Impaired Liver Function Research Articles

Efficacy of endovascular treatment for completely occlusive acute–subacute portal and mesenteric vein thrombosis with severe complications in patients without cirrhosis

PurposeCompletely occlusive acute–subacute portal and mesenteric vein thrombosis (PVMVT) with severe complications is fatal. Endovascular treatments (EVTs) of acute–subacute PVMVT are not standardized. Thrombectomy combined with continuous catheter-directed thrombolysis is considered an effective treatment. Here, we aimed to evaluate the outcome of EVTs of completely occlusive acute–subacute PVMVT with severe complications in patients without cirrhosis.Materials and methodsNineteen patients (nine men and 10 women; age, 60.1 ± 16.8 years) with completely occlusive acute–subacute PVMVT were retrospectively assessed. Acute–subacute PVMVT was defined as symptom onset within 40 days, with no cavernous transformation observed on contrast-enhanced computed tomography. The patients were treated with EVTs, a combination of thrombectomy (including aspiration thrombectomy, plain old balloon angioplasty, single injection of thrombolytic agents, and stent placement) and continuous catheter-directed thrombolysis. Kaplan–Meier analyses were performed to assess all-cause mortality, acute–subacute PVMVT-related mortality, and portal vein (PV) patency. The degree of recanalization and patency of PV, complications, factors related to acute–subacute PVMVT-related mortality, and factors related to patency of PV were also evaluated.ResultsThe all-cause and acute–subacute PVMVT-related mortality rates were 36.8% (7/19) and 31.6% (6/19), respectively. Seven (36.8%) and 11 (57.9%) patients achieved complete and partial recanalization, respectively. Among the 18 patients who achieved recanalization, follow-up images after 608.7 ± 889.5 days confirmed recanalization in 83.3% (15/18) patients, and 53.3% (8/15) of these patients achieved patency of PV. Seven patients (36.8%) developed complications, and two (10.5%) required interventional treatment for complications. Deterioration of liver function significantly worsened the prognosis (P = 0.046), while anticoagulation therapy significantly maintained portal patency (P = 0.03).ConclusionThis endovascular method for acute–subacute PVMVT, which combines thrombectomy and continuous catheter-directed thrombolysis EVT approach was effective for thrombus resolution. However, further studies must define conditions that improve patient prognosis.

Subcostal transversus abdominis plane block for postoperative analgesia in liver transplant recipients: a before-and-after study

IntroductionPostoperative pain management after orthotopic liver transplantation is complex due to impaired liver function and frequent acute kidney dysfunction. Subcostal transversus abdominis plane (TAP) block may be of interest in...

Outcome of patients with HCC and liver dysfunction under immunotherapy: a systematic review and meta-analysis.

Immunotherapy-based regimes have changed the management of HCC. However, evidence of efficacy in patients with impaired liver function is unknown. This systematic review and meta-analysis assesses survival of HCC patients and liver dysfunction treated with immunotherapy-based regimens. Systematic review and meta-analysis of original articles or abstracts reporting survival of HCC patients treated with immunotherapy according to liver function between 2017 and 2022. Overal survival (OS) according to restricted mean survival time (RMST) and median OS, and hazard ratio (HR) of Child-Pugh B or B/C versus Child-Pugh A were assessed while considering the line of treatment. Of the 2218 articles considered, 15 articles recruiting 2311 patients were included. Of these, 639 (27.7%) were Child-Pugh B and 34 (1.5%) C. RMST was 8.36 (95% CI, 6.15-10.57; I2 =93%) months, estimated from 8 studies. The HR was reported in 8 studies for survival between Child-Pugh B versus Child-Pugh A and metanalysis disclosed a 1.65 HR (95% CI,1.45-1.84; I2 =0% heterogeneity; p = 0.45). Treatment line data were available for 47% of the patients and 3 studies included patients treated with atezolizumab-bevacizumab in the first line. The high heterogeneity across studies reflects the incapacity of the current evidence to support the indication of immunotherapy in HCC patients with relevant liver dysfunction. It is mandatory to report complementary information to Child-Pugh classification such as prior liver decompensation, use of concomitant medication to control ascites, or signs of clinically significant portal hypertension to allow better patient stratification in future studies.

Quanduzhong capsules for the treatment of grade 1 hypertension patients with low-to-moderate risk: A multicenter, randomized, double-blind, placebo-controlled clinical trial.

