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BACKGROUND: Altered bacterial translocation is associated with changes in hepatic function and the progression from compensated to decompensated cirrhosis. Child-Turcotte-Pugh (CTP) score is an essential indicator of liver severity. Thus, we aimed to study differences in the blood microbiome together with metabolome profile between HCV-infected patients with CTP class B (CTP-B, significant functional compromise) and patients with CTP class A (CTP-A, well-compensated cirrhosis). METHODS: We conducted a cross-sectional study in patients with advanced HCV-related cirrhosis (n = 88) stratified by CTP-B and CTP-A. Bacterial 16S rRNA sequencing was sequenced by MiSeq Illumina technology and non-targeted metabolomics was performed by GC-MS and LC-MS ESI+ and ESI- to complement the analysis. RESULTS: Patients with CTP-B had lower levels of richness (Chao1), and alpha diversity (Shannon and Simpson indexes) at phylum level than patients with CTP-A. Likewise, we observed significant differences in beta diversity between groups at phylum, class, and order levels, showing lower diversity in patients with CTP-B. Higher relative abundance of Proteobacteria (p = 0.012), Alphaproteobacteria (p = 0.005), Sphingomonadales (p = 0.012) and Sphingomonadaceae (p = 0.016) were significantly associated with CTP-B. The phylum Proteobacteria was positively correlated with ethanolamine and oleic acid (p = 0.005 and p = 0.004, respectively) and negatively with p-cresol (p = 0.006). In addition, the order Sphingomonadales and the family Sphingomonadaceae was also negatively correlated with p-cresol (p = 0.001 and p = 0.001). CONCLUSIONS: Blood microbial diversity was significantly decreased in patients with CTP-B, who presented an enrichment of Proteobacteria, Alphaproteobacteria, Sphingomonadales and Sphingomonadaceae compared to patients with CTP-A.

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Cirrosis Hepática , Microbiota , ARN Ribosómico 16S , Humanos , Masculino , Cirrosis Hepática/sangre , Cirrosis Hepática/microbiología , Cirrosis Hepática/virología , Femenino , Persona de Mediana Edad , Estudios Transversales , ARN Ribosómico 16S/genética , Anciano , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Índice de Severidad de la Enfermedad , Adulto , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/sangre , Hepatitis C Crónica/microbiología , Metaboloma , Metabolómica , Sangre/microbiología , Sangre/virología

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BACKGROUND: Portal hypertension is a common diagnosis in Sub-Saharan African countries, with the majority of patients presenting late. This study aimed to understand Clinical characteristics, aetiology, the treatment offered in our setting, and factors associated with portal hypertension at a tertiary-level hospital, in Tanzania. METHODOLOGY: A prospective cross-sectional observational single hospital-based study was conducted at MNH, from May 2021 to April 2022. A minimum of 152 subjects were required with an error of less than 5% and a study power of 80% at a 95% confidence interval. A structured questionnaire was used to collect data. Ethical clearance was obtained from the MUHAS/MNH IRB. RESULTS: A total of 154 eligible participants consented and participated in this study. The mean age of participants was 42 ± 15.8 years (range 2-87). Most of the study participants were males 64.9% with a male-to-female (M: F) ratio of 1.8:1. Vomiting blood was the common symptom among the study participants 51.3%. Schistosomiasis 53.9% and viral infection 26.6% were the common etiologies followed by alcohol abuse 7.8%. Most were medically treated at 89.61% followed by radiological treatment at 8.44% while only 1.95% of patients received surgical treatment. There was a significant association between the grade of oesophagal varices and bleeding consequences (p-value < 0.01). CONCLUSION: The majority of patients were medically treated while patients who require surgical care are unable to assess it. We recommend the establishment of a transplant services program to counteract the unmet need and more retrospective research toward policy establishment.

