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BACKGROUND & AIMS: Acute on chronic liver failure (ACLF) causes high short-term mortality in patients with previously stable chronic liver disease. To date there are no models to predict which patients are likely to develop ACLF, and existing models to predict ACLF mortality are based on limited cohorts. We sought to create novel risk prediction scores using a large cohort of patients with cirrhosis. METHODS: We performed a retrospective cohort study of 74 790 patients with incident cirrhosis in the Veterans Health Administration database using randomized 70% derivation/30% validation sets. ACLF events were identified per the European ACLF criteria. Multivariable logistic regression was used to derive prediction models for developing ACLF at 3, 6 and 12 months, and ACLF mortality at 28 and 90 days. Mortality models were compared to model for end-stage liver disease (MELD), MELD-sodium and the Chronic Liver Failure Consortium (CLIF-C) ACLF score. RESULTS: Models for the developing ACLF had very good discrimination (concordance [C] statistics 0.83-0.87) at all timepoints. Models for ACLF mortality also had good discrimination at 28 and 90 days (C-statistics 0.79-0.82), and were superior to MELD, MELD-sodium and the CLIF-C ACLF score. The calibration of the novel models was excellent at all timepoints. CONCLUSION: We have obtained highly-predictive models for developing ACLF, as well as for ACLF short-term mortality in a diverse United States cohort. These may be used to identify outpatients at significant risk of ACLF, which may prompt closer follow-up or early transplant referral, and facilitate decision making for patients with diagnosed ACLF, including escalation of care, expedited transplant evaluation or palliation.
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Insuficiência Hepática Crônica Agudizada , Doença Hepática Terminal , Insuficiência Hepática Crônica Agudizada/diagnóstico , Humanos , Cirrose Hepática , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
The 2019 European Association for the Study of the Liver (EASL) Clinical Practice Guidelines (hereinafter referred to as the EASL Guidelines) extracted the required evidence from detailed research materials, and rigorously graded and condensed the varying strengths of evidence into 32 recommendations and 14 statements (recommendations and reminders) for drug-induced Liver Injury (DILI). This guideline has important reference values for helping clinicians to further improve their understanding of DILI and the level of clinical diagnosis, treatment and prevention; however, there are still several issues worthy of further discussion.
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Doença Hepática Induzida por Substâncias e Drogas , Guias de Prática Clínica como Assunto , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/terapia , China , Humanos , Sociedades MédicasRESUMO
The standard of care (SOC) for the treatment of HCV genotype 2 (HCV-2) was pegylated interferon alpha plus ribavirin (PEG-IFN/RBV) at weight-based doses for a response-guided duration. The launches of sofosbuvir and daclatasvir in 2014 have resulted in new, better tolerated and shorter treatment. The combination of sofosbuvir and RBV for 12 weeks appears to be the new SOC in both European and American guidelines. The cost and therefore the access to this treatment remains a problem in many countries because of major economic constraints. For the few more difficult-to-treat patients, a combination of direct acting antivirals may be suitable and is being studied in ongoing trials. Because of rapidly changing treatment recommendations, the decision to treat HCV-2 patients with currently approved drugs or to wait until a better option is available in the future, must be made according to the stage of fibrosis.
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Quimioterapia Combinada/tendências , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Ribavirina/uso terapêutico , Uridina Monofosfato/análogos & derivados , Quimioterapia Combinada/métodos , Genótipo , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/genética , Humanos , Prevalência , Sofosbuvir , Uridina Monofosfato/uso terapêuticoRESUMO
Seven drugs have been approved for the treatment of chronic hepatitis B. Antiviral treatment has been shown to be effective in suppressing hepatitis B virus replication, decreasing inflammation and fibrosis in the liver, and preventing progression of liver disease. However, current medications do not eradicate hepatitis B virus; therefore, a key question is which patients need to start treatment and which patients can be monitored. Professional societies have developed guidelines to assist physicians in recognition, diagnosis, and optimal management of patients with chronic hepatitis B. These guidelines suggest preferred approaches, and physicians are expected to exercise clinical judgment to determine the most appropriate management based on the circumstances of the individual patient. This article reviews recommendations in hepatitis B guidelines and the basis for those recommendations, and we discuss what we do in our practice to illustrate factors that may influence decisions regarding hepatitis B management.
