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1.
Hepatol Commun ; 8(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38358371

RESUMEN

BACKGROUND: The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression. METHODS: Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients' sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study. RESULTS: Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2-deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r=0.4179, p<0.001), alanine transaminase (r=0.4704, p<0.0001), and gamma-glutamyl transpeptidase activities (r=0.6629, p<0.0001) but not with serum bilirubin. In addition, patients with PSC with advanced fibrosis demonstrated significantly higher type-I IFN values. Among the type-I IFN subtypes IFNα, ß and IFNω could be detected in patients with PSC with IFNω showing the highest concentration among the subtypes and being the most abundant among patients with PSC. CONCLUSIONS: The selectively elevated bioactive type-I IFNs specifically the dominating IFNω could suggest a novel inflammatory pathway that might also have a hitherto unrecognized role in the pathomechanism of PSC.


Asunto(s)
Colangitis Esclerosante , Interferón Tipo I , Hígado , Animales , Humanos , Ratones , Alanina Transaminasa , Fibrosis , Interferón Tipo I/sangre , Hígado/patología
3.
Cancers (Basel) ; 15(20)2023 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-37894467

RESUMEN

Statins, which are inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, are an effective pharmacological tool for lowering blood cholesterol levels. This property makes statins one of the most popular drugs used primarily to prevent cardiovascular diseases, where hyperlipidemia is a significant risk factor that increases mortality. Nevertheless, studies conducted mainly in the last decade have shown that statins might prevent and treat liver cancer, one of the leading causes of cancer-related mortality worldwide. This narrative review summarizes the scientific achievements to date regarding the role of statins in liver tumors. Molecular biology tools have revealed that cell growth and proliferation can be inhibited by statins, which further inhibit angiogenesis. Clinical studies, supported by meta-analysis, confirm that statins are highly effective in preventing and treating hepatocellular carcinoma and cholangiocarcinoma. However, this effect may depend on the statin's type and dose, and more clinical trials are required to evaluate clinical effects. Moreover, their potential hepatotoxicity is a significant caveat for using statins in clinical practice. Nevertheless, this group of drugs, initially developed to prevent cardiovascular diseases, is now a key candidate in hepato-oncology patient management. The description of new drug-statin-like structures, e.g., with low toxicity to liver cells, may bring another clinically significant improvement to current cancer therapies.

4.
Biomedicines ; 11(8)2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37626820

RESUMEN

The field of hepatocellular carcinoma (HCC) has faced significant change on multiple levels in the past few years. The increasing emphasis on the various HCC phenotypes and the emergence of novel, specific therapies have slowly paved the way for a personalized approach to primary liver cancer. In this light, the role of percutaneous liver biopsy of focal lesions has shifted from a purely confirmatory method to a technique capable of providing an in-depth characterization of any nodule. Cancer subtype, gene expression, the mutational profile, and tissue biomarkers might soon become widely available through biopsy. However, indications, expectations, and techniques might suffer changes as the aim of the biopsy evolves from providing minimal proof of the disease to high-quality specimens for extensive analysis. Consequently, a revamped position of tissue biopsy is expected in HCC, following the reign of non-invasive imaging-only diagnosis. Moreover, given the advances in techniques that have recently reached the spotlight, such as liquid biopsy, concomitant use of all the available methods might gather just enough data to improve therapy selection and, ultimately, outcomes. The current review aims to discuss the changing role of liver biopsy and provide an evidence-based rationale for its use in the era of precision medicine in HCC.

