104 research outputs found
Analogs in the treatment of chronic hepatitis B: real life experience with tenofovir and entecavir
No full textINTRODUCTION: Tenofovir and entecavir are potent antiviral agents. By suppressing viral replication, they induce histological improvement and finally delay the progression of chronic hepatitis B and the development of complications. They are rarely associated with serious side effects. Our data from a real life experience support data from the literature and suggest some minimal difference that may be useful in tailoring therapy.
PATIENTS AND METHODS: We retrospectively analyzed 54 patients affected by chronic hepatitis B (31 and 23 treated by entecavir and tenofovir, respectively). Eight patients were cirrhotic. At baseline and 4-12 and 24 weeks after starting therapy, biochemical and virological analysis were performed in all patients. Renal function tests (serum creatinine, creatinine clearance and blood urea), serum (calcium and phosphate blood level) and urine electrolyte were also studied.
RESULTS: All the patients reached virological control within 24 weeks. Only in the group treated by tenofovir we observed a complete viral suppression within 12 weeks. Some patients treated with tenofovir showed increased creatinine clearance without serum creatinine alteration. No significant side effects were reported with the exception of one case of persistent headache in the entecavir group for which the drug was suspended.
CONCLUSIONS: Entecavir and tenofovir are effective in suppressing viral replication in patients with chronic hepatitis B. Tenofovir is more potent than entecavir and viral replication is blocked within 12 weeks of therapy. Tenofovir administration is associated with slight increase of creatinine clearance without alteration of serum creatinine levels. The choice of one or the other should be made according to target and specific patients characteristics. In patients with high serum viral load where the complete and quick control of viral replication is the main target, tenofovir may represent the best choice
Non-alcoholic fatty liver disease in type-2 diabetes mellitus: population analysis, metabolic profile and referral management pathway
No full textIntroduction: Non-alcoholic fatty liver disease is strongly associated with type-2 diabetes mellitus, with diabetic patients being at higher risk for adverse outcomes. The aim of this thesis was to explore in detail the clinical and metabolic phenotype of diabetics screened for NAFLD in primary care and to develop a referral management pathway for this population. Moreover, this thesis investigated the impact of alterations of the gut-liver axis on the severity of liver disease in such cohort.
Methods: In this cross-sectional study, consecutive diabetic patients from primary care were screened for liver disease and NAFLD. Nuclear magnetic resonance and liquid chromatography-mass spectrometry were used to explore the metabolic profile of the patients against severity of liver disease. Stool meta-taxagenomics allowed for the analysis of the composition of the microbiome, while gut permeability was investigated using an in-vitro model and an ex-vivo measurement of faecal protease activity. Inflammatory cytokines profile was also analysed in serum as well as in faecal samples.
Results: Clinically significant NAFLD was highly prevalent in the diabetic population in primary care. According to the results of this study, applying FIB-4 with a cut-off of 1.3 in this population would miss up to 38% of the patients with significant liver disease. The BIMAST score, which was derived based on simple clinical parameters, was validated both internally and externally, outperformed conventional screening methods and optimised risk-stratification in primary care. Among the metabolites, only lysine deficiency was associated with increased hepatic collagen content. Moreover, specific changes in gut microbiome were associated with more severe liver disease, while intestinal permeability tended to increase with liver disease severity. A combination of host and microbiota-related factors were associated with a leakier gut in this population.
Conclusions: Current risk-stratification for NAFLD among diabetics in primary care can be improved. Exploring the gut-liver axis may offer diagnostic as well as therapeutical insights in this population.Open Acces
in people with type‐2 diabetes in the community. Cost effectiveness of screening strategies
No full textBackground and Aims
As screening for the liver disease and risk-stratification pathways are not established in patients with type-2 diabetes mellitus (T2DM), we evaluated the diagnostic performance and the cost-utility of different screening strategies for MASLD in the community.
Methods
Consecutive patients with T2DM from primary care underwent screening for liver diseases, ultrasound, ELF score and transient elastography (TE). Five strategies were compared to the standard of care: ultrasound plus abnormal liver function tests (LFTs), Fibrosis score-4 (FIB-4), NAFLD fibrosis score, Enhanced liver fibrosis test (ELF) and TE. Standard of care was defined as abnormal LFTs prompting referral to hospital. A Markov model was built based on the fibrosis stage, defined by TE. We generated the cost per quality-adjusted life year (QALY) gained and calculated the incremental cost-effectiveness ratio (ICER) over a lifetime horizon.
Results
Of 300 patients, 287 were included: 64% (186) had MASLD and 10% (28) had other causes of liver disease. Patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287) and 3% (8/287), respectively. Among those with significant fibrosis classified by LSM≥8.1 kPa, false negatives were 54% from ELF and 38% from FIB-4. On multivariate analysis, waist circumference, BMI, AST levels and education rank were independent predictors of significant and advanced fibrosis. All the screening strategies were associated with QALY gains, with TE (148.73 years) having the most substantial gains, followed by FIB-4 (134.07 years), ELF (131.68 years) and NAFLD fibrosis score (121.25 years). In the cost-utility analysis, ICER was £2480/QALY for TE, £2541.24/QALY for ELF and £2059.98/QALY for FIB-4.
Conclusion
Screening for MASLD in the diabetic population in primary care is cost-effective and should become part of a holistic assessment. However, traditional screening strategies, including FIB-4 and ELF, underestimate the presence of significant liver disease in this setting
Derivation and validation of the BIMAST score for predicting the presence of fibrosis due to Metabolic dysfunction-associated steatotic liver disease among diabetic patients in the community
No full textBackground & aims
Current screening pathways, developed from tertiary care cohorts, underestimate the presence of Metabolic-dysfunction associated steatotic liver disease (MASLD) in patients with type 2 diabetes mellitus (T2DM) in the community. We developed, validated, and assessed cost-effectiveness of a new score for screening the presence of fibrosis due to MASLD in primary care.
