baseline: 45.7kPa; week
4: 33.8kPa, p = 0.047), with no significant changes between week 4 and
EOT (30.8kPa, p = 0.153) and between EOT and 48-week follow up
(31.2kPa, p = 0.317). A higher decrease in LSM was observed in patients
with baseline ALT ⩾ twofold upper limit normal (2 × ULN) than in those with ALT < 2 ×
ULN (–5.7kPa versus –1.6kPa). Patients who presented a decrease in LSM
⩾ 10% during treatment compared with those with LSM < 10% decrease, showed lower SSM
values, higher platelet counts and lower bilirubin levels at 24-week follow up. Those
with decrease in SSM ⩾ 10%, presented a higher increase in platelets than those with SSM
< 10% change (p = 0.015).
Conclusions:
LSM and SSM decrease very rapidly during DAA treatment in cACLD patients suggesting
that it most probably reflects a reduction in inflammation rather than in fibrosis.
cACLD patients should be maintained under surveillance independently of stiffness
changes, because advanced fibrosis can still be present.
Available prognostic models for mortality after an acute variceal hemorrhage have limitations that restrict their clinical value. We assessed the performance of a novel prognostic approach based on ...classification and regression tree (CART) analysis.
Logistic regression (LR) and CART analyses were performed to identify prognostic models for mortality at 6 weeks in a single-center cohort of 267 consecutive patients with acute variceal bleeding. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the models. Prognostic models were fitted and validated by split-sample technique (training set, 164 patients, 2001-2005; test set, 103 patients, 2006-2008).
After 6 weeks, 21% of patients experienced rebleeding and 24% died. The best LR model was based on Child-Pugh score, creatinine level, bacterial infection, and hepatocellular carcinoma. CART analysis provided a simple algorithm based on the combined use of just 3 variables (Child-Pugh score, creatinine level, and bacterial infection), allowing accurate early discrimination of 3 distinct prognostic subgroups with 8% (low risk), 17% (intermediate), and 50% to 73% (high) mortality. Its accuracy was similar to the LR model (area under the ROC curves, 0.81 vs 0.84; P = .17) and better than that of Child-Pugh (0.75; P = .05) and model for end-stage liver disease (0.74; P = .05). The prognostic accuracy of both LR and CART models was validated in the test set (area under the ROC curve values, 0.81 and 0.83, respectively).
A simple CART algorithm based on Child-Pugh score, creatinine level, and infection allowed an accurate predictive assessment of 6-week mortality after acute variceal bleeding.
Objectives: to establish the clinical and economic consequences (resource utilization and healthcare costs) of non-alcoholic fatty liver in the setting of the usual clinical practice in Spain. ...Patients and methods: an observational, retrospective study was performed based on a review of the medical records of adult patients greater than or equal to 18 years of age who sought medical care from 2017 to 2018. Patients were categorized into two groups according to fibrosis stage (estimation method: FIB-4): a) F0-F2; and b) F3-F4 (advanced fibrosis). Follow-up lasted one year. Primary endpoints included comorbidity, concomitant medication, resource utilization and costs. Results were analyzed using a multivariate approach with p < 0.05. Results: a total of 8,151 patients were recruited with a mean age of 61.1 years and 51.5 % were male. By group: a) mild fibrosis n = 7,127, 87.4 %; and b) advanced fibrosis n = 1,024, 12.6 % (6.8 % with liver cirrhosis). The most common comorbidities included 63 % dyslipidemia, 52 % obesity, 52 % hypertension and 35 % diabetes. The average number of drugs used was 2.1 per patient. Patients with advanced fibrosis (F3-F4) had a higher average number of concomitant medications (2.5 vs 2.1; p < 0.001) and a higher AST/ALT ratio (1.1 vs 0.8; p < 0.001). The average cost (patient-year) for subjects with advanced fibrosis, corrected for covariates, was higher (euro1,812 vs euro1,128, p < 0.001). Age, morbidity, concomitant medication, fibrosis stage and total costs were higher in patients with diabetes. Conclusions: patients with advanced fibrosis were associated with more comorbidity and concomitant medications, which resulted in higher healthcare costs for the National Health System. Keywords: Fatty liver. Non-alcoholic. Liver fibrosis. Resource utilization. Costs.
Management of acute variceal bleeding has greatly improved over recent years. Available data indicates that general management of the bleeding cirrhotic patient by an experienced multidisciplinary ...team plays a major role in the f inal outcome of this complication. It is currently recommended to combine pharmacological and endoscopic therapies for the initial treatment of the acute bleeding. Vasoactive drugs (preferable somatostatin or terlipressin) should be started as soon as a variceal bleeding is suspected (ideally during transfer to hospital) and maintained afterwards for 2-5 d. After stabilizing the patient with cautious fluid and blood support, an emergency diagnostic endoscopy should be done and, as soon as a skilled endoscopist is available, an endoscopic variceal treatment (ligation as f irst choice, sclerotherapy if endoscopic variceal ligation not feasible) should be performed. Antibiotic prophylaxis must be regarded as an integral part of the treatment of acute variceal bleeding and should be started at admission and maintained for at least 7 d. In case of failure to control the acute bleeding, rescue therapies should be immediately started. Shunt therapies (especially tran sjugular intrahepatic portosystemic shunt) are very effective at controlling treatment failures after an acute variceal bleeding. Therapeutic developments and increasing knowledge in the prognosis of this complication may allow optimization of the management strategy by adapting the different treatments to the expected risk of complications for each patient in the near future. Theoretically, this approach would allow the initiation of early aggressive treatments in high-risk patients and spare low-risk individuals unnecessary proce dures. Current research efforts will hopefully clarify this hypothesis and help to further improve the outcomes of the severe complication of cirrhosis.
