Liver Function Status Research Articles

Management of Hepatocellular Carcinoma in 2024: The Multidisciplinary Paradigm in an Evolving Treatment Landscape.

Liver cancer is the third most common cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) makes up the majority of liver cancer cases. Despite the stabilization of incidence rates in recent years due to effective viral hepatitis treatments, as well as improved outcomes from early detection and treatment advances, the burden of HCC is anticipated to rise again due to increasing rates of metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease. The treatment landscape is evolving and requires a multidisciplinary approach, often involving multi-modal treatments that include surgical resection, transplantation, local regional therapies, and systemic treatments. The optimal approach to the care of the HCC patient requires a multidisciplinary team involving hepatology, medical oncology, diagnostic and interventional radiology, radiation oncology, and surgery. In order to determine which approach is best, an individualized treatment plan should consider the patient's liver function, functional status, comorbidities, cancer stage, and preferences. In this review, we provide an overview of the current treatment options and key trials that have revolutionized the management of HCC. We also discuss evolving treatment paradigms for the future.

The role of Recombinant interleukin-2 in the treatment of patients with chronic hepatitis B.

Dysregulated immune response occurring in chronic hepatitis B prevents the virus elimination and contributes to progression of the infectious process. The aim of the study was to evaluate the effectiveness (biochemical, immunological, virological) of combination treatment with tenofovir and Recombinant interleukin-2 in chronic hepatitis B patients.
 Material and methods. A comparative analysis of the results from laboratory examination of chronic hepatitis B patients in two comparison groups, comparable in sex, age, stage of fibrosis, viral load, was carried out: group I (n = 27) received tenofovir, according to the accepted recommendations, and recombinant interleukin-2 (rIL-2), group II (n = 25) — tenofovir.
 Results. Before the onset of antiviral therapy all patients with chronic hepatitis B had increased hepatic transaminases, alkaline phosphatase and gammaglutamyl transpeptidase from 1.2 to 5 norms as well as dysregulated cellular immunity factors with significantly decreased absolute count of CD4+, CD8+, CD16+ and increased CD20+ lymphocytes. After 12 months of treatment, patients in observation groups showed normalized cytolysis and cholestasis with insignificant intergroup differences. The level of absolute count of CD4+, CD8+ T-cells and CD16+ lymphocytes in the I group increased (by 24.7%, 24.1%, 34.5%, respectively, all p 0.001 relative to the initial values), not observed in comparison group. The level of CD20+ lymphocytes in group 1 was decreased by 35.9%, and in group 2 — by 7.9% (pI–II 0.001). In group 1, the level of HBsAg after 12 months of treatment became lower by 52% (p 0.001).
 Conclusion. The conducted pilot study showed that the combination etiopathogenetic therapy of patients with chronic hepatitis B using tenofovir and rIL-2 improves liver functional state, restores the disturbed balance of immunocompetent cells: by increasing level of CD4+, CD8+ T-lymphocytes, CD16+ lymphocytes and reducing the count of CD20+ cells, and also allows to steadily reduce blood serum HBsAg level.

Individualized nutritional intervention improves the nutritional status of liver cancer patients after transcatheter arterial chemoembolization.

Introduction: to explore the effect of individualized nutritional intervention on the nutritional status of patients with liver cancer after transcatheter arterial chemoembolization (TACE). Methods: 56 patients who underwent TACE in our hospital from March 2022 to March 2023 were selected as the study subjects. The patients were randomly divided into a control group (28 cases) and an intervention group (28 cases). The control group received routine dietary intervention, while the intervention group received individualized nutritional intervention. We analyzed the body mass index (BMI), nutritional risk screening 2002 (NRS 2002), nutritional status, liver function status, and incidence of complications in two groups of patients before TACE, 3 days after TACE, and 1 month after TACE. Results: on the third day after TACE, the nutritional related indicators of both groups of patients showed a significantly decrease compared to those before TACE (p < 0.05), while the majority of liver function indicators significantly increased (p < 0.05). Compared with those at 3 days after TACE, the nutritional status of the intervention group patients significantly improved (p < 0.05) and liver function indicators significantly decreased (p < 0.05) 1 month after TACE. One month after TACE, all nutritional indicators in the intervention group were significantly higher than those in the control group (p < 0.05), and AST was significantly lower than that in the control group (p < 0.05). The incidence of gastrointestinal complications and electrolyte disorders in the intervention group were significantly lower than that in the control group (p < 0.05). Conclusion Individualized nutritional intervention can effectively improve nutritional status, improve liver function, and reduce the incidence of postoperative complications in liver cancer patients after TACE. It was worth promoting.