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Hipertensión Portal , Humanos , Masculino , Femenino , Hipertensión Portal/diagnóstico , Hipertensión Portal/terapia , Hipertensión Portal/fisiopatología , Hipertensión Portal/epidemiología , Hipertensión Portal/etiología , Tanzanía/epidemiología , Adulto , Estudios Transversales , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven , Anciano , Adolescente , Anciano de 80 o más Años , Niño , Preescolar , Factores de Riesgo , Várices Esofágicas y Gástricas/terapia , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/etiología , Resultado del Tratamiento , Centros de Atención Terciaria , Hemorragia Gastrointestinal/terapia , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/epidemiología

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BACKGROUND: Chemoembolization with small drug-eluting microspheres is widely used in the treatment of hepatocellular carcinoma (HCC). OBJECTIVES: This study aimed to evaluate the efficacy and safety of transarterial chemoembolization with doxorubicin-eluting 30-60-µm microspheres (DEB-TACE) in patients with Barcelona Clinic Liver Cancer (BCLC) stage A and B HCC. MATERIALS AND METHODS: In this single-center study, 88 patients with HCC (BCLC A/B: 15.9%/84.1%) who underwent 137 DEB-TACE sessions between January 2015 and December 2020 were retrospectively assessed. Response to treatment was assessed 4-8 weeks after each DEB-TACE procedure according to mRECIST (Modified Response Evaluation Criteria in Solid Tumors) criteria. Progression-free survival (PFS), time to progression (TTP), overall survival (OS), and adverse events were recorded. RESULTS: In 88 patients (84.1% males; median age, 66.0 years; range, 22-83), the median follow-up was 17 months (range, 2-64). Eight patients (9.1%) had a complete response, 42 (47.8%) had partial regression, 10 (11.3%) had stable disease, and 28 (31.8%) had progressive disease. There was a statistically significant difference between serum alpha-fetoprotein (AFP) levels before and after DEB-TACE treatment (p < 0.001). The median OS was 17 months (95% confidence interval [CI], 10.3-23.7). Cox regression analyses found that preprocedural serum AFP level (400+ vs. < 400; p = 0.024), Child Pugh classification (B vs. A; p = 0.019), and number of DEB-TACE sessions (1 vs. > 1; p = 0.003) were independent risk factors affecting OS. The median PFS was 8 months (95% CI, 5.8-10.2) and TTP was 6 months (1-14 months). CONCLUSION: Chemoembolization with 30-60-µm microspheres is an effective and safe treatment for HCC. The number of DEB-TACE sessions is also one of the factors affecting OS.

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PURPOSE: This study aimed to evaluate the efficacy of percutaneous microwave ablation (MWA) for treating hepatic malignant tumors and to identify factors influencing tumor recurrence post-treatment. METHODS: A total of 249 patients with hepatic malignant tumors treated at the Shandong Cancer Hospital and Institute were included, and 101 patients were analyzed. Disease-free and overall survival rates were assessed at 1, 2, and 3 years post-MWA. Correlations between tumor recurrence and factors such as Child-Pugh B classification and lesion count were examined, and a meta-analysis was conducted to identify independent risk factors for recurrence. RESULTS: The study found disease-free survival rates of 80.2%, 72.3%, and 70.3% at 1, 2, and 3 years post-MWA, with overall survival rates at 99%, 97%, and 96%. Significant correlations were observed between tumor recurrence, Child-Pugh B classification, and the number of lesions. Meta-analysis confirmed lesion count and Child-Pugh B classification as independent risk factors for recurrence following MWA treatment. CONCLUSION: The study underscores the importance of considering Child-Pugh B classification and lesion count in predicting tumor recurrence after MWA for hepatic malignant tumors. These findings offer valuable insights for clinicians in decision-making and post-treatment monitoring.

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Introduction Research on non-invasive tools for detecting gastro-esophageal varices is underway. We investigated the Platelet-Albumin-Bilirubin (PALBI) score in comparison with the Child-Turcotte-Pugh (CTP) and MELD-Na (MELD-Na) scores in patients with liver cirrhosis. Methods Three hundred and twenty-three patients with liver cirrhosis were studied. The PALBI, CTP and MELD-Na scores were calculated and analyzed for gastroesophageal varices and their characteristics using SPSS version 26 (IBM Corp., Armonk, NY, USA). Results Two hundred and sixty-four patients had esophageal varices and 102 presented with variceal hemorrhage. Mean PALBI, CTP and MELD-Na scores were significantly higher for patients with varices versus without varices (p < 0.05). Unlike the mean MELD-Na score, the mean PALBI and CTP scores were significantly higher in patients with large high-risk varices as compared to patients with small low-risk varices (p < 0.05). The mean CTP scores were significantly higher in patients with variceal hemorrhage than those without hemorrhage (p < 0.05), while the difference between mean PALBI and MELD-Na was insignificant, in this regard. The PALBI score had better sensitivity than the CTP and MELD-Na scores in indicating the presence of varices but was similar to the CTP score in predicting high-risk varices. Conclusion The PALBI score proves to have good utility and efficiency in predicting varices in comparison to CTP and MELD-Na scores. It can determine high-risk stigmata of variceal hemorrhage with similar performance as the CTP Score.