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Antivirais/uso terapêutico , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Guias de Prática Clínica como Assunto , HumanosRESUMO
PURPOSE: To investigate early imaging prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) refractory to standard chemotherapy after yttrium-90 ((90)Y) radioembolization therapy. MATERIALS AND METHODS: In an institutional review board-approved prospective correlative study, 21 consecutive patients with ICC refractory to standard chemotherapy underwent (90)Y radioembolization therapy. Target and overall Response Evaluation Criteria In Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) treatment responses were assessed. The mRECIST and EASL criteria were modified for application on delayed phases of dynamic contrast-enhanced cross-sectional imaging studies. Conventional definitions for complete and partial response were applied; these responses comprised objective response. Restaging imaging was obtained at 1- and 3-month intervals until patient death. Survival analyses by Kaplan-Meier and log-rank proportional models including application of the landmark method to avoid lead-time bias were performed from the day of treatment. Significance was set at P < .05. RESULTS: Median overall survival (OS) from the time of (90)Y therapy was 16.3 months (95% confidence interval, 7.2-25.4 mo). Significant differences between mRECIST and EASL versus RECIST were found when categorizing patients into responders and nonresponders (P < .001). Significantly prolonged OS was observed for patients with targeted objective response based on modified mRECIST and EASL criteria (P = .005 and P = .001, respectively) at 3 months. RECIST was not found to correlate with survival at 1- or 3-month follow-up. CONCLUSIONS: Modified target mRECIST and EASL criteria that employ delayed-phase contrast enhancement at 3 months after (90)Y radioembolization therapy for ICC predicted OS. RECIST did not correlate with survival.
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Neoplasias dos Ductos Biliares/radioterapia , Colangiocarcinoma/radioterapia , Embolização Terapêutica/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Compostos Radiofarmacêuticos/efeitos adversos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Radioisótopos de Ítrio/efeitos adversosRESUMO
Background and objectives: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality without liver transplantation (LT). The selection criteria for LT in these patients are not well defined. The objective of this study was to determine factors associated with post-transplant survival in ACLF. Methods: This was a single-center retrospective study of patients who underwent living donor liver transplantation (LDLT) for ACLF between 2012 and 2022. Out of 1093 transplants, 110 patients had underlying ACLF, based on the European Association for the Study of the Liver-Chronic Liver Failure Consortium (EASL-CLIF) criteria. We looked at factors associated with 1-year posttransplant survival. Results: The median model for end-stage liver disease (MELD) score was 33.5 (31-38), and the 1-year posttransplant survival was 72%. Six risk factors were associated with posttransplant survival, namely, body mass index > 30 kg/m2 [HR, 4.4; 95% CI, 1.8-10.7], platelet count < 66,000/µl [HR, 2.91; CI,1.2-6.6], poor response to medical treatment [HR, 2.6; CI, 1.1-5.7], drug-resistant bacterial or fungal cultures [HR, 4.2; CI, 1.4-12.4], serum creatinine > 2.5 mg/dl [HR, 3.4; CI, 1.5-7.7], and graft-to-recipient weight ratio < 0.7 [HR, 4.8; CI, 1.4-16.3]. The 1-year post-transplant survival was 84% in patients with 0-2 risk factors (n = 89) and was 6% with 3 risk factors (n = 15) (P < 0.001). For 1-year posttransplant survival, the area under curve (AUC) for the current model was 0.8 (0.69-0.9). The AUC for CLIF-ACLF, Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), and EASL-CLIF ACLF grades was < 0.5. Conclusion: In LT for ACLF, acceptable survival can be achieved when less than three high-risk factors are present.