Several laboratory variables indicate severity and prognosis of COVID-19.

While several laboratory variables have been used to assess COVID-19 disease, to our knowledge, no attempt has previously been made to compare differences across different patient groups. We attempted to evaluate the relationship between laboratory variables and severity of the disease as well as on prognosis. We searched BioLINCC database and identified three studies which had separately included outpatients, inpatients, and ICU patients. For this re-analysis, we extracted data on general demography, laboratory variables and outcome. In total, 2454 participants (496 outpatients [Study 1], 478 inpatients [Study 2], and 1480 ICU patients [Study 3]) were included in the analysis. We found three laboratory variables (i.e., creatinine, aspartate transferase, and albumin) were not only prognostic factors for outcome of inpatients with COVID-19, but also reflected disease severity as they were significantly different between inpatients and ICU patients. These three laboratory variables are an indication of kidney function, liver function, and nutritional status. For patients with COVID-19, in addition to monitoring infectious disease indicators, we need to pay attention to liver function, renal function, and take timely measures to correct them to improve prognosis.

Physiological and biochemical in vivo study of polyphenols and 20-hydroxyecdisone from quinoa grains effect on resistance to physical exercise in Wistar rats

Increasing the ability of the human body to adapt to physical stress is relevant from the standpoint of using foods for special uses containing functional food ingredients (FFI) with effectiveness proven in vivo. The purpose of this study was to evaluate the effect of FFI from Chenopodium quinoa grains with a high content of polyphenols and phytoecdysteroids on the physical endurance of male Wistar rats. Material and methods. The experiment was carried out during 36 days using 50 weaned male Wistar rats. The animals were randomly divided into 3 groups (n=12): Control, Run and Run-FFI. Rats of the Control and Run groups received a standard semisynthetic diet during the experiment. Rats of the Run-FFI group received a semi-synthetic diet with the addition of FFI in an amount of 0.055±0.003%, containing phytoecdysteroids (50.4±0.6 mg/g) and polyphenols (212.0±2.0 mg/g). During the experiment, the rats were assessed for their neuromotor function (grip strength of front paws), memory, and behavioral reactions in the "Elevated Plus Maze" (EPM), "Conditioned Passive Avoidance Reflex" (CPAR) and "Open Field" (OF) tests. Once a week, animals from the Run and Run-FFI groups were subjected to moderate physical load on a "Treadmill". On the 36th day of the experiment, the animals of these groups were subjected to exhausting physical load. Immediately after running, the animals were placed in metabolic cages to collect daily urine. At the end of the experiment, the content of corticosterone, the activity of catalase, indicators of protein, lipid and mineral metabolism, indexes of the liver functional state and antioxidant defense system parameters were analyzed in the blood serum; the level of prostaglandin E2 and dopamine were determined in daily urine. Results. Physiological tests (CRAR, OF) showed that weekly exercise increased anxiety in laboratory animals. The FFI introduction into the diet led to normalization of the assessed parameters (EPM). As a result of 36-day consumption of FFI against the background of physical loads, a significant decrease by 22% in the main stress marker, corticosterone, was revealed in the blood of rats, as well as significant increase by 23% in the stress inhibitor - prostaglandin E2 urinary excretion, compared with animals of the Run group to the level not differed from the indicators of the control animals. There were no differences in endurance performance between the Run and Run-FFI groups on the results of the exhaustive exercise. Consumption of FFI prevented the formation of excess ammonia, significantly reducing the level of urea in the blood and normalizing its excretion to control levels in the urine, which was increased in the Run group by 19%. Conclusion. The results obtained demonstrated the adaptogenic properties of the developed FFI in response to stress caused by weekly moderate and acute exhaustive physical activity. The obtained data on the biological effect of the developed FPI on the adaptive potential of laboratory animals will serve as an experimental basis for its inclusion in the composition of specialized foods.

