Liver Function Research Articles

Recurrence and influencing factors of hepatitis B surface antigen seroclearance induced by peginterferon alpha-based regimens

BACKGROUND The long-term stability of hepatitis B surface antigen (HBsAg) seroclearance following peginterferon alpha (peg-IFN-α)-based therapy has not been extensively studied, leaving the full potential and limitations of this strategy unclear. AIM To assess HBsAg recurrence after seroclearance achieved by peg-IFN-α regimens. METHODS This prospective, multicenter, observational study was conducted from November 2015 to June 2021 at three Chinese hospitals: The Second Affiliated Hospital of Xi’an Jiaotong University, Ankang Central Hospital, and The Affiliated Hospital of Yan’an University. Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus (HBV) markers, HBV DNA, and liver function. The primary outcome was HBV recurrence, defined as the reemergence of HBsAg, HBV DNA, or both, at least twice within 4-8 weeks of follow-up. RESULTS In total, 121 patients who achieved HBsAg seroclearance were enrolled. After a median follow-up of 84.0 (48.0, 132.0) weeks, four subjects were lost to follow-up. HBsAg recurrence was detected in 16 patients. The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%. Multivariate logistic regression analysis demonstrated that consolidation time < 12 weeks [odds ratio (OR) = 28.044, 95%CI: 4.525-173.791] and hepatitis B surface antibody disappearance during follow-up (OR = 46.445, 95%CI: 2.571-838.957) were strong predictors of HBsAg recurrence. HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed. CONCLUSION HBsAg seroclearance following peg-IFN-α treatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%.

Sensitivity of diagnosis of spontaneous bacterial peritonitis is higher with the automated cell count method

BACKGROUND Spontaneous bacterial peritonitis (SBP) is one of the most important complications of patients with liver cirrhosis entailing high morbidity and mortality. Making an accurate early diagnosis of this infection is key in the outcome of these patients. The current definition of SBP is based on studies performed more than 40 years ago using a manual technique to count the number of polymorphs in ascitic fluid (AF). There is a lack of data comparing the traditional cell count method with a current automated cell counter. Moreover, current international guidelines do not mention the type of cell count method to be employed and around half of the centers still rely on the traditional manual method. AIM To compare the accuracy of polymorph count on AF to diagnose SBP between the traditional manual cell count method and a modern automated cell counter against SBP cases fulfilling gold standard criteria: Positive AF culture and signs/symptoms of peritonitis. METHODS Retrospective analysis including two cohorts: Cross-sectional (cohort 1) and case-control (cohort 2), of patients with decompensated cirrhosis and ascites. Both cell count methods were conducted simultaneously. Positive SBP cases had a pathogenic bacteria isolated on AF and signs/symptoms of peritonitis. RESULTS A total of 137 cases with 5 positive-SBP, and 85 cases with 33 positive-SBP were included in cohort 1 and 2, respectively. Positive-SBP cases had worse liver function in both cohorts. The automated method showed higher sensitivity than the manual cell count: 80% vs 52%, P = 0.02, in cohort 2. Both methods showed very good specificity (> 95%). The best cutoff using the automated cell counter was polymorph ≥ 0.2 cells × 109/L (equivalent to 200 cells/mm3) in AF as it has the higher sensitivity keeping a good specificity. CONCLUSION The automated cell count method should be preferred over the manual method to diagnose SBP because of its higher sensitivity. SBP definition, using the automated method, as polymorph cell count ≥ 0.2 cells × 109/L in AF would need to be considered in patients admitted with decompensated cirrhosis.

New rabbit model for benign biliary stricture formation with repeatable administration

BACKGROUND The treatment of benign biliary strictures (BBS) is a challenging clinical problem. At present, there is a lack of ideal models for the study of BBS treatment. AIM To develop a novel animal model of BBS to simulate studies on the processes and mechanisms in the human condition. METHODS A rabbit model of benign bile duct stricture was established by surgical injury of the bile duct. After removal of the gallbladder, a drainage tube was placed through the cystic duct at the stump, and a BBS model was induced by surgical injury at the lower end of the common bile duct. RESULTS Compared with the control group, the model rabbits showed gross jaundice, increased serum bilirubin, and decreased liver function. Cholangiography showed segmental bile duct stenosis in the model rabbits. Pathological staining showed inflammatory cell infiltration and fibrosis in the biliary tract of rabbits in the model group. This was consistent with the clinical manifestations of BBS. This model provided serology, imaging, pathology, and other aspects of BBS. CONCLUSION We have successfully established an animal model of benign stricture of the lower bile duct with repeatable administration, which is consistent with the clinical manifestations of BBS.