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BACKGROUND: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS: 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS: Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2-4 laboratory abnormalities in key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS: Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.
Assuntos
Ácidos Aminoisobutíricos , Benzimidazóis , Benzopiranos , Carbamatos , Ciclopropanos , Hepatite C Crônica , Hepatite C , Compostos Heterocíclicos de 4 ou mais Anéis , Lactamas Macrocíclicas , Leucina/análogos & derivados , Neoplasias Hepáticas , Prolina/análogos & derivados , Sulfonamidas , Humanos , Idoso , Sofosbuvir/uso terapêutico , Sofosbuvir/farmacologia , Antivirais , Hepacivirus/genética , Hepatite C Crônica/complicações , Taiwan/epidemiologia , Quinoxalinas/uso terapêutico , Hepatite C/tratamento farmacológico , Hepatite C/complicações , Neoplasias Hepáticas/tratamento farmacológico , Bilirrubina , GenótipoRESUMO
BACKGROUND & AIMS: Allelic variants of fucosyltransferases 2 and 3 (FUT2/3) influence serum levels of CA19-9, a screening parameter commonly used for detection of biliary malignancy in PSC. We aimed at improving diagnostic accuracy of CA19-9 by determining the impact of FUT2/3 genotypes. METHODS: CA19-9 levels were measured in 433 PSC patients, 41 of whom had biliary malignancy. Genotypes for FUT3 and FUT2 were used to assign patients to one of three groups: A, no FUT3 activity regardless of FUT2 activity; B, both FUT2 and FUT3 activity and C, no FUT2 activity without loss of FUT3 activity. Group-specific cut-off values were determined by Youden's index. RESULTS: The median CA19-9 values of cancer-free patients were significantly different (p<0.001) in Groups A (2.0U/ml), B (17.0U/ml), and C (37.0U/ml). Biliary malignancy patients in Groups B and C had significantly higher CA19-9 values than cancer-free patients (p<0.001). The optimal cut-off, as determined by ROC analysis, for all patients was 88.5U/ml. Optimal cut-off values in Groups A, B, and C were 4.0U/ml, 74.5U/ml, and 106.8U/ml, respectively. Use of these values improved sensitivity of CA19-9 in Groups B and C. Further, use of group-dependent cut-off values with 90% sensitivity resulted in a 42.9% reduction of false positive results. CONCLUSIONS: Use of FUT2/3 genotype-dependent cut-off values for CA19-9 improved sensitivity and reduced the number of false positive results.
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Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos , Antígeno CA-19-9/sangue , Colangiocarcinoma/diagnóstico , Colangite Esclerosante/complicações , Fucosiltransferases/genética , Adulto , Neoplasias dos Ductos Biliares/sangue , Neoplasias dos Ductos Biliares/genética , Colangiocarcinoma/sangue , Colangiocarcinoma/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
This review of the literature consists of three sections. First, papers concerning non-alcoholic fatty liver disease (NAFLD) awareness among the general population, general practitioners, and liver and non-liver specialists were retrieved and analyzed to highlight the perception of disease, verify knowledge of current recommendations, and identify the main difficulties experienced in clinical practice. Next, position papers and clinical practice guidelines issued by International and National Hepatological Scientific Societies were identified and critically assessed in order to pinpoint the areas of convergence/difference. Finally, practical suggestions on NAFLD diagnosis and management in daily practice are provided and the open questions highlighted.