Clearance tests to assess liver function state of animals using compounds with high hepatic metabolism

The article is devoted to the study of the medicinal substances metabolism in the liver and the possibility of using clearance tests with lidocaine and caffeine in veterinary medicine. It has been established that liver is the main organ where metabolism takes place, which is carried out in two stages involving the reactions of microsomal oxidation of fermentable cytochrome P450. Substances with a high metabolic rate undergo presystemic elimination. In liver pathologies, the metabolism of xenobiotics changes, substances with a high metabolism can cause toxic effects with a single application, with a low one – with cumulation. Intravenous clearance test with lidocaine showed that the lower the concentration of metabolites after 15 and 30 minutes, the more unfavorable the prognosis for survival. The test can also be used on dogs. The clearance test with caffeine can be performed intravenously, by respiratory methods or through saliva sampling. The test showed results comparable to the lidocaine test. However, clearance tests are influenced by many factors, so researchers recommend using them as an additional research method.

The predictive potential of sorbitol in assessing the liver functional state of productive animals

The predictive potential of sorbitol in assessing the liver functional state of productive animals

Impact of guideline adherence on the prognosis of Barcelona clinic liver cancer stage B hepatocellular carcinoma.

Patients with Barcelona clinic liver cancer (BCLC) stage B hepatocellular carcinoma (HCC) are considerably heterogeneous in terms of tumor burden, liver function, and performance status. To improve the poor survival outcomes of these patients, treatment approaches other than transarterial chemoembolization (TACE), which is recommended by HCC guidelines, have been adopted in real-world clinical practice. We hypothesize that this non-adherence to treatment guidelines, particularly with respect to the use of liver resection, improves survival in patients with stage B HCC. To assess guideline adherence in South Korean patients with stage B HCC and study its impact on survival. A retrospective analysis was conducted using data from 2008 to 2016 obtained from the Korea Central Cancer Registry. Patients with stage B HCC were categorized into three treatment groups, guideline-adherent, upward, and downward, based on HCC guidelines recommended by the Asian Pacific Association for the Study of the Liver (APASL), the European Association for the Study of the Liver (EASL), and the American Association for the Study of Liver Diseases (AASLD). The primary outcome was HCC-related deaths; tumor recurrence served as the secondary outcome. Survival among the groups was compared using the Kaplan-Meier method and the log-rank test. Predictors of survival outcomes were identified using multivariable Cox regression analysis. In South Korea, over the study period from 2008 to 2016, a notable trend was observed in adherence to HCC guidelines. Adherence to the EASL guidelines started relatively high, ranging from 77% to 80% between 2008 and 2012, but it gradually declined to 58.8% to 71.6% from 2013 to 2016. Adherence to the AASLD guidelines began at 71.7% to 75.9% from 2008 to 2010, and then it fluctuated between 49.2% and 73.8% from 2011 to 2016. In contrast, adherence to the APASL guidelines remained consistently high, staying within the range of 90.14% to 94.5% throughout the entire study period. Upward treatment, for example with liver resection, liver transplantation, or radiofrequency ablation, significantly improved the survival of patients with BCLC stage B HCC compared to that of patients treated in adherence to the guidelines (for patients analyzed according to the 2000 EASL guidelines, the 5-year survival rates were 63.4% vs 27.2%, P < 0.001), although results varied depending on the guidelines. Progression-free survival rates were also significantly improved upon the use of upward treatments in certain groups. Patients receiving upward treatments were typically < 70 years old, had platelet counts > 105/μL, and serum albumin levels ≥ 3.5 g/dL. Adherence to guidelines significantly influences survival in South Korean stage B HCC patients. Curative treatments outperform TACE, but liver resection should be selected with caution due to disease heterogeneity.

The Clinical Courses and Prognosis of Cirrhotic Patients after First Acute Decompensation: Prospective Cohort Study.

