RESUMEN
Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD+) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD+'s therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids. eNAD+ correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Concordantly, post-hepatectomy liver failure (PHLF) was associated with higher eNAD+ peaks (n = 10; p = 0.0063). Post-operative eNAD+ levels decreased significantly (p < 0.05), but in advanced stages of liver fibrosis or cirrhosis, this decline not only diminished but actually showed a trend towards an increase. The expression of NAD+ biosynthesis rate-limiting enzymes, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), were upregulated significantly in the liver tissue of patients with higher liver fibrosis stages (p < 0.0001). Finally, the administration of NAD+ in a 3D hepatocyte spheroid model rescued hepatocytes from TNFalpha-induced cell death and improved viability (p < 0.0001). In a mouse model of extended liver resection, NAD+ treatment significantly improved survival (p = 0.0158) and liver regeneration (p = 0.0186). Our findings reveal that eNAD+ was upregulated in PHLF, and rate-limiting enzymes of NAD+ biosynthesis demonstrated higher expressions under liver fibrosis. Further, eNAD+ administration improved survival after extended liver resection in mice and enhanced hepatocyte viability in vitro. These insights may offer a potential target for future therapies.
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Hepatectomía , Fallo Hepático , NAD , NAD/metabolismo , Animales , Humanos , Ratones , Fallo Hepático/etiología , Fallo Hepático/metabolismo , Fallo Hepático/patología , Fallo Hepático/cirugía , Masculino , Hepatocitos/metabolismo , Persona de Mediana Edad , Femenino , Ratones Endogámicos C57BL , Cirrosis Hepática/metabolismo , Cirrosis Hepática/cirugía , Modelos Animales de Enfermedad , AncianoRESUMEN
BACKGROUND: Liver stiffness (LS) measurement with two-dimensional shear wave elastography (2D-SWE) correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve. The size of the spleen increases due to tissue proliferation, fibrosis, and portal vein congestion, which can indirectly reflect the situation of liver fibrosis/cirrhosis. It was reported that the size of the spleen was related to posthepatectomy liver failure (PHLF). So far, there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF. This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area (SPA) for the prediction of PHLF in hepatocellular carcinoma (HCC) patients and to develop a risk prediction model. AIM: To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model. METHODS: This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022. Within 1 wk before partial hepatectomy, ultrasound examination was performed to measure LS and SPA, and blood was drawn to evaluate the patient's liver function and other conditions. Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram. Nomogram performance was validated further. The diagnostic performance of the nomogram was evaluated with receiver operating characteristic curve compared with the conventional models, including the model for end-stage liver disease (MELD) score and the albumin-bilirubin (ALBI) score. RESULTS: A total of 562 HCC patients undergoing hepatectomy (500 in the training cohort and 62 in the validation cohort) were enrolled in this study. The independent predictors of PHLF were LS, SPA, range of resection, blood loss, international normalized ratio, and total bilirubin. Better diagnostic performance of the nomogram was obtained in the training [area under receiver operating characteristic curve (AUC): 0.833; 95% confidence interval (95%CI): 0.792-0.873; sensitivity: 83.1%; specificity: 73.5%] and validation (AUC: 0.802; 95%CI: 0.684-0.920; sensitivity: 95.5%; specificity: 52.5%) cohorts compared with the MELD score and the ALBI score. CONCLUSION: This PHLF nomogram, mainly based on LS by 2D-SWE and SPA, was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.
