Background
Preliminary evidence suggests that inherited hypercoagulable disorders can lead to an increased risk of significant liver fibrosis.
Objective
We aimed to investigate the prevalence of ...significant fibrosis in patients with inherited thrombophilia, assessed by using liver stiffness (LS), and to compare this prevalence to that found in a large population‐based cohort from the same region.
Methods
This was a single‐center, cross‐sectional study. A complete laboratory analysis for liver disease, LS by transient elastography and an abdominal ultrasound were performed in patients with inherited thrombophilia diagnosed between May 2013‐February 2017. These patients were propensity score matched (ratio 1:4) with a population‐based cohort from the same region (PREVHEP‐ETHON study; NCT02749864; N = 5988).
Results
Of 241 patients with inherited thrombophilia, eight patients (3.3%) had significant fibrosis (LS ≥8 kPa). All of them had risk factors for liver disease and met diagnostic criteria for different liver diseases. After matching 221 patients with thrombophilia with 884 patients of the PREVHEP‐ETHON cohort, the prevalence of significant fibrosis was similar between both cohorts (1.8% vs. 3.6%, p = 0.488). Multivariate analysis showed that age and liver disease risk factors, but not belonging to the thrombophilia cohort, were associated with the presence of significant fibrosis. The magnitude of the increased risk of significant fibrosis in patients with risk factors for liver disease was also similar in both cohorts.
Conclusions
Our findings do not provide evidence supporting an association between inherited thrombophilia and an increased risk of significant liver fibrosis, independent of the presence of liver‐related causes of fibrosis.
The consumption of alcoholic beverages is harmful to human health. In recent years, consumption patterns of alcoholic beverages have changed in our society, and binge drinking has generalized. It is ...considered to be a socio-sanitary problem with few known consequences in terms of individual and third-party social impacts(in the form of violence or traffic accidents) and its organic impact(affects the liver and other organs and systems, such as the nervous and cardiovascular systems) and represents an important financial burden due to its increasing economic impact. This review provides a global approach to binge drinking and emphasizes its epidemiological character, the effect of this type of consumption and the possible management of a problem with an increasing tendency in our society.
Aim
Non‐malignant portal vein thrombosis (PVT) is a complication of liver cirrhosis. The aim of this study was to evaluate the annual incidence of PVT and related risk factors.
Methods
We ...retrospectively reviewed clinical, laboratory, and radiological data collected prospectively from September 2016 to September 2017. A follow‐up of 36 months was performed in a subset of patients to determine the cumulative incidence of PVT and related complications.
Results
The study included 567 patients. The incidence of PVT at 12, 24, and 36 months was 3.7%, 0.8%, and 1.4%, respectively. Patients with PVT were compared with patients without PVT, and showed differences in albumin (p = 0.04), aspartate aminotransferase (p = 0.04), hemoglobin (p = 0.01), and prothrombin activity (p = 0.01). The presence of hydropic decompensation (57.1% vs. 30.1%; p 0.004), gastroesophageal varices (76.2% vs. 39.5%; p = 0.05), variceal bleeding (52.4% vs. 22.7%; p < 0.001), hepatic encephalopathy (38.1% vs. 9.9%; p = 0.01), spontaneous bacterial peritonitis (9.5% vs. 1.7%; p < 0.001), and use of beta‐blockers (71.4% vs. 27.7%; p < 0.001) were significantly associated. In the multivariate analysis, use of beta‐blockers and hepatic encephalopathy appeared as risk factors, and high albumin levels a protective factor.
Conclusions
The incidence of PVT was 3.7%. Beta‐blockers and hepatic encephalopathy were risks factors. High albumin levels were a protective factor.
AIM: To investigate the plasma levels of betatrophin in patients with cirrhosis.METHODS: Forty patients diagnosed at the clinic with liver cirrhosis according to biological, ultrasonographic,or ...histological criteria were included.The severity of cirrhosis was classified according to Pugh’s modification of Child’s classification and MELD score. Insulin resistance(IR) was assessed by the Homeostasis Model Assessment. A total of 20 patients showed a MELD score higher than 14. The control group consisted in 15 sex-and aged-matched subjects.Fasting blood samples were obtained for subsequent analysis. Serum insulin was determined by Liaison automated immune chemiluminiscence assay(DiaSorin S.p.A.) using a sandwich assay. The sensitivity of the assay was 0.2 μU/mL. The intra and interassay variation coefficients were < 4% and < 10%,respectively. The normal values were between 2 and17 μU/mL. Human active betatrophin was analyzed by specific quantitative sandwich ELISA(Aviscera Bioscience). The sensitivity of the assay was 0.4 ng/mL, and the intra and interassay reproducibility were< 6% and < 10%, respectively.RESULTS: Plasma betatrophin levels were significantly increased in patients with cirrhosis compared with those in healthy subjects(P = 0.0001). Betatrophin levels were also associated with disease severity, being higher in Child-Pugh C patients compared to Child-Pugh B(P< 0.0005) and in patients who displayed a MELD score higher than 14 points compared to patients with lower punctuation(P = 0.01). In addition, we found a positive correlation between plasma betatrophin levels and the severity of cirrhosis according to Child-Pugh classification(r = 0.53; P < 0.01) or MELD score(r = 0.45; P <0.01). In the overall cohort, a moderate correlation between serum betatrophin and plasmatic bilirrubin(r= 0.39; P < 0.01) has been observed, as well as an inverse correlation between betatrophin and albumin(r =-0.41; P < 0.01) or prothrombin time(r =-0.44;P <0.01). Moreover, insulin resistance was observed in82.5% of the cirrhotic patients. In this group of patients,betatrophin levels were significantly higher than those in the group of patients without IR(P < 0.05).CONCLUSION: Plasma betatrophin is increased in patients with cirrhosis. This increase is related to the severity of cirrhosis, as well as with the emergence of insulin resistance.
