Frequency of Hypoglycemia in Cirrhotic Patients Undergoing Endoscopy.

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.

Systemic Chemotherapy for Advanced Hepatocellular Carcinoma in Patients With Child-Pugh class B.

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.

Clinical outcomes by Child-Pugh Class in patients with advanced hepatocellular carcinoma in a community oncology setting.

Aim: Many pivotal trials in advanced hepatocellular carcinoma (HCC) require participants to have Child-Pugh A disease. However, many patients in real-world practice are Child-Pugh B or C. This study examined treatment patterns and clinical outcomes in patients with advanced HCC treated with first-line systemic therapy. Materials & methods: In this retrospective study, patients with HCC treated with first-line systemic therapy (2010-2017) were identified from US Oncology Network records. Outcomes included overall survival and progression-free survival, by Child-Pugh Class and prior liver-directed therapy. Results: Of 352 patients, 78.7% were Child-Pugh A or B, 96.6% received first-line sorafenib, and 33.8% received first-line-prior liver-directed therapy. Survival outcomes were similar for Child-Pugh A or B, and longer after first-line prior liver-directed therapy. Conclusion: First-line systemic therapy is beneficial in patients with Child-Pugh A or B, and after first-line prior liver-directed therapy. These findings may help position systemic therapy in the community setting.

Portal vein thrombosis in patients with hepatocellular carcinoma and early cirrhosis-prevalence and risk factors.

Introduction: Hepatocellular carcinoma (HCC) is frequently associated with portal vein thrombosis (PVT) with prevalence ranging from 25% to 50%. PVT is associated with poor prognosis, limiting the available therapeutic options for these patients. Our objective was to determine the prevalence and risk factors for PVT in patients with HCC. Method: A retrospective analysis was performed on the prospectively collected data from January 2018 to March 2020. All patients with HCC discussed in our weekly multidisciplinary liver clinic were reviewed. Multivariate analysis was done to identify the independent risk factors for PVT in HCC patients. A p-value of <0.05 was considered significant. Result: Of 316 patients, the prevalence of PVT was 31% (n = 98). Larger tumour size (p < 0.001), raised Alpha Fetoprotein (AFP) level (p = 0.036) and higher Child-Pugh class (p = 0.008) were significantly associated with PVT. In 216 patients with preserved liver function (Child-Pugh class A), PVT was seen in 53 (24.5%) patients. Large tumour size (p < 0.001) and higher AFP levels (p = 0.021) were independent risk factors. Conclusion: Overall prevalence of PVT in HCC was 31% whereas 24.5% in patients with early cirrhosis (Child-Pugh class A). We identified various risk factors associated with PVT in our local population, highlighting the importance of early and regular screening of cirrhotic patients including Child-Pugh class A.

Study of Gonadal Hormones in Males With Liver Cirrhosis and Its Correlation With Child-Turcotte-Pugh and Model for End-Stage Liver Disease Scores.

BACKGROUND AND AIMS: Liver cirrhosis influences gonadal hormone metabolism by multiple mechanisms and causes gonadal dysfunction. This study aimed to study sex hormones in males with cirrhosis and determine their correlation with prognostic scores. METHODS:  An observational study was conducted between October 2019 and August 2021 in India. Sixty males with liver cirrhosis and 60 healthy age-matched controls were enrolled. Serum-free testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (Prl) were checked. Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD-Na) scores were calculated. RESULTS: Mean age of patients was 46.9±8.38 years. Forty-three were alcoholics. A total of 29 (48.33%) patients had low levels of free T. Cirrhotic males had lower testosterone and higher estradiol levels and lower T:E2 ratio compared to controls. Levels of luteinizing hormone, follicle-stimulating hormone, and prolactin were comparable. Lower testosterone was significantly associated with advancing age, alcoholism, duration of cirrhosis, loss of libido, and ascites. The higher the CTP scores, the lower the free testosterone levels and the higher the E2 levels. There was no significant association between low free testosterone levels and MELD-Na score. CONCLUSIONS: Age, alcohol, duration of disease, and low albumin levels are risk factors for hypogonadism in cirrhosis. There was a significant positive correlation between low free testosterone levels and poor CTP scores.