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Fígado Gorduroso/diagnóstico , Fígado Gorduroso/terapia , Biópsia , Gastroenterologia , Humanos , Hepatopatia Gordurosa não Alcoólica , Guias de Prática Clínica como Assunto , Padrões de Prática MédicaRESUMO
BACKGROUND & AIMS: The European Network on Radioembolization with Yttrium-90 resin microspheres study group (ENRY) conducted a retrospective study to evaluate the outcomes among elderly (≥ 70 years) and younger patients (<70 years) with unresectable hepatocellular carcinoma (HCC) who received radioembolization at 8 European centers. METHODS: Patients with confirmed diagnosis of unresectable HCC who either progressed following resection or locoregional treatment and/or who were considered poor candidates for chemoembolization were evaluated by a multidisciplinary team for radioembolization with (90)Y-resin microspheres (SIR-Spheres; Sirtex Medical). The survival outcome and all adverse events were compared between the two age groups. RESULTS: Between 2003 and 2009, 128 elderly and 197 younger patients received radioembolization. Patients in both groups had similar demographic characteristics. Many elderly and younger patients alike had multinodular, BCLC stage C disease, invading both lobes (p = 0.648). Elderly patients had a lower tumor burden, a smaller median target liver volume (p = 0.016) and appeared more likely to receive segmental treatment (p = 0.054). Radioembolization was equally well tolerated in both cohorts and common procedure-related adverse events were predominantly grade 1-2 and of short duration. No significant differences in survival between the groups were found (p = 0.942) with similar median survival in patients with early, intermediate or advanced BCLC stage disease. CONCLUSIONS: Radioembolization appears to be as well-tolerated and effective for the elderly as it is for younger patients with unresectable HCC. Age alone should not be a discriminating factor for the management of HCC patients.
Assuntos
Carcinoma Hepatocelular/terapia , Embolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Microesferas , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/efeitos adversosRESUMO
BACKGROUND & AIMS: Differing threshold levels of hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) are recommended by international guidelines for commencement of antiviral therapy. These guidelines advocate therapy for patients with significant fibrosis (METAVIR score ≥F2); we assessed the accuracy of these guideline-defined thresholds in identifying patients with ≥F2 fibrosis. METHODS: We applied the European (European Association for the Study of the Liver [EASL] 2012), Asian-Pacific (Asian-Pacific Association for the Study of the Liver [APASL] 2012), American (American Association for the Study of Liver Diseases [AASLD] 2009), and United States Panel Algorithm (USPA 2008) criteria to 366 consecutive hepatitis B e antigen-negative patients with liver biopsy samples: EASL, ALT >laboratory-defined upper limit of normal (ULN) and HBV DNA ≥2000 IU/mL (n = 171); APASL, ALT >2-fold laboratory-defined ULN and HBV DNA ≥2000 IU/mL (n = 87); AASLD, ALT >2-fold the updated ULN (0.5-fold ULN [corresponding to ≤19 U/L] for women and 0.75-fold the ULN [corresponding to ≤30 U/L] for men) and HBV DNA ≥20,000 IU/mL (n = 53); and USPA, ALT >updated ULN (>0.5-fold ULN for women and >0.75-fold ULN for men) and HBV DNA ≥2000 IU/mL (n = 173). RESULTS: Overall, 113 patients (30.9%) had ≥F2 fibrosis, which was more frequent among patients who fulfilled any guideline criteria (45.7% vs 17.9% for those who did not fulfill any criteria, P < .0001). In applying the EASL, AASLD, APASL, and USPA criteria, sensitivity and specificity values for detection of ≥F2 fibrosis were 45.6%, 58.5%, 56.3%, and 45.7% (P = .145) and 82.1%, 73.8%, 77.1%, and 82.4% (P = .366), respectively. The EASL criteria (area under the receiver operating characteristic [AUROC] curve, 0.66; 95% confidence interval [CI], 0.61-0.71) and USPA criteria (AUROC, 0.66; 95% CI, 0.58-0.73) performed better than APASL (AUROC, 0.64; 95% CI, 0.59-0.69; P = .421) and significantly better than the AASLD criteria (AUROC, 0.59; 95% CI, 0.54-0.64; P = .013). CONCLUSIONS: In hepatitis B e antigen-negative patients with chronic hepatitis, the EASL, AASLD, APASL, and USPA criteria identify patients with ≥F2 fibrosis with low levels of accuracy. However, the EASL and USPA criteria are the most accurate for identification of these patients.