Despite their relatively low prevalence, vascular diseases of the liver represent a significant health problem in the field of liver disease. A common characteristic shared by many such diseases is ...their propensity to cause portal hypertension together with increased morbidity and mortality. These diseases are often diagnosed in young patients and their delayed diagnosis and/or inappropriate treatment can greatly reduce life expectancy. This article reviews the current body of evidence concerning Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia, cirrhotic portal vein thrombosis and other rarer vascular diseases including arterioportal fistulas. It also includes a section on the diagnostic imaging of vascular diseases of the liver and their treatment from a haematological standpoint (study of thrombotic diathesis and anticoagulation therapy). All recommendations are based on published studies extracted from PubMed. The quality of evidence and strength of recommendations were rated in accordance with the GRADE system (Grading of Recommendations, Assessment Development and Evaluation). In the absence of sufficient evidence, recommendations were based on the opinion of the committee that produced the guide.
No therapies have been proven to increase survival after a hepatic encephalopathy (HE) episode. We hypothesize that two doses of albumin could improve 90-day survival rates after a HE episode. ...Methods: (1) A randomized double-blind, placebo-controlled trial (BETA) was conducted in 12 hospitals. The effect of albumin (1.5 g/kg at baseline and 1 g/kg on day 3) on 90-day survival rates after a HE episode grade II or higher was evaluated. (2) A meta-analysis of individual patient’s data for survival including two clinical trials (BETA and ALFAE) was performed. Results: In total, 82 patients were included. Albumin failed to increase the 90-day transplant-free survival (91.9% vs. 80.5%, p = 0.3). A competing risk analysis was performed, observing a 90-day cumulative incidence of death of 9% in the albumin group vs. 20% in the placebo (p = 0.1). The meta-analysis showed a benefit in the albumin group, with a lower rate of clinical events (death or liver transplant) than patients in the placebo (HR, 0.44; 95% CI, 0.21–0.82), when analyzed by a competing risk analysis (90-days mortality rate of 11% in the albumin group vs. 30% in the placebo, p = 0.02). Conclusions: Repeated doses of albumin might be beneficial for patient’s survival as an add-on therapy after an HE episode, but an adequately powered trial is needed.
we aimed to assess the influence of metabolic syndrome on fibrosis regression (using liver-stiffness measurement (LSM) and serological scores) and the relationship with the expression of lysyl ...oxidase-like-2 as a potential goal of antifibrotic therapy.
We included 271 patients treated with Direct Antiviral Therapy (DAAs) in our hospital who achieved a sustained virological response (SVR); physical examination, blood tests, and LSM were made at baseline (B) and 24 months (24 M) after SVR. Hemodynamic studies and transjugular liver biopsies were performed on 13 patients.
At B, 68 patients were F1 (25.1%); F2
= 59 (21.7%); F3
= 44 (16.05%); and 100 were F4 (36.9%). Although the LSM (absolute value) improved in 82% of patients (
= 222), it progressed in 17.5% of patients (
= 48). At 24 M, 48 patients met the metabolic syndrome (MetS) criteria and there was an increase in patients with a BMI of >25 kg/m
(
< 0.001). At B and 24 M, a BMI of >25 kg/m
is a risk factor for significant fibrosis or steatosis at 24 M (
< 0.05) and progression on LSM (
< 0.001), as well as MetS at B and 24 M (OR 4.1 IC (1.4-11.7),
= 0.008; and OR 5.4 IC (1.9-15.4),
= 0.001, respectively). Regarding the correlation between LSM and the liver biopsy, we found that only six out of 13 patients had a matching LSM and biopsy. We found a statistically significant decrease in LOXL2 levels at 24 M with respect to B (
< 0.001) with higher serological value in patients with elastography of >9 kPa vs. <9 kPa (
= 0.046).
