Studies have produced conflicting results of the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus–associated cirrhosis treated with direct-acting antivirals (DAAs). Data ...from clinics are needed to accurately assess the occurrence rate of HCC in patients with cirrhosis in the real world.
We collected data from a large prospective study of 2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C virus–associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child-Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic and community liver centers in Sicily, Italy. HCC occurrence was evaluated by Kaplan-Meier curves. Cox regression analysis was used to identify variables associated with HCC development.
A sustained virologic response (SVR) was achieved by 2,140 patients (total = 95.2%; 95.9% with Child Pugh class A and 88.3% with Child Pugh class B; P < .001). Seventy-eight patients (3.5%) developed HCC during a mean follow-up of 14 months (range = 6–24 months). At 1 year after exposure to DAAs, HCC developed in 2.1% of patients with Child-Pugh class A with an SVR and 6.6% of patients with no SVR and in 7.8% of patients with Child-Pugh class B with an SVR and 12.4% of patients with no SVR (P < .001 by log-rank test). Albumin level below 3.5 g/dL (hazard ratio = 1.77, 95% confidence interval = 1.12–2.82, P = .015), platelet count below 120 × 109/L (hazard ratio = 3.89, 95% confidence interval = 2.11–7.15, P < .001), and absence of an SVR (hazard ratio = 3.40, 95% confidence interval = 1.89–6.12, P < .001) were independently associated increased risk for HCC. The mean interval from exposure to DAAs to an HCC diagnosis was 9.8 months (range = 2–22 months) and did not differ significantly between patients with (n = 64, 9.2 months) and without (n = 14, 12.0 months) an SVR (P = .11). A larger proportion of patients with an SVR had a single HCC lesion (78% vs 50% without an SVR; P = .009) or an HCC lesion smaller than 3 cm (58% vs 28% without an SVR; P = .07).
In an analysis of data from a large prospective study of patients with hepatitis C virus–associated compensated or decompensated cirrhosis, we found that the SVR to DAA treatment decreased the incidence of HCC over a mean follow-up of 14 months.
We present a calculation of \(f_B\) in the static limit, obtained by numerical simulation of quenched QCD, at \(\beta=6.2\) on a \(18^3 \times 64\) lattice, using the SW-Clover quark action. The ...decay constant has been extracted by studying heavy(static)-light correlation functions of different smeared operators, on a sample of 220 gauge field configurations. We have obtained \(f_B^{static}=(290 \pm 15 \pm 45)\) MeV, where the first error comes from the uncertainty in the determination of the matrix element and the second comes from the uncertainty in the lattice spacing. We also obtain \(M_{B_s}-M_{B_d}= (70 \pm 10)\) MeV and \(f^{stat}_{B_s}/f^{stat}_{B_d}=1.11(3)\). A comparison of our results with other calculations of the same quantity is made.
According to the current European Association for the Study of Liver guidelines, transarterial chemoembolization (TACE) is the recommended first-line therapy for patients with intermediate-stage ...(Barcelona Clinic Liver Cancer-B class) hepatocellular carcinoma (HCC). The efficacy of this therapy is supported by robust evidence; however, there is still a lack of standardization in treatment methodology, and TACE protocols are widely variable. Moreover, TACE can be associated with a number of contraindications. Despite these limitations, research on TACE is still ongoing with the aim of optimizing the use of this methodology in the current management of HCC. In particular, TACE represents a control in comparative studies, and it is currently being investigated in combination schemes, for example, with sorafenib. In this review, we briefly describe the current scenario and the clinical innovations regarding TACE for the treatment of HCC.
Evidence suggests that long-term albumin administration (LTA) prolongs overall survival in patients with cirrhosis and refractory ascites. However, LTA is not yet standard care, and the effects of ...its combination with TIPS (Transjugular Intrahepatic Portosystemic Shunt) placement remains unclear.
This observational study compared two groups of patients with cirrhosis and ascites who required at least one large volume paracentesis (LVP). The first group, observed from January 2019 to December 2021, received standard medical treatment (SMT: diuretics and albumin administration after LVP). The second group, observed from January 2022 to February 2024, received SMT plus LTA at a dosage of 40 mg/week. The primary endpoint was mortality and the cause-specific Cox model was used to estimate covariate effects. The Fine and Gray competing risks regression model was used account for death, and LT as competing risk.
A total of 153 patients were analyzed: 63 in the SMT+LTA group and 90 in the SMT group. No differences in liver disease etiology, age, gender, Child-Pugh score, presence of Hepatocellular Carcinoma(HCC), Hepatic Encephalopathy(HE), and eligibility for TIPS and OLT are observed between the two groups.
During the follow-up(median 9 months; range 2-67), 11 patients in the LTA group(17.4%) and 9 in the SMT group(10%) underwent TIPS(p=ns), 7(11.1%) and 8(9%) patients were transplanted in LTA and SMT group respectively(p=ns), and 16 patients in the LTA group(25.4%) versus 71 in the SMT group(79%) died(p<0.001).