Background: Duzhong [DZ (Eucommia ulmoides Oliv.)] is regarded as a traditional Chinese medicine with a history dating back more than 2000years. This herb is considered a nourishing herb in China and is commonly used as a tonic to strengthen muscles and bones, nourish the kidneys and liver, and soothe miscarriages. Moreover, there is evidence that DZ is capable of regulating blood pressure (BP), and several compounds isolated from DZ have been shown to have a BP-lowering effect. Quanduzhong capsules contain an extract of DZ [Eucommia ulmoides Oliv. (Eucommiaceae; Eucommiae cortex)] that is effective in treating hypertension. This multicenter, randomized, double-blind, placebo-controlled clinical trial sought to evaluate the clinical efficacy of Quanduzhong capsules in the treatment of low-to-moderate risk grade 1 hypertension patients. Materials and methods: A total of 60 patients from 3 centers with documented low-to-moderate risk grade 1 hypertension were randomly assigned in a 1:1 ratio to the test group or the control group. After a 1week lead-in period using sham Quanduzhong capsules, all patients who met the entry criteria (29 cases in the test group and 29 cases in the control group) entered the 4week test period. The test group took Quanduzhong capsules, and the control group continued to take sham Quanduzhong capsules. The primary endpoints [24-h mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) determined via 24-h ambulatory blood pressure monitoring (ABPM); office SBP and DBP] and secondary endpoints [mean arterial pressure; mean pulse; daytime mean SBP and DBP; nocturnal mean SBP and DBP; SBP and DBP load; area under the blood pressure (BP) curve; morning peak BP; early morning SBP and DBP; smoothness index of SBP and DBP; 24h BP mean coefficient of variation (CV); percentage of patients with circadian restoration in ABPM; home BP; quality of life evaluated by WHO Quality of Life-BREF questionnaire; grading and quantitative evaluation of hypertension symptoms; values of plasmatic renin activity, angiotensin II, aldosterone, β-2 microglobulin and homocysteine] were assessed following the treatment. Drug-related adverse events and adverse drug reactions were also compared. Results: After a 4week test period, a significant difference in the DBP CV between the two groups was observed (-2.49 ± 4.32 vs. 0.76 ± 4.3; p < .05). Moreover, the mean office SBP change was -7.62 ± 9.32mmHg, and the mean DBP change was -4.66 ± 6.03 (p < .05). Among the three subjects with abnormal homocysteine levels in the test group, homocysteine levels decreased by 6.23 ± 9.15μmol/L after treatment. No differences were observed between the two groups in any other indicators. After 4weeks of treatment, there were no significant differences between the groups in terms of safety indicators (p > .05). No abnormal vital signs (except BP) or severe liver or renal function impairment were observed during the treatment periods; in addition, adverse events and drug reactions were mild. Conclusion: Treatment with Quanduzhong capsules reduced office SBP and DBP as well as DBP CV determined by 24-h ambulatory BP monitoring in patients with grade 1 hypertension at low-to-moderate risk. Clinical Trial Registration: https://www.chictr.org.cn/showproj.aspx?proj=32531, identifier ChiCTR1900021699.

Role of Autophagy and Apoptosis in Aluminum Exposure-Induced Liver Injury in Rats.

Aluminum (Al) exposure can lead to different degrees of damage to various organ systems of the body. It has been previously revealed that Al exposure can damage the liver, causing liver dysfunction. However, the specific mechanism remains unclear. This research aims to uncover the damaging effect of Al exposure on rat liver and to demonstrate the role of autophagy and apoptosis in this effect. Thirty-two Wistar rats were randomly divided into the control group (C group), low-dose Al exposure group (L group), middle-dose Al exposure group (M group), and high-dose Al exposure group (H group) (n = 8). The rats, respectively, received intraperitoneal injections of 0, 5, 10, and 20mg/kg·day AlCl3 solution for 4weeks (5 times/week). After the experiment, changes in the ultrastructure and autolysosome in rat liver were observed; the liver function, apoptosis rate, as well as levels of apoptosis-associated proteins and autophagy-associated proteins were detected. The results indicated that Al exposure damaged rat liver function and structure and resulted in an increase in autolysosomes. TUNEL staining revealed an elevated number of apoptotic hepatocytes after Al exposure. Moreover, we found from Western blotting that the levels of autophagy-associated proteins Beclin1 and LC3-II were increased; apoptotic protein Caspase-3 level was elevated and the Bcl-2/Bax ratio was reduced. Our research suggested that Al exposure can lead to high autophagy and apoptosis levels of rat hepatocytes, accompanied by hepatocyte injury and impaired liver function. This study shows that autophagy and apoptosis pathways participate in Al toxication-induced hepatocyte injury.