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Carcinoma Hepatocelular , Diagnóstico por Imagen de Elasticidad , Hepatectomía , Fallo Hepático , Neoplasias Hepáticas , Hígado , Nomogramas , Bazo , Humanos , Hepatectomía/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Diagnóstico por Imagen de Elasticidad/métodos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Estudios Prospectivos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Hígado/diagnóstico por imagen , Hígado/cirugía , Hígado/patología , Bazo/diagnóstico por imagen , Bazo/patología , Bazo/cirugía , Fallo Hepático/etiología , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Medición de Riesgo/métodos , Valor Predictivo de las Pruebas , Tamaño de los Órganos , Adulto , Curva ROC , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/cirugía , Cirrosis Hepática/patología , Cirrosis Hepática/complicacionesRESUMEN
INTRODUCTION: Liver transplantation (LT) is a well-established method applied for the treatment of various liver diseases, including primary and secondary malignancies, as well as acute liver failure triggered by different mechanisms. In turn, liver failure (PHLF) is the most severe complication observed after liver resection (LR). PHLF is an extremely rare indication for LT. The aim of the present study was to assess the results of LT in patients with PHLF. METHODS: Relevant cases were extracted from the prospectively collected database of all LTs performed in our center. All clinical variables, details of the perioperative course of each patient and long-term follow-up data were thoroughly assessed. RESULTS: Between January 2000 and August 2023, 2703 LTs were carried out. Among them, six patients underwent LT for PHLF, which accounted for 0.2% of all patients. The median age of the patients was 38 years (range 24-66 years). All patients underwent major liver resection before listing for LT. The 90-day mortality after LT was 66.7% (4 out of 6 patients), and all patients experienced complications in the posttransplant course. One patient required early retransplantation due to primary non-function (PNF). The last two transplanted patients are alive at 7 years and 12 months after LT, respectively. CONCLUSIONS: In an unselected population of patients with PHLF, LT is a very morbid procedure associated with high mortality but should be considered the only life-saving option in this group.
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Hepatectomía , Fallo Hepático , Trasplante de Hígado , Complicaciones Posoperatorias , Humanos , Trasplante de Hígado/métodos , Trasplante de Hígado/efectos adversos , Adulto , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Femenino , Hepatectomía/métodos , Hepatectomía/efectos adversos , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Fallo Hepático/etiología , Fallo Hepático/cirugía , Adulto Joven , Resultado del TratamientoRESUMEN
Autoimmune hepatitis (AIH) is a complex condition with unclear origins, involving genetic susceptibility and environmental triggers that lead to immune system dysfunction. We report a case of a pregnant woman from a mosquito-borne disease-endemic area who presented jaundice, abdominal pain, and pruritus, complicated by acute liver failure. Immunological markers showed AIH triggered by dengue virus infection, which was confirmed by a positive IgM test. Treatment with supportive care followed by steroids and azathioprine resulted in favorable outcomes, averting the need for a liver transplant. Although AIH can be triggered by viruses, the role of dengue in its pathogenesis remains poorly understood. Regular clinical monitoring is vital for managing AIH, particularly during pregnancy, due to variable immune status and treatment responses. Further research is necessary to understand the link between dengue infection and AIH. Individualized treatment strategies are crucial, especially during pregnancy, in order to ensure favorable outcomes.
La hepatitis autoinmune (HAI) es una condición compleja con etiología poco clara, que engloba componentes genéticos y ambientales que pueden desencadenar disfunción del sistema inmunológico. Presentamos el caso de una gestante de una zona endémica de dengue que se presentó con ictericia, dolor abdominal y prurito, complicándose con insuficiencia hepática aguda. Los marcadores inmunológicos indicaron HAI desencadenada por la infección del virus del dengue, confirmada por una prueba positiva de IgM. El tratamiento con cuidados de soporte seguido de corticoterapia y azatioprina tuvo resultados clínicos y laboratoriales favorables, evitando la necesidad de un trasplante de hígado. Diversos virus han sido descritos como desencadenantes de HAI; sin embargo, el papel del virus del dengue en su patogénesis sigue siendo desconocido. El monitoreo clínico regular es vital para el manejo de la HAI, especialmente durante el embarazo, debido a las alteraciones inmunológicas y las diversas respuestas al tratamiento. Se necesita más investigación para dilucidar el vínculo entre la infección por dengue y el desarrollo de HAI. El tratamiento individualizado en estos pacientes es crucial, especialmente durante el embarazo, para disminuir el riesgo de complicaciones.