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Introduction, aim, and objective: Despite recent evidence suggesting the blood creatinine level is a significant predictor of survival in liver cirrhosis patients, the conventional Child-Pugh (CP) score has held a longstanding position as a valuable prognostic indicator in cirrhotic individuals. This study aimed to compare the predictive capabilities of the modified CP score and the traditional CP score in decompensated cirrhosis patients to evaluate their prognostic power. The objective of this study was to assess the prognostic value of the modified and traditional CP scores in individuals with decompensated cirrhosis by assessing their predictive accuracy. METHODS: A total of 100 patients diagnosed with decompensated cirrhosis participated in this prospective study. Each patient's Child-Pugh score and class were determined using admission data, with scores ranging from 5 to 15. Serum creatinine was incorporated as the sixth variable to compute the modified CP score, which ranges from 5 to 19. RESULTS: The percentages of individuals aged 16-30, 31-40, 41-50, 51-60, and above 60 years were as follows: 16.0%, 29.0%, 26.0%, and 11.0%, respectively. The patients had a mean age of 44.71 years and a standard deviation of 13.40 years. Out of the 100 patients studied, 26% were female and 74% were male. Fifty-two percent of patients had mild hepatic encephalopathy, while 24% had moderate encephalopathy and 24% had severe encephalopathy. In cases of moderate and severe hepatic encephalopathy, the creatinine-modified Pugh score showed a considerably large area under the curve (AUC=0.852) on the receiver operating characteristics (ROC) curve. CONCLUSION:  When blood creatinine is taken into account, it can enhance the Child-Pugh classification's prognostic usefulness. This is especially true for patients with moderate to severe hepatic encephalopathy, where serum creatinine is a key factor in accurately predicting both survival and complications associated with cirrhosis.

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BACKGROUND:  Liver cirrhosis is the replacement of normal liver parenchyma by fibrous tissue and nodularity. Cirrhosis liver has a negative effect on the body's ability to regulate blood glucose levels because the liver cannot release the amount of glucose it would ultimately cirrhotic patients are at risk of hypoglycemia. OBJECTIVE:  To determine the frequency of hypoglycemia in cirrhotic patients just before endoscopy after being nil per mouth (NPO) for 6 hours. METHODOLOGY:  This cross-sectional study was done at the Department of Gastroenterology Lady Reading Hospital, Peshawar from 1st April 2023 to 30th September 2023. Patients aged > 20 years of both genders, having Child-Pugh class C cirrhosis, and undergoing upper gastrointestinal (GI) endoscopy were enrolled in the study while patients with a history of diabetes using oral or parenteral hypoglycemic medications, patients taking steroids, patients with hepatocellular carcinoma and patients with hepatic encephalopathy were excluded. Diagnosis of liver cirrhosis was based on clinical examination, serum albumin level, and prothrombin time followed by characteristic findings on ultrasound. Serum glucose level was determined in the blood sample of the patient from the hospital laboratory.  Results: One hundred and ninety-six patients were enrolled including 130 (67.4%) males and 66 (32.6%) females. Age of the patients ranged from 20 to 60 years. The mean age of the participants was 46.68±10.239 years. Hypoglycemia was found in 48% of patients with liver cirrhosis. A significant association of hypoglycemia was found with disease duration and Child-Pugh class. CONCLUSION:  Hypoglycemia is a frequent finding in patients with liver cirrhosis and needs urgent management to prevent complications. Prolonged illness and patients with Child-Pugh class C cirrhosis are more likely to have hypoglycemia.

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The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA-coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child-Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro-inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver-related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes.