The circadian rhythm gene Bmal1 ameliorates acute deoxynivalenol-induced liver damage.

Deoxynivalenol (DON) is widely emerging in various grain crops, milk, and wine products, which can trigger different toxic effects on humans and animals by inhalation or ingestion. It also imposes a considerable financial loss on the agriculture and food industry each year. Previous studies have reported acute and chronic toxicity of DON in liver, and liver is not only the main detoxification organ for DON but also the circadian clock oscillator directly or indirectly regulates critical physiologically hepatic functions under different physiological and pathological conditions. However, researches on the association of circadian rhythm in DON-induced liver damage are limited. In the present study, mice were divided into four groups (CON, DON, Bmal1OE, and Bmal1OE + DON) and AAV8 was used to activate (Bmal1) expression in liver. Then mice were gavaged with 5mg/kg bw/day DON or saline at different time points (ZT24 = 0, 4, 8, 12, 16, and 20h) in 1day and were sacrificed 30min after oral gavage. The inflammatory cytokines, signal transducers, and activators of transcription Janus kinase/signal transducers and activator of transcription 3 (JAKs/STAT3) pathway and bile acids levels were detected by enzyme-linked immunosorbent assay (ELISA), western blotting, and target metabolomics, respectively. The DON group showed significantly elevated interleukin-1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) levels (P < 0.05 for both) and impaired liver function with rhythm disturbances compared to the CON and Bmal1OE groups. At the molecular level, expressions of some circadian clock proteins were significantly downregulated (P < 0.05 for both) and JAKs/STAT3 pathway was activated during DON exposure, accompanied by indicated circadian rhythm disturbance and inflammatory damage. Importantly, Bmal1 overexpression attenuated DON-induced liver damage, while related hepatic bile acids such as cholic acid (CA) showed a decreasing trend in the DON group compared with the CON group. Our study demonstrates a novel finding that Bmal1 plays a critical role in attenuating liver damage by inhibiting inflammatory levels and maintaining bile acids levels under the DON condition. Therefore, Bmal1 may also be a potential molecular target for reducing the hepatotoxic effects of DON in future studies.

Urinary trihalomethane concentrations and liver function indicators: a cross-sectional study in China.

While it is known that exposure to disinfection by-products (DBPs), including trihalomethanes (THMs), impairs liver function, few epidemiological studies have explored this association. Here, we determined the concentrations of four urinary trihalomethanes (chloroform [TCM], and three Br-THMs, bromodichloromethane [BDCM], dibromochloromethane [DBCM], and bromoform [TBM]), and nine serum liver function indicators in 182 adults ≥ 18years of age, examined at a medical examination center in Wuxi, China, in 2020 and 2021. Generalized linear model analysis revealed positive associations between urinary DBCM and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), total protein (TP), and albumin (ALB). Urinary Br-THMs and total THMs (TTHMs) were positively associated with ALT, AST, TBIL, indirect bilirubin (IBIL), TP, and ALB (all P < 0.05). Urinary THMs were not associated with alkaline phosphatase (ALP) or glutamine transaminase (GGT) (all P > 0.05). Generalized additive model-based penalized regression splines were used to confirm these associations. In conclusion, THM exposure was associated with altered serum biomarkers of liver function.

Лечение пациентов с хронической HDV‑инфекцией – опыт реальной клинической практики в Московской области