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Dengue , Hepatitis Autoinmune , Humanos , Femenino , Embarazo , Hepatitis Autoinmune/etiología , Dengue/complicaciones , Adulto , Complicaciones Infecciosas del Embarazo , Fallo Hepático/etiologíaRESUMEN
Liver resection (LR) is the primary treatment for hepatic tumors, yet posthepatectomy liver failure (PHLF) remains a significant concern. While the precise etiology of PHLF remains elusive, dysregulated inflammatory processes are pivotal. Therefore, we explored the theragnostic potential of extracellular high-mobility-group-box protein 1 (HMGB1), a key damage-associated molecular pattern (DAMP) released by hepatocytes, in liver recovery post LR in patients and animal models. Plasma from 96 LR patients and liver tissues from a subset of 24 LR patients were analyzed for HMGB1 levels, and associations with PHLF and liver injury markers were assessed. In a murine LR model, the HMGB1 inhibitor glycyrrhizin, was administered to assess its impact on liver regeneration. Furthermore, plasma levels of keratin-18 (K18) and cleaved cytokeratin-18 (ccK18) were quantified to assess suitability as predictive biomarkers for PHLF. Patients experiencing PHLF exhibited elevated levels of intrahepatic and circulating HMGB1, correlating with markers of liver injury. In a murine LR model, inhibition of HMGB1 improved liver function, reduced steatosis, enhanced regeneration and decreased hepatic cell death. Elevated levels of hepatic cell death markers K18 and ccK18 were detected in patients with PHLF and correlations with levels of circulating HMGB1 was observed. Our study underscores the therapeutic and predictive potential of HMGB1 in PHLF mitigation. Elevated HMGB1, K18, and ccK18 levels correlate with patient outcomes, highlighting their predictive significance. Targeting HMGB1 enhances liver regeneration in murine LR models, emphasizing its role in potential intervention and prediction strategies for liver surgery.
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Proteína HMGB1 , Hepatectomía , Fallo Hepático , Anciano , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Biomarcadores , Muerte Celular , Modelos Animales de Enfermedad , Ácido Glicirrínico/farmacología , Hepatectomía/efectos adversos , Hepatocitos/metabolismo , Proteína HMGB1/metabolismo , Proteína HMGB1/sangre , Queratina-18/metabolismo , Queratina-18/sangre , Hígado/metabolismo , Hígado/patología , Fallo Hepático/etiología , Fallo Hepático/metabolismo , Fallo Hepático/patología , Regeneración Hepática , Ratones Endogámicos C57BLRESUMEN
BACKGROUND Cryptococcosis is an invasive fungal infection caused by Cryptococcus species complex. C. neoformans is one of the pathogenic species within the genus. C. neoformans infections often present as an opportunistic infection in severely immunocompromised individuals. Infection of the pericardium in the setting of liver failure is uncommon. We present a case of cryptococcal pericarditis in a patient with liver failure. CASE REPORT A 47-year-old man with a past medical history of psoriatic arthritis, and alcohol use disorder presented to the emergency department with a 2-week history of progressively worsening generalized weakness, malaise, and yellowish skin changes. Physical examination revealed scleral icterus, jaundiced skin, and ascites. Initial laboratory workup revealed thrombocytopenia, transaminitis (aspartate transaminase (AST) level of 502 IU/L, alanine transaminase (ALT) level of 82 IU/L), hyperbilirubinemia (total bilirubin of 15.7 mg/dL), International Nationalized Ratio (INR) of 3.6, and lactic acidosis (lactic acid of 11.7 mmol/L). The patient developed encephalopathy and acute hypoxic respiratory failure requiring intubation. A bedside point-of-care cardiac ultrasound, performed following intubation, revealed a pericardial effusion without signs of tamponade. This finding was later confirmed by a formal transthoracic echocardiogram. Percutaneous pericardiocentesis was performed, and the pericardial fluid culture revealed the presence of C. neoformans. Human immunodeficiency virus (HIV) tests were negative. The patient received antifungal therapy. Due to his poor prognosis, he was transitioned to comfort care and eventually died. CONCLUSIONS This case report describes an unusual presentation of acute liver failure complicated by cryptococcal pericarditis, emphasizing the importance of considering atypical fungal infections in such patients.
