Efficacy of transarterial chemoembolization treatment with 30-60-µm microspheres in patients with hepatocellular carcinoma.

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.

Effect of Hepatic Impairment on the Pharmacokinetics of Fenfluramine and Norfenfluramine.

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.

Lenvatinib as Second-Line Treatment after Atezolizumab plus Bevacizumab for Unresectable Hepatocellular Carcinoma: Clinical Results Show Importance of Hepatic Reserve Function.

INTRODUCTION: Lack of an established methodology for post-progression systemic treatment following atezolizumab plus bevacizumab (Atez/Bev) administration is an important clinical issue. The present study aimed to elucidate the potential of lenvatinib as a second-line treatment option after Atez/Bev failure. METHODS: From 2020 to 2022, 101 patients who received lenvatinib as second-line treatment were enrolled (median 72 years, males 77, Child-Pugh A 82, BCLC-A:B:C:D = 1:35:61:4), while 29 treated with another molecular targeting agent (MTA) during the period as second-line treatment were enrolled as controls. The therapeutic efficacy of lenvatinib given as second-line treatment was retrospectively evaluated. RESULTS: Median progression-free survival/median overall survival for all patients was 4.4/15.7 months and for those with Child-Pugh A was 4.7 months/not-reached. When prognosis was compared with patients who received another MTA, there was no significant difference for PFS (3.5 months, p = 0.557) or OS (13.6 months, p = 0.992), and also no significant differences regarding clinical background factors. mRECIST findings showed that objective response and disease control rates in patients treated with lenvatinib were 23.9% and 70.4%, respectively (CR:PR:SD:PD = 3:14:33:21), while those shown by RECIST, ver. 1.1, were 15.4% and 66.2%, respectively (CR:PR:SD:PD = 1:10:36:24). Adverse events (any grade ≥10%) were appetite loss (26.7%) (grade 1:2:3 = 2:15:10), general fatigue (21.8%) (grade 1:2:3 = 3:13:6), protein in urine (16.8%) (grade 1:2:3 = 0:4:13), and hypertension (13.9%) (grade 1:2:3 = 1:8:5). CONCLUSION: Although lenvatinib treatment might not provide a pseudo-combination immunotherapy effect following Atez/Bev failure, lenvatinib when used as second-line treatment after Atez/Bev failure might be expected to be comparable as compared to its use as first-line treatment.

Evaluation of Pretreatment Albumin-Bilirubin Grade as a Better Prognostic Factor Compared to Child-Pugh Classification in Patients with Hepatocellular Carcinoma Receiving Transarterial Chemoembolization Combined with Radiotherapy.

This study assessed the use of pretreatment albumin--bilirubin (ALBI) grade as a prognostic factor in patients with hepatocellular carcinoma (HCC) receiving combined transarterial chemoembolization (TACE) and radiotherapy (RT). Patients who underwent RT following TACE between January 2011 and December 2020 were analyzed retrospectively. The survival outcomes of patients in regard to the ALBI grade and Child-Pugh (C-P) classification were evaluated. A total of 73 patients with a median follow-up of 16.3 months were included. Thirty-three (45.2%) and forty patients (54.8%) were categorized into ALBI grades 1 and 2-3, respectively, while sixty-four (87.7%) and nine (12.3%) were C-P classes A and B, respectively (p = 0.003). The median progression-free survival (PFS) and overall survival (OS) for ALBI grade 1 vs. 2-3 were 8.6 months vs. 5.0 months (p = 0.016) and 27.0 months vs. 15.9 months (p = 0.006), respectively. The median PFS and OS for C-P class A vs. B were 6.3 months vs. 6.1 months (p = 0.265) and 24.8 months vs. 19.0 months (p = 0.630), respectively. A multivariate analysis showed that ALBI grades 2-3 were significantly associated with worse PFS (p = 0.035) and OS (p = 0.021). In conclusion, the ALBI grade could be a good prognosticator in HCC patients who were treated with combined TACE-RT.

Feasibility of Imaging-Based Quantitative Hepatic Function Assessment: Gd-EOB-DTPA-Enhanced Liver MR Imaging Combined with T1 Mapping.