Objective. This study aims to analyze the results of using bulevirtide, an HBV and HDV entry inhibitor, in real-world practice in patients with chronic hepatitis D in the Moscow region. The analysis focuses on the effectiveness and safety of bulvertide treatment, both as monotherapy and in combination with peginterferon, during the compensated and decompensated stages of liver cirrhosis. Patients and methods. The study evaluated the efficacy and safety of bulevirtide treatment in two patient groups. The first group consisted of 61 patients with compensated disease, including 27 individuals with Child–Pugh class A liver cirrhosis. The second group included 8 patients with Child–Pugh class B cirrhosis. Results. Among patients with compensated disease, a 48-week treatment with bulevirtide resulted in a significant decrease in HDV RNA levels from 6.9 log10 to undetectable (p &lt; 0.001). Furthermore, alanine aminotransferase (ALT) levels decreased from 64.0 to 37.0 U/l (p &lt; 0.001). The median reduction in HDV RNA levels from baseline was -5.1 log10 (monotherapy: -4.2 log10, dual therapy: -5.7 log10). The virological response rate was 94% (monotherapy: 88%, dual therapy: 96%) with «full virological response» (aviremia) observed in 66% of patients and normal ALT levels in 59% of patients (compared to 22% at baseline). Virological efficacy improved over the course of treatment. Similar virological response dynamics were observed in patients with compensated cirrhosis compared to the overall group. In patients with decompensated cirrhosis, a virological response was observed in 6 out of 8 patients during treatment, and a biochemical response (a decrease in ALT levels from 60.0 U/I to 45.0 U/l) in 5 out of 8 patients. After 48 weeks of treatment, all 5 patients who reached this point achieved a virological response (decrease in HDV RNA levels from 5.1 log10 to 3.0 log10, median decrease of -2.5 log10 from baseline). One patient on monotherapy achieved «full virological response» (aviremia). Improvement of liver function was observed, including a reduction in liver damage severity based on Child–Pugh score to the compensated cirrhosis level (6 points), down-staging from Child–Pugh class B to A in 3 patients, and clinical resolution of ascites in 7 out of 8 patients and hepatic encephalopathy in 3 out of 5 patients. Bilirubin, albumin, INR, prothrombin time remained stable. The treatment was well tolerated, no serious adverse events, cases of treatment withdrawal were registered. The reduction in leukocyte and platelet counts, related to interferon, did not necessitate treatment adjustment. Conclusion. The analysis of bulevirtide use in patients with CHD in real-world practice demonstrated high treatment efficacy, safety and good tolerability, even in cases of compensated and decompensated liver cirrhosis. This study also presents the first experience of antiviral therapy for decompensated liver cirrhosis in Russia, supporting the recommendation of bulevirtide for patients with impaired liver function. Furth er development of an optimal treatment algorithm, including for patients with impaired liver function, is needed, as well as clarification of the treatment effect on clinical outcomes and disease prognosis. Key words: bulevirtide, chronic hepatitis D, compensated cirrhosis, decompensated cirrhosis, chronic liver failure

Опыт противовирусной терапии хронического гепатита D на стадии цирроза с нарушениями функции печени

Objective. To evaluate the possibility of using bulevirtide, the HBV and HDV entry inhibitor, in patients with chronic hepatitis D (CHD) at the stage of decompensated cirrhosis. Patients and methods. The results of the use of bulevirtide 2 mg in 14 patients with CHD at the stage of cirrhosis with impaired liver function – class B (13 patients) and C (1 patient) according to Child–Pugh were analyzed; 12 patients received monotherapy with bulevirtide, 2 patients received combination therapy with bulevirtide and peginterferon. Results. The use of bulevirtide for 48 weeks demonstrated a reduction in HDV RNA levels from 6.1 log10 to 3.6 log10 (p = 0.006); the achievement of a virological response in 70% of patients, a decrease in the level of alanine aminotransferase (ALT) from 52 to 29 U/L (р = 0,04), an increase in the frequency of detection of normal ALT levels compared with the baseline (from 43 to 82%), a decrease in liver stiffness from 20.8 kPa to 18.6 kPa (p = 0.016) (with a median decrease of 10.1 kPa); safety and good tolerability (no serious adverse events (AEs), severe or moderate AEs, cases of discontinuation of treatment). Positive dynamics of liver function parameters was observed: a decrease in the severity of liver disease to the level of compensated cirrhosis (decline in Child–Pugh score by 2 points), the frequency of hepatic encephalopathy (from 86 to 9%), ascites (from 64 to 18%), bilirubin levels, increased levels of albumin, prothrombin. The dynamics of the number of leukocytes and platelets during treatment did not require treatment correction. Conclusion. The analysis of the first experience in Russia of antiviral therapy for CHD and decompensated cirrhosis allows us to recommend the use of bulevirtide in this category of patients. Further studies are needed to clarify the optimal treatment regimens, the impact of treatment on clinical outcomes, the risk of hepatic complications (decompensation, HCC, death from liver failure or transplantation) and patient survival. Key words: bulevirtide, chronic hepatitis D, decompensated cirrhosis, chronic liver failure

Эффективность и безопасность булевиртида в лечении хронического гепатита D – опыт реальной практики в Санкт-Петербурге