Assuntos
Alanina Transaminase/sangue , DNA Viral/sangue , Pesquisa sobre Serviços de Saúde , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/complicações , Cirrose Hepática/diagnóstico , Guias de Prática Clínica como Assunto , Adulto , Biópsia , Feminino , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: To determine the frequency and factors associated with the presence of intratumoral gas-containing areas in hepatocellular carcinoma (HCC) on computed tomography (CT) scans obtained 4-6 weeks after transarterial chemoembolization. MATERIALS AND METHODS: From June 2010 to December 2011, 201 patients underwent 286 chemoembolization procedures for HCC (n = 497 tumors) and were retrospectively included. The presence of intratumoral gas was assessed on CT 4-6 weeks after chemoembolization. Clinical and biologic data and tumoral and chemoembolization procedure characteristics were noted. Factors associated with the presence of intratumoral gas were evaluated. Tumor response was assessed by using European Society for the Study of the Liver criteria. Tumors containing gas or not containing gas were compared by univariate and multivariate analysis. RESULTS: Intratumoral gas was found in 26 tumors (5%) after 26 chemoembolization procedures (9.1%) in 26 patients (13%). Gas was related to abscess formation in three patients (11.5%). On multivariate analysis, a large mean tumor diameter at baseline (72.4 mm vs 40.2 mm; P = .003), chemoembolization with drug-eluting beads (P = .033), and superselective approach (P = .024) were independently associated with the presence of gas. Tumors that exhibited gas-containing areas at 1 month had a significantly higher objective response rate than those that did not (P < .0001). CONCLUSIONS: Intratumoral gas-containing areas after chemoembolization are rarely related to the formation of abscesses. The presence of intratumoral gas on CT 4-6 weeks after chemoembolization could be a surrogate marker for marked tumor necrosis.
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Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Distribuição de Qui-Quadrado , Feminino , Gases , Humanos , Abscesso Hepático/diagnóstico por imagem , Abscesso Hepático/etiologia , Abscesso Hepático/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Análise Multivariada , Necrose , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Carga TumoralRESUMO
PURPOSE: During the course of cancer treatment, patients whose disease progresses despite therapy are offered alternative options. Similarly, patients with hepatocellular carcinoma (HCC) whose disease progresses following arterial locoregional therapies (LRTs) cross over to undergo systemic therapies or participate in clinical trials. Per current guidelines, patients must meet inclusion criteria (most importantly Child-Pugh class A status) to qualify for systemic options. The present study analyzed the candidacy for systemic agents or clinical trials of patients whose disease progresses despite LRTs. MATERIALS AND METHODS: A total of 245 patients with HCC were treated with LRTs (chemoembolization, n = 123; yttrium-90 [(90)Y] radioembolization, n = 122) as part of a previously published comparative effectiveness study; 96 patients exhibiting disease progression were followed prospectively. Modes of progression (cancer stage, Child-Pugh class) were analyzed to determine candidacy for systemic therapy or clinical trials, as well as assess ultimate treatment(s) received. RESULTS: Among the 96 patients with disease progression, 52% and 48% had Child-Pugh class A and class B/C disease, respectively, thereby substantially limiting the latter group's eligibility for systemic therapy and/or clinical trials. Of those whose disease progressed who had advanced-stage HCC, 63% had Child-Pugh class B/C disease. By size and necrosis criteria, the local disease progression rate was higher with chemoembolization than with (90)Y radioembolization (P = .006 and P = .016, respectively). Of the 96 patients with disease progression, only 13 (13%) ultimately received systemic agents or entered clinical trials. CONCLUSIONS: Most patients with advanced HCC that progresses following LRTs were not candidates for clinical trials or systemic agents. There is a need for future research efforts directed at treatment options or novel trial designs that will permit inclusion of patients with progressive liver disease and suboptimal liver function.