OBJECTIVE: to investigate the feasibility of gadoxetic acid (Gd-EOB-DTPA) enhanced MRI combined with T1 mapping in quantitative hepatic function assessment. METHODS: this study retrospectively enrolled 94 patients with Gd-EOB-DTPA enhanced MRI combined with T1 mapping, divided into group A (grade A, n=73), group B (grade B, n=14) and group C (grade C, n=7) based on Child-Pugh classification. Liver T1 relaxation times on plain scan (T1P) and hepatocellular phase (T1E) were measured. Decrease in T1 (T1D) and the percentage of decrease in T1 (T1D%) were calculated as follows: T1D=T1P-T1E, T1D%= T1D/T1P×100%. The relationship between T1P, T1E, T1D, T1D% and liver function classification was analyzed. RESULTS: T1P, T1D, and T1D% in group A were significantly higher than those of group B and C. T1E in group A was lower than those of group B and C. T1D% was significantly different between group B and C. There was no significant difference in T1P, T1E, T1D between groups B and C. T1E was positively correlated with liver function levels, T1P and T1D had a negative correlation with liver function levels. T1P, T1E, T1D, T1D% were significantly different between cirrhotic and non-cirrhotic groups. T1D% of less than 70% suggests liver dysfunction. CONCLUSION: Gd-EOB-DTPA enhanced liver MRI combined with T1 mapping is feasible for quantitative assessment of hepatic function.

Prognosis and treatment pattern of advanced hepatocellular carcinoma after failure of first-line atezolizumab and bevacizumab treatment.

BACKGROUND: The combination of atezolizumab and bevacizumab (Atezo-Bev) has become the standard first-line therapy for patients with advanced hepatocellular carcinoma (HCC), but the prognosis and treatment pattern after its treatment failure are unclear. METHODS: We reviewed the medical records of patients who failed first-line Atezo-Bev treatment for advanced HCC from January 2018 to May 2021 in four Taiwan medical centers. Post-first-line survival (PFLS) was defined as the date from the failure of Atezo-Bev treatment to the date of death or last follow-up. RESULTS: A total of 41 patients were included in the study. All patients had Child-Pugh A liver reserve before the initiation of Atezo-Bev treatment, but the liver reserve of 6 (15%) and 7 (17%) patients deteriorated to Child-Pugh B and C, respectively, after treatment failure. The median PFLS was 5.9 months. PFLS significantly differed among patients with various liver reserves after the failure of Atezo-Bev treatment (median 9.6 vs 3.8 vs 1.2 months, for Child-Pugh A, B, and C; p < 0.001). In total, 30 (73%) patients received second-line systemic therapy, and they exhibited significantly longer PFLS (median 8.0 vs 1.8 months, p = 0.033) than patients who did not. Deteriorated liver function and not receiving second-line therapy remained associated with inferior PFLS in multivariate analysis. The most common second-line therapies were sorafenib (n = 19, 63%) and lenvatinib (n = 9, 30%), with no significant differences in efficacies. CONCLUSION: Receiving second-line therapy and good liver reserve were associated with favorable PFLS after the failure of first-line Atezo-Bev treatment.

An mALBI-Child-Pugh-based nomogram for predicting post-hepatectomy liver failure grade B-C in patients with huge hepatocellular carcinoma: a multi-institutional study.