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Heces , Microbioma Gastrointestinal , Inmunoglobulina A , Cirrosis Hepática , Peritonitis , ARN Ribosómico 16S , Humanos , Cirrosis Hepática/microbiología , Peritonitis/microbiología , Peritonitis/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Heces/microbiología , ARN Ribosómico 16S/genética , Anciano , Adulto , Estudios de Casos y Controles

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BACKGROUND: Atezolizumab plus bevacizumab is the standard of care for advanced hepatocellular carcinoma (HCC) in the first-line setting, although was only evaluated in patients with Child-Pugh (CP) A liver function in the IMbrave150 trial. We sought to determine the outcomes of these patients based on CP score and ALBI grade in the US population. METHODS: This multicenter cohort study included patients with HCC who received atezolizumab with bevacizumab as first-line systemic therapy between March 2018 and November 2023. Overall survival (OS) was determined using the Kaplan-Meier method and multivariate analyses were performed using Cox proportional hazard regression method. RESULTS: Among 322 patients, 226, 86, and 10 patients had CP-A, CP-B, and CP-C liver function, respectively. Median age was 66.5 years, 78.6% were male, and 82.6% were White. Median OS (mOS) was 21.6 months for those with CP-A, 9.1 months for those with CP-B7, and 4.7 months for those with CP-B8-C12 (P < .0001). Among patients with CP-A, those with ALBI grade 1 had an mOS of 34.9 months versus 14.2 months in those with grade 2. In multivariate analyses, CP score, ALBI grade, hepatitis B, performance status, and macrovascular invasion were significantly associated with survival. CONCLUSIONS: CP score is an important prognostic tool for patients with HCC receiving atezolizumab plus bevacizumab, and this regimen remains a viable option for patients with CP-B7 with no additional safety concern, although the benefit is significantly less than those with CP-A. ALBI score has independent predictive value in patients with CP-A liver function.

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BACKGROUND AND OBJECTIVES: Sarcopenia in cirrhosis is associated with poor survival and adverse pre and post-transplant outcomes. The study aimed at determining the prevalence of sarcopenia and its association with the severity, complications and etiology of liver disease. METHODS: As many as 416 cirrhotic patients who met the inclusion criteria underwent muscle strength testing using a dynamometer. As many as 109 probable sarcopenia patients underwent computed tomography (CT) scan to measure skeletal muscle index (SMI) at the L3 vertebral level and gait-speed testing. The gender-specific cut-offs used to define sarcopenia were an SMI of 36.54 cm2/m2 in males and 30.21 cm2/m2 in females. A gait speed ≤ 0.8 m/s was taken as a cut-off to define severe sarcopenia in both genders. RESULTS: The mean age was 54.7 ± 9.51 years and male:female ratio was 2.2:1.The mean body mass index (BMI) was 24.2 ± 1.34 kg/m2. Alcohol and non-alcoholic steatohepatitis (NASH) were the two most common etiologies (45.9% and 31.2%). The proportion of patients belonging to Child-Pugh class A, B and C was 26.6%, 48.6% and 24.8%, respectively. Forty out of 109 (36.7%) patients had a model for end-stage liver disease (MELD) > 14. Ascites, upper gastrointestinal bleeding and hepatic encephalopathy (HE) were present in 59 (54.1%), 60 (55.0%) and 24 (22.0%) patients, respectively. The prevalence of probable sarcopenia, sarcopenia and severe sarcopenia was found to be 26.20%, 10.09% and 6.73%, respectively. Sarcopenia and severe sarcopenia were associated with Child-Pugh class (p < 0.001, p < 0.001), MELD (p = 0.007, 0.002), upper gastrointestinal bleed (p = 0.007, 0.004), ascites (p = 0.038, 0.025) and HE (0.001, < 0.001). CONCLUSION: The prevalence of sarcopenia and severe sarcopenia was found to be 10.09% and 6.73%, respectively. Sarcopenia and severe sarcopenia had a significant association with the severity and complications of cirrhosis. However, no association was observed with etiology of liver disease.