5.
Diagnostics (Basel) ; 13(9)2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37174934

RESUMEN

Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary hepatic malignant tumor, after hepatocellular carcinoma (HCC). Its incidence has risen worldwide, yet the only potentially curative treatment, surgical resection, is seldom applicable, and the median overall survival remains extremely low. So far, there are no personalized therapy regimens. This study investigated whether routine immunohistochemical stains have diagnostic and/or prognostic value in iCCA. Clinical, imaging, and pathology data were retrospectively gathered for patients diagnosed with iCCA, HCC, or liver metastases assessed using liver needle biopsies. Three study groups with an equal number of cases (n = 65) were formed. In the iCCA group, CK19, CA19-9, CK7, and CEA demonstrated the highest sensitivities (100%, 100%, 93.7%, and 82.6%, respectively). The most relevant stains used for diagnosing HCCs were Glypican 3, CD34 (sinusoidal pattern), and Hep Par 1, with corresponding sensitivities of 100%, 100%, and 98.2%. The immunohistochemical panels for diagnosing metastatic tumors were chosen after correlating the clinical data and morphologic H&E aspects. Moderate/intensely positive CK7 expression and absent/low amount of intratumoral immune cells were favorable prognostic factors and correlated with increased overall survival in both the univariate analysis and the multivariate regression adjusted for age, existence of cirrhosis, number of tumors, and tumor differentiation.

6.
Cancer Immunol Immunother ; 72(4): 1003-1014, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36251029

RESUMEN

Cholangiocarcinoma, the second most common liver malignancy, after hepatocarcinoma is highly aggressive and usually diagnosed in advanced cases. In the era of personalized medicine, targeted therapy protocols are limited for cholangiocarcinoma and the only potential curative treatment, surgical resection, is seldom applicable.This retrospective study included all cases with pathology-confirmed intrahepatic cholangiocarcinoma admitted in a tertiary healthcare facility during a 10-year timeframe. Clinical information, laboratory values, imaging studies, and survival data were retrieved, and PD-L1 immunostaining was performed on representative pathology slides, for each case. From the total of 136 included cases (49 surgical resections and 87 liver biopsies), 38.97% showed PD-L1 positivity on tumoral cells, 34.8% on tumor infiltrating immune cells, 10.11% on epithelial cells within the peritumoral area and 15.95% on immune cells from the peritumoral area. Overall survival was significantly higher in the first two scenarios. However, after adjusting for age, tumor number, tumor size, and tumor differentiation in a multivariate analysis, only PD-L1 positivity on tumor infiltrating immune cells remained a favorable prognostic for survival. High immune cell counts also correlated with increased overall survival.Our study demonstrated that PD-1/PD-L1 checkpoint pathway in the microenvironment of intrahepatic cholangiocarcinoma bears prognostic significance. PD-L1 expression on immune cells, in both resection and biopsy specimens, might be a strong independent predictor for a favorable outcome.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Pronóstico , Estudios Retrospectivos , Antígeno B7-H1/metabolismo , Colangiocarcinoma/patología , Linfocitos Infiltrantes de Tumor , Conductos Biliares Intrahepáticos/metabolismo , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/metabolismo , Microambiente Tumoral
7.
Theranostics ; 12(13): 5836-5855, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35966579

RESUMEN

Liquid biopsies do promise a lot, but are they keeping it? In the past decade, additional novel biomarkers qualified to be called like that, of which, some took necessary hurdles resulting in FDA approval and clinical use. Some others are since a while around, well known and were once regarded to be a game changer in cancer diagnosis or cancer screening. But, during their clinical use limitations were observed from statistical significance and questions raised regarding their robustness, that eventually led to be dropped from associated clinical guidelines for certain applications including cancer diagnosis. The purpose of this review isn't to give a broad overview of all current liquid biopsy as biomarkers, weight them and promise a brighter future in cancer prevention, but rather to take a deeper look on two of those who do qualify to be called liquid biopsies now or then. These two are probably of greatest interest conceptually and methodically, and likely have the highest chances to be in clinical use soon, with a portfolio extension over their original conceptual usage. We aim to dig deeper beyond cancer diagnosis or cancer screening. Actually, we aim to review in depth extracellular vesicles (EVs) and compare with circulating tumour cells (CTCs). The latter methodology is partially FDA approved and in clinical use. We will lay out similarities as taking advantage of surface antigens on EVs and CTCs in case of characterization and quantification. But drawing readers' attention to downstream application based on capture/isolation methodology and simply on their overall nature, here apparently being living material eventually recoverable as CTCs are vs. dead material with transient effects on recipient cell as in case of EVs. All this we try to bring in perspective, compare and conclude towards which future direction we are aiming for, or should aim for. Do we announce a winner between CTCs vs EVs? No, but we provide good reasons to intensify research on them.