OBJECTIVE: Post-hepatectomy liver failure (PHLF) is a severe complication in patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. This study aims to develop a nomogram of PHLF grade B-C in patients with huge HCC (diameter ≥ 10 cm). METHODS: We retrospectively collected clinical information of 514 and 97 patients who underwent hepatectomy for huge HCC at two medical centers between 2016 and 2021. Univariate and multivariate analysis were carried out to screen the independent risk factors of PHLF grade B-C, which were visualized as a nomogram. RESULTS: Three Hundred Forty Three Thousand One Hundred Seventy One  and 97 HCC patients were included in the training cohort, internal validation cohort, and external validation cohort, with probabilities of PHLF grade B-C of 15.1%, 12.9%, and 22.7%, respectively. Pre-operative modified albumin-bilirubin (mALBI) grade (p < 0.001), Child-Pugh classification (p = 0.044), international normalized ratio (INR) (p = 0.005), cirrhosis (p = 0.019), and intraoperative blood loss (p = 0.004) were found to be independently associated with PHLF grade B-C in the training cohort. All the five independent factors were considered in the establishment of the nomogram model. In the internal validation cohort and external validation cohort, the area under receiver operating characteristic curve for the nomogram in PHLF grade B-C prediction reached 0.823 and 0.740, respectively. Divided into different risk groups according to the optimal cut-off value, patients in the high-risk group reported significantly higher frequency of PHLF grade B-C than those in the low-risk group, both in the training cohort and the validation cohort (p < 0.001). CONCLUSIONS: The proposed noninvasive nomogram based on mALBI-Child-Pugh and three other indicators achieved optimal prediction performance of PHLF grade B-C in patients with huge HCC.

Comparison of Liver Fibrosis and Function Indices with Extracellular Volume Using Dual-energy CT: A Retrospective Study.

BACKGROUND: Dual-Energy Computed Tomography (DECT) enables the direct measurement of iodine accumulation in the extracellular space. OBJECTIVE: To compare measures of liver fibrosis and function with Extracellular Volume (ECV) from iodine/water images using DECT. METHODS: Data was obtained from 119 consecutive patients who underwent abdominal DECT. A region of interest was set in the right lobe of the liver, pancreas, spleen, and aorta on iodine density images. ECV was calculated using the following formula: ECV = (1 - hematocrit) × [iodine concentration in the liver (or pancreas, spleen) / iodine concentration in the aorta]. The severity of liver fibrosis was estimated using the aminotransferase/platelet ratio index (APRI) and the Fibrosis-4 (FIB-4) index. Liver function was assessed by the Child-Pugh classification and albumin-bilirubin (ALBI) grade. Data were analyzed by the Spearman rank correlation coefficient, one-way analysis of variance, and post hoc analysis. RESULTS: The correlation between ECV and fibrosis indices (APRI and FIB-4) was only significant, with a weak magnitude for liver ECV quantification at the equilibrium phase (r=0.25 and r=0.20, respectively). The correlations between liver function index and ECV quantification were more robust than with fibrosis index. The highest correlations (r=0.50) were found between ALBI grade and liver ECV at the equilibrium phase. Liver ECV values at the equilibrium phase had a significant difference between ALBI grade 1 vs. 2 and grade 1 vs. 3. CONCLUSION: Liver ECV quantification by DECT is more suitable for evaluating liver function than liver fibrosis severity.

Effectiveness of Lenvatinib Versus Sorafenib for Unresectable Hepatocellular Carcinoma in Patients with Hepatic Decompensation.

BACKGROUND/AIM: Lenvatinib and sorafenib are currently available to treat patients with advanced hepatocellular carcinoma (HCC). However, since the clinical trials evaluating the efficacy of lenvatinib and sorafenib included only patients with Child-Pugh class A, little is known about the effectiveness of the treatments in patients with hepatic decompensation. We compared the effectiveness of lenvatinib and sorafenib in decompensated patients with unresectable HCC. METHODS: Consecutive patients who were classified as Child-Pugh class B or C and received lenvatinib or sorafenib as first-line systemic therapy for unresectable HCC between November 2018 and April 2020 at a tertiary referral center were included in this retrospective study. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), time-to-progression, best overall tumor response, and safety profiles. RESULTS: Among 94 patients, 34 received lenvatinib and 60 received sorafenib. The median OS was 4.1 months (95% confidence interval [CI], 2.9-5.2): 4.2 months (95% CI, 2.9-5.3) for lenvatinib and 4.1 months (95% CI, 2.7-6.4) for sorafenib. The treatment regimen was not associated with significant improvement in OS after adjusting for covariables (adjusted hazard ratio [aHR], 0.92; 95% CI, 0.54-1.54; P = 0.74). The treatment regimen was not an independent predictor of PFS (lenvatinib vs. sorafenib; aHR, 0.77; 95% CI, 0.48-1.24; P = 0.28). HRs were maintained even after balancing with the inverse probability treatment weighting method. Objective response rates were 11.8% and 6.7% in patients receiving lenvatinib and sorafenib, respectively (P = 0.45). Ten patients in both groups (five in the lenvatinib group and five in the sorafenib group) underwent dose modification due to adverse events, and significant difference was not observed between the treatment groups (P = 0.49). CONCLUSION: The effectiveness of lenvatinib and sorafenib was comparable for the treatment of unresectable HCC in decompensated patients.