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Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Ensaios Clínicos como Assunto/métodos , Neoplasias Hepáticas/terapia , Seleção de Pacientes , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Distribuição de Qui-Quadrado , Progressão da Doença , Definição da Elegibilidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To present data on safety, antitumoral response, and survival following yttrium-90 ((90)Y) radioembolization for patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: The present study expands on the cohort of 24 patients with ICC described in a pilot study, and includes 46 patients treated with (90)Y radioembolization at a single institution during an 8-year period. Via retrospective review of a prospectively collected database, patients were stratified by performance status, tumor distribution (solitary or multifocal), tumor morphology (infiltrative or peripheral), and presence/absence of portal vein thrombosis. Primary endpoints included biochemical and clinical toxicities, and secondary endpoints included imaging response (World Health Organization [WHO] and European Association for the Study of Liver Disease [EASL] criteria) and survival. Uni-/multivariate analyses were performed. RESULTS: Ninety-two treatments were performed, with a mean of two per patient. Fatigue and transient abdominal pain occurred in 25 patients (54%) and 13 patients (28%), respectively. Treatment-related gastroduodenal ulcer developed in one patient (2%). WHO imaging findings included partial response (n = 11; 25%), stable disease (n = 33; 73%), and progressive disease (n = 1; 2%). EASL imaging findings included partial/complete response (n = 33; 73%) and stable disease (n = 12; 27%). Survival varied based on presence of multifocal (5.7 mo vs 14.6 mo), infiltrative (6.1 mo vs 15.6 mo), and bilobar disease (10.9 mo vs 11.7 mo). Disease was converted to resectable status in five patients, who successfully underwent curative (ie, R0) resection. CONCLUSIONS: Radioembolization with (90)Y is safe and demonstrates antitumoral response and survival benefit in select patients with ICC. Results are most pronounced in patients with solitary tumors, for whom conversion to curative resection is possible.
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Colangiocarcinoma/radioterapia , Embolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Idoso , Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Compostos Radiofarmacêuticos/efeitos adversos , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversosRESUMO
A sophisticated understanding of the rapidly changing field of oncology, including a broad knowledge of oncologic disease and the therapies available to treat them, is fundamental to the interventional radiologist providing oncologic therapies, and is necessary to affirm interventional oncology as one of the four pillars of cancer care alongside medical, surgical, and radiation oncology. The first part of this review intends to provide a concise overview of the fundamentals of oncologic clinical trials, including trial design, methods to assess therapeutic response, common statistical analyses, and the levels of evidence provided by clinical trials.
Assuntos
Ensaios Clínicos como Assunto/métodos , Oncologia/métodos , Neoplasias/terapia , Radiografia Intervencionista , Projetos de Pesquisa , Ensaios Clínicos como Assunto/estatística & dados numéricos , Intervalos de Confiança , Interpretação Estatística de Dados , Progressão da Doença , Intervalo Livre de Doença , Determinação de Ponto Final , Medicina Baseada em Evidências , Humanos , Estimativa de Kaplan-Meier , Oncologia/estatística & dados numéricos , Neoplasias/diagnóstico por imagem , Neoplasias/mortalidade , Neoplasias/patologia , Radiografia Intervencionista/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Fatores de Tempo , Resultado do TratamentoRESUMO
Background: Liver transplantation (LT) is an effective therapy for acute-on-chronic liver failure (ACLF) but is limited by organ shortages. We aimed to identify an appropriate score for predicting the survival benefit of LT in HBV-related ACLF patients. Methods: Hospitalized patients with acute deterioration of HBV-related chronic liver disease (n = 4577) from the Chinese Group on the Study of Severe Hepatitis B (COSSH) open cohort were enrolled to evaluate the performance of five commonly used scores for predicting the prognosis and transplant survival benefit. The survival benefit rate was calculated to reflect the extended rate of the expected lifetime with vs. without LT. Findings: In total, 368 HBV-ACLF patients received LT. They showed significantly higher 1-year survival than those on the waitlist in both the entire HBV-ACLF cohort (77.2%/52.3%, p < 0.001) and the propensity score matching cohort (77.2%/27.6%, p < 0.001). The area under the receiver operating characteristic curve (AUROC) showed that the COSSH-ACLF II score performed best (AUROC 0.849) at identifying the 1-year risk of death on the waitlist and best (AUROC 0.864) at predicting 1-year outcome post-LT (COSSH-ACLFs/CLIF-C ACLFs/MELDs/MELD-Nas: AUROC 0.835/0.825/0.796/0.781; all p < 0.05). The C-indexes confirmed the high predictive value of COSSH-ACLF IIs. Survival benefit rate analyses showed that patients with COSSH-ACLF IIs 7-10 had a higher 1-year survival benefit rate from LT (39.2%-64.3%) than those with score <7 or >10. These results were prospectively validated. Interpretation: COSSH-ACLF IIs identified the risk of death on the waitlist and accurately predicted post-LT mortality and survival benefit for HBV-ACLF. Patients with COSSH-ACLF IIs 7-10 derived a higher net survival benefit from LT. Funding: This study was supported by the National Natural Science Foundation of China (No. 81830073, No. 81771196) and the National Special Support Program for High-Level Personnel Recruitment (Ten-thousand Talents Program).