Multivariate analysis showed that LTA(HR:0.16; p<0.001), creatinine(HR:1.40; p=0.025), bilirubin (HR:1.16; p=0.014), viral etiology (HR:0.24; p=0.013), and TIPS placement (HR:0.10; p<0.001) were independently associated with mortality. The same results were observed when substituting TIPS placement with TIPS eligibility (Figure 1).
For patients with refractory ascites, LTA in addition to SMT significantly prolongs overall survival and may serve as a disease-modifying treatment, particularly for those contraindicated for TIPS.
The epidemiology of liver cirrhosis is evolving and the etiology, complications, and comorbidities of cirrhosis are continuously changing, presenting new challenges.
We reported data from an ...observational, monocentric study including 1,617 patients with liver cirrhosis admitted to our liver unit from January 2014 to December 2023.
The mean age of patients was 66.8 years, with a male predominance except for autoimmune etiology. During the observation period, the number of hospitalized patients with active HCV infection decreased from 47.9% in 2014 to 9.2% in 2023, while patients with HCV cirrhosis in sustained virologic response (SVR) increased from 15.6% in 2014 to 26.2% in 2023. Hospitalizations for HBV-related cirrhosis remained stable (5.5% in 2014 and 8.5% in 2023. Patients for alcohol-related cirrhosis increased from 16.6% in 2014 to 23.9% 2023 and patients with metabolic cirrhosis increased from 10.6% in 2014 to 36.8% in 2023. The rate of patients with autoimmune cirrhosis (3.0% in 2014 and 4.2% in 2023) and cryptogenic cirrhosis (6.0% in 2014 to 7.9% in 2023) remained stable over the years. Patients with alcohol-related cirrhosis (mean age 59.5 years), HBV cirrhosis (62.1 years) and autoimmune etiologies (62.2 years) were younger than patients with HCV cirrhosis (69.3 years), metabolic cirrhosis (68.3 years) and cryptogenic cirrhosis (67.6 years). The most frequent complication for hospitalization was HCC in active (47.8%) and SVR (58.2%) HCV cirrhosis, and in HBV cirrhosis (47.3%), with the ascites was more frequent in alcohol-related (45.8%) and metabolic (34.1%) cirrhosis Patients with metabolic cirrhosis had the most extrahepatic comorbidities (66.3% diabetic, 18.0% chronic kidney disease, and 20.7% heart disease).
Liver cirrhosis epidemiology is changing, with decreasing HCV infections but increasing alcohol-related and metabolic cases. Complications and comorbidities require tailored management strategies. Effective public health interventions and adaptive healthcare approaches are crucial to address these evolving challenges.
Oxidizing conditions must be maintained in the endoplasmic reticulum (ER) to allow the formation of disulfide bonds in secretory proteins. Here we report the cloning and characterization of a ...mammalian gene (ERO1-L) that shares extensive homology with the Saccharomyces cerevisiae ERO1 gene, required in yeast for oxidative protein folding. When expressed in mammalian cells, the product of the human ERO1-L gene co-localizes with ER markers and displays Endo-H-sensitive glycans. In isolated microsomes, ERO1-L behaves as a type II integral membrane protein. ERO1-L is able to complement several phenotypic traits of the yeast thermosensitive mutant ero1-1, including temperature and dithiothreitol sensitivity, and intrachain disulfide bond formation in carboxypeptidase Y. ERO1-L is no longer functional when either one of the highly conserved Cys-394 or Cys-397 is mutated. These results strongly suggest that ERO1-L is involved in oxidative ER protein folding in mammalian cells.
In the present study, a constitutive analysis of the evolution of the mechanical response of a CrN/NbN superlattice coating exposed to high temperature has been performed. Parametric approaches were ...used to obtain a single master curve describing the experimental data as well as time-temperature-hardness maps to extrapolate the material response. Although the parametric approaches gave an excellent description of the data, an additional effort was devoted to identifying a constitutive equation similar to the power-law function widely used in creep. An excellent description was obtained for a hardness exponent close to 18 and an apparent activation energy ranging from 400 to 500kJ/mol. Possible micro-mechanisms giving reason for this value of the apparent activation energy were discussed.
Thin (40nm and 160nm) CrN coatings were deposited on steel by reactive magnetron sputtering deposition, varying the N2 flow. The coatings were characterized in the as-deposited condition and after ...annealing in air at 500 degree C for 1h, by X-Ray Diffraction, Transmission Electron Microscopy, Raman and Fourier Transform Infrared spectroscopies. Hardness was measured by nanoindentation. Coatings have a nanocrystalline microstructure with the phase shifting from Cr2N to CrN, increasing grain size, thermal stability and resistance to oxidation with increasing N2. Also intrinsic coating hardness is influenced by both N2 flow during deposition and film thickness, as a result of changes in phase composition and microstructural properties.
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