The European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium suggested that the clinical courses after acute decompensation (AD) stratify the long-term prognosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre acute-on-chronic liver failure (pre ACLF), and ACLF. However, previous studies included patients with a history of previous AD and had limitations associated with identifying the clinical factors related to prognosis after the first AD. The prospective Korean Acute-on-Chronic Liver Failure (KACLiF) cohort included cirrhotic patients who were hospitalised with first AD between July 2015 and August 2018. We analysed the factors associated with readmission after the first AD and compared the characteristics and prognosis among each subgroup to evaluate the risk factors for the occurrence of pre ACLF after AD. A total of 746 cirrhotic patients who were hospitalised with first AD were enrolled. The subgroups consisted of SDC (n = 565), UDC (n = 29), pre ACLF (n = 28), and ACLF (n = 124). Of note, pre ACLF showed a poorer prognosis than ACLF. The risk factors associated with readmission within 3 months of first AD were non-variceal gastrointestinal (GI) bleeding, hepatic encephalopathy (HE), and high MELD score. Viral aetiology was associated with the occurrence of pre ACLF compared with alcohol aetiology regardless of baseline liver function status. Cirrhotic patients with first AD who present as non-variceal GI bleeding and HE can easily relapse. Interestingly, the occurrence of AD with organ failure within 3 months of first AD (pre ACLF) has worse prognosis compared with the occurrence of organ failure at first AD (ACLF). In particular, cirrhotic patients with viral hepatitis with/without alcohol consumption showed poor prognosis compared to other aetiologies. Therefore, patients with ACLF after AD within 3 months should be treated more carefully and definitive treatment through LT should be considered.

Effect of milk thistle and silimevit on the functional state and protein synthesizing-function of the liver of laying hens under conditions of cadmium load

The purpose of the work was to study the effect of Cadmium on liver function disorders and to develop practical recommendations for using silimevit and milk thistle to reduce the toxic effect of Cadmium on chickens. To achieve the set goal in experiments on chickens under cadmium load, it was necessary to solve the following tasks: to study the effect of Cadmium on the protein synthesis function of the liver of laying hens; to study the effect of Cadmium on the functional state of the liver of laying hens; to investigate the effect of silimevit and the fruits of milk thistle on the functional state of the liver of laying hens under cadmium load; to investigate the effect of silimevit and milk thistle fruits on the protein synthesis function of the liver of laying hens under cadmium load and to justify the use of silimevit and milk thistle to prevent cadmium toxicosis in chickens. Drinking cadmium sulfate to laying hens violates the liver's functional state and protein-synthesizing function. A decrease in total protein and albumin content in their blood was established (Р &lt; 0.001). An increase in alanine and aspartate aminotransferase activity was detected (Р &lt; 0.001). Silimevit and milk thistle positively affect the functional state of the liver of laying hens under cadmium load, as evidenced by a decrease in the activity of aminotransferases in their blood serum. Silimevit and spotted thistle, under the cadmium load of laying hens, positively affect the liver's protein-synthesizing function, evidenced by an increase in total protein and albumin fraction. Feeding laying hens under cadmium load with slime feed contributed to a better-normalizing effect on the activity of aminotransferases and protein-synthesizing function of the chickens' liver than milk thistle.

The Complexity of the Tumor Microenvironment in Hepatocellular Carcinoma and Emerging Therapeutic Developments

This review explores various aspects of the HCC TME, including both cellular and non-cellular components, to elucidate their roles in tumor development and progression. Specifically, it highlights the significance of cancer-associated fibroblasts (CAFs) and their contributions to tumor progression, angiogenesis, immune suppression, and therapeutic resistance. Moreover, this review emphasizes the role of immune cells, such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T-cells (Tregs), in shaping the immunosuppressive microenvironment that promotes tumor growth and immune evasion. Furthermore, we also focused only on the non-cellular components of the HCC TME, including the extracellular matrix (ECM) and the role of hypoxia-induced angiogenesis. Alterations in the composition of ECM and stiffness have been implicated in tumor invasion and metastasis, while hypoxia-driven angiogenesis promotes tumor growth and metastatic spread. The molecular mechanisms underlying these processes, including the activation of hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) signaling, are also discussed. In addition to elucidating the complex TME of HCC, this review focuses on emerging therapeutic strategies that target the TME. It highlights the potential of second-line treatments, such as regorafenib, cabozantinib, and ramucirumab, in improving overall survival for advanced HCC patients who have progressed on or were intolerant to first-line therapy. Furthermore, this review explores the implications of the Barcelona Clinic Liver Cancer (BCLC) staging and classification system in guiding HCC management decisions. The BCLC system, which incorporates tumor stage, liver function, and performance status, provides a framework for treatment stratification and prognosis prediction in HCC patients. The insights gained from this review contribute to the development of novel therapeutic interventions and personalized treatment approaches for HCC patients, ultimately improving clinical outcomes in this challenging disease.