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Criptococosis , Pericarditis , Humanos , Masculino , Persona de Mediana Edad , Criptococosis/diagnóstico , Criptococosis/complicaciones , Pericarditis/microbiología , Pericarditis/diagnóstico , Fallo Hepático/etiología , Cryptococcus neoformans/aislamiento & purificación , Antifúngicos/uso terapéutico , Huésped Inmunocomprometido , Resultado FatalRESUMEN
The influence of liver fibrosis on the rate of liver regeneration and complications following ALPPS has yet to be fully understood. This study aimed to scrutinize the effects of liver fibrosis on the postoperative complications, and prognosis subsequent to ALPPS. Clinical data were collected from patients with primary liver cancer who underwent ALPPS at Peking Union Medical College Hospital between May 2014 and October 2022. The degree of liver fibrosis was assessed using haematoxylin-eosin staining and Sirius red staining. This study encompassed thirty patients who underwent ALPPS for primary liver cancer, and there were 23 patients with hepatocellular carcinoma, 5 with cholangiocarcinoma, and 2 with combined hepatocellular-cholangiocarcinoma. The impact of severe liver fibrosis on the rate of liver regeneration was not statistically significant (P = 0.892). All patients with severe complications belonged to the severe liver fibrosis group. Severe liver fibrosis exhibited a significant association with 90 days mortality (P = 0.014) and overall survival (P = 0.012). Severe liver fibrosis emerges as a crucial risk factor for liver failure and perioperative mortality following the second step of ALPPS. Preoperative liver function impairment is an important predictive factor for postoperative liver failure.
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Hepatectomía , Cirrosis Hepática , Fallo Hepático , Neoplasias Hepáticas , Humanos , Masculino , Femenino , Cirrosis Hepática/cirugía , Cirrosis Hepática/patología , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Persona de Mediana Edad , Fallo Hepático/etiología , Fallo Hepático/patología , Hepatectomía/efectos adversos , Anciano , Pronóstico , Complicaciones Posoperatorias/etiología , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Vena Porta/patología , Vena Porta/cirugía , Colangiocarcinoma/cirugía , Colangiocarcinoma/patología , Colangiocarcinoma/mortalidad , Adulto , Regeneración Hepática , Factores de Riesgo , Estudios Retrospectivos , Resultado del Tratamiento , LigaduraRESUMEN
OBJECTIVE: Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post-hepatectomy liver failure (PHLF) among surgically-treated jaundiced patients with hilar cholangiocarcinoma (HCCA). METHODS: We retrospectively reviewed surgically-treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated. RESULTS: A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic-pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly-acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%. CONCLUSION: For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi-center studies for training and validation are required for further validation.
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Neoplasias de los Conductos Biliares , Hepatectomía , Ictericia , Tumor de Klatskin , Fallo Hepático , Humanos , Masculino , Hepatectomía/efectos adversos , Femenino , Persona de Mediana Edad , Tumor de Klatskin/cirugía , Tumor de Klatskin/patología , Estudios Retrospectivos , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Fallo Hepático/etiología , Fallo Hepático/prevención & control , China/epidemiología , Ictericia/etiología , Hígado/cirugía , Hígado/patología , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Pronóstico , Adulto , Tamaño de los ÓrganosAsunto(s)
Enfermedad de Still del Adulto , Humanos , Femenino , Embarazo , Enfermedad de Still del Adulto/diagnóstico , Enfermedad de Still del Adulto/complicaciones , Adulto , Periodo Posparto , Fallo Hepático/etiología , Fallo Hepático/diagnóstico , Complicaciones del Embarazo/diagnóstico , Recién NacidoRESUMEN
INTRODUCTION: Adult-onset Still disease (AOSD) is a rare inflammatory condition with a monophasic, intermittent, or chronic clinical course, and a subset may experience life-threatening complications such as hemophagocytic lymphohistiocytosis (HLH). This study aims to characterize concurrent AOSD and HLH and identify variables independently associated with in-hospital death. METHODS: We performed a medical records review of AOSD with and without HLH from the 2016-2019 National Inpatient Sample database. We performed a multivariable logistic regression analysis for in-hospital death. Results were reported as adjusted odds ratios (OR adj ). RESULTS: There were 5495 hospitalizations with AOSD, of which 340 (6.2%) had HLH. Thirty (9.0%) of the combined AOSD and HLH group died in the hospital compared with 75 (1.5%) of those without HLH. Multivariable analysis in AOSD inpatients showed that disseminated intravascular coagulation (OR adj 6.13), hepatic failure (OR adj 7.16), infection (OR adj 3.72), respiratory failure (OR adj 6.89), and thrombotic microangiopathy (OR adj 14.05) were associated with higher odds of death. However, HLH itself was not an independent predictor of mortality in AOSD population. CONCLUSIONS: HLH occurred in a small minority of inpatients with AOSD. HLH itself was not an independent risk factor for in-hospital death. Disseminated intravascular coagulation, hepatic failure, infection, respiratory failure, and thrombotic microangiopathy were associated with higher odds of in-hospital death in AOSD. Better awareness of these life-threatening complications may improve hospital outcomes.