Liver failure after Bacillus cereus food poisoning, an under-recognized entity: A case report

BACKGROUND Bacillus cereus (B. cereus ) is known to cause 2 types of foodborne diseases; the diarrheal and emetic syndromes. They are largely underreported due to their usually self-limiting course. Rare and sometimes fatal cases of liver failure, pulmonary hemorrhage and cerebral oedema have been reported mainly in children and young adults. We present here a case of liver failure associated with B. cereus food poisoning in a middle-aged patient. CASE SUMMARY A 48-year-old female patient presented to the emergency department for emesis, diarrhea, chills without fever, asthenia and diffuse abdominal cramps that started less than 30 minutes after eating a rice salad. Her past medical history was relevant for cholecystectomy and a cured Hashimoto’s disease. She did not take any medication, drugs and declared a consumption of one glass of wine per week. In the emergency department, she was treated with acetaminophen, metoclopramide, ondansetron, and an intravenous normal saline infusion. Blood gas analysis revealed a metabolic acidosis with hyperlactatemia, coagulation revealed a low prothrombin activity [32 %; normal values (N): 70-140] and a low Factor V activity (15%; N: > 70). Transaminases were elevated with hyperbilirubinemia, elevated lipase and rhabdomyolysis. N-acetylcysteine treatment was introduced. Abdominal echography revealed no signs of chronic hepatopathy or hepatomegaly. Day after the admission, psychomotor activity improved, transaminases and lipase started decreasing. Rhabdomyolysis gradually worsened to peak on day 3. Screening tests for liver disease were negative for viral and autoimmune cause of liver failure. Stools cultures were positive for colonies of the B. cereus group which were also identified in the rice salad samples processed whereas blood cultures were negative. The patient’s condition improved gradually including her liver function parameters and psychomotor activity which allowed her discharged home on day 9. CONCLUSION We describe a rare case of hepatocellular dysfunction due to a foodborne B. cereus intoxication in an adult patient. Even if it is uncommon, the severity of liver dysfunction reported and mechanism of the cereulide toxin toxicity on liver suggest that acetaminophen should be avoided in case of a foodborne intoxication and n-acetylcysteine could be a potential therapy helping to prevent hepatocytes necrosis due to the oxidative stress induced by mitochondrial dysfunction.

Potential of traditional Chinese medicine in the treatment of nonalcoholic fatty liver disease: A promising future

In this editorial, we provide insights into the publication by Niu et al featured in the latest edition of the World Journal of Gastroenterology . Specifically, our focus was on exploring the potential of traditional Chinese medicine (TCM) in treating nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet through various mechanisms. NAFLD is a common liver condition, affecting approximately 25% of the world's population. It is closely linked to metabolic syndrome, insulin resistance, excessive body weight, and irregular lipid processing, leading to fat accumulation in the liver, as well as oxidative stress and inflammation. While maintaining a healthy diet and active lifestyle are essential for managing NAFLD, treatment options are limited due to undefined pathogenesis and a lack of specific medications. TCM, rooted in traditional Chinese practices, presents a promising alternative through its "syndrome differentiation and treatment" principles, enhancing liver lipid metabolism, reducing inflammation, and addressing fibrosis. Certain herbs, such as Poria cocos , Puaria lobata , and Salvia miltiorrhiza , have shown significant efficacy in reducing fat deposition and improving liver function. Due to systematic research and analysis of mechanisms, TCM is anticipated to yield new approaches to prevent and treat NAFLD, increasing its clinical application.

Comprehensive approach to esophageal variceal bleeding: From prevention to treatment

Esophageal variceal bleeding is a severe complication often associated with portal hypertension, commonly due to liver cirrhosis. Prevention and treatment of this condition are critical for patient outcomes. Preventive strategies focus on reducing portal hypertension to prevent varices from developing or enlarging. Primary prophylaxis involves the use of non-selective beta-blockers, such as propranolol or nadolol, which lower portal pressure by decreasing cardiac output and thereby reducing blood flow to the varices. Endoscopic variceal ligation (EVL) may also be employed as primary prophylaxis to prevent initial bleeding episodes. Once bleeding occurs, immediate treatment is essential. Initial management includes hemodynamic stabilization followed by pharmacological therapy with vasoactive drugs such as octreotide or terlipressin to control bleeding. Endoscopic intervention is the cornerstone of treatment, with techniques such as EVL or sclerotherapy applied to directly manage the bleeding varices. In cases where bleeding is refractory to endoscopic treatment, transjugular intrahepatic portosystemic shunt may be considered to effectively reduce portal pressure. Long-term management after an acute bleeding episode involves secondary prophylaxis using beta-blockers and repeated EVL sessions to prevent rebleeding, complemented by monitoring and managing liver function to address the underlying disease. In light of new scientific evidence, including the findings of the study by Peng et al , this editorial aims to review available strategies for the prevention and treatment of esophageal varices.