Asunto(s)
Vesículas Extracelulares , Células Neoplásicas Circulantes , Biomarcadores de Tumor , Recuento de Células , Vesículas Extracelulares/patología , Humanos , Biopsia Líquida/métodos , Células Neoplásicas Circulantes/patología
8.
World J Clin Cases ; 10(17): 5531-5540, 2022 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-35979136

RESUMEN

The systemic nature of cirrhosis and portal hypertension has long been recognized, and the amount of data characterizing the interplay between each system is becoming ever so complex. Lung involvement was among the first described associated entities in cirrhosis, with reports dating back to the late nineteenth century. However, it appears that throughout the years, interest in the pulmonary complications of portal hypertension has generally faded, especially in contrast to other decompensating events, as expertise in this field has primarily been concentrated in highly experienced tertiary care facilities and liver transplantation centers. Despite affecting up to 10%-15% of patients with advanced liver disease and having a proven prognostic impact, hepato-pulmonary syndrome, porto-pulmonary hypertension, and hepatic hydrothorax are frequently misdiagnosed, mistreated, or misinterpreted. This lack of precision might adversely impact patient care, referral to expert centers, and, ultimately, liver disease-related mortality and successful transplantation odds. The present minireview aims to increase awareness of the pulmonary complications of chronic liver disease by providing a brief overview of each of the three entities. The paper focuses on the essential theoretical aspects, addressing the most critical knowledge gaps on the one hand and, on the other hand, critically discussing one key issue for each complication.

9.
World J Gastroenterol ; 28(15): 1508-1525, 2022 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-35582128

RESUMEN

Cholangiocarcinoma (CCA) arises from the ductular epithelium of the biliary tree, either within the liver (intrahepatic CCA) or more commonly from the extrahepatic bile ducts (extrahepatic CCA). This disease has a poor prognosis and a growing worldwide prevalence. The poor outcomes of CCA are partially explained by the fact that a final diagnosis is challenging, especially the differential diagnosis between hepatocellular carcinoma and intrahepatic CCA, or distal CCA and pancreatic head adenocarcinoma. Most patients present with an advanced disease, unresectable disease, and there is a lack in non-surgical therapeutic modalities. Not least, there is an acute lack of prognostic biomarkers which further complicates disease management. Therefore, there is a dire need to find alternative diagnostic and follow-up pathways that can lead to an accurate result, either singlehandedly or combined with other methods. In the "-omics" era, this goal can be attained by various means, as it has been successfully demonstrated in other primary tumors. Numerous variants can reach a biomarker status ranging from circulating nucleic acids to proteins, metabolites, extracellular vesicles, and ultimately circulating tumor cells. However, given the relatively heterogeneous data, extracting clinical meaning from the inconsequential noise might become a tall task. The current review aims to navigate the nascent waters of the non-invasive approach to CCA and provide an evidence-based input to aid clinical decisions and provide grounds for future research.


Asunto(s)
Adenocarcinoma , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Adenocarcinoma/patología , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/terapia , Conductos Biliares Intrahepáticos/patología , Biomarcadores , Biomarcadores de Tumor/metabolismo , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/metabolismo , Colangiocarcinoma/terapia , Humanos , Neoplasias Hepáticas/patología , Neoplasias Pancreáticas , Neoplasias Pancreáticas
10.
Liver Int ; 42(8): 1891-1901, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35608939

RESUMEN

BACKGROUND & AIMS: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. METHODS: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered. RESULTS: Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84-11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24-12.74], 11.76% [95% CI 4.73-22.30], 20.69% [95% CI 11.35-31.96] and 34.52% [95% CI 17.03-52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49-4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29-7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection. CONCLUSIONS: This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period.