Development of a Model to Predict Liver Decompensation prior to Transarterial Chemoembolization Refractoriness in Patients with Intermediate-Stage Hepatocellular Carcinoma.

Introduction: Transarterial chemoembolization (TACE) is the first-line treatment for patients with intermediate-stage hepatocellular carcinoma (HCC). For patients without an adequate response, current finding suggests that treatment with molecular target agents, approved for advanced stage, might present benefits. However, this requires a preserved liver function. This study aims to evaluate possible predictors of early deterioration of hepatic reserve, prior to TACE refractoriness, in a cohort of patients treated with TACE. Methods: Retrospective analysis of 99 patients with Child-Pugh class A and intermediate-stage HCC who underwent TACE as the first-line treatment. All patients were submitted to a biochemical and medical evaluation prior to initial TACE and every month afterward. Response to initial TACE was evaluated at 1 month. The time to Child-Pugh class deterioration before TACE refractoriness was assessed. Results: Ninety-nine patients were included. Objective response rate (ORR) to initial TACE was assessed as present in 59 (63.4%) and as absent in 34 (36.6%) patients. Liver decompensated before TACE refractoriness in 51 (51.5%) patients, and the median time to liver decompensation was 14 (IQR 8-20) months after first TACE. In multivariate analysis, beyond up-to-7 criteria (HR 2.4, p = 0.031), albumin <35 mg/dL (HR 3.5, p < 0.001) and absence of ORR (HR 2.4, p = 0.020) were associated with decreased overall survival free of liver decompensation. Moreover, beyond up-to-7 criteria, albumin <35 mg/dL and absence of ORR associated negatively with 6-month survival free of liver decompensation. Our model created using those variables was able to predict liver decompensation at 6 months with an AUROC of 0.701 (p = 0.02). Conclusions: The absence of ORR after initial TACE, beyond up-to-7 criteria and albumin <35 mg/dL, was a predictive factor for early liver decompensation before TACE refractoriness in our population. Such patients might benefit from treatment escalation to systemic therapy, in monotherapy or in combination with TACE.

Introdução: A quimioembolização transarterial (TACE) é o tratamento de primeira linha para doentes com carcinoma hepatocelular (HCC) em estadio intermédio. Em doentes sem resposta adequada, a evidência atual sugere que o tratamento com agentes de alvo molecular, aprovado para estágio avançado, pode apresentar benefícios. Porém, isso requer função hepática preservada. O objetivo deste estudo é avaliar possíveis preditores de deterioração precoce da reserva hepática, antes da refratariedade ao TACE, em uma coorte de doentes tratados com TACE. Métodos: Análise retrospectiva de noventa e nove doentes com Child-Pugh classe A e HCC em estadio intermédio que foram submetidos a TACE como tratamento de primeira linha. Todos os doentes foram submetidos a uma avaliação bioquímica e médica antes do TACE inicial e a cada mês após. A resposta ao TACE inicial foi avaliada em 1 mês. O tempo para a deterioração da classe Child-Pugh antes da refratariedade a TACE foi avaliado. Resultados: Noventa e nove doentes foram incluídos. A resposta radiológica objetiva (ORR) ao TACE inicial foi avaliada como presente em 59 (63.4%) e ausente em 34 (36.6%) doentes. Descompensação hepática ocorreu, antes da refratariedade a TACE, em 51 (51.5%) doentes e o tempo médio para a descompensação hepática foi de 14 (IQR 8­20) meses, após o primeiro TACE. Na análise multivariada, além dos critérios up-to-7 (HR 2,4, p = 0.031), albumina <35 mg/dL (HR 3,5, p < 0.001) e ausência de ORR (HR 2,4, p = 0.020) foram associados a diminuição da sobrevida livre de descompensação hepática. Além disso, a sobrevida de 6 meses livre de descompensação hepática apresentou associação, além dos critérios up-to-7 , albumina <35 mg/dL e ausência de ORR. Foi criado um modelo com essas variáveis, capaz de prever a descompensação hepática com AUROC de 0,701 (p = 0.02). Conclusões: A ausência de ORR após TACE inicial, além dos critérios up-to-7 e albumina <35 mg/dL foram fatores preditivos para descompensação hepática antes da refratariedade a TACE na nossa população. Esses doentes podem beneficiar do escalonamento do tratamento para a terapia sistêmica, em monoterapia ou em combinação com TACE.