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Mortalidad Hospitalaria , Linfohistiocitosis Hemofagocítica , Enfermedad de Still del Adulto , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/epidemiología , Linfohistiocitosis Hemofagocítica/mortalidad , Enfermedad de Still del Adulto/diagnóstico , Enfermedad de Still del Adulto/epidemiología , Enfermedad de Still del Adulto/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estados Unidos/epidemiología , Coagulación Intravascular Diseminada/epidemiología , Coagulación Intravascular Diseminada/diagnóstico , Coagulación Intravascular Diseminada/etiología , Fallo Hepático/etiología , Fallo Hepático/epidemiología , Fallo Hepático/diagnóstico , Factores de Riesgo , Anciano , Microangiopatías Trombóticas/epidemiología , Microangiopatías Trombóticas/diagnóstico , Estudios Retrospectivos , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/epidemiología , Hospitalización/estadística & datos numéricos , Bases de Datos FactualesRESUMEN
BACKGROUND: Posthepatectomy liver failure remains a potentially life-threatening complication after hepatectomy. Soluble suppression of tumourigenicity 2 is an injury-related biomarker. The aim of the study was to assess soluble suppression of tumourigenicity 2 elevation after hepatectomy and whether it can predict posthepatectomy liver failure. METHODS: This was a single-centre retrospective study including all patients who underwent a liver resection between 2015 and 2019. Plasma concentrations of soluble suppression of tumourigenicity 2 were measured before surgery and at postoperative days 1, 2, 5 and 7. Posthepatectomy liver failure was defined according to the International Study Group of Liver Surgery and the morbidity rate was graded according to the Clavien-Dindo classification. RESULTS: A total of 173 patients were included (75 underwent major and 98 minor resection); plasma levels of soluble suppression of tumourigenicity 2 increased from 43.42 (range 18.69-119.96) pg/ml to 2622.23 (range 1354.18-4178.27) pg/ml on postoperative day 1 (P < 0.001). Postoperative day 1 soluble suppression of tumourigenicity 2 concentration accurately predicted posthepatectomy liver failure ≥ grade B (area under curve = 0.916, P < 0.001) and its outstanding performance was not affected by underlying disease, liver pathological status and extent of resection. The cut-off value, sensitivity, specificity, positive predictive value and negative predictive value of postoperative day 1 soluble suppression of tumourigenicity 2 in predicting posthepatectomy liver failure ≥ grade B were 3700, 92%, 85%, 64% and 97% respectively. Soluble suppression of tumourigenicity 2high patients more frequently experienced posthepatectomy liver failure ≥ grade B (64.3% (n = 36) versus 2.6% (n = 3)) and Clavien-Dindo IIIa higher morbidity rate (23.2% (n = 13) versus 5.1% (n = 6)) compared with soluble suppression of tumourigenicity 2low patients. CONCLUSIONS: Soluble suppression of tumourigenicity 2 may be a reliable predictor of posthepatectomy liver failure ≥ grade B as early as postoperative day 1 for patients undergoing liver resection. Its role in controlling hepatic injury/regeneration needs further investigation. Registration number: ChiCTR-OOC-15007210 (www.chictr.org.cn/).
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Biomarcadores , Hepatectomía , Fallo Hepático , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Hepatectomía/efectos adversos , Estudios Retrospectivos , Persona de Mediana Edad , Fallo Hepático/etiología , Fallo Hepático/sangre , Fallo Hepático/prevención & control , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Anciano , Biomarcadores/sangre , Adulto , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/sangre , Valor Predictivo de las PruebasRESUMEN
OBJECTIVE: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. BACKGROUNDS: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. METHODS: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. RESULTS: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. CONCLUSION: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.