Advances in traditional Chinese medicine treatment of non-alcoholic fatty liver disease via farnesoid X receptor

Non-alcoholic fatty liver disease(NAFLD) is a chronic metabolic condition with rapidly increasing incidence, becoming a public health issue of worldwide concern. Studies have shown that farnesoid X receptor(FXR)-based modulation of downstream targets can improve liver function and metabolic status in the patients with NAFLD and may be a potential drug target for treating this di-sease. Great progress has been achieved in the development of drugs targeting FXR for the treatment of NAFLD. A number of studies have explored the traditional Chinese medicine and their active ingredients for the treatment of NAFLD via FXR considering the high safety and efficacy and mild side effects. This paper systematically describes the mechanism of traditional Chinese medicines in the treatment of NAFLD via FXR and the downstream targets, aiming to provide precise targets for the drug development and clinical treatment of NAFLD.

Effect of sustained release bolus oral administration on body condition change, blood parameters, and uterine health in primiparous cows under heat stress.

The transition period is very stressful for primiparous cows due to their first calving experience and will be more challenging if it occurs under heat stress conditions. Heat stress reduces the feed intake of dairy cows. Therefore, it reduces the consumption of minerals and vitamins. Oral administration of boluses through the provision of mineral-vitamin compounds can reduce metabolic abnormalities after calving. The present study aimed to evaluate effect of sustained-release bolus on body condition score (BCS) change, serum metabolites, uterine health, and reproductive status in primiparous cows. Heifers were selected at the beginning of the close-up period (n = 60, BCS = 3.35 ± 0.12). There were 2 experimental treatments at the time of calving: (1) heifers without bolus oral administration (H - Bo, n = 30); (2) heifers with bolus oral administration (H + Bo, n = 30). The results showed that although the rate of BCS loss was lower in the group receiving bolus, the effect of bolus was not significant. The effect of bolus on blood level of glucose, non-esterified fatty acids (NEFA), and beta-hydroxybutyrate (BHBA) was not significant; however, the highest concentration of albumin (P = 0.05) was observed in the H + Bo group on day 42 after calving. The concentration of aspartate transaminase (AST) tended to increase (P = 0.06) on day 14 after calving and entire the study. Total antioxidant capacity (TAC) was affected (P < 0.05) by bolus throughout the period of study, and the highest (P < 0.05) concentration of glutathione peroxidase (GPX) and superoxide dismutase (SOD) was observed in H + Bo group on day 42 after calving. The H + Bo group had the lowest (P < 0.05) vaginal discharge score (VDS). In general, oral administration of the sustained-release bolus in heifers significantly affected the antioxidant factors and uterine health, as well as had positive effects on liver function, body condition, and reproduction status.

Hepatorenal and renocardial syndrome in young patients with acute glomerulonephritis

In this paper we discuss classical types of acute glomerulonephritis in young adults, when the intake of paracetamol and diclofenac led to a dysfunctional and organic liver injury, at the same time it negatively affected the course of acute glomerulonephritis. To study the characteristics of the development of acute reno-cardial syndrome (ARCS) Goal: Assessment of cause and effect relations of renal, hearts and liver injuries in young adults in acute post-streptococcal glomerulonephritis (APSG). With acute nephritic syndrome (ANS) complicated by acute kidney injury (AKI) and without it, to identify the role of the etiological factor on the course of APSG. Methods and Material: 220 male patients with APSG with ANS aged 18-20 were examined. The patients were divided into 2 groups based on the functional state of kidneys. The first group included 140 patients with APSG without ANS, the second group included 80 patients with AKI. Results: Out 66 patients had subclinical liver injury, which resulted from the effect of antipyretic hepatotoxic drugs taken in the initial stage of the disease. Due to the toxic and immunological liver injury, levels of transaminases increase, and albumin levels decrease. These changes occur along with the development of APSG and are correlated with some laboratory values. Impairment of cardiovascular function was observed in all 220 patients. ECG and Echocardiography studies conducted during the cardiac asthma attacks occurred as a decrease of voltage, broadening of the P wave, lengthening of the PQ interval, broadening of the QRS complex, dilatations of the right and left atrium. The severity of clinical manifestations of AKI and ARCS correlates with the degree of macrohematuria, GFR decrease, complement C3 fraction, monocyte. Conclusion. In APSG liver injury has a toxicoallergic character. Frequency of liver injury depends on specific features of a particular organism, it does not depend on the dose of the taken drug. In case of any type of acute glomerulonephritis it is necessary to assess the functional state of liver and after the treatment of the main disease hepatologist follow-up of patients is recommended. Thus in the development of acute reno-cardial syndrome (ARCS) the degree of manifestation of hypervolemia with hypertension, as a result of active immune inflammation of the glomerular apparatus with the development of AKI, plays the main role in the development of ARCS with APSG.. As a rule ARCS in case of APSG with ANS in young adults has a successful outcome.