Objective. To study the efficacy and safety of bulevirtide, the HBV and HDV entry inhibitor in patients with chronic hepatitis D, including compensated cirrhosis, in real practice. Materials and methods. Analysis of the interim 24-week results of bulevirtide therapy (monotherapy and combination with peginterferon) in 24 patients including patients with HIV co-infection. Results. After 24 weeks of treatment, the virological response rate was 75%, including patients on monotherapy (63%) and combination therapy (100%). The levels of HDV RNA declined by -2.9, -2.6 and -4.3 log10 copies/ml from initial, respectively. In 7 patients the level of HDV RNA was undetectable (3 patients on monotherapy, 4 patients on combination therapy). All patients had normal ALT. The effectiveness of treatment (virologic and biochemical response) increased with a longer treatment period, from 12 to 24 weeks. Treatment was well tolerated with no serious, severe or moderate adverse events reported. The discontinuation of treatment was observed in only one case, despite the achievement of a virological response, in an 80-year-old patient with cirrhosis, due to a deterioration in liver function, probably due to the progressive course of the disease. Conclusion. The interim real practice results demonstrated high efficacy and good tolerability of bulevirtide in patients with CHD (chronic hepatitis D), including compensated cirrhosis, and patients with HIV co-infection. Bulevirtide is recommended as the treatment of choice for CHD (as monotherapy or combination therapy with peginterferon). Key words: bulevirtide, chronic hepatitis D, combination therapy, HIV co-infection, monotherapy, peginterferon, real practice

Опыт противовирусной терапии хронического гепатита D в Кабардино-Балкарской Республике

Objective. To study the results of the application of an innovative strategy for antiviral therapy of chronic hepatitis D (CHD) in real practice. Patients and methods. Evaluation of the efficacy and tolerability of bulevirtide, HBV and HDV entry inhibitor, in 8 patients with CHD: in monotherapy in 3 patients, combined therapy with peginterferon alfa in 5 patients. Results. High virological efficacy of both treatment regimens was demonstrated for 48 weeks: all patients on monotherapy, 4 of 5 patients on combination therapy achieved a virological response. The maximum decline in viral load was 5.8 log10 from baseline with monotherapy, 6.6 log10 with combination therapy. HDV RNA undetectable level was observed in all patients on combination therapy (in 2 patients – by week 12, in 1 – by week 24, in 1 – by week 36) and in 1 patient on monotherapy (by week 24). In 2 patients with undetectable HDV RNA level, the resumption of viremia was noted after interruptions in treatment, which emphasizes the need for adherence to treatment for the formation of a stable virological response. The tolerability of treatment was good, no serious adverse events, cases of withdrawal of treatment, deterioration of liver function in cirrhosis were reported. The number of white blood cells remained stable (3.2–3.4 × 109/l), the number of platelets decreased by week 24 from 104 to 83 thousand cells × 109/l, followed by self-recovery to the baseline by week 48. Conclusion. The data obtained confirm the validity of the choice of an innovative strategy for antiviral therapy of HCD in real practice, indicate the high efficacy and good tolerability of bulevirtide in monotherapy and combination therapy in patients with CHD, including with compensated cirrhosis. Key words: bulevirtide, chronic hepatitis D, combination therapy, monotherapy, peginterferon, real practice

Противовирусная терапия хронического гепатита D в Республике Крым – опыт реальной практики

Objective. The analysis of the results of antiviral therapy of chronic hepatitis D (HDV) in real practice using bulevirtide, an inhibitor of the entry of hepatitis B and D viruses (HDV) into the hepatocyte. Patients and methods. Intermediate treatment results were studied in 6 patients with HDV, including 3 patients with compensated cirrhosis who received bulevirtide in combination with pegylated interferon-α for 48 weeks, as well as in 3 patients who continued treatment (in combination therapy or monotherapy) for up to 60–64 weeks. Results. After 48 weeks of combination therapy, the HDV RNA level decreased from 6.5 log10 to 1.0 log10 ( p = 0.015), the median decrease was 3.4 log10, the frequency of virological response was 83%, and aviremia was 50%. Virological efficacy increased with treatment. In 3 patients, an increase in the initially normal level of alanine aminotransferase (ALT) associated with the use of interferon was noted, followed by a decrease or normalization; in 2 patients with initially moderate and high liver activity, ALT levels decreased by 35 and 354 U/l, respectively. Virological and biochemical response was maintained in all 3 patients who continued treatment up to 60–64 weeks, including aviremia in 1 patient. No serious adverse events, cases of withdrawal of treatment or deterioration of liver function in cirrhosis have been reported. Conclusion. The analysis of the intermediate results of CHD treatment in real practice has demonstrated the effectiveness, safety and good tolerability of bulevirtide, including at the stage of compensated liver cirrhosis. Further study of optimal treatment regimens is needed to achieve treatment goals and improve the prognosis of the disease. Key words: bulevirtide, chronic hepatitis D