Effectiveness and safety of lenvatinib plus anti-programmed death-1 antibodies in patients with hepatocellular carcinoma: A real-world cohort study.

OBJECTIVE: Lenvatinib plus anti-programmed death-1 (anti-PD-1) antibody combinations have shown potent anti-tumor effect in phase I/II trials in advanced or unresectable hepatocellular carcinoma (HCC), but real-world data are limited. METHODS: To investigate the effectiveness and safety of lenvatinib plus anti-PD-1 antibodies in a real-world cohort, we retrospectively evaluated 210 patients with unresectable or advanced HCC treated with these regimens between October 2018 and February 2022. RESULTS: The objective response rate and disease control rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 were 28.1% and 75.2%. Median overall survival (OS) and progression-free survival (PFS) in the overall cohort were 17.2 and 8.4 months, respectively. Median OS and PFS of patients receiving first-line treatment reached 18.9 and 9.6 months. Median OS was significantly longer in patients with Child-Pugh class A versus B (18.8 vs. 5.9 months, respectively), as was median PFS (9.1 vs. 4.4 months). Patients with albumin-bilirubin (ALBI) grade 1 versus grade 2/3 also had significantly greater median OS (23.5 vs. 13.4 months). Treatment-related adverse events (AEs) occurred in 79.5% of patients. Patients with ALBI grade 2/3 had a higher rate of grade 3/4 AEs than patients with ALBI grade 1 (57.5% vs. 38.5%). CONCLUSION: Lenvatinib combined with anti-PD-1 antibody therapy was effective in patients with sufficient liver function reserve. Further study is needed to improve therapeutic efficacy and AE management in patients with Child-Pugh class B or ALBI grade 2/3.

Individualized portal pressure gradient threshold based on liver function categories in preventing rebleeding after TIPS.

BACKGROUND: The evidence in Portal pressure gradient (PPG) < 12 mmHg after transjugular intrahepatic portosystemic shunt (TIPS) for preventing rebleeding mostly comes from observations in uncovered stents era. Moreover, association between Child-Pugh classes and post-TIPS hepatic encephalopathy (HE) has indicated that tolerance of PPG reduction depends on liver function. This study aimed to investigate the optimal PPG for covered TIPS and explore the optimal threshold tailored to the Child-Pugh classes to find individualized PPG to balance rebleeding and overt HE. METHODS: This multicenter retrospective study analyzed rebleeding, OHE, and mortality of patients associated with post-TIPS PPGs (8, 10, 12, and 14 mmHg) in the entire cohort and among different Child-Pugh classes. Propensity score matching (PSM) and competing risk analyses were performed for sensitivity analyses. RESULTS: We included 2100 consecutively screened patients undergoing TIPS. In all patients, PPG < 12 mmHg reduced rebleeding after TIPS (p = 0.022). In Child-Pugh class A, none of the PPG thresholds were discriminative of clinical outcomes. In Child-Pugh class B, 12 mmHg (p = 0.022) and 14 mmHg (p = 0.037) discriminated rebleeding, but 12 mmHg showed a higher net benefit. In Child-Pugh class C, PPG < 14 mmHg had a lower rebleeding incidence (p = 0.017), and exhibited more net benefit than 12 mmHg. CONCLUSION: Different PPG standards may be required for patients with different liver function categories. A PPG threshold < 12 mmHg might be suitable for patients in Child-Pugh class B, while < 14 mmHg might be optimal for patients in Child-Pugh class C.

ASARA, a prediction model based on Child-Pugh class in hepatocellular carcinoma patients undergoing transarterial chemoembolization.