Comparative therapeutic efficacy of oral administration of gluconeogenic precursors with nicotinamide and intravenous hypertonic dextrose solution for management of subclinical ketosis in Chilika buffaloes.

Ketosis in dairy animals originates from negative energy status, associated increased absorption, and production of ketone bodies exceeding their use by the ruminants as an energy source. The present therapeutic experiment was carried out in 29 herds of Chilika buffaloes in 16 villages of three adjoining districts of Chilika Lake, Puri, Khurda, and Ganjam. Twenty Chilika buffaloes, detected positive for subclinical ketosis, were randomly selected for the study and divided into 2 groups, groups II and III, and were treated with hypertonic dextrose solution intravenously or gluconeogenic precursors along with nicotinamide orally, along with other supportive drugs in both the groups. Ten lactating Chilika buffaloes with no signs of ketosis and detected negative on Rothera test were included in the study as healthy controls (group I). Blood and milk samples were collected from all the 30 recruited buffaloes on days 0 (pre-treatment), 7, 14, and 28 for haematological and biochemical analysis. The subclinical ketosis in Chilika buffaloes did not have overt clinical signs. However, close examination revealed gradual drop in milk yield (100%), inappetence (59%), debility (46%), and uncoordinated gait (10%) without excitatory nervous signs. On day 7 following treatment, blood glucose concentration increased significantly. The mean serum triglyceride concentration of group III, treated with gluconeogenic precursors with nicotinamide, continued to decline significantly on subsequent observations. The serum enzyme activity, indicating status of liver function, declined following treatment in both the therapeutic groups. The intravenous administration of hypertonic dextrose solution compared to use of oral gluconeogenic precursors along with nicotinamide efficiently restored recovery from the subclinical ketosis in Chilika buffaloes.

Expert consensus on precise diagnosis and management of primary hepatocellular carcinoma in advanced stage (2023 version)

not matching with chinese abstract stage in China. By adopting the "Delphi" consensus formation method, a set of precise staging criteria and corresponding preferred treatment protocols were agreed upon for Chinese patients with hepatocellular carcinoma in advanced stage, taking into account different tumor characteristics, vascular embolism grading, distant metastasis and liver function status, portal hypertension, hepatitis B virus replication status, etc., as well as the prognosis of the patients. This consensus is intended to provide a more detailed, scientific, and reasonable reference basis for the selection of individualized diagnosis and treatment plans for frontline clinicians.

Clinical characteristics of liver injury induced by immune checkpoint inhibitors in patients with advanced biliary tract carcinoma.

Immune-related liver injuries are closely associated with the liver's fundamental state. Patients with advanced biliary tract carcinoma (BTC) have poor liver function. We evaluated the clinical data of immune-related liver injury in patients with advanced BTC and gastric cancer (GC) during immune checkpoint inhibitor (ICI) treatment between February 2019 and July 2022 at Peking University First Hospital. Twenty-five patients with advanced BTC were identified. Fifteen patients (60%) experienced immune-related liver injury during ICI treatment. We also evaluated the clinical status of patients with GC in another group receiving immunotherapy. The results demonstrated that the incidence of immune-related liver injury was higher in patients with BTC than in GC cancer (p=0.040). Multivariate analysis suggested that the type of malignant tumor and baseline liver function status were high-risk factors for grade 2 and higher immune-related liver injuries. Two patients were diagnosed with immune-related cholangitis. Both biliary enzymes can be decreased to a certain degree by corticosteroid and ursodeoxycholic acid (UDCA) therapy but are difficult to reduce to normal levels. Liver function normalized, and symptoms improved after local treatment for cholestasis (stent implantation or PTBD). We observed a higher incidence of immune-related liver injury after ICI treatment in patients with advanced BTC. Effect of baseline liver function on the incidence of liver injury associated with immunotherapy. Interventional therapy provides rapid relief from cholestasis and is an indispensable and effective approach to the treatment of immune-related cholangitis.