Regression of LSM was reached in 82% of patients. Downregulated LOXL2 was demonstrated post-SVR, with overexpression in cirrhotic patients being a potential therapy goal in selected patients.
Porto-sinusoidal vascular disease (PSVD) is an uncommon cause of portal hypertension (PHT) characterized by typical manifestations of PHT in the absence of an identifiable cause such as cirrhosis or ...splenoportal thrombosis. There are different etiological factors, including oxaliplatin. We present the case of a 67-year-old male with a history of locally advanced rectal cancer in 2007 treated with chemotherapy (capecitabine, folinic acid, 5-fluorouracil and oxaliplatin), radiotherapy and surgery with a definitive colostomy. He was admitted for lower gastrointestinal bleeding from the colostomy with no anemia or hemodynamic repercussion. Colonoscopy was performed and no lesions were found. Abdominal computed tomography (CT) showed peristomal varices with porto-systemic collaterals at that level. There was splenomegaly, no evidence of chronic liver disease and the splenoportal axis was permeable. Laboratory tests showed chronic thrombocytopenia. Laboratory results excluded other causes of liver disease, hepatic elastography showed a value of 7.2 kPa and upper gastrointestinal endoscopy ruled out esophagogastric varices. The catheterisation of hepatic veins demonstrated a hepatic venous pressure gradient of 13.5 mmHg and liver biopsy revealed sinusoidal dilatation with sinusoidal and perivenular fibrosis. Because of the clinical context of the patient with a history of treatment with oxaliplatin, he was diagnosed with peristomal ectopic varices secondary to porto-sinusoidal vascular disease. Due to bleeding recurrence, it was finally decided to place a transjugular intrahepatic portosystemic shunt (TIPS).
To evaluate the long-term outcome of an acute hemodynamic response-guided protocol in which acute responders to intravenous propranolol received traditional nonselective beta-blockers (NSBBs) and ...acute nonresponders received carvedilol.
Retrospective review of a protocol for primary prophylaxis of variceal bleeding guided by the acute hemodynamic response to intravenous propranolol. Fifty-two acute responders treated with traditional NSBB (
. propranolol or nadolol) were compared with 24 acute nonresponders receiving carvedilol. A second hemodynamic study was performed in 27 and 13 patients, respectively. The primary endpoint was development of first or further decompensation. Secondary endpoints included death from any cause, association between acute and chronic hemodynamic response, and baseline clinical and laboratory variables related to the acute hemodynamic response.
Acute responders and acute nonresponders presented similar 1, 2, and 3-year probabilities of first decompensation (NSBB: 0%, 13.7%, 26.1%
carvedilol: 0%, 20%, 20%,
= 0.968) or further decompensation (21.2%, 26.1%, 40.9%
21.2%, 50.0%, 50.0%,
= 0.525). A previous episode of hepatic encephalopathy was the only independent predictor of decompensation hazard ratio (95% confidence interval): 8.03 (2.76-23.37). Mortality rates were similar in acute responders and acute nonresponders with compensated (
= 0.428) or decompensated cirrhosis (
= 0.429). No clinical, laboratory, endoscopic or hemodynamic parameter predicted the acute hemodynamic response. In patients receiving traditional NSBB, the acute and chronic changes of hepatic venous pressure gradient were correlated (
= 0.59,
= 0.001). Up to 69.2% of acute nonresponders gained chronic response with carvedilol.
Early identification and treatment with carvedilol of acute nonresponders to intravenous propranolol improves the clinical outcome of this high-risk group of patients, probably due to its greater effects for reducing portal pressure.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. There is increasing interest in developing specific markers to serve as predictors of response to ...sorafenib and to guide targeted therapy. Using a sequencing platform designed to study somatic mutations in a selection of 112 genes (HepatoExome), we aimed to characterize lesions from HCC patients and cell lines, and to use the data to study the biological and mechanistic effects of case-specific targeted therapies used alone or in combination with sorafenib. We characterized 331 HCC cases in silico and 32 paired samples obtained prospectively from primary tumors of HCC patients. Each case was analyzed in a time compatible with the requirements of the clinic (within 15 days). In 53% of the discovery cohort cases, we detected unique mutational signatures, with up to 34% of them carrying mutated genes with the potential to guide therapy. In a panel of HCC cell lines, each characterized by a specific mutational signature, sorafenib elicited heterogeneous mechanistic and biological responses, whereas targeted therapy provoked the robust inhibition of cell proliferation and DNA synthesis along with the blockage of AKT/mTOR signaling. The combination of sorafenib with targeted therapies exhibited synergistic anti-HCC biological activity concomitantly with highly effective inhibition of MAPK and AKT/mTOR signaling. Thus, somatic mutations may lead to identify case-specific mechanisms of disease in HCC lesions arising from multiple etiologies. Moreover, targeted therapies guided by molecular characterization, used alone or in combination with sorafenib, can effectively block important HCC disease mechanisms.
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