BACKGROUND: Due to the high heterogeneity among hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE), the prognosis of patients varies significantly. The decision-making on the initiation and/or repetition of TACE under different liver functions is a matter of concern in clinical practice. Thus, we aimed to develop a prediction model for TACE candidates using risk stratification based on varied liver function. METHODS: A total of 222 unresectable HCC patients who underwent TACE as their only treatment were included in this study. Cox proportional hazards regression was performed to select the independent risk factors and establish a predictive model for the overall survival (OS). The model was validated in patients with different Child-Pugh class and compared to previous TACE scoring systems. RESULTS: The five independent risk factors, including alpha-fetoprotein (AFP) level, maximal tumor size, the increase of albumin-bilirubin (ALBI) grade score, tumor response, and the increase of aspartate aminotransferase (AST), were used to build a prognostic model (ASARA). In the training and validation cohorts, the OS of patients with ASARA score ≤ 2 was significantly higher than that of patients with ASARA score > 2 (P < 0.001, P = 0.006, respectively). The ASARA model and its modified version "AS(ARA)" can effectively distinguish the OS (P < 0.001, P = 0.004) between patients with Child-Pugh class A and B, and the C-index was 0.687 and 0.706, respectively. For repeated TACE, the ASARA model was superior to Assessment for Retreatment with TACE (ART) and ALBI grade, maximal tumor size, AFP, and tumor response (ASAR) among Child-Pugh class A patients. For the first TACE, the performance of AS(ARA) was better than that of modified hepatoma arterial-embolization prognostic (mHAP), mHAP3, and ASA(R) models among Child-Pugh class B patients. CONCLUSIONS: The ASARA scoring system is valuable in the decision-making of TACE repetition for HCC patients, especially Child-Pugh class A patients. The modified AS(ARA) can be used to screen the ideal candidate for TACE initiation in Child-Pugh class B patients with poor liver function.

Development and validation of a modified albumin-bilirubin grade and α-fetoprotein score (mALF score) for hepatocellular carcinoma patients receiving atezolizumab and bevacizumab.

AIM: Predicting the survival of hepatocellular carcinoma (HCC) patients receiving atezolizumab and bevacizumab (Atez/bev) remains a challenge. This study aims to validate the modified albumin-bilirubin grade and α-fetoprotein score (mALF score). METHODS: This retrospective, multicenter study included 426 HCC patients receiving Atez/Bev. Each patient was randomized 3:2 to a training set (n = 255) and a validation set (n = 171). We investigated prognostic factors in the training set and developed an easily applicable mALF score, which was evaluated in the validation set. RESULTS: We built the mALF score using baseline mALBI grade 2b or 3 (HR 2.36, 95% CI 1.37-4.05, p = 0.002) and α-fetoprotein ≥ 100 ng/ml (HR 2.61, 95% CI 1.49-4.55, p < 0.001), which were identified as unfavorable prognostic factors in a multivariate analysis. The 1-year OS rates were 82.7% (95% CI 68.9-90.8) in patients who meet neither of the criteria (mALF 0 points, n = 101), 61.7% (95% CI 44.5-74.9) in patients who meet either of the two criteria (mALF 1 point, n = 109), and 24.6% (95% CI 9.0-44.3) in patients who meet both criteria (mALF 2 points, n = 45); the difference was statistically significant (p < 0.001). The median PFS in patients with mALF 0, 1, and 2 points was 9.5 months (95% CI 4.3-NA), 6.6 months (95% CI 6.0-8.0), and 3.8 months (95% CI 3.0-5.2), respectively, which amounted to a significant difference (p < 0.001). These results were confirmed in the validation set (1-year OS rates, 0/1/2 points = 94.2%/62.1%/46.3%, p < 0.001; median PFS, 0/1/2 points = 9.3/6.7/4.7 months, p = 0.018). CONCLUSION: The mALF score can reliably predict the prognosis of HCC patients receiving Atez/Bev.

Pharmacokinetic Assessment and Treatment Effect of Lusutrombopag in Child-Pugh Class C Patients: Review of Patient Data from Two Clinical Studies and Post-Marketing Surveillance.