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Cirrosis Hepática , Sarcopenia , Índice de Severidad de la Enfermedad , Humanos , Sarcopenia/epidemiología , Sarcopenia/etiología , Sarcopenia/complicaciones , Sarcopenia/diagnóstico , Masculino , Femenino , Prevalencia , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Persona de Mediana Edad , Fuerza Muscular , Tomografía Computarizada por Rayos X , Anciano , Adulto

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BACKGROUND: The World Health Organization (WHO) reports that Asia and Africa have the highest Chronic Liver Disease (CLD) mortality rate. Cirrhosis, responsible for 22.2 fatalities per 100,000 people, is India's 10th most common cause of mortality. The increasing prevalence of chronic liver disease necessitates a study to identify predictive factors for patients who visit the emergency department. Identifying elements that enhance the predictive value of mortality in unstable patients with CLD complications is important in emergency departments. This study aims to determine Clinical and Laboratory Parameters as mortality predictors in adult chronic liver disease patients. METHODOLOGY: The study was conducted at the emergency department of a tertiary healthcare center in Northern India. Patients with chronic liver disease above 18 years of age who satisfied the inclusion criteria were clinically evaluated. Clinical and demographic details were collected, and data was analyzed. RESULTS: Two hundred thirty-six patients were enrolled. The mean age was 50.77 ± 14.26 years. 78.4% of the participants were men. Abdominal distension, affecting 59.7% of patients, was the most common presenting ailment, followed by melena and hematemesis, affecting 41.9% and 32.6%, respectively. The mean stay in the emergency department was 10.29 ± 8.10 h. Refractory septic shock, the leading cause of mortality, accounts for 69.2% of all deaths, alongside grade 4 hepatic encephalopathy and massive Upper Gastrointestinal (UGI) bleeding, as identified in our study. Factors such as altered mental sensorium, high respiratory rate, low SpO2, increased heart rate, low systolic blood pressure, low diastolic blood pressure, and low Glasgow Coma Scale (GCS) on Emergency Department (ED) arrival are significantly associated with mortality. CONCLUSIONS: Chronic liver disease, a prevalent condition in India, most commonly seen in middle aged men and lower socioeconomic groups. The parameters independently associated with mortality in our study were presence of altered mental sensorium, Glasgow coma scale, Child Pugh class and need for ICU admission. Understanding the presentation pattern, and mortality predictors can help ED physicians in managing acute events and follow-ups.

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Background: Anticoagulation (AC) is used for stroke prevention in atrial fibrillation (AF). Direct Oral Anticoagulants (DOACs) are safe in patients with AF without cirrhosis, they are hardly studied in patients with advanced cirrhosis. Our study evaluates the safety and outcomes of DOACs in patients with Child-Pugh class C cirrhosis (CPC). Methods: We queried TriNetX Database. Patients with CPC and AF were divided into three cohorts: patients on DOACs, no AC, and warfarin. Three study arms were created using a 1:1 propensity score matching system (PSM). Results: Totally 16 029 patients met the inclusion criteria. Of those, 20.2% (n = 3235) were on DOACs, 47.1% (n = 7552) were not on AC, and 32.7% (n = 5242) were on warfarin. First arm comparing AC versus no AC, a statistically significant benefit was identified in 3-year mortality risk (47% vs 71%, P < 0.0001) and transplant status (17% vs 5%, p < 0.0001) with AC. However, no significant difference was identified regarding intracranial hemorrhage and GI bleeding risk. Second arm comparing patients on DOACs versus no AC, we identified mortality benefit (40% vs 72%, P < 0.0001) and a higher transplant rate (9% vs 3.2%, P < 0.0001) with DOACs. Intracranial hemorrhage rates (6% vs 4%, P = 0.03) were higher in patients on DOACs. Third arm comparing patients on DOACs versus Warfarin, a statistically significant lower risk of intracranial hemorrhage (6.6% vs 8.7%, P = 0.004) and GI bleed (2% vs 2.4%, P < 0.0001) were identified in patients on DOACs. Conclusion: Anticoagulation is safe in patients with CPC with AF and may provide a mortality benefit. DOACs are a safer alternative to warfarin.