Unlocking the Power of Late-Evening Snacks: Practical Ready-to-Prescribe Chart Menu for Patients with Cirrhosis.

The efficacy of the late-evening snack (LES) has been extensively studied due to the impact of the longest intermeal duration occurring at night in patients with cirrhosis. While actual clinical guidelines on nutrition in chronic liver disease recommend an LES, no specific nutritional compositions have been reported by the European Association for the Study of the Liver (EASL) and the European Society for Clinical Nutrition and Metabolism (ESPEN). Late-evening snacks vary greatly among studies, including natural foods and/or nutritional supplements, yet oral supplements still need to fully meet the LES's nutritional composition. In addition, many hepatologists need to gain experience in nutritional approaches and have access to registered dieticians who can help them manage patients with liver disease. Therefore, this review study aims to summarise evidence regarding using LESs and the mechanisms behind long starvation in patients with cirrhosis. It also provides a practical nutritional guide with several LES options based on common natural foods tailored to special patients' nutritional requirements and geographical backgrounds. In preventing accelerated starvation and related protein malnutrition and sarcopenia in patients with cirrhosis, the nutritional composition of LESs is essential. The proper and straightforward application of the LES's rational nutrition is an advantage to cirrhotic patients and should be carried out by healthcare professionals to enhance the overall liver function and nutritional status of patients with cirrhosis.

Indolent cancer and pattern of progression: Two missing parameters in trial design for hepatology.

The indolent and aggressive behaviors of HCC might have a role in clinical trial (CT) results; however, the indolent HCC is less analyzed compared to others cancer. Indolent profile could be characterized as follows: (1) patients with low risk of progression itself due to the HCC molecular profile and/or due to the interaction between cancer cell their microenvironment; (2) patients who achieve objective response or present spontaneous regression; and (3) patients who develop radiological progression with no consequence on either the liver function or general status, and without trigger a change in the tumor stage. Patients with "indolent HCC" generally never develop cancer-related symptoms neither die for HCC-related causes. Thus, we hypothesize that the imbalance in the proportion of "indolent" versus "aggressive HCC" between arms or the underestimation/overestimation of HCC behavior at baseline in single-arm CT could be associated with CT failure or under-overestimation of trial results. The "indolent progression" may also explain the discrepancy between radiological progression-based end points and survival. Moreover, we discuss the related causes that explain the indolent profile of HCC and propose (1) refining the progression-related end point by the pattern of progression to minimize the limitations of the current end points; (2) considering alternative statistical tools for survival analysis such as milestone survival, or restricted mean survival time to capture the value of indolent HCC. According to these considerations, we propose incorporating novel end points into the single arm of phase I/II CT as exploratory analysis or as a secondary end point in phase III CT.

Uji Aktivitas ALT, AST dan Histopatologi Ekstrak Etanol Rimpang Temu Kunci (Boesenbergia rotunda (L.) Mansf) pada Tikus Putih Jantan

Experimental research in the field of hepatology on the development of traditional medicine into a potential pharmacological solution to protect the liver from cirrhosis. Accordingly, this study investigated the effect of ethanol extract of temu kunci rhizome on liver cirrhosis. The rats were divided into six groups, the normal control group was given nothing but pellets and sufficient water, the negative control group was given orally CMC-Na 0.5%, 200 mg acetylcysteine (dose converted to rat) was given to the positive control group, and the treatment group was given ethanol extract of temu kunci rhizome doses of 250, 500, 750 mg/kg BW, given daily for 10 days. Then on the 10th day after 1 hour of extract administration, induction was carried out with paracetamol 800 mg/kg BW orally; 16 hours after induction, rats were sacrificed, blood was taken for ALT and AST enzyme examination, then liver organs were taken for histopathological examination. The administration of ethanol extract of temu kunci rhizome can prevent liver damage by reducing ALT and AST enzyme levels in rat blood serum. The best dose in reducing ALT and AST enzymes was produced by giving 500 mg/kg BW of temu kunci rhizome ethanol extract every day for 10 days. At a dose of 500 mg/kg BW ethanol extract of temu kunci rhizome morphologically (evaluation with H&amp;E staining) can also repair liver tissue damaged by paracetamol induction. The development of liver damage can be interpended by using ethanol extract of temu kunci rhizome, so that the status of liver morphology, structure and function of the liver can be maintained.