INTRODUCTION: Patients with thrombocytopenia and chronic liver disease are at increased risk of bleeding during invasive procedures due to low platelet counts. Lusutrombopag, an orally active thrombopoietin receptor agonist, increases platelet count and reduces the need for platelet transfusion in chronic liver disease patients with thrombocytopenia undergoing a planned invasive procedure. The safety of lusutrombopag in patients with Child-Pugh class C chronic liver disease is not known. The present analysis was performed to determine the pharmacokinetics, efficacy, and safety of lusutrombopag in patients with Child-Pugh class C chronic liver disease. METHODS: Data for patients with Child-Pugh class C chronic liver disease were collected from three data sets: a phase 1/2 Child-Pugh class C study (n = 5) (JapicCTI-163289 [Japan Pharmaceutical Information Center]), a phase 3 pivotal study (L-PLUS 2, n = 3) (NCT02389621 [Clinicaltrials.gov]), and ongoing post-marketing surveillance (n = 27) (JapicCTI-163432 [Japan Pharmaceutical Information Center]). Patients received lusutrombopag at 3 mg for up to 7 days. Safety and efficacy assessments were collected from two clinical studies and the post-marketing surveillance; pharmacokinetic data were collected from the phase 1/2 study. RESULTS: Mean Cmax and AUC0-τ were lower in Child-Pugh class C patients than Child-Pugh class A and B; individual patients' Cmax and AUC0-τ values overlapped among Child-Pugh classes. In lusutrombopag patients who did not receive platelet transfusion (n = 4 in phase 1/2, n = 1 in phase 3, n = 24 in post-marketing surveillance), the median (range) maximum platelet count was 88.5 × 109/L (54-105 × 109/L), 80 × 109/L, and 91 × 109/L (41-186 × 109/L; n = 23), respectively. There were no treatment-related adverse events or treatment-related serious adverse events. One patient from the phase 1/2 study had a non-serious portal vein thrombosis, which was not considered treatment-related. CONCLUSIONS: The analysis presented in this study suggests that lusutrombopag increases platelet counts in Child-Pugh class C patients and is safe and well tolerated in this patient population. TRIAL REGISTRATION: L-PLUS 2: NCT02389621 (Clinicaltrials.gov). Phase 1/2: JapicCTI-163289 (Japan Pharmaceutical Information Center [JAPIC]). Post-marketing surveillance: JapicCTI-163432 (JAPIC).

Gallstone Disease in Cirrhosis-Pathogenesis and Management.

Gallstones are more common in patients with cirrhosis of the liver, and the incidence increases with severity of liver disease. Pigment stones are the most frequent type of gallstones (GSs) in cirrhotics, and majority remain asymptomatic. Hepatitis C virus infection and nonalcoholic fatty liver disease are the underlying etiologies of liver diseases that most often associated with GSs. Multiple altered mechanisms in cirrhosis such as chronic hemolysis due to hypersplenism, reduced bile acid synthesis and transport, decreased cholesterol secretion, decreased apolipoprotein A-I and A-II secretion, gallbladder hypo-motility, autonomic dysfunction, and portal hypertension collectively lead to increased risk of lithogenesis. Asymptomatic GSs should be followed up closely and offered laparoscopic cholecystectomy once symptomatic in Child-Pugh class A and B patients. The model for the end-stage liver disease score is the best predictor of the outcome after cholecystectomy. In patients of Child-Pugh class C, conservative or minimally invasive approaches should be used to treat complications of GSs.

Therapeutic efficacy of atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma in patients with Child-Pugh class A or B liver function in real-world clinical practice.