QTc interval prolongation in the patients with primary biliary cholangitis.

BACKGROUND: The QT interval prolongation was associated with fatal arrhythmias and cardiac death. However, there were not adequate data to clarify the situation of QT interval prolongation in primary biliary cholangitis (PBC) patients. The aim of this study was to clarify the rate and the associated risk factors of corrected QT (QTc) interval prolongation in PBC patients. METHODS: From January 2016 to December 2020, PBC patients were retrospectively enrolled. The rate of QTc interval prolongation was surveyed and the associated risk factors were clarified by univariate and multivariate analyses. RESULTS: Among the 189 PBC patients, 24.3% (46/189) had the QTc interval prolongation. The univariate analysis showed that age, Child-Pugh classification, creatinine, international normalized ratio (INR), and platelet (PLT) were associated with QTc interval prolongation in the PBC patients. The multivariate analysis further showed only age (p = .028) and Child-Pugh classification (p = .035) were the associated risk factors. It had the highest risk of QTc interval prolongation (as high as 64.3%) in the patients who were more than 62.5 years old and with Child-Pugh C. CONCLUSION: The QTc interval prolongation was frequent in PBC patients, especially in the patients with decompensated cirrhosis. The rate of QTc interval prolongation was as high as 64.3% in the PBC patients who were more than 62.5 years old and classified as Child-Pugh C.

Research status and progress on surgical treatment of postoperative recurrence of hepatocellular carcinoma / 器官移植

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. At present, hepatectomy is one of the most frequent therapeutic options, whereas the high postoperative recurrence rate severely affects the long-term survival of HCC patients. Therefore, it is urgent to choose appropriate therapeutic regime to treat the recurrence of HCC to improve the long-term survival of HCC patients. Surgical treatment is an efficacious treatment for recurrent HCC, including re-hepatectomy, salvage liver transplantation and radiofrequency ablation. Currently, individualized treatment is recommended for postoperative recurrence of HCC. The selection of treatment should be conducted based on the tumor conditions after the first hepatectomy, the characteristics of recurrent tumors, baseline data of patients and recurrence time, etc., aiming to formulate appropriate treatment regimes for patients. In this article, these surgical regimes were reviewed and compared to explore appropriate surgical schemes for postoperative recurrence of HCC, aiming to provide reference for prolonging the survival of HCC patients.

Copper concentrations are prevalently associated with antithrombin III, but also with prothrombin time and fibrinogen in patients with liver cirrhosis: A cross-sectional retrospective study.