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BACKGROUND: The models for assessing liver function, mainly the Child-Pugh (CP), albuminbilirubin (ALBI), and platelet-ALBI (PALBI) classifications, have been validated for use in estimating the prognosis of hepatocellular carcinoma (HCC) patients. However, thrombocytopenia is a common finding and may influence the prognostic value of the three models in HCC. AIM: To investigate and compare the prognostic performance of the above three models in thrombocytopenic HCC patients. METHODS: A total of 135 patients with thrombocytopenic HCC who underwent radical surgery were retrospectively analyzed. Preoperative scores on the CP, ALBI and PALBI classifications were estimated accordingly. Kaplan-Meier curves with log-rank tests and Cox regression models were used to explore the significant factors associated with overall survival (OS) and recurrence-free survival (RFS). RESULTS: The preoperative platelet counts were significantly different among the CP, ALBI and PALBI groups. After a median follow-up of 28 mo, 39.3% (53/135) of the patients experienced postoperative recurrence, and 36.3% (49/135) died. Univariate analysis suggested that α-fetoprotein levels, tumor size, vascular invasion, and ALBI grade were significant predictors of OS and RFS. According to the multivariate Cox regression model, ALBI was identified as an independent prognostic factor. However, CP and PALBI grades were not statistically significant prognostic indicators. CONCLUSION: The ALBI grade, rather than CP or PALBI grade, is a significant prognostic indicator for thrombocytopenic HCC patients.

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Established treatments for advanced hepatocellular carcinoma (HCC) with Child-Pugh cirrhosis B (CPB, moderate hepatic dysfunction) are lacking. A recently published randomized phase 2 study in CPB HCC investigating the safety and efficacy of namodenoson (25 mg BID), an A3 adenosine-receptor agonist vs. placebo, suggested a favorable safety profile and a positive efficacy signal in patients with HCC with a CPB score of 7 (CPB7). The present study reports a 61-year-old woman with CPB7 HCC who received namodenoson for over 6 years through this study and its open-label extension. Computed tomography scans demonstrated partial and complete responses after 7 weeks and 4 years of treatment, respectively. Low albumin levels (31 g/l) and elevated baseline levels of alanine transaminase and aspartate aminotransferase (68 U/l and 44 U/l, respectively) were reported. After 4 weeks of treatment, these levels normalized and were stable for over 6 years. No treatment-emergent adverse events were noted. At the time of reporting, the response is ongoing as manifested by imaging studies and liver function evaluation.

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Trilaciclib is a first-in-class, intravenous cyclin-dependent kinase 4 and 6 inhibitor approved for reducing the incidence of chemotherapy-induced myelosuppression in adult patients with extensive-stage small cell lung cancer receiving a platinum/etoposide-containing or topotecan-containing regimen. No dose adjustment is recommended for participants with mild hepatic impairment (HI) based on previous population pharmacokinetic (PK) analysis. This open-label, parallel-group study examined the impact of moderate and severe HI on the PK of trilaciclib. The study employed a reduced study design. Participants with moderate (Child-Pugh B, n = 8) and severe (Child-Pugh C, n = 5) HI and matched healthy controls (n = 11) received a single intravenous dose of trilaciclib 100 mg/m2. The unbound fraction of trilaciclib was comparable between the HI groups and the matched healthy control group. The unbound trilaciclib extent of exposure (i.e., area under the concentration-time curve) in participants with moderate and severe HI was ∼40% and ∼60% higher, respectively, compared with healthy matched controls based on Child-Pugh classification. Ad hoc analysis using National Cancer Institute classification showed similar results. The US Food and Drug Administration-approved trilaciclib dose of 240 mg/m2 should be reduced by ∼30%, to 170 mg/m2, for patients with moderate or severe HI.

Asunto(s)

Antineoplásicos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Antineoplásicos/farmacocinética , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Triazoles/farmacocinética , Triazoles/administración & dosificación , Hepatopatías/metabolismo , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/administración & dosificación , Lactonas/farmacocinética , Lactonas/administración & dosificación , Adulto , Área Bajo la Curva , Neoplasias Pulmonares/tratamiento farmacológico , Pirimidinas , Pirroles