BACKGROUND/AIM: Atezolizumab plus bevacizumab (Atez/Bev) treatment is recommended for unresechepatocellular carcinoma (u-HCC) patients classified as Child-Pugh A (CP-A). This study aimed to elucidate the prognosis of patients treated with Atez/Bev, especially CP-A and -B cases. MATERIALS/METHODS: From September 2020 to March 2022, 457 u-HCC patients treated with Atez/Bev were enrolled (median age 74 years, male:female = 368:89, CP-A:CP-B = 427:30, Child-Pugh score [CPS] 5:6:7:8:9 = 271:156:21:8:1). Therapeutic response was evaluated using RECIST ver.1.1. Clinical features and prognosis were retrospectively evaluated. RESULTS: There were no significant differences between CP-A and -B patients in regard to best response (CR:PR:SD:PD = 16:91:194:81 vs. 0:7:13:8, p = 0.739; objective response rate/disease control rate = 28.0%/78.8% vs. 25.0%/71.4%). Analysis performed using inverse probability weighting adjustments of clinical factors other than those related to hepatic reserve function with a p value < 0.10 for comparisons between patients with CP-A and -B showed that the progression-free survival (PFS) rate for CP-A cases was better (6-/12-/18-month: 58.2%/36.1%/27.8% vs. 49.6%/8.7%/non-estimable [NE], p < 0.001), as was overall survival (OS) rate (6-/12-/18-month: 89.9%/71.7%/51.4% versus 63.6%/18.4%/NE; p < 0.001). Median PFS (mPFS) and median OS (mOS) for the CPS-5 were 9.5 months/NE, and 5.1/14.0 months for the CPS-6 (both p < 0.001). Furthermore, for modified albumin-bilirubin grade (mALBI)-1/2a/2b, mPFS was 9.4/8.5/5.3 months (p < 0.001) and mOS was NE/17.8/13.4 months (p < 0.001). CONCLUSION: Better hepatic function, such as mALBI grade 1 or 2a are thought to indicate a better condition for obtaining sufficient prognosis with Atez/Bev treatment for u-HCC patients, whereas for CP-B patients, who mainly shown an mALBI grade of 2b or 3, Atez/Bev might have less therapeutic efficacy.

Evaluation of adrenal function in hemodynamically stable patients with liver cirrhosis.

Aim of the study: To estimate the prevalence of adrenal insufficiency (AI) in hemodynamically stable cirrhotic patients and to evaluate the potential association with patients' clinical characteristics, cirrhosis etiology and liver disease severity. Material and methods: The cross-sectional study included 132 stable liver cirrhosis patients. Severity of liver disease was graded using the Child-Pugh classification and Model for End-stage Liver Disease (MELD) score. The adrenal function was evaluated by measuring basal and peak cortisol after 60 minutes following the short Synacthen test (SST). Differences in terms of demographic data, clinical information and liver disease severity were compared between cirrhotic patients with and without AI. Results: Out of 132 cirrhotic patients, 86 patients had evidence of AI based on the peak serum cortisol value while the prevalence was lower (67 patients out of 132) when basal cortisol level was taken as the basis. A total of 82 patients were classified as Child-Pugh class C, with an average MELD score of 20 ±7.1. Most patients with AI had Child-Pugh class C. Patients with AI had a higher prevalence of ascites, gastrointestinal hemorrhage, and hepatic encephalopathy, a higher MELD score and a lower serum sodium level compared to patients with normal adrenal function. AI was not related to the etiology of cirrhosis but was related to the severity of liver disease and the degree of hyponatremia. Conclusions: Adrenal insufficiency is common among hemodynamically stable patients with cirrhosis. It is related to the severity of liver disease and the degree of hyponatremia.

Management of hepatocellular carcinoma from diagnosis in routine clinical practice.

Aim: To assess real-world management of patients diagnosed with hepatocellular carcinoma (HCC) within an integrated delivery network. Materials & methods: A retrospective cohort analysis of adults newly diagnosed with HCC from January 2014 to March 2019. Overall survival and treatment journey were assessed over the entire available follow-up period per patient. Results: Of the 462 patients, 85% had ≥1 treatment. The 24-month overall survival rate (95% CI) from first treatment was 77% (72-82%). Majority of Child-Pugh class A (71%) and B (60%) patients received locoregional therapy first. Half (53.6%) of the patients with liver transplantation first were Child-Pugh class C patients. Sorafenib was the predominant systemic therapy. Conclusion: This integrated delivery network data analysis offers a comprehensive insight into the real-world management of HCC.

Time-course changes in liver functional reserve after successful sofosbuvir/velpatasvir treatment in patients with decompensated cirrhosis.