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Background & aims: Severe alcoholic hepatitis (SAH) is a grave condition, and the presence of acute kidney injury (AKI) further jeopardizes patient survival. However, the impact of AKI on survival in SAH has not been assessed from this region of Asia. Materials and methods: This study was conducted on consecutive alcohol-associated liver disease (ALD) patients hospitalized in Gastroenterology Department, SCB Medical College, Cuttack, India, between October 2016 and December 2018. On diagnosis of SAH (mDF score ≥32), demographic, clinical, and laboratory parameters were recorded, and survival was compared between patients with and without AKI (AKIN criteria). In addition, survival was compared among SAH patients defined by other criteria and prognostic models in the presence and absence of AKI. Results: 309 (70.71%) of ALD patients had SAH, and 201 (65%) of them had AKI. SAH patients with AKI had higher total leucocyte count, total bilirubin, serum creatinine, serum urea, INR, MELD (UNOS), MELD (Na+), CTP score, mDF score, Glasgow score, ABIC score, and increased prevalence of acute on chronic liver failure (ACLF) as per EASL-CLIF Consortium criteria (P < 0.001). Further, they had prolonged hospital stay, and increased death during hospitalization, at 28 days as well as 90 days (P < 0.001). Significant differences in survival were also seen in SAH (as per MELD, ABIC, and GAHS criteria) patients above the marked cut offs in respect to AKI. Conclusions: Over two-thirds of ALD patients had SAH, and about two-thirds had AKI. Patients with SAH and AKI had an increased prevalence of ACLF, longer hospital stay, and increased mortality during hospitalization at 28 days and 90 days. Lay summary: SAH is a critical condition, and the presence of AKI negatively affects their survival. Hence, early identification of SAH and AKI, as well as early initiation of treatment, is crucial for better survival. Our study from the coastal part of eastern India is the first to demonstrate the prevalence of SAH among patients with ALD along with the prevalence of AKI among SAH patients in this region. This knowledge will be helpful in managing these patients from this region of world.