Asunto(s)
COVID-19 , Carcinoma Hepatocelular , Neoplasias Hepáticas , COVID-19/complicaciones , Prueba de COVID-19 , Estudios de Cohortes , Estudios Transversales , Humanos , Estudios Retrospectivos , SARS-CoV-2
11.
Med Ultrason ; 24(4): 499-502, 2022 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-35437528

RESUMEN

Desmoplastic small round cell tumour (DSRCT) is a rare and highly aggressive mesenchymal neoplasm with poor prognosis that develops in male adolescents and young adults. We report the case of a 32-year-old male admitted with abdominal distension and ascites. An ultrasonography (US) scan showed multiple peritoneal masses with large ascites. The dominant mass had a hypervascular homogenous aspect at contrast-enhanced ultrasound with wash-out in the venous phase. Thoracoabdominal CT, performed for staging the disease, confirmed the US aspect. The US-guided percutaneous biopsy revealed DSRCT of the peritoneum. Chemotherapy was then started with minimal clinical improvement, increase in tumoral burden and death after three months. US and US-guided biopsy played an essential role in diagnosing this case. The aggressive course of the disease and seeding at paracentesis sites are the particularities of the presented case.


Asunto(s)
Ascitis , Tumor Desmoplásico de Células Pequeñas Redondas , Adolescente , Adulto Joven , Humanos , Masculino , Adulto , Ascitis/diagnóstico por imagen , Peritoneo/diagnóstico por imagen , Tumor Desmoplásico de Células Pequeñas Redondas/diagnóstico por imagen , Biopsia Guiada por Imagen , Ultrasonografía , Ultrasonografía Intervencional
12.
J Clin Med ; 11(5)2022 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-35268381

RESUMEN

(1) Background: The pursuit of finding biomarkers for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has never been so paramount in the days of personalized medicine. The main objective of our study is to identify new biomarkers for diagnosing HCC, and to identify which patients are at risk of developing tumor recurrence, decompensation, or even possesses the risk of cancer-related death. (2) Methods: We have conducted an untargeted metabolomics study from the serum of 69 European patients­32 compensated cirrhotic patients without HCC (controls), and 37 cirrhotic patients with HCC with compensated underlying liver disease (cases), that underwent curative treatment (surgery or ablation), performing ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-QTOF- (ESI+)-MS) with an emphasis on lipid metabolites. (3) Results: 1,25-dihydroxy cholesterol (m/z = 419.281), myristyl palmitate (m/z = 453.165), 25-hydroxy vitamin D2 (m/z = 413.265), 12-ketodeoxycholic acid (m/z = 391.283), lysoPC (21:4) (m/z = 558.291), and lysoPE (22:2) (m/z = 534.286) represent notable biomarkers that differentiate compensated cirrhosis from early HCC, and ceramide species are depleted in the serum of HCC patients. Regarding prognosis, no metabolite identified in our study could determine tumor relapse. To distinguish between the HCC patients that survived curative treatment and those at risk that developed tumor burden, we have identified two notable phosphocholines (PC (30:2); PC (30:1)) with AUROCs of 0.820 and 0.807, respectively, that seem to increase when patients are at risk. In a univariate analysis, arachidonic acid was the only metabolite to predict decompensation (OR = 0.1, 95% CI: 0−0.16, p < 0.005), while in the multivariate analysis, dismally, no variable was associated with decompensation. Furthermore, in the multivariate analysis, we have found out for the first time that the increased expression of 1,25-dihydroxy cholesterol, myristyl palmitate, 12-keto deoxycholic acid, lysoPC (21:4), and lysoPE (22:2) are independent markers of survival. (4) Conclusions: Our study reveals that lipids play a crucial role in discriminating compensated cirrhosis and early hepatocellular carcinoma, and might represent markers of survival and prognosis in personalized and minimally invasive medicine.