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Carcinoma Hepatocelular , Hepatectomía , Hipertensión Portal , Neoplasias Hepáticas , Nomogramas , Humanos , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Hepatectomía/métodos , Hepatectomía/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Hipertensión Portal/cirugía , Hipertensión Portal/etiología , Anciano , Factores de Riesgo , Complicaciones Posoperatorias/etiología , Fallo Hepático/etiología , Fallo Hepático/cirugía , Estudios Retrospectivos , AdultoRESUMEN
Recombinant human type II tumour necrosis factor receptor-antibody fusion protein (rh TNFR:Fc) is an immunosuppressant approved for treating rheumatoid arthritis (RA). This case report describes a case of hepatitis B reactivation in a patient with drug-induced acute-on-chronic liver failure. A 58-year-old woman with a history of RA was treated with rh TNFR:Fc; and then subsequently received 25 mg rh TNFR:Fc, twice a week, as maintenance therapy. No anti-hepatitis B virus (HBV) preventive treatment was administered. Six months later, she was hospitalized with acute jaundice. HBV reactivation was observed, leading to acute-on-chronic liver failure. After active treatment, the patient's condition improved and she recovered well. Following careful diagnosis and treatment protocols are essential when treating RA with rh TNFR:Fc, especially in anti-hepatitis B core antigen antibody-positive patients, even when the HBV surface antigen and the HBV DNA are negative. In the case of HBV reactivation, liver function parameters, HBV surface antigen and HBV DNA should be closely monitored during treatment, and antiviral drugs should be used prophylactically when necessary, as fatal hepatitis B reactivation may occur in rare cases. A comprehensive evaluation and medication should be administered in a timely manner after evaluating the patient's physical condition and closely monitoring the patient.
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Virus de la Hepatitis B , Hepatitis B , Receptores Tipo II del Factor de Necrosis Tumoral , Proteínas Recombinantes de Fusión , Activación Viral , Femenino , Humanos , Persona de Mediana Edad , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/virología , Artritis Reumatoide/inmunología , Artritis Reumatoide/complicaciones , Hepatitis B/virología , Hepatitis B/tratamiento farmacológico , Hepatitis B/complicaciones , Hepatitis B/inmunología , Virus de la Hepatitis B/patogenicidad , Virus de la Hepatitis B/fisiología , Fallo Hepático/virología , Fallo Hepático/etiología , Proteínas Recombinantes de Fusión/uso terapéutico , Activación Viral/efectos de los fármacos , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Receptores Tipo II del Factor de Necrosis Tumoral/farmacología , Inmunosupresores/efectos adversos , Inmunosupresores/farmacologíaRESUMEN
INTRODUCTION: Previous research has demonstrated the impact of postoperative phosphate levels on liver regeneration and outcomes after liver resection surgeries, a potential predictor for regenerative success and liver failure. However, little is known about the association between low preoperative serum phosphate levels and outcomes in liver resections. METHODS: We performed a retrospective analysis of liver resections performed at our institution. Patients were categorized based on preoperative phosphate levels (low versus normal). Our primary outcome measure was posthepatectomy liver failure. RESULTS: A total of 265 cases met the study criteria. 71 patients (26.7%) had low preoperative phosphate levels. The incidence of posthepatectomy liver failure was higher in the low preoperative phosphate group (19.2% versus 12.4%). However, after propensity score matching, rates of posthepatectomy liver failure were similar between low and normal preoperative phosphate cohorts (13% versus 14%, P = 0.83). CONCLUSIONS: Low preoperative phosphate levels were not associated with worse postoperative outcomes in this study. Further studies are warranted to investigate this association and its relevance as a clinical prognostic factor for postoperative liver failure.
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Hepatectomía , Fosfatos , Complicaciones Posoperatorias , Periodo Preoperatorio , Humanos , Femenino , Estudios Retrospectivos , Masculino , Persona de Mediana Edad , Hepatectomía/efectos adversos , Fosfatos/sangre , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/sangre , Fallo Hepático/sangre , Fallo Hepático/etiología , Adulto , Resultado del Tratamiento , Puntaje de PropensiónRESUMEN
Hepatitis E virus (HEV) is one of the important causes of acute viral hepatitis worldwide, and its incidence rate is increasing year by year. HEV infection can lead to acute, subacute, or acute-on-chronic liver failure with a high mortality rate among some particular patient population, who are pregnant women, older, chronic liver diseases like chronic hepatitis B and cirrhosis, or immunocompromised. The clinical characteristics of HEV infection, the pathogenesis of HEV-related liver failure, and the progress in diagnosis and treatment will be elaborated upon in this article from these three aspects in order to improve clinicians' ability to identify and prevent HEV-related liver failure and its clinical outcomes.