Use of hepatocyte transplantation after extensive liver resections in experiment.

he aim of our research is to prove, that the transplanted hepatocytes can survive and compensate for inadequate liver function in experimental animals. Thesis discusses the basic principles of hepatocyte transplantations, the process of their adaptation and effect on the organism as well as possibilities of their further use as apromising treatment method.In the experiment we used hepatocytes isolated and produced from explanted livers of laboratory rats. Hepatocytes form the basis of liver tissue and are responsible for anumber of metabolic processes ocurring in the liver, therefore is the possibility of their use as acell therapy one of the alternative treatment methods for liver failure.Into the laboratory experiment, rats of the Sprague Dawleyspecies were placed, which we divided into five groups of equal numbers. Groups consisted of healthy rats, rats after 2/3 liver resection and rats with liver damage induced by intraperitoneal administration of thioacetamide.Two groups with impaired liver had hepatocytes prepared in advance transplanted into their portal vein.Hepatocyte function was assessed in the blood serum and compared with acontrol group of healthy animals and groups with liver damage without the application of hepatocytes at the same time intervals.Whole experiment lasted 21 days. On the last day of the experiment all the animals were killed by decapitation.Livers of all animals were explanted and sent for histopathological analysis which used classical histological methods. After evaluating the results we observed significant changes of evaluated laboratory levels in blood serum and weight in experimental animals after the transplantation of hepatocytes in comparison with the laboratory results of the control group of healthy animals and groups with liver damage without transplanted hepatocytes. The results of our experiment show that by biochemical and histological analysis we managed to clearly prove the function of transplanted hepatocytes in the model of laboratory rat with impaired liver function (Tab. 5, Fig. 17 , Ref. 17) Keywords: liver, transplantation, hepatocytes, liver tumors, resection of liver, liver failure, experiment.

Health risk assessment associated with priority potentially hazardous chemical compounds detected in canned meat and meat-and-vegetable food for infants

Assessment of public health safety associated with chemical contaminants consumed with food is an important component for solving the tasks of ensuring the sanitary and epidemiological well-being of the population. For these purposes, it is necessary to establish priority potentially dangerous compounds among the identified undeclared and unintended chemical contaminants for further consumers risk assessment. In conditions of unacceptable levels of health risk, it is necessary to decide whether it is advisable to develop new or change existing hygiene standards for these substances. The aim of the study was to assess the health risk associated with priority potentially dangerous unintended chemical components of contamination in canned meat and meat-and-vegetable products for infants (using the example of N-nitrosoamines). Material and methods. The selection of priority chemical compounds and public health risk assessment were carried out in accordance with the procedure for identifying undeclared and potentially dangerous unintended chemicals in food and using modified approaches based on the results of previous studies. Health risk assessment for infants consuming canned meat and meat-and-vegetables containing priority chemicals was carried out in accordance with the methodology approved by the Eurasian Economic Commitee, as well as using the Guidelines for assessing risks to public health when exposed to environmental pollutants. To characterize the calculated risk levels, the classification proposed in the draft document «Guidelines for assessing risks to public health when exposed to environmental pollutants» was used. Results. N-nitrosoamines are classified as chemical contaminants that are a priority for public health risk assessment, identified on the basis of the potential hazard category. A comparative health risk assessment for the target group consumers of canned meat and meat-and-vegetables sold on the territory of the Russian Federation and the Socialistic Republic of Vietnam showed the presence of an unacceptable risk to the health of the Russian population in relation to non-carcinogenic adverse health effects associated with the intake of N-nitrosodimethylamine (NDMA) (hazard quotient HQ=1.1) and N-nitrosodibuthylamine (HQ=5.25). Many experimental (animal) researches confirm the formation of negative effects and potential harm to humans, formed by the consumption of N-nitrosoamines with food. At the same time, the level of the exposure of N-nitrosoamines during oral administration was assessed mainly from the side of carcinogenic effects, however, this study reflects the hazard, including from non-carcinogenic risks associated not only with NDMA and N-nitrosodiethylamine, for which there is a hygienic standard, but also for other N-nitrosoamines, for which there is no hygienic regulation. In turn, the European Food Safety Agency's (EFSA) study notes that it is necessary to conduct a risk assessment for human health in relation to other N-nitrosoamines identified in food, and, if necessary, rationing of these compounds, which is also confirmed by this study. Conclusion. The conducted health risk assessment of the target population of Russia (infants from 6 months to 3 years) consuming the studied types of products containing N-nitrosoamines showed the presence of unacceptable levels of non-carcinogenic health risks in relation to the development processes and impaired liver function. In connection with the identified risks to the health of the target population, it is advisable to establish maximum permissible levels not only for the amount of NDMA and N-nitrosodiethylamine, but also for other N-nitrozoamines identified by the results of the study, with their subsequent regulation.