14.
Ultrasonography ; 41(2): 263-278, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35073625

RESUMEN

The use of contrast-enhanced ultrasonography (CEUS) has recently become synonymous with high-standard ultrasonography (US). From expanding the reach of US diagnostics to improving the precision of various invasive procedures, CEUS is rapidly becoming a standard in numerous niches. However, proficiency in CEUS comes with a cost, both from a learning curve and material standpoint, and as every growing field, lacks firm evidence and standardization. Therefore, in the current paper, we aim to provide an evidence-based review of available methods and to discuss the advantages and pitfalls of CEUS in interventional procedures, trying to provide strong evidence whenever available, or at least an educated expert opinion if data are lacking.

15.
Chirurgia (Bucur) ; 116(eCollection): 1-8, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34463246

RESUMEN

Intermediate stage hepatocarcinoma, classified b Barcelona Clinic Liver Cancer (BCLC) comprises a large number of patients, with diverse characteristics, being defined by multiple tumours, preserved liver function and good performance status. The recommended treatment for this stage is transarterial chemoembolization (TACE), but there are a few studies that discuss the role of surgery in this stage. We report a case of a 59-year-old woman diagnosed with BCLC B hepatocarcinoma (two tumours of 34 and 25 mm, in liver segments 5 and 6) who was successfully treated with surgical resection. This patient had additional risk factors like morbid obesity, clinically significant portal hypertension, and thrombocytopenia. Despite these characteristics, the evolution was favourable. In conclusion, we believe that surgery has an important role in the treatment of well-selected BCLC B patients and a good preoperative assessment of the patient can minimize the perioperative risk.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Femenino , Hepatectomía , Humanos , Neoplasias Hepáticas/terapia , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Resultado del Tratamiento
16.
J Clin Med ; 10(16)2021 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-34441984

RESUMEN

Background: Hepatic hydrothorax (HH) is an understudied complication of decompensated cirrhosis. We aimed to evaluate the long-term prognosis of patients with HH by comparing them with a matched non-HH group. Methods: This retrospective study included 763 consecutive patients hospitalized for decompensated cirrhosis and ascites. Ninety-seven patients with HH were matched for survival analysis with non-HH patients based on liver disease severity. Results: The prevalence of HH was 13.1%. Patients with HH had significantly worse overall liver function. Upon matching, patients with HH had a lower long-term survival (15.4% vs. 30.9% at 5 years) with a mean overall survival of 22.2 ± 2.2 months for the HH group vs. 27.1 ± 2.6 months for the non-HH group (Log Rank-0.05). On multivariate survival analysis using Cox regression, the MELD-Na score, ALBI grade, hepato-renal syndrome, and grade III ascites had a significant impact on mortality in patients with HH. In patients with HH, a MELD-Na score ≥ 16, ALBI grade III, hepato-renal syndrome, or severe ascites delineated high-mortality risk groups. Conclusions: HH is consistently associated with more advanced liver disease. Patients with HH have worse long-term survival, their prognosis being closely intertwined with overlapping decompensating events.