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Virus de la Hepatitis E , Hepatitis E , Fallo Hepático , Humanos , Hepatitis E/diagnóstico , Hepatitis E/epidemiología , Hepatitis E/terapia , Virus de la Hepatitis E/fisiología , Fallo Hepático/etiología , Fallo Hepático/virologíaRESUMEN
Post-hepatectomy liver failure (PHLF) is a potentially life-threatening complication following liver resection. Hepatocellular carcinoma (HCC) often occurs in patients with chronic liver disease, which increases the risk of PHLF. This study aimed to investigate the ability of the combination of liver function and fibrosis markers (ALBI score and FIB-4 index) to predict PHLF in patients with HCC. Patients who underwent hepatectomy for HCC between August 2012 and September 2022 were considered for inclusion. Multivariable logistic regression analysis was used to identify factors associated with PHLF, and ALBI score and FIB-4 index were combined based on their regression coefficients. The performance of the combined ALBI-FIB4 score in predicting PHLF and postoperative mortality was compared with Child-Pugh score, MELD score, ALBI score, and FIB-4 index. A total of 215 patients were enrolled in this study. PHLF occurred in 35 patients (16.3%). The incidence of severe PHLF (grade B and grade C PHLF) was 9.3%. Postoperative 90-d mortality was 2.8%. ALBI score, FIB-4 index, prothrombin time, and extent of liver resection were identified as independent factors for predicting PHLF. The AUC of the ALBI-FIB4 score in predicting PHLF was 0.783(95%CI: 0.694-0.872), higher than other models. The ALBI-FIB4 score could divide patients into two risk groups based on a cut-off value of - 1.82. High-risk patients had a high incidence of PHLF of 39.1%, while PHLF just occurred in 6.6% of low-risk patients. Similarly, the AUCs of the ALBI-FIB4 score in predicting severe PHLF and postoperative 90-d mortality were also higher than other models. Preoperative ALBI-FIB4 score showed good performance in predicting PHLF and postoperative mortality in patients undergoing hepatectomy for HCC, superior to the currently commonly used liver function and fibrosis scoring systems.
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Carcinoma Hepatocelular , Fallo Hepático , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Hepatectomía/efectos adversos , Neoplasias Hepáticas/patología , Pronóstico , Albúmina Sérica/análisis , Fallo Hepático/diagnóstico , Fallo Hepático/etiología , Fibrosis , Estudios RetrospectivosRESUMEN
BACKGROUND & OBJECTIVES: Sarcopenia is a morbi-mortality risk factor in digestive surgery, though its impact after major hepatectomy (MH) remains unknown. This prospective pilot study investigated whether volume and function of a regenerating liver is influenced by body composition. METHODS: From 2011 to 2016, 125 consecutive patients had computed tomography and 99mTc-labelled-mebrofenin SPECT-scintigraphy before and after MH at day 7 and 1 month for measurements of liver volumes and functions. L3 vertebra muscle mass identified sarcopenia. Primary endpoint was the impact of sarcopenia on regeneration capacities (i.e. volume/function changes and post-hepatectomy liver failure (PHLF) rate). Secondary endpoint was 3-month morbi-mortality. RESULTS: Sarcopenic patients (SP; N = 69) were significantly older than non-sarcopenic (NSP), with lower BMI and more malignancies, but with comparable liver function/volume at baseline. Postoperatively, SP showed higher rates of ISGLS_PHLF (24.6 % vs 10.9 %; p = 0.05) but with comparable rates of severe morbidity (23.2 % vs 16.4 %; p = 0.35), overall (8.7 % vs 3.6 %; p = 0.3) and PHLF-related mortality (8,7 % vs 1.8 %; p = 0.075). After matching on the extent of resection or using propensity score, regeneration and PHLF rates were similar. CONCLUSION: This prospective study using first sequential SPECT-scintigraphy showed that sarcopenia by itself does not affect liver regeneration capacities and short-term postoperative course after MH.