Evaluating liver function and the impact of immune checkpoint inhibitors in the prognosis of hepatocellular carcinoma patients: A systemic review and meta-analysis.

Most patients with hepatocellular carcinoma (HCC) have underlying cirrhosis and a compromised liver function. Immune checkpoint inhibitors (ICIs) have emerged as an important approach for HCC treatment. The purpose of our study was to explore the prognostic significance of liver function in HCC patients receiving ICIs. Hazard ratios (HR) with 95% confidence intervals (CI) were used to evaluate the relationship between liver function and overall survival (OS)/progression-free survival (PFS). 41 articles with 4483 patients with HCC were included. The pooled results revealed that either Child-Pugh score (OS:HR=2.01,95%CI:1.69-2.38; PFS:HR=1.39,95%CI:1.15-1.68) or albumin-bilirubin (ALBI) score (OS:HR=2.04,95%CI:1.55-2.69; PFS:HR=1.42,95%CI:1.21-1.67) can predict the patient prognosis. The Child-Pugh score has some degree of subjectivity, and the ALBI score can better stratify patients. Therefore, the ALBI score was used to evaluate patients' liver function and determine treatment options. Further subgroup analysis found that the results of prospective studies were statistically significant only for the ALBI score with regards to OS (HR=1.69,95%CI:1.26-2.26). Meanwhile, the effect of liver function on the efficacy of ICIs in the large-sample studies was not as obvious as that in small-sample studies. Moreover, the incidence of adverse events did not significantly increase in patients with impaired liver function. Poor liver function is associated with a poor prognosis in patients with HCC receiving ICIs. The ALBI score is simpler and reliable for patient stratification than the Child-Pugh score. Although the survival time of patients with impaired liver function may be relatively short, ICIs still have great potential for therapeutic applications.

Hyperammonemic encephalopathy in Staphylococcus aureus necrotizing fasciitis

This study described a rare case of necrotizing fasciitis presenting as neural dysfunction. The patient's serum ammonia level was significantly elevated; however, no liver function impairment was observed. Hyperammonemia is frequently related to the liver's ammonia metabolism failure. In literature reviews, infections also induce critical complications in specific circumstances. Herein, a rare case of Staphylococcus aureus necrotizing fasciitis with a hyperammonemic encephalopathy presentation was offered.

Clinical Characteristics of Kawasaki Disease Combined with Liver Function Impairment in Children

Clinical Characteristics of Kawasaki Disease Combined with Liver Function Impairment in Children

Protective role of Coenzyme Q10 on ultrastructure effect of sodium fluoride on the liver of adult male albino rats

Background and aim Fluoride causes liver function impairment, decrease in metabolic activities, and inhibits certain antioxidant enzymes and molecules. This study aims to clarify the possible histological alterations caused by sodium fluoride (NaF) on the liver structure and the potential protective role of Coenzyme Q10 (CoQ10) against NaF. Materials and methods Thirty adult albino male rats weighing about 200–250 g were equally divided into three groups. The first is the control group, the second received NaF in a dose of 10 mg/kg/day for 30 days, and the third group received CoQ10 in a dose of 10 mg/kg/day for 30 days and NaF. The rats were killed when the experiment was finished by inhalation of ether. The liver tissue samples were treated for light and electron microscopy. Results In NaF-treated group, the hepatocytes lost their regular configuration in liver cords that radiate from the central vein with dilated blood sinusoids separating them. Disorganization of cytoplasm was observed with destructed mitochondria and destructed rough endoplasmic reticulum. The nucleus was heterochromatic, irregular, and showed nuclear membrane deformity. The blood sinusoids were dilated and filled with red blood cells. In the protective group with CoQ10 a partial recovery occurred. The hepatocyte became nearly normal with few changes as some vaculations in the cytoplasm and dilated in blood sinusoids. Conclusion NaF has deteriorating effects on the liver and CoQ10 has protective effects against these changes and produced a significant improvement.