17.
World J Gastroenterol ; 27(23): 3290-3302, 2021 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-34163112

RESUMEN

Hemostasis is a complex physiological process based on the balance between pro-coagulant and anticoagulant systems to avoid pathological bleeding or thrombosis. The changes in standard coagulation tests in liver disease were assumed to reflect an acquired bleeding disorder, and cirrhotic patients were considered naturally anticoagulated. In the light of the new evidence, the theory of rebalanced hemostasis replaced the old concept. According to this model, the hemostatic alteration leads to a unique balance between pro-coagulant, anticoagulant, and fibrinolytic systems. But the balance is fragile and may prone to bleeding or thrombosis depending on various risk factors. The standard coagulation tests [INR (international normalized ratio), platelet count and fibrinogen] only explore parts of the hemostasis, not offering an entire image of the process. Rotational thromboelastometry (ROTEM) and thromboelastography (TEG) are both point of care viscoelastic tests (VET) that provide real-time and dynamic information about the entire hemostasis process, including clot initiation (thrombin generation), clot kinetics, clot strength, and clot stability (lysis). Despite prolonged PT/INR (international normalized ratio of prothrombin time) and low platelet counts, VET is within the normal range in many patients with both acute and chronic liver disease. However, bleeding remains the dominant clinical issue in patients with liver diseases, especially when invasive interventions are required. VET has been shown to asses more appropriately the risk of bleeding than conventional laboratory tests, leading to decrial use of blood products transfusion. Inappropriate clotting is common but often subtle and may be challenging to predict even with the help of VET. Although VET has shown its benefit, more studies are needed to establish cut-off values for TEG and ROTEM in these populations and standardization of transfusion guidelines before invasive interventions in cirrhotic patients/orthotopic liver transplantation.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Hepatopatías , Trastornos de la Coagulación Sanguínea/diagnóstico , Pruebas de Coagulación Sanguínea , Hemostasis , Humanos , Hepatopatías/diagnóstico , Hepatopatías/terapia , Tromboelastografía
18.
Sci Rep ; 11(1): 8298, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33859329

RESUMEN

Two 3-oxo-Δ4 fetal bile acids, 3-oxachola-4,6-dien-24-oic acid (1) and 7α-hydroxy-3-oxochol-4-en-24-oic acid (2), occur normally in the human fetus but remain elevated in neonates and children with severe cholestatic liver disease due to an autosomal recessive inborn error of metabolism affecting Δ4-3-oxo-steroid 5ß-reductase (AKR1D1). Relatively little is known about 1 and 2 in adult patients with liver disease. The chemical synthesis of 1 and 2 is therefore described and their quantitation in plasma by ultrarapid chromatography-triple quadrupole mass spectrometry. Plasma concentrations of 1 and 2 were investigated in 25 adult patients with varying degrees of liver cirrhosis with and without hepatocellular carcinoma (HCC). Highly statistically significant correlations (P < 0.0001) were found between severity of liver cirrhosis, determined by the Child-Pugh and MELD scores, with plasma 1 and 2 concentrations, both alone and combined. The presence of HCC did not influence these correlations. Plasma cholic, chenodeoxycholic, deoxycholic, lithocholic or ursodeoxycholic acids, free and as their glycine or taurine conjugates, did not correlate with Child-Pugh or MELD score when corrected for multiple comparisons. These findings demonstrate that plasma levels of fetal bile acids 3-oxachola-4,6-dien-24-oic acid and 7α-hydroxy-3-oxochol-4-en-24-oic acid and likely deteriorating AKR1D1 activity indicate the severity of liver cirrhosis measured by the Child-Pugh and MELD scores.


Asunto(s)
Ácidos y Sales Biliares/sangre , Cirrosis Hepática/diagnóstico , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Carcinoma Hepatocelular/complicaciones , Femenino , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Oxidorreductasas/metabolismo , Índice de Severidad de la Enfermedad
19.
J Clin Med ; 10(5)2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33668839

RESUMEN

Hepatocellular carcinoma (HCC) is probably the epitome of a screening target, with a well-defined high-risk population, accessible screening methods, and multiple curative-intent treatments available for early disease. Per major societies guideline consensus, biannual ultrasound (US) surveillance of the at-risk patients is the current standard of care worldwide. Yet, despite its documented success in the past decades, this standard is far from perfect. While the whole community is working to further tighten the knots, a worrying number of cases still slip through this safety net. Consequently, these patients lose their chance to a curative solution which leads to a high disease burden with disproportionate mortality. While US will probably remain the fundamental staple in the screening strategy, key questions are seeking better answers. How can its caveats be addressed, and the technique be improved? When are further steps needed? How to increase accuracy without giving up on accessibility? This narrative review discusses the place of US surveillance in the bigger HCC picture, trying to navigate through its strengths and limits based on the most recent available evidence.

20.
JHEP Rep ; 3(3): 100260, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33644725

RESUMEN

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. METHODS: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). CONCLUSIONS: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. LAY SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.

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