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Compuestos de Anilina , Glicina , Hepatectomía , Regeneración Hepática , Sarcopenia , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X , Humanos , Sarcopenia/diagnóstico por imagen , Sarcopenia/etiología , Sarcopenia/complicaciones , Estudios Prospectivos , Masculino , Femenino , Regeneración Hepática/fisiología , Anciano , Persona de Mediana Edad , Proyectos Piloto , Tamaño de los Órganos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Radiofármacos , Compuestos de Organotecnecio , Iminoácidos , Fallo Hepático/diagnóstico por imagen , Fallo Hepático/etiología , Fallo Hepático/cirugíaRESUMEN
The patient was a male infant, born full-term, admitted to the hospital at 28 days of age due to jaundice for 20 days and abdominal distension for 15 days. The patient developed symptoms of jaundice, hepatosplenomegaly, massive ascites, and progressively worsening liver function leading to liver failure, severe coagulation disorders, and thrombocytopenia one week after birth. Various treatments were administered, including anti-infection therapy, fluid restriction, use of diuretics, use of hepatoprotective and choleretic agents, intermittent paracentesis, blood exchange, and intravenous immunoglobulin, albumin, and plasma transfusions. However, the patient's condition did not improve, and on the 24th day of hospitalization, the family decided to discontinue treatment and provide palliative care. Sequencing of the patient's liver tissue and parental blood samples using whole-exome sequencing did not identify any pathogenic variants that could explain the liver failure. However, postmortem liver tissue pathology suggested congenital hepatic fibrosis (CHF). Given the rarity of CHF causing neonatal liver failure, further studies on the prognosis and pathogenic genes of CHF cases are needed in the future. This article provides a comprehensive description of the differential diagnosis of neonatal liver failure and introduces a multidisciplinary diagnostic and therapeutic approach to neonatal liver failure.
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Enfermedades Genéticas Congénitas , Ictericia , Fallo Hepático , Lactante , Recién Nacido , Humanos , Masculino , Cirrosis Hepática , Fallo Hepático/etiologíaAsunto(s)
Diabetes Mellitus Tipo 2 , Hígado , Enfermedad del Hígado Graso no Alcohólico , Humanos , Abdomen , Hígado/diagnóstico por imagen , Hígado/patología , Pronóstico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/mortalidad , Enfermedad del Hígado Graso no Alcohólico/cirugía , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Cirrosis Hepática/etiología , Cirrosis Hepática/mortalidad , Diagnóstico por Imagen de Elasticidad , Biopsia/efectos adversos , Neoplasias Hepáticas/etiología , Carcinoma Hepatocelular/etiología , Fallo Hepático/etiología , Trasplante de Hígado , Factores de RiesgoRESUMEN
BACKGROUND: Posthepatectomy liver failure (PHLF) remains a life-threatening complication after hepatectomy. To reduce PHLF, a preoperative assessment of liver function is indispensable. For this purpose, 99mTc-mebrofenin hepatobiliary scintigraphy with SPECT (MSPECT) can be used. The aim of the current study was to evaluate the predictive value of MSPECT for PHLF in patients with non-colorectal liver tumors (NCRLT) compared to patients with colorectal liver metastasis (CRLM) undergoing extended liver resection. METHODS: We included all patients undergoing extended liver resections via two-stage procedures between January 2019 and December 2021 at the University Medical Center Hamburg-Eppendorf, Germany. All patients received a preoperative MSPECT. RESULTS: Twenty patients were included. In every fourth patient, PHLF was observed. Four patients had PHLF grade C. There were no differences between patients with CRLM and NCRLT regarding PHLF rate and future liver remnant (FLR) volume. Patients with CRLM had higher mebrofenin uptake in the FLR compared to those with NCRLT (2.49%/min/m2 vs. 1.51%/min/m2; p = 0.004). CONCLUSION: Mebrofenin uptake in patients with NCRLT was lower compared to those patients with CRLM. However, there was no difference in the PHLF rate and FLR volume. Cut-off values for the mebrofenin uptake might need adjustments for different surgical indications, surgical procedures, and underlying diseases.