BACKGROUND: Patients treated with direct-acting antivirals for hepatitis C exhibit high cure rates and improved survival. However, there is limited knowledge on their long-term clinical evolution.
OBJECTIVE: In this study, we aimed to analyse the risk of hepatocarcinoma and hepatic decompensation in patients treated with direct-acting antivirals.
METHODS: We conducted a retrospective single-centre study of Portuguese patients with advanced fibrosis treated with direct-acting antiviral agents between 2015 and 2022 at a tertiary hospital.
RESULTS: Out of 460 patients, 50 (10.9 %) developed hepatocarcinoma and 36 (7.8 %) experienced hepatic decompensation. The risk for hepatocarcinoma was higher in patients aged over 55 (HR 4.87, 95 % CI 2.34-10.13, p < 0.001), with signs of portal hypertension (HR 3.83, 95 % CI 2.05-7.13, p < 0.001) and arterial hypertension (HR 1.98, 95 % CI 1.09-3.58, p = 0.024). Alcohol consumption (HR 3.30, 95 % CI 1.22-8.94, p = 0.019), signs of portal hypertension (HR 4.56, 95 % CI 2.19-9.48, p < 0.001) and hepatocarcinoma (HR 3.47, 95 % CI 1.69-7.10, p < 0.001) increased the risk of hepatic decompensation.
CONCLUSIONS: Our study found a high incidence of hepatocarcinoma and hepatic decompensation, along with high mortality, in patients with advanced fibrosis treated with direct-acting antivirals. We identified risk factors such as arterial hypertension, alcohol consumption, and signs of portal hypertension, highlighting their role in clinical management and patient monitoring.

BACKGROUND: Advanced Hepatocarcinoma (HCC) is an important health problem worldwide. Recently, the REFLECT trial demonstrated the non-inferiority of Lenvatinib compared to Sorafenib in I line setting, thus leading to the approval of new first-line standard of care, along with Sorafenib.
OBJECTIVE: With aim to evaluate the optimal choice between Sorafenib and Lenvatinib as primary treatment in clinical practice, we performed a multicentric analysis with the propensity score matching on 184 HCC patients.
RESULTS: The median overall survival (OS) were 15.2 and 10.5 months for Lenvatinib and Sorafenib arm, respectively. The median progression-free survival (PFS) was 7.0 and 4.5 months for Lenvatinib and Sorafenib arm, respectively. Patients treated with Lenvatinib showed a 36% reduction of death risk (p = 0.0156), a 29% reduction of progression risk (p = 0.0446), a higher response rate (p < 0.00001) and a higher disease control rate (p = 0.002). Sorafenib showed to be correlated with more hand-foot skin reaction and Lenvatinib with more hypertension and fatigue. We highlighted the prognostic role of Barcelona Clinic Liver Cancer (BCLC) stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), bilirubin, alkaline phosphatase and eosinophils for Sorafenib. Conversely, albumin, aspartate aminotransferase (AST), alkaline phosphatase and Neutrophil-Lymphocyte Ratio (NLR) resulted prognostic in Lenvatinib arm. Finally, we highlighted the positive predictive role of albumin > Normal Value (NV), ECOG > 0, NLR < 3, absence of Hepatitis C Virus positivity, and presence of portal vein thrombosis in favor of Lenvatinib arm. Eosinophil < 50 and ECOG > 0 negatively predicted the response to Sorafenib.
CONCLUSIONS: SLenvatinib showed to better perform in a real-word setting compared to Sorafenib. More researches are needed to validate the predictor factors of response to Lenvatinib rather than Sorafenib.

Hepatitis B virus (HBV) infection remains a global public health problem. HBV vaccination is the most effective tool to reduce the incidence of HBV disease. Despite there has not been new clinical developments for the treatment of chronic hepatitis B in the last few years, changing epidemiology and current insights on natural history, diagnostic tools and therapy indications make necessary an update of the former version of the consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B infection published in 2012. The current document updates the management of chronic hepatitis B. The treatment of choice is the long-term administration of a nucleos(t)ide analogue with high barrier to resistance (entecavir, tenofovir or tenofovir alafenamide). Pegylated interferon may be an option in patients with non-advanced liver disease, but its applicability is limited due to the low efficacy and poor tolerability. All patients must be monitored for the risk of progression to advanced liver disease and development of hepatocellular carcinoma.

Photodynamic therapy (PDT) is a technique with well-established principles that often demands repeated applications for sequential elimination of tumor cells. An important question concerns the way surviving cells from a treatment behave in the subsequent one. Threshold dose is a core concept in PDT dosimetry, as the minimum amount of energy to be delivered for cell destruction via PDT. Concepts of threshold distribution have shown to be an important tool for PDT results analysis in vitro. In this study, we used some of these concepts for demonstrating subsequent treatments with partial elimination of cells modify the distribution, which represents an increased resistance of the cells to the photodynamic action. HepG2 and HepaRG were used as models of tumor and normal liver cells and a protocol to induce resistance, consisted of repeated PDT sessions using Photogem® as a photosensitizer, was applied to the tumor ones. The response of these cells to PDT was assessed using a standard viability assay and the dose response curves were used for deriving the threshold distributions. The changes in the distribution revealed that the resistance protocol effectively eliminated the most sensitive cells. Nevertheless, HepaRG cell line was the most resistant one among the cells analyzed, which indicates a specificity in clinical applications that enables the use of high doses and drug concentrations with minimal damage to the surrounding normal tissue.

We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality.
All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected.
Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7,067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1,000 people-year. In addition to aging and smoking, time on ART (OR 1.11; 95% CI 1.05-1.17) and PI use (OR 1.72; 95% CI 1.0-2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99-1.0; P=.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08-3.92) were associated with higher mortality.
Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS.

BACKGROUND: Gadoxetic acid and gadopentetate dimeglumine are gadolinium-based contrast agents (GBCAs) with an established role in HCC detection and characterization.
OBJECTIVE: To compare gadopentetate dimeglumine and gadoxetic acid-enhanced magnetic resonance imaging (MRI) for image quality and hepatocellular carcinoma (HCC) detection/conspicuity.
METHODS: In this IRB approved cross-over pilot prospective study, 12 patients (all men; mean age, 56 years) with chronic liver disease at risk of HCC underwent two repeat MRI examinations using gadopentetate dimeglumine and gadoxetic acid (mean interval between studies, 5 days). Two independent observers analyzed images for image quality and HCC detection/conspicuity. Per-lesion sensitivity, positive predictive value, quantitative enhancement, and lesion-to-liver contrast ratio were calculated for both contrast agents.
RESULTS: There was no significant difference in image quality scores between both GBCAs (P = 0.3). A total of 20 HCCs were identified with reference standard in 12 patients (mean size 2.6 cm, range, 1.0-5.0 cm). Higher sensitivity was seen for observer 1 for gadoxetic acid-set in comparison with gadopentetate dimeglumine-set (sensitivity increased from 85.7% to 92.8%), while no difference was noted for observer 2 (sensitivity of 78.5%). Lesion conspicuity was significantly higher on hepatobiliary phase (HBP) images compared to arterial phase images with both GBCAs for both observers (P < 0.05). Lesion-to-liver contrast ratios were significantly higher for HBP compared to all dynamic phases for both agents (P < 0.05).
CONCLUSIONS: Our initial experience suggests that gadoxetic acid-set was superior to gadopentetate dimeglumine-set in terms of HCC detection for one observer, with improved lesion conspicuity and liver-to-lesion contrast on HBP images.