AIM: Direct-acting antivirals (DAAs) are currently available even for patients with decompensated cirrhosis. Reportedly, hepatic functional reserve improved in the short term after achievement of sustained virologic response (SVR). We aimed to clarify the outcomes after achievement of SVR in patients with decompensated cirrhosis who were treated by DAAs in real-world clinical practice. METHODS: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted in 86 patients with decompensated cirrhosis, who were evaluated for 48 weeks post-treatment. RESULTS: The cohort included 8 patients with Child-Pugh class A, 56 with B, and 22 with C. The proportion of Child-Pugh class A patients increased from 9.1% at baseline to 44.1% at 48 weeks post-treatment, while that of class B and C patients decreased from 66.2% to 35.1% and from 24.7% to 14.3%, respectively. Among the patients with Child-Pugh class B and C, univariate analysis identified low total bilirubin, Child-Pugh score, Child-Pugh class B, ALBI score, and high serum albumin as factors associated with improvement to Child-Pugh class A. The optimal cut-off value of the factors for predicting improvement to Child-Pugh class A were 1.4 mg/dl for total bilirubin, 2.9 g/dl for serum albumin, 8 points for Child-Pugh score, and -1.88 for ALBI score. CONCLUSION: Achievement of SVR with sofosbuvir/velpatasvir improved the liver functional reserve at 12 weeks post-treatment and maintained the stable effects until 48 weeks post-treatment in patients with decompensated cirrhosis. Specifically, the patients with less advanced conditions had the likelihood of improving to Child-Pugh class A at 48 weeks post-treatment.

Comparison of Modified Child-pugh (MCP), Albumin-bilirubin (ALBI), and Child-pugh (CP) score for predicting of survival in Hepatocellular Carcinoma Patients Treated with Transcatheter Arterial Chemoembolization.

BACKGROUND: Both modified Child-Pugh (MCP) and Albumin-bilirubin (ALBI) grade were reported that simpler, more objective and evidence-based alternative to the Child-Pugh (CP) class for assessing liver function. AIMS: To investigate whether the MCP and ALBI grade could better evaluate the liver reserve of Hepatocellular Carcinoma (HCC) patients treated with TACE (transcatheter arterial chemoembolization) than CP grade. METHODS: Three hundred seventy-six consecutive HCC patients treated with TACE between December 2007 and October 2011 were enrolled. The baseline characteristics and clinical information were collected. Homogeneity and discriminatory ability were compared between the MCP grade and ALBI class or CP grade. RESULTS: Compared with the CP and ALBI, the MCP grade had a higher predictive accuracy for overall survival (OS) in terms of homogeneity and discriminatory ability. Most of the HCC patients had CP class A disease (84.0%) at presentation, and within this CP class, although the ALBI grade revealed two clear and nonoverlapping groups, the MCP grade revealed three clearly different prognostic groups. Both in the ALBI grade 1 or ALBI grade 2 group, the MCP grade still showed a significant progressive decrease in OS from the smallest to the largest grades, but the CP class was unsatisfactory in stratifying these patients. CONCLUSIONS: The stratification ability and prognostic predictive power of the MCP grade for HCC patients treated with TACE may be better than that of the ALBI grade or CP class.

Magnesium deficiency in liver cirrhosis: a retrospective study.

BACKGROUND: Magnesium, known as "the forgotten electrolyte", is an essential element of life. Magnesium deficiency is implicated in many diseases, including liver cirrhosis. This study aimed to explore the prevalence of magnesium deficiency in liver cirrhosis and investigate the relationship between magnesium levels and complication of liver cirrhosis and clinical outcomes. PATIENTS AND METHODS: Cirrhotic patients with serum magnesium levels measured were retrospectively identified from 2016 to 2017. Demographics, laboratory parameters, complications were collected. The Child-Pugh class, MELD score, and ALBI score were calculated. RESULTS: The mean serum magnesium level of all 152 patients was lower than the normal, including 92 patients diagnosed with magnesium deficiency. Compared to Child-Pugh class A, magnesium levels were significantly lower in the patients with Child-Pugh class B or C (F = 10.26, p < .05). Magnesium levels were also considerably lower in the group with MELD score ≥21, compared to the other two groups with MELD score < 15 or 15-20 (F = 6.59, p < .05). Similarly, magnesium levels were significantly lower in the group with ALBI score > -1.39 (grade 3), compared to the other two groups with ALBI with score ≤ -2.6 (grade 1) or > -2.6, ≤ -1.39 (grade 2) (F = 8.44, p<.001). Furthermore, magnesium levels were lower in cirrhotic patients with infection. Magnesium-deficient patients had lower transplant-free survival rates than non-deficient patients. CONCLUSION: Magnesium deficiency is highly prevalent in cirrhotic patients. Magnesium deficiency is related to worse transplant-free survival, infection and the severity of liver cirrhosis.