BACKGROUND: Concerning the link between copper excess and the pathogenesis of chronic liver diseases, its retention is reckoned to develop as a complication of cholestasis. Recently, it has been found that cholestatic liver injury involves largely inflammatory cell-mediated liver cell necrosis, with consequent reduced hepatic mass, more than occurring through direct bile acid-induced apoptosis. On the other hand, interference with protein synthesis could be expected to result, ending in an altered ability of the liver to retain copper. Little is known about the association between serum copper and clotting factors in cirrhotics. We aimed at studying a possible relationship between increased levels of copper and an aspect of the haemostatic process in liver cirrhosis patients, assessing an index of protein synthesis (albumin) and parameters of protein synthesis/coagulation/fibrinolysis, such as prothrombin time (PT), antithrombin (AT) III and fibrinogen. METHODS: Records from 85 patients suffering from liver cirrhosis of various aetiology and different severity were retrospectively examined. Serum concentrations of copper were determined by atomic absorption spectrophotometer. An index of protein synthesis, such as albumin and parameters of both synthesis and coagulation/hypercoagulation such as PT %, AT III%, levels of fibrinogen were taken into account to study possible correlations to serum copper. The severity of cirrhosis was evaluated by the Child-Pugh (C-P) classification. The relationship among variables were studied by linear regression. RESULTS: Copper levels of patients suffering from liver cirrhosis were increased respect to those of controls, 102.7+/-28.7 versus 80.4+/-19.5 mcg/dL, (P = .0009), independently from disease severity, and were positively predicted by PT% (P = 0. 017), fibrinogen (P = 0.007) and AT III% (P = 0.000), at linear regression. Among the previous parameters, to which serum albumin was added, the unique predictor of copper levels was AT III%, at multiple regression (P = 0. 010); AT III% was negatively predicted by the C-P classification (P = 0.000); copper levels, adjusted for C-P classification, were predicted by AT III% (P = 0.020) and fibrinogen concentrations, but not by PT% (P = 0.09). CONCLUSION: The copper concentration is reckoned as responsible for production of the hydroxyl radicals. On the basis that oxidants may enhance the activity of the extrinsic coagulation cascade, ultimately leading to thrombin formation, via their combined effects on stimulation of tissue factor activity and inhibition of fibrinolytic pathways, the positive relationship of copper to coagulation/hypercoagulation parameters (mainly AT III) in our research could find a plausible interpretation.

Relation between the severity of liver cirrhosis and neurological symptoms, nerve conduction study results, and motor unit number estimation.

Liver cirrhosis is a global health problem that can be associated with several neurological manifestations. We aimed to assessment of the relation between the severity of the liver cirrhosis and the neurological symptoms, nerve conduction studies (NCS), as well as detecting subclinical neuropathic affection using motor unit number estimation (MUNE) technique. This cross-sectional study was conducted on 56 cirrhotic patients and 61 age- and sex-matched healthy controls. Neurological manifestations, Child-Pugh classification, Model for End-Stage Liver Disease score, NCS and MUNE using a modified spike-triggered averaging technique were studied. Forty-five (80.3%) of the cirrhotic patients had neurological manifestations. Muscle cramps were the most frequently reported manifestation, followed by fatigue and then numbness. NCS abnormality was significantly related to the presence of neurological symptoms (p < 0.001) and not only to peripheral numbness. Only fatigue was significantly related to the lower MUNE values (p < 0.017). Child-Pugh classification progression was significantly related to the presence of fatigue and abnormal NCS results (p < 0.001); no similar relation was detected between the Child-Pugh classification and the MUNE value (p = 0.103). Higher MELD scores were significantly related to NCS abnormalities (p = 0.014) and negatively correlated, although not significantly, with the MUNE values (r = -0.246 and p = 0.067). The progression of liver cirrhosis was related to the presence of neurological manifestations and nerve conduction abnormalities. Nerve conduction abnormalities may be present even in the absence of clinical numbness. A decline in motor unit number could explain the pathophysiology of fatigue in cirrhotic patients.

Hepatocellular carcinoma with indocyanine green excretory defect: a case report and review of the literature.

Constitutional indocyanine green (ICG) excretory defect is rare. However, ICG excretory defect concomitant with hepatocellular carcinoma (HCC) is extremely rare, and only six reports of hepatectomy in patients with constitutional ICG excretory defect have been published in the English language literature through 2020. In this study, we report a case of combined HCC and ICG excretory defect and discuss its clinicopathological features and outcomes. The case featured a 68-year-old man who was admitted to the hospital with a diagnosis of resectable HCC. The preoperative ICG retention rate at 15 minutes was 82.9%. Despite this finding, the Child-Pugh assessment and hepatobiliary-specific magnetic resonance imaging (MRI) did not reveal any abnormal findings. Therefore, we diagnosed the patient with constitutional ICG excretory defect and performed partial hepatectomy. For patients requiring hepatectomy, the indications and procedure for surgery should be considered. These should be based on liver function tests such as gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI.

Real-world hospital mortality of liver cirrhosis inpatients in Japan: a large-scale cohort study using a medical claims database: Prognosis of liver cirrhosis.