Methods
Consecutive T2DM patients underwent screening for liver diseases with transient elastography (TE). Based on predictors of significant/advanced fibrosis, we generated the BIMAST score (based on aspartate aminotransferase (AST) and body mass index (BMI)) and validated it internally and externally (Royal Free Hospital, London and Palermo Hospital). For cost-effectiveness analysis, 6 screening strategies were compared against standard of care: BIMAST score, ultrasound plus abnormal liver function tests, FIB-4, NAFLD fibrosis score, ELF and transient elastography (TE). A Markov model was built based on fibrosis status. Cost per quality-adjusted life year (QALY) gained and the incremental cost-effectiveness ratio (ICER) were estimated over a lifetime.
Results
Among 300 patients enrolled, 64% (186) had MASLD and 10% (28) other causes of liver disease. In the whole population, patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287), and 3% (8/287), respectively. In primary care, BIMAST performed better than other non-invasive markers at predicting significant and advanced fibrosis. Moreover, BIMAST reduced false negatives from 54% (ELF) and 38% (FIB-4) to 10%. In both validation cohorts, BIMAST performance was as good as FIB-4. In the cost-utility analysis, ICER was £2,337.92/QALY for BIMAST.
Conclusion
The BIMAST predicts the presence of significant fibrosis in the community, reduces false negatives and is cost-effective. The BIMAST score should be included in the holistic assessment of diabetic patients
A remark on norm inflation for nonlinear wave equations
No full textIn this note, we study the ill-posedness of nonlinear wave equations (NLW). Namely, we show that NLW experiences norm inflation at every initial data in negative Sobolev spaces. This result covers a gap left open in a paper of Christ, Colliander, and Tao (2003) and extends the result by Oh, Tzvetkov, and the second author (2019) to non-cubic integer nonlinearities. In particular, for some low dimensional cases, we obtain norm inflation above the scaling critical regularity. We also prove ill-posedness for NLW, via norm inflation at general initial data, in negative regularity Fourier-Lebesgue and Fourier-amalgam spaces.</p
Transport of Gaussian measures under the flow of one-dimensional fractional nonlinear Schrödinger equations
No full textWe study the transport property of Gaussian measures on Sobolev spaces of periodic functions under the dynamics of the one-dimensional cubic fractional nonlinear Schrödinger equation. For the case of second-order dispersion or greater, we establish an optimal regularity result for the quasi-invariance of these Gaussian measures, following the approach by Debussche and Tsutsumi (2021). Moreover, we obtain an explicit formula for the Radon-Nikodym derivative and, as a corollary, a formula for the two-point function arising in wave turbulence theory. We also obtain improved regularity results in the weakly dispersive case, extending those by the first author and Trenberth (2019). Our proof combines the approach introduced by Planchon, Tzvetkov and Visciglia (2020) and that of Debussche and Tsutsumi (2021).</p
On the unique ergodicity for a class of 2 dimensional stochastic wave equations
No full textWe study the global-in-time dynamics for a stochastic semilinear wave equation with cubic defocusing nonlinearity and additive noise, posed on the 2-dimensional torus. The noise is taken to be slightly more regular than space-time white noise. In this setting, we show existence and uniqueness of an invariant measure for the Markov semigroup generated by the flow over an appropriately chosen Banach space. This extends a result of the second author [Comm. Math. Phys. 377 (2020), pp. 1311–1347] to a situation where the invariant measure is not explicitly known.</p
Procoagulant imbalance is associated with hepatic and vascular complications in patients with MASLD and diabetes. Key role of factor VIII
No full textBackground: Metabolic-dysfunction associated steatotic liver disease (MASLD) promotes fibrosis and vascular complications, especially if associated with type 2 diabetes. Aim: To evaluate the association between procoagulant imbalance, hepatic and vascular damage. Methods: 185 diabetic MASLD patients (62±11ys, 59% males) underwent assessment of of FibroScan® (LSM≥8 kPa), macro- and micro-vascular complications. In 96 patient PNPLA3 genotyping, coagulation factors (i.e., factor (F)VIII, protein C (PC), antithrombin and thrombin generation assay were also assessed. Results: The endogenous-thrombin-potential [ETP (with/without thrombomodulin), called ETP-TM ratio)] and the FVIII/PC ratio increased from tertile 1 to 3 (from 0.65±0.15 to 0.92±0.41, p<0.001), as well as FVIII/PC (from 1.23±0.41 to 1.57±0.77, p=0.003) and were independently associated with increasing LSM values (b-coefficient, 6.11; CI95% 3.59-8.64; b-coefficient, 4.80; CI95% 2.28-7.32). Antithrombin and PC correlated to LSM≥ 8kpa (OR 0.92, CI95% 0.88-0.97; OR 0.97, CI95% 0.94-0.99). When added to the model, PNPLA3 modified some of these associations, but remained independently associated with peak-thrombin ratio (b-coefficient 0.063; CI95% 0.001-0.126) and antithrombin (b-coefficient -6.14; CI95% -11.82 -0.46). FVIII and fibrinogen were independently associated with micro-vascular complications. Conclusion: MASLD diabetic patients display a procoagulant profile, which is independently associated with the severity of hepatic fibrosis and micro-vascular complications. PNPLA3 determine a possible procoagulant profile associated with fibrosis, but further studies are warranted to elucidate this mechanism
Editorial: importance of an elevated mean platelet volume for prediction of major adverse cardiovascular events in non-alcoholic liver disease – authors’ reply
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