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Background & Aims: The World Health Organization (WHO) HBV and HCV elimination targets, set in 2016 and based on projections to 2030, were unable to consider the impact of intervening factors. To evaluate the impact of the COVID-19 pandemic on viral hepatitis elimination programs, the European Association for the Study of the Liver (EASL) conducted a survey in liver centers worldwide in 2021. Methods: A web-based questionnaire was distributed (May-July 2021) to all EASL members representing clinical units providing HBV and HCV hepatitis care. Results are expressed as absolute numbers and reduction rates for each care activity. Results: Data were collected from 32 European and 12 non-European clinical centers. Between January 2019 (pre-pandemic) and December 2020 (during the pandemic), chronic HBV consultations decreased by 32% and 26%, new referrals by 38% and 39%, HBV testing rates by 39% and 21% (for HBsAg detection) and 30% and 22% (for HBV DNA detection), and new HBV treatments by 20% and 44% (p = 0.328) in European and non-European centers, respectively. With regard to HCV during the same time frame, the overall reductions were 39% and 50% for consultations, 49% and 49% for new referrals, 11% and 38% for HCV RNA detection, and 51% and 54% for new HCV antiviral treatments for European and non-European Centers, respectively (p = 0.071). Conclusions: All steps in the viral hepatitis care cascade have been hampered by the COVID-19 pandemic, with a comparable impact across different centers. These data reaffirm the pandemic's major effect on global viral hepatitis elimination programs and suggest that actions to achieve the WHO 2030 targets should be reconsidered and revised to account for each country's progress relative to pre-pandemic values. Lay summary: The EASL multinational survey conclusively shows that viral hepatitis elimination programs, expected to provide control of hepatitis B and hepatitis C worldwide by 2030, have been held back by the COVID-19 pandemic in clinical centers from several European and non-European countries, with a comparable impact across centers. Limitations in the cascade of care for both HBV and HCV were linked to limited access to screening, consultations, specific testing, and actual treatment. As restrictions for COVID-19 begin to lift, efforts to diagnose and provide treatment for viral hepatitis should remain high on the list of priorities for public health officials to maintain the WHO elimination efforts. Measures that have been put in place to control the COVID-19 pandemic could be transferred to increasing the diagnosis and linkage to care of people with hepatitis.
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Portal hypertension is defined by an increase in the portosystemic venous gradient. In most cases, increased resistance to portal blood flow is the initial cause of elevated portal pressure. More than 90% of cases of portal hypertension are estimated to be due to advanced chronic liver disease or cirrhosis. Transjugular intrahepatic portosystemic shunts, a non-pharmacological treatment for portal hypertension, involve the placement of a stent between the portal vein and the hepatic vein or inferior vena cava which helps bypass hepatic resistance. Portal hypertension may also be a result of extrahepatic portal vein thrombosis or compression. In these cases, percutaneous portal vein recanalisation restores portal trunk patency, thus preventing portal hypertension-related complications. Any portal blood flow impairment leads to progressive parenchymal atrophy and triggers hepatic regeneration in preserved areas. This provides the rationale for using portal vein embolisation to modulate hepatic volume in preparation for extended hepatic resection. The aim of this paper is to provide a comprehensive evidence-based review of the rationale for, and outcomes associated with, the main imaging-guided interventions targeting the portal vein, as well as to discuss the main controversies around such approaches.
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Background and aims: Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide. Despite the high prevalence, no screening recommendations yet exist. We designed a prospective observational study to estimate the prevalence of NAFLD in the family of patients with NAFLD and develop a predictive model for identifying it. Methodology: The prevalence of NAFLD in patients' family members was estimated using ultrasonography, and univariate and multivariate odds were calculated for its predictors. A model was created using the significant parameters on multivariate odds, and its performance was tested using the area under the receiver operating characteristic (AUROC). Results: Among 447 family members of 191 patients with NAFLD, the prevalence of NAFLD was 55.9%. Family members with NAFLD were younger and had lower serum levels of aspartate aminotransferase, alanine aminotransferase (ALT), triglycerides. The liver stiffness measurement and controlled attenuation parameter values were also lesser in family members compared to the index cases. Age, body mass index (BMI), and ALT were independent predictors of NAFLD in the family members. A model combining age and BMI had an AUROC of 0.838 [95% confidence interval (CI) 0.800-0.876, P < 0.001]. Age ≥30 years and BMI ≥25 kg/m2 had an odds ratio of 33.5 (95% CI 17.0-66.0, P < 0.001) for prediction of NAFLD, in comparison to BMI <25 kg/m2 and age <30 years. Conclusion: Family members of patients with NAFLD are at increased risk of NAFLD. Screening strategies using BMI and age ensure early identification and could be beneficial in clinical practice.