AIM: Prognosis of liver cirrhosis patients is poor when ascites is present and liver function is impaired, but such up-to-date information from a large-scale, real-world setting is limited in Japan. We aimed to investigate the hospital mortality of Japanese liver cirrhosis inpatients. METHODS: This retrospective cohort study included data on liver cirrhosis inpatients between January 2011 and September 2018 extracted from an administrative claims database. The outcome was in-hospital mortality. The 1- and 3-year cumulative survival rates were examined for liver cirrhosis etiology, Child-Pugh classification, or ascites presence/absence using Kaplan-Meier analysis. The survival up to 1 year for tolvaptan prescription/nonprescription was examined. RESULTS: We analyzed the data of 57 769 inpatients. Survival rates did not substantially differ among etiologies, with a better prognosis for alcohol etiology and poorer prognosis for hepatitis C virus. According to the Child-Pugh classification, the 1- and 3-year survival rates were 90.2% and 75.3% for grade A, 73.5% and 53.9% for grade B, and 41.9% and 28.9% for grade C, respectively. Patients without ascites had a higher survival rate (83.2% and 67.0% at 1 and 3 years, respectively) than those with ascites (51.9% and 36.3%, respectively). Based on examining matched patients with ascites using a propensity score, prognosis was poor in general but was better at 6 months (58.1%) or similar at 1 year (47.1%) in patients prescribed tolvaptan compared to those not prescribed tolvaptan (54.8% and 47.5%, respectively). CONCLUSIONS: Poorer prognosis was suggested in inpatients with cirrhosis who had a worse Child-Pugh grade and ascites.

The Pattern of Dyslipidemia in Chronic Liver Disease Patients.

Introduction Patients with chronic liver disease are expected to report derangements in serum lipid profiles. Lipid profile monitoring is not a part of the routine management of these patients in our hospital. Few recent studies show how lipid profile varies with the severity of disease and should be considered in the management planning of such patients. The objective of this study was to determine the pattern of dyslipidemia in chronic liver disease patients. Materials and methods A cross-sectional study was conducted involving 171 patients of all genders aged between 18 years and 60 years presenting with chronic liver disease with disease severity graded on Child-Pugh class as A, B, and C. Lipid profile was acquired in all these patients and was compared across various subgroups. Individual serum lipid parameters were graded as normal, high, or very high. Each patient was required to provide written informed consent. Statistical Package for Social Sciences (SPSS) version 21.0 (IBM Corp. Armonk, NY) was used to analyze data statistically, taking a p-value of ≤0.05 as significant. Results The mean age of patients was 51.2±7.3 years. The male to female ratio came out to be 1.5:1, with 103 (60.2%) male and 68 (39.8%) female patients included in the study. The disease was classified as Child-Pugh A in 20 (11.7%) patients, Child-Pugh B in 67 (39.2%) patients, and Child-Pugh C in 84 (49.1%) patients. Forty-four (25.7%) patients were hypertensive while 62 (36.3%) were diabetic. The mean body mass index (BMI) of these patients was 25.9±2.4 kg/m2. Mean serum values among Child-Pugh A, Child-Pugh B, and Child-Pugh C of low-density lipoproteins (LDL) (113.15±14.08 vs. 95.58±14.25 vs. 53.46±5.90 mg/dl; p-value 0.001), high-density lipoproteins (HDL) (50.60±3.19 vs. 40.70±2.95 vs. 35.40±3.88 mg/dl; p-value 0.001), total cholesterol (174.20±17.33 vs. 164.00±17.82 vs. 128.64±24.73 mg/dl; p-value 0.001), and triglycerides (127.15±8.98 vs. 100.84±27.12 vs. 93.36±25.56 mg/dl; p-value 0.001) decreased significantly with increasing severity of disease. Nineteen (11.1%) patients had hyperlipidemia (serum values of two or more parameters above normal) while 152 (88.9%) patients had normal lipid profile. When stratified, no statistically significant difference was found in the frequency of hyperlipidemia across various subgroups based on the patient's gender, age, duration, and severity of the disease, BMI, or diabetic and hypertensive status. Conclusions A substantial proportion of patients with chronic liver disease had hyperlipidemia which varied with the severity of disease on Child-Pugh classification. Routine monitoring of the lipid profile of such patients is necessary for timely identification and management of dyslipidemia to improve the outcome of such patients. It also suggests an important role of lipid profile in the risk stratification and treatment of chronic liver disease patients and warrants further studies in this regard.