Background
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease and is found in 70% of obese people. The evidence available to date suggests that bariatric surgery ...could be an effective treatment by reducing weight and also by improving metabolic complications in the long term. This work aimed to compare, in a diet-induced NAFLD animal model, the effect of both sleeve gastrectomy (SG) and very-low calorie diet (VLCD).
Methods
Thirty-five Wistar rats were divided into control rats (
n
= 7) and obese rats fed a high-fat diet (HFD). After 10 weeks, the obese rats were subdivided into four groups: HFD (
n
= 7), VLCD (
n
= 7), and rats submitted to either a sham operation (
n
= 7) or SG (
n
= 7). Both liver tissue and blood samples were processed to evaluate steatosis and NASH changes in histology (Oil Red, Sirius Red and H&E); presence of endothelial damage (CD31, Moesin/p-Moesin, Akt/p-Akt, eNOS/p-eNOS), oxidative stress (iNOS) and fibrosis (αSMA, Col1, PDGF, VEGF) proteins in liver tissue; and inflammatory (IL6, IL10, MCP-1, IL17α, TNFα), liver biochemical function, and hormonal (leptin, ghrelin, visfatin and insulin) alterations in plasma.
Results
Both VLCD and SG improved histology, but only SG induced a significant weight loss, improved endothelial damage, and a decreased cardiovascular risk by reducing insulin resistance (IR), leptin, total cholesterol, and triglyceride levels. There were no relevant variations in the inflammatory and fibrosis markers.
Conclusion
Our study suggests a slight superiority of SG over VLCD by improving not only the histology but also the IR and cardiovascular risk markers related to NAFLD.
The prevalence of chronic non-communicable diseases, particularly metabolic syndrome (MetS), has increased among the prison population. Nevertheless, we have limited data on metabolic ...dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of this syndrome. We aimed to investigate the prevalence and risk factors of MASLD and MASLD-associated liver fibrosis in the penitentiary population in Catalonia, Spain.
A cross-sectional observational study involving eight penitentiary centers. Participants had at least one metabolic disorder and were at a closed-regimen penitentiary. Individuals with concomitant liver diseases and/or alcohol risk consumption were excluded. Significant fibrosis and MASLD were defined as liver stiffness ≥8 kPa and a controlled attenuation parameter ≥275 dB/m by vibration-controlled transient elastography (VCTE), respectively. After exclusions, metabolic inmates with VCTE were analyzed. Logistic regression analysis was performed to identify predictors of MASLD and MASLD-associated significant fibrosis.
Out of the 4338 inmates studied, 1290 (29.7%) had metabolic disorders, and 646 (14.9%) underwent VCTE. The mean age was 48.0 years (SD 12.1), and 89.5% were male. MASLD prevalence was 33.9%. Significant fibrosis and MASLD-associated significant fibrosis were found in 16.4% and 9.4% of inmates, respectively. In the multivariate analysis, T2D, waist circumference, MetS, and higher ALT values were identified as independent risk factors for MASLD and MASLD-associated significant fibrosis amongst the prison population.
Metabolic disorders including MASLD are highly prevalent among inmates. The prevalence of significant fibrosis seems notably higher than that of the general population, underscoring the need for targeted screening programs and therapeutic interventions in the incarcerated population.
The gut microbiome has a recognized role in Non-alcoholic fatty liver disease (NAFLD) and associated comorbidities such as Type-2 diabetes and obesity. Stool transplantation has been shown to improve ...disease by restoring endothelial function and insulin signaling. However, more patient-friendly treatments are required. The present study aimed to test the effect of a defined bacterial consortium of nine gut commensal strains in two in vivo rodent models of Non-alcoholic steatohepatitis (NASH): a rat model of NASH and portal hypertension (PHT), and the Stelic animal (mouse) model (STAM™). In both studies the consortium was administered orally q.d. after disease induction. In the NASH rats, the consortium was administered for 2 weeks and compared to stool transplant. In the STAM™ study administration was performed for 4 weeks, and the effects compared to vehicle or Telmisartan at the stage of NASH/early fibrosis. A second group of animals was followed for another 3 weeks to assess later-stage fibrosis. In the NASH rats, an improvement in PHT and endothelial function was observed. Gut microbial compositional changes also revealed that the consortium achieved a more defined and richer replacement of the gut microbiome than stool transplantation. Moreover, liver transcriptomics suggested a beneficial modulation of pro-fibrogenic pathways. An improvement in liver fibrosis was then confirmed in the STAM™ study. In this study, the bacterial consortium improved the NAFLD activity score, consistent with a decrease in steatosis and ballooning. Serum cytokeratin-18 levels were also reduced. Therefore, administration of a specific bacterial consortium of defined composition can ameliorate NASH, PHT, and fibrosis, and delay disease progression.
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