Clinical course of hepatitis C virus-positive patients with decompensated liver cirrhosis in the era of direct-acting antiviral treatment.

AIM: The aim of the present study was to investigate the clinical course in hepatitis C virus (HCV)-positive patients with decompensated liver cirrhosis after direct-acting antivirals (DAAs) have been used for HCV infection. METHODS: This multicenter study prospectively analyzed a registered cohort composed of 73 HCV-positive patients with decompensated cirrhosis who attended our 11 institutions between January 2018 and July 2018. Prognoses, including changes in the liver reserve, hepatocellular carcinoma (HCC), decompensation events, and survival, were analyzed up to July 2020, as was the initiation of DAA treatment. RESULTS: Sixty-four (87.7%) and nine (12.3%) patients had Child-Pugh class (C-P) B and C at baseline, respectively. Within 2 years after enrollment, 17 patients (23.3%) received treatment with DAAs, and 31 patients (42.5%) developed uncontrolled HCC, switched to palliative care, or died. Patients who received DAA treatment were significantly younger and had significantly higher alanine aminotransferase levels and lower platelet counts than the patients who did not receive DAA treatment. The rates of overall survival, cumulative HCC occurrence, and cumulative hospitalization for any hepatic decompensation event at 2 years were 64.8%, 13.1%, and 65.6%, respectively. Overall survival was significantly shorter and the HCC occurrence and hospitalization rates were significantly higher in C-P C patients than in C-P B patients. CONCLUSIONS: Among HCV-positive patients with decompensated cirrhosis, approximately one-fourth received DAA treatment, but more than 40% of the patients lost the opportunity for treatment with DAAs.

Using Child-Pugh Class to Optimize Voriconazole Dosage Regimens and Improve Safety in Patients with Liver Cirrhosis: Insights from a Population Pharmacokinetic Model-based Analysis.

BACKGROUND: Cirrhotic patients are at a high risk of fungal infections. Voriconazole is widely used as prophylaxis and in the treatment of invasive fungal disease. However, the safety, pharmacokinetics, and optimal regimens of voriconazole are currently not well defined in cirrhotic patients. DESIGN: Retrospective pharmacokinetics study. SETTING: Two large, academic, tertiary-care medical center. PATIENTS: Two hundred nineteen plasma trough concentrations (Cmin ) from 120 cirrhotic patients and 83 plasma concentrations from 11 non-cirrhotic patients were included. METHODS: Data pertaining to voriconazole were collected retrospectively. A population pharmacokinetics analysis was performed and model-based simulation was used to optimize voriconazole dosage regimens. RESULTS: Voriconazole-related adverse events (AEs) developed in 29 cirrhotic patients, and the threshold Cmin for AE was 5.12 mg/L. A two-compartment model with first-order elimination adequately described the data. The Child-Pugh class and body weight were the significant covariates in the final model. Voriconazole clearance in non-cirrhotic, Child-Pugh class A and B cirrhotic (CP-A/B) and Child-Pugh class C cirrhotic (CP-C) patients was 7.59, 1.86, and 0.93 L/hour, respectively. The central distribution volume and peripheral distribution volume was 100.8 and 55.2 L, respectively. The oral bioavailability was 91.6%. Model-based simulations showed that a loading dose regimen of 200 mg/12 hours intravenously or orally led to 65.0-75.7% of voriconazole Cmin in therapeutic range on day 1, and the appropriate maintenance dosage regimens were 75 mg/12 hours and 150 mg/24 hours intravenously or orally for CP-A/B patients, and 50 mg/12 hours and 100 mg/24 hours intravenously or orally for CP-C patients. The predicted probability of achieving the therapeutic target concentration for optimized regimens at steady-state was 66.8-72.3% for CP-A/B patients and 70.3-74.0% for CP-C patients. CONCLUSIONS: These results recommended that the halved loading dose regimens should be used, and voriconazole maintenance doses in cirrhotic patients should be reduced to one-fourth for CP-C patients and to one-third for CP-A/B patients compared to that for patients with normal liver function.