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BACKGROUND: Radiation-induced liver damage (RILD) occasionally occurs following carbon-ion radiotherapy (CIRT) for liver tumors, such as hepatocellular carcinoma (HCC), in patients with impaired liver function disease. However, the associated risk factors remain unknown. The present study aimed to determine the risk factors of RILD after CIRT. METHODS: We retrospectively analyzed 108 patients with HCC treated with CIRT at the Osaka Heavy Ion Therapy Center between December 2018 and December 2022. RILD was defined as a worsening of two or more points in the Child-Pugh score within 12 months following CIRT. The median age of the patients was 76 years (range 47-95 years), and the median tumor diameter was 41 mm (range 5-160 mm). Based on the pretreatment liver function, 98 and 10 patients were categorized as Child-Pugh class A and B, respectively. We analyzed patients who received a radiation dose of 60 Gy (relative biological effectiveness [RBE]) in four fractions. The median follow-up period was 9.7 months (range 2.3-41.1 months), and RILD was observed in 11 patients (10.1%). RESULTS: Multivariate analysis showed that pretreatment Child-Pugh score B (p = 0.003, hazard ratio [HR] = 6.90) and normal liver volume spared from < 30 Gy RBE (VS30 < 739 cm3) (p = 0.009, HR = 5.22) were significant risk factors for RILD. The one-year cumulative incidences of RILD stratified by Child-Pugh class A or B and VS30 < 739 cm3 or ≥ 739 cm3 were 10.3% or 51.8% and 39.6% or 9.2%, respectively. CONCLUSION: In conclusion, the pretreatment Child-Pugh score and VS30 of the liver are significant risk factors for RILD following CIRT for HCC.

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Carcinoma Hepatocelular , Radioterapia de Iones Pesados , Neoplasias Hepáticas , Traumatismos por Radiación , Humanos , Neoplasias Hepáticas/radioterapia , Carcinoma Hepatocelular/radioterapia , Radioterapia de Iones Pesados/efectos adversos , Anciano , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Anciano de 80 o más Años , Pronóstico , Traumatismos por Radiación/etiología , Traumatismos por Radiación/patología , Factores de Riesgo , Hígado/efectos de la radiación , Hígado/patología

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Background: Although diaphragm ultrasound can be used for detecting residual neuromuscular blockade post-surgery, there exists notable dearth in contemporary research exploring the correlation between preoperative Child-Pugh classification and the effectiveness of sugammadex in reversing rocuronium-induced blockade as evaluated by diaphragmatic ultrasonography. Methods: This was a prospective, double-blind, non-randomized controlled clinical trial conducted on patients scheduled for laparoscopic liver resection surgery. The participants were categorized into two groups, A and B, based on their preoperative Child-Pugh classification. Prior to anesthesia induction, baseline diaphragm thickness was evaluated using ultrasonography. Throughout the surgical procedure, a deep neuromuscular blockade was maintained with rocuronium. Post-surgery, sugammadex (2 mg/kg) was intravenously administered to patients in both groups upon reaching a train-of-four ratio of 0.2. Diaphragm thickness was assessed at 0, 10, and 30 min, as well as 2 h after extubation, to analyze thickening fractioning (TF) and thickness recovery fractioning (TRF). Results: No significant differences in TF or TRF were observed between the two groups at 0, 10, and 30 min, as well as 2 h after extubation. Furthermore, there were no significant variances in hemodynamic stability following sugammadex administration. However, patients in the Child-Pugh B group experienced a significantly prolonged time from sugammadex administration to tracheal extubation (19 ± 8.0 min vs. 11 ± 6.1 min) and an extended post-anesthesia care unit stay (123 ± 28.3 min vs. 103 ± 26.0 min) compared to those in the Child-Pugh A group. Conclusion: The preoperative Child-Pugh grades may not exhibit a significant association with the reversal effect of sugammadex on rocuronium, as evaluated through diaphragmatic ultrasonography. Clinical trial registration: Registered in the ClinicalTrials.gov (NCT05028088) on July 18, 2021.

RESUMEN

Fenfluramine (Fintepla®) is approved for the treatment of seizures associated with the rare epileptic encephalopathies Dravet syndrome and Lennox-Gastaut syndrome. Fenfluramine is extensively metabolized; thus, patients with hepatic impairment (HI) might experience changes in exposure to fenfluramine or its metabolites. In this phase 1 study, we investigated the pharmacokinetics (PK) and safety of a single oral dose of 0.35 mg/kg fenfluramine in subjects with mild (n = 8), moderate (n = 8), or severe (n = 7) HI (Child-Pugh A/B/C, respectively) and healthy control subjects (n = 22) matched for sex, age, and BMI. All subjects underwent serial sampling to determine total plasma concentrations of fenfluramine and its active metabolite, norfenfluramine. Hepatic impairment was associated with increases in fenfluramine exposures, mainly area-under-the-curve (AUC). Geometric least squares mean ratios (90% confidence intervals) for fenfluramine AUC0-∞ in mild, moderate, and severe HI versus healthy controls were 1.98 (1.36-2.90), 2.13 (1.43-3.17), and 2.77 (1.82-4.24), respectively. Changes in exposure to norfenfluramine in mild, moderate, and severe HI were minimal compared with normal hepatic function. Exposures to fenfluramine and norfenfluramine in all HI groups were within the ranges that have been characterized in the overall development program, including ranges examined in exposure-response relationships for efficacy and safety in patients, and determined to have an acceptable safety profile. Mild and moderate HI had a modest effect on fenfluramine exposure that was not clinically meaningful, whereas the higher fenfluramine exposure in severe HI may require dose reduction based on general caution in this population. The modest decrease in norfenfluramine exposure is not considered clinically relevant.

