Carmen Martín-Sierra

Background: Liver stiffness (LS) predicts liver complication occurrence in patients with hepatitis C virus (HCV) infection after sustained virological response (SVR). The FibroScan-AST (FAST) score, which includes aspartate aminotransferase (AST) and controlled attenuation parameter (CAP; measured by FibroScan), may improve the prediction ability of isolated LS. Our aim was to compare the predictive capacity of LS vs FAST in this setting. Methods: Multicenter cohort study including individuals with HIV/HCV coinfection or HCV monoinfection from Spain if they had (1) LS ≥9.5 kPa pretreatment, (2) SVR with a direct-acting antiviral (DAA)–based regimen, and (3) LS and CAP measurement at SVR. Fatty liver disease (FLD) was defined as CAP ≥248 dB/m. The primary outcome was the occurrence of a liver complication (decompensation or hepatocellular carcinoma [HCC]) after SVR. Results: Three hundred patients were included; 213 (71%) had HIV. At SVR, 131 (44%) had FLD. The FAST score was 0.67 in 34 (12%) patients. After a median (Q1–Q3) follow-up of 73 (53–83) months, 36 (12%) liver complications (15 [5%] HCC) occurred. LS was independently associated with an increased risk of developing liver complications (sub–hazard ratio [sHR], 1.06; 95% CI, 1.04–1.08; P < .001). In a separate model, FAST ≥0.35 was also independently associated with greater risk of liver complications (sHR, 8.12; 95% CI, 3.11–21.17; P < .001). The area under the receiver operating characteristics curve of the model based on LS was 0.83 (95% CI, 0.76–0.91), and that of the model based on FAST was 0.80 (95% CI, 0.72–0.88; P = .158). Conclusions: The FAST score predicts the development of liver events after SVR but does not improve the predictive capacity of LS alone at this time point.

Background: Liver stiffness (LS) is not reduced in 10%–30% of patients who achieve sustained viral response (SVR) after hepatitis C virus (HCV) elimination with direct-acting antivirals (DAA). Our aim was to analyze whether the parameters associated with cellular aging measured at the DAA initiation date are related to LS reduction upon achieving SVR. Methods: In a prospective cohort study (GEHEP-011) we measured several parameters associated with cellular aging, such as telomere attrition, mitochondrial alterations, and soluble biomarkers associated with senescence-associated secretory phenotype at the DAA initiation date, and examined their associations with a significant (≥20%) LS decrease at the SVR time point. Results: In total, 175 individuals were included in this study. In 101 (57.7%) patients, the LS reduction was ≥20% at SVR. In the multivariate analysis adjusted for sex, age, CXCL10, hsPCR, and CCL11 levels, greater relative telomere length (RTL) emerged as the sole variable independently associated with a significant LS decrease in SVR (1.102; 95% confidence interval, 1.001–1.1214; P = .047). Furthermore, changes in LS, including significant decrease, decrease <20%, or increase, were congruently associated with RTL (P = .011). Conclusions: Greater RTL was independently associated with a significant LS reduction in SVR. Thus, increased cellular aging may be responsible for the absence of liver regeneration after HCV eradication. Further studies are required to assess the long-term effects of cellular aging after SVR. Clinical Trials Registration: NCT04460157.

Background/Objectives: Cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) represent major primary liver cancers, affecting one of the most vital organs in the human body. T regulatory (Treg) cells play an important role in liver cancers through the immunosuppression of antitumor immune responses. The current study focuses on the characterization of circulating natural killer (NK) cells and T cell subsets, including Treg cells, in CCA and HCC patients, before and after surgical tumor resection, in order to understand the effect of tumor resection on the homeostasis of peripheral blood NK cells and T cells. Methods: Whole blood assays were performed to monitor immune alterations and the functional competence of circulating lymphocytes in a group of ten healthy individuals, eight CCA patients, and twenty HCC patients, before and one month after the surgical procedure, using flow cytometry, cell sorting, and qRT-PCR. Results: Before tumor resection, both HCC and CCA patients display increased percentages of CD8⁺ Treg cells and decreased frequencies of circulating CD4⁺ Treg cells. Notwithstanding, no functional impairment was detected on circulating CD4⁺ Treg cells, neither in CCA nor in HCC patients. Interestingly, the frequency of peripheral CD4⁺ Treg cells increased from 0.55% ± 0.49 and 0.71% ± 0.54 (in CCA and HCC, respectively) at T0 to 0.99% ± 0.91 and 1.17% ± 0.33 (in CCA and HCC, respectively) at T1, following tumor resection. Conclusions: Our results suggest mechanisms of immune modulation induced by tumor resection.