Relationship between methylenetetrahydrofolate reductase gene polymorphisms and methotrexate drug metabolism and toxicity.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, and methotrexate (MTX) is the key drug for ALL. Studies on the relationship between High-Dose methotrexate (HD-MTX) toxicity and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genes have drawn different conclusions. This study aimed to investigate the relationship between the polymorphism of MTHFR C677T and A1298C genes and the toxicity responses of MTX. The MTHFR C677T and A1298C genotypes of 271 children with ALL who received HD-MTX chemotherapy in southern China from September 2017 to June 2021 were analyzed, and the toxicity of HD-MTX was evaluated and analyzed according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0. The MTHFR C677T and A1298C gene polymorphisms were not correlated with the 48-hour MTX blood concentrations (P>0.05). Unconditional logistic regression model analysis also revealed that the risk of liver function impairment [odds ratio (OR) =1.656, 95% confidence interval (CI): 1.179-2.324, P<0.05] and mucosal damage (OR =1.508, 95% CI: 1.042-2.183, P<0.05) were 1.656 and 1.508 times higher for the heterozygous mutant (CT), and homozygous mutant (TT) mutant type than for the wild-type (CC), wild-type, respectively. The risk of neutropenia and liver function impairment were 0.498 (OR =0.498, 95% CI: 0.251-0.989, P<0.05) and 6.067 (OR =6.067, 95% CI: 1.183-31.102, P<0.05) times higher in low-risk children with CT+TT mutant genotypes than in those with CC wild genotypes, respectively. Furthermore, the risk of mucosal damage was 1.906 times higher in high-risk children with the CT+TT genotype than in those with the CC genotype (OR =1.906, 95% CI: 1.033-3.518, P<0.05). The MTHFR A1298C genotypes differed in the incidence of liver function damage and gastrointestinal toxic reactions in children with ALL. Nonetheless, no increased risk of liver function impairment nor gastrointestinal reactions in children with the heterozygous mutant (AC)+CC mutation was observed. Advancements in MTHFR genotype testing in children with ALL and the introduction of personalised treatments based on genotype results during HD-MTX chemotherapy will help to predict, prevent, and reduce the occurrence of adverse MTX-related toxic reactions.

Albumin-Bilirubin Grade Analyses of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: A Post Hoc Analysis of the Phase III IMbrave150 Study

Introduction: Atezolizumab + bevacizumab showed survival benefit in patients with unresectable hepatocellular carcinoma (HCC) versus sorafenib in the Phase III IMbrave150 study. This exploratory analysis examined the prognostic impact of a baseline albumin-bilirubin (ALBI) score. Methods: Patients with treatment-naïve unresectable HCC, ≥1 measurable untreated lesion, and Child-Pugh class A liver function were randomized 2:1 to receive atezolizumab 1,200 mg + bevacizumab 15 mg/kg every 3 weeks or sorafenib 400 mg twice daily. Overall survival (OS) and progression-free survival (PFS) were assessed in the intention-to-treat population by ALBI/modified (m)ALBI grade. Time to deterioration (TTD; defined as time to 0.5-point increase from the baseline ALBI score over 2 visits or death) of liver function and safety were investigated. Results: Of 501 enrolled patients, 336 were randomized to receive atezolizumab + bevacizumab (ALBI grade [G] 1: n = 191; G2: n = 144 [mALBI G2a: n = 72, G2b: n = 72]; missing ALBI grade: n = 1) and 165 to sorafenib (ALBI G1: n = 87; G2: n = 78 [mALBI G2a: n = 37; G2b: n = 41]). Median follow-up was 15.6 months. OS and PFS improved with atezolizumab + bevacizumab versus sorafenib in patients with ALBI G1 (OS HR: 0.50 [95% CI: 0.35, 0.72]; PFS HR: 0.61 [95% CI: 0.45, 0.82]). In patients with ALBI G2 or mALBI G2a or G2b, PFS was numerically longer with atezolizumab + bevacizumab versus sorafenib, but no OS benefit was seen. Median TTD in the intention-to-treat population was 10.2 months (95% CI: 8.0, 11.0) with atezolizumab + bevacizumab versus 8.6 months (95% CI: 6.2, 11.8) with sorafenib (HR: 0.82 [95% CI: 0.65, 1.03]). Safety profiles of atezolizumab and bevacizumab were consistent with previous analyses, regardless of ALBI grade. Conclusion: ALBI grade appeared to be prognostic for outcomes with both atezolizumab + bevacizumab and sorafenib treatment in patients with HCC. Atezolizumab + bevacizumab preserved liver function for a numerically longer duration than sorafenib.