Outcomes of Bariatric Surgery in Patients with Liver Cirrhosis: a Systematic Review.

Obesity is commonly associated with non-alcoholic fatty liver disease and is a significant cause of chronic liver disease and cirrhosis. Some patients undergoing bariatric surgery suffer from cirrhosis of the liver. Currently, there is a lack of consensus on the management of these patients and the safety and efficacy of bariatric surgery in this group. This review aims to update our previously published systematic review on the same topic. A total of 21 studies reporting experience on patients with cirrhosis undergoing bariatric surgery were included. Sleeve gastrectomy was the most common surgery performed, followed by Roux-en-Y gastric bypass. The results show that bariatric surgery may be feasible in carefully selected patients with obesity and cirrhosis although they have slightly higher morbidity and mortality rates.

Factors affecting the recovery of hepatic reserve after sustained virologic response by direct-acting antiviral agents in chronic hepatitis C virus-infected patients.

BACKGROUND AND AIM: Since the advent of direct-acting antiviral (DAA) therapy, the total eradication of hepatitis C virus has been achievable with the recovery of hepatic reserve after achievement of sustained virologic response (SVR). Hence, here, we examined the factors affecting the recovery of hepatic reserve. METHODS: We followed up 403 patients (male: 164, female: 239; genotype 1: 299, genotype 2: 104; median age: 69 years) for at least 3 years after they achieved SVR to DAA therapy. Of these patients, 75 (18.6%) had a history of hepatocellular carcinoma (HCC). Biochemical tests were periodically performed, and the hepatic reserve was evaluated based on the albumin-bilirubin grade. We examined background factors such as age, biochemical test results, HCC occurrence and portosystemic shunt by computed tomography. RESULTS: At the start of treatment, the albumin-bilirubin grades were grades 1, 2, and 3 in 241, 157, and 5 patients, respectively, and 3 years later, 117 of 162 (72%) patients with grade 2 or 3 improved to grade 1. Multivariate analysis identified the HCC occurrence after achievement of SVR (hazard ratio [HR]: 3.08, P < 0.0138), male sex (HR: 3.45, P = 0.0143), hemoglobin level of <11.5 g/dL (HR: 4.19, P = 0.0157), the presence of a portosystemic shunt (HR: 3.07, P = 0.0349), and alanine aminotransferase levels <45 U/L (HR: 2.67, P = 0.0425) as factors inhibiting improvement to grade 1. However, old age was not an inhibitory factor. CONCLUSION: Our results demonstrate that hepatic reserve could be improved even in elderly patients over a long course of time.

Effect of Hepatic Impairment on Cobimetinib Pharmacokinetics: The Complex Interplay Between Physiological Changes and Drug Characteristics.

Cobimetinib is a kinase inhibitor indicated for use in combination with vemurafenib for treatment of unresectable/metastatic melanoma with specific BRAF mutations. Cobimetinib is extensively metabolized in liver; thus, patients with hepatic impairment (HI) might have increased cobimetinib exposure. In this study, we investigated the impact of HI on the pharmacokinetics (PK) and safety of cobimetinib. Subjects with normal hepatic function and mild to severe HI were enrolled. All subjects received a single oral dose of 10 mg cobimetinib, and serial blood samples were collected at specified times. Cobimetinib PK in subjects with mild and moderate HI was similar to that in those with normal liver function. However, subjects with severe HI, on average, showed ∼30% lower total AUC0-∞ and ∼2-fold higher unbound AUC0-∞ compared with those with normal hepatic function. These exposure differences can be explained by lower albumin levels observed in subjects with severe HI, the strong correlation between albumin level and the unbound fraction and the general PK variability of cobimetinib. In addition, previous studies with cobimetinib showed a lack of an exposure-response relationship for efficacy and safety. Therefore, collectively, our results suggest that the starting dose for patients with hepatic impairment can be the same as that for those with normal hepatic function.