Lockdown due to the coronavirus disease 2019 (COVID-19) pandemic led to increases in weight in part of the population. Weight gain leads to hepatic steatosis (HS). Antiretroviral treatment could also influence HS in people with human immunodeficiency virus (PWH). The impact of lockdown on HS in PWH is unknown. The aim of this study was to analyze the changes in HS, as measured by the controlled attenuation parameter (CAP), during the COVID-19 pandemic in PWH. This was a cohort study that included PWH who attended a tertiary care center in southern Spain from January 2018 to December 2021. The CAP was evaluated by transient elastography. Only those who had a valid CAP before and after March 2020 were included. HS was defined as CAP ≥248 dB/m. Six hundred eighty PWH were attended and 488 (71.8%) were included. Two hundred and fourteen (43.9%) had HS at baseline and 239 (49%) at the end of the follow-up (P = .036). The median change in CAP among PWH taking tenofovir alafenamide (TAF) was 8.5 (interquartile range [IQR], −24 to 46.3) dB/m versus −4 (IQR, −35 to 27) dB/m among PWH receiving TAF-free regimens (P = .003). After multivariate analysis, adjusted by sex and age, weight gain (adjusted odds ratio [AOR], 1.09 [95% confidence interval {CI}, 1.05–1.14]; P < .001), TAF therapy (AOR, 1.59 [95% CI, 1.07–2.35]; P = .021), plasma triglycerides (AOR, 1.01 [95% CI, 1–1.01]; P < .001), and fasting blood glucose (AOR, 1.01 [95% CI, 1–1.02]; P = .027) were associated with HS at the end of follow-up. The frequency of HS increased during the COVID-19 pandemic among PWH. TAF is associated with HS development, regardless of metabolic factors.

Background: Chronic inflammation is involved in the initiation and progression of various cancers, including liver cancer. The current study focuses on the characterization of the peripheral immune response in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patients, before and after surgical procedure, in order to assess the effect of tumor resection in the immune system homeostasis and to determine possible prognostic factors associated with high-grade tumors. We developed a whole-blood assay to monitor immune alterations and functional competence of peripheral monocytes in a group of 10 healthy individuals (HG), in 20 HCC patients and 8 CCA patients, by multi-color flow cytometry, qRT-PCR, and ELISA techniques. Results: The qRT-PCR analysis showed an upregulation of TNFα expression by classical and intermediate monocytes purified from HCC patients presenting tumors in grade G3-G4 as compared to G1-G2 HCC patients. Moreover, ELISA assay confirmed elevated serum levels of TNFα in G3-G4 compared to G1-G2 HCC patients. A significant decrease of circulating non-classical monocytes was detected in both CCA and HCC patients before and after surgical procedure. In addition, a functional defect in circulating classical and intermediate monocytes was observed in both groups of cancer patients when compared to the HG, with partial recovery after the surgical intervention. Conclusions: This integrated analysis permitted the identification of altered functional competence of monocyte subsets in CCA and HCC patients. In addition, our results point to a potential role of TNFα as a prognostic peripheral biomarker in HCC patients, indicating the presence of high-grade tumors that should be further validated.

Hepatocellular carcinoma and cholangiocarcinoma are the most common primary malignant liver tumors. Since the liver plays a key role in lipid metabolism, the study of serum phospholipid (PL) profiles may provide a better understanding of alterations in hepatic lipid metabolism. In this study, we used a high‐resolution HILIC‐LC–MS lipidomic approach to establish the serum phospholipidome profile of patients with liver cancer before (T0) and after tumor resection (T1) and a control group (CT) of healthy individuals. After the analysis of PL profiles, we observed that the phospholipidome of patients with liver cancer was significantly modified after the tumor resection procedure. We observed an upregulation of some phosphatidylcholine (PtdCho) species, namely, PtdCho(36:6), PtdCho(42:6), PtdCho(38:5), PtdCho(36:5), PtdCho(38:6) and choline plasmalogens (PlsCho), and/or 1‐O‐alkyl‐2‐acyl‐glycerophosphocholine (PakCho) in patients with liver cancer at T0 compared to the CT group, and a downregulation after tumor resection (T1) when compared to T0. These results show that LC–MS can detect different serum PL profiles in patients with liver cancer, before and after tumor resection, by defining a specific PL fingerprint that was used to determine the effect of tumor and tumor resection on lipid metabolism.