Asunto(s)

Fenfluramina , Humanos , Masculino , Femenino , Fenfluramina/farmacocinética , Fenfluramina/efectos adversos , Adulto , Persona de Mediana Edad , Adulto Joven , Hepatopatías/metabolismo , Área Bajo la Curva , Inhibidores Selectivos de la Recaptación de Serotonina/farmacocinética , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/sangre

RESUMEN

BACKGROUND: Limited data exist on the prevalence of myosteatosis (i.e., excess accumulation of fat in skeletal muscles) in hepatocellular carcinoma (HCC) patients, and no systematic review or meta-analysis has been conducted in this context. METHODS: We searched for articles published from inception until November 2023 to assess the prevalence of myosteatosis in patients with HCC. RESULTS: Ten studies with 3316 patients focusing on myosteatosis and HCC were included. The overall prevalence of myosteatosis in HCC patients was 50% [95% Confidence Interval (CI): 35-65%]. Using the body mass index-based criteria (two studies), the prevalence was 34%, while gender-based criteria (eight studies) yielded 54% (p = 0.31). In Asian studies (n = 8), the prevalence was 45%, compared to 69% in non-Asian countries (two studies) (p = 0.02). For viral-associated HCC (eight studies), the prevalence was 49%, rising to 65% in non-alcoholic fatty liver disease-associated cases (three studies) and 86% in alcoholic liver disease-associated cases (three studies) (p < 0.01). The prevalence of myosteatosis was higher in Child-Pugh class C (3 studies, 91%) than in A (7 studies, 73%) or B (6 studies, 50%) (p = 0.02), but with no difference between Barcelona Clinic Liver Cancer stage A (3 studies, 66%), B (4 studies, 44%) and C (3 studies, 62%) (p = 0.80). Patients with myosteatosis had a significantly higher mortality (six studies) (Relative Risk: 1.35 (95%CI: 1.13-1.62, p < 0.01). CONCLUSION: The prevalence of myosteatosis is high in HCC patients and is associated with more severe liver disease and higher mortality rates.

RESUMEN

Background/Aim: Numerous agents, including immune checkpoint inhibitors, are now available for hepatocellular carcinoma (HCC) treatment. Most trials involving systemic chemotherapy have included patients with Child-Pugh class A, while excluding or minimally enrolling those with Child-Pugh class B, due to liver dysfunction-related mortality. This study aimed to identify prognostic factors for survival in Child-Pugh class B patients receiving sorafenib (SOR), lenvatinib (LEN), atezolizumab plus bevacizumab (ATZ+BEV), or hepatic arterial infusion chemotherapy (HAIC). Patients and Methods: From December 2003 to June 2023, 137 patients with advanced HCC receiving systemic chemotherapies (SOR: n=43, LEN: n=16, ATZ+BEV: n=18, HAIC: n=60) were enrolled. Results: Overall survival (OS) and response rates did not differ significantly across treatments (SOR: 8.3 months, LEN: 10.2 months, ATZ+BEV: 8.5 months, HAIC: 7.3 months). Patients on HAIC and LEN had a lower rate of discontinuing treatment within three months compared to those on ATZ+BEV and SOR. HAIC was associated with fewer changes in ALBI score and better preservation of liver function. Multivariate logistic regression identified serum α-fetoprotein >400 ng/ml [hazard ratio (HR)=1.94; p=0.001], tumor count >5 (HR=1.55; p=0.043), and Child-Pugh score (HR=2.53; p=0.002) as independent predictors of OS. Conclusion: OS and response rates were similar across systemic chemotherapies. Prognosis for HCC in Child-Pugh class B patients was associated with liver function, necessitating further research for optimal treatment.