Interrogating the Antiobesity Efficacy of Flacourtia Inermis Roxb. Fruits in High Fat Diet-induced Obese Rats

Background Flacourtia inermis Roxb. (Salicaceae) is an underutilized edible fruit known for its antioxidant-rich bioactive compounds. This study explores the antiobesity potential of F. inermis ethanolic fruit extract (FF2) in a high-fat diet (HFD) induced obesity model using Wistar albino rats. Materials and Methods Wistar albino rats were randomly assigned into five groups (n = 6). Group 1 served as the normal control and received a normal diet (ND), while Groups II–V were induced with obesity by being fed an HFD for 10 weeks. Group II acted as the obese control, receiving 100% HFD throughout the study. Groups III, IV, and V also received HFD throughout the study but were supplemented with Orlistat (30 mg/kg b.w), and FF2 extract at doses of 200 mg/kg, and 400 mg/kg, respectively, from week 11 until week 15. Treatment impact of FF2 on body weight, body mass index (BMI), serum lipid levels, glucose levels, liver function parameters, and histopathological evaluations of liver and adipose tissue were investigated. Results The study unveiled that F. inermis fruits exerted potent antiobesity effects, with FF2 treatment (at 200 mg/kg and 400 mg/kg) substantially decreasing body weight gain and BMI in comparison to the HFD group. Supplementation of FF2 alongside an HFD reduced body weight gain, glucose levels, and serum lipid profile. Both doses of FF2 counteracted the adverse effects induced by HFD, with lower triglycerides (TG), total cholesterol, and LDL cholesterol levels, and higher HDL cholesterol levels in the treated groups compared to the positive control. Additionally, FF2 extract showed dose-dependent improvements in serum lipid and glucose levels, as well as, hepatic profile, indicated by decreased AST, ALP, and ALT levels, suggesting potential benefits in managing dyslipidemia, hyperglycemia, and liver health associated with obesity. Histological examination of white adipose tissue provided further evidence of the antiobesity effect. Conclusion The study highlights FF2’s therapeutic potential in managing obesity and associated metabolic disorders. Further investigations into FF2’s mechanisms and clinical application are essential for its development as an antiobesity therapeutic agent in functional food formulations.

Unprecedented Co-occurrence: Identification of a Pathogenic Genetic Variant in the KMT2B Gene in a Wilson Disease Patient with a Pathogenic ATP7B Mutation

The pathophysiology of dystonia in Wilson disease (WD) is complex and poorly understood. Copper accumulation in the basal ganglia, disrupts dopaminergic pathways, contributing to dystonia’s development via neurotransmitter imbalance. Despite advances in diagnosis and management, WD with dystonia remains a challenging condition to treat. We aim to report the unprecedented co-occurrence of pathogenic genetic variants in both the ATP7B and KMT2B genes in a patient with WD. A 13-year-old male presented at 12 with dysarthria and bilateral Kayser-Fleischer rings. Over months, dystonia spread to his left foot, upper limb, and trunk, accompanied by slowed daily activities. Diagnostic tests included MRI for brain structure, abdominal ultrasound for liver function, serum ceruloplasmin and copper levels to assess copper metabolism, and 24-hour urine copper tests for excretion levels. Whole exome sequencing was conducted using genomic DNA from peripheral blood samples. Variant classification followed guidelines from the American College of Medical Genetics and Genomics. The sequencing revealed compound heterozygous pathogenic variants in the ATP7B gene: NM_000053.4:c.2165dupT and NM_000053.4:c.813C>A. A pathogenic variant in the KMT2B gene, NM_014727:c.3052delA, was identified. This case highlights WD co-occurrence with ATP7B and KMT2B mutations, suggesting KMT2B as a potential genetic modifier.

Deucravacitinib in Plaque Psoriasis: Laboratory Parameters Through 4 Years of Treatment in the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious versus placebo and apremilast and was well tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) parent trials. At Week 52, patients could enroll in the ongoing POETYK long-term extension (LTE) (NCT04036435) trial and receive open-label deucravacitinib. Changes in blood laboratory parameters known to be associated with Janus kinase (JAK) 1,2,3 inhibitors were evaluated through 4 years of deucravacitinib treatment. Methods: Changes from baseline in lipid (cholesterol, triglycerides), chemistry (alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine, creatine phosphokinase [CPK]), and hematology (hemoglobin, lymphocytes, neutrophils, platelets) parameters in the blood known to be affected by JAK1,2,3 inhibitors in clinical trials were evaluated through Week 208 (4 years; data cutoff, November 1, 2023). Treatment discontinuations due to laboratory abnormalities were assessed. Results: A total of 1519 patients received ≥1 deucravacitinib dose (total exposure, 4392.8 person-years); 1203 (79.2%) had ≥52 weeks and 542 (35.7%) had ≥208 weeks of continuous deucravacitinib exposure (median, 185 weeks). No trends or clinically meaningful mean changes from baseline were observed in any of the above laboratory parameters. In total, 3 patients discontinued treatment due to increased CPK, and 1 patient each discontinued due to lymphopenia, abnormal hepatic function, increased ALT, and increased AST. Discontinuations due to triglyceride elevations were not observed. Conclusion: In PSO-1/PSO-2/LTE, no trends or clinically meaningful mean changes from baseline were observed in lipid, chemistry, or hematology parameters, in contrast to signature changes (eg, increased cholesterol, creatinine, serum transaminases, CPK, cytopenias) observed with JAK1,2,3 inhibitors. Discontinuations due to laboratory abnormalities noted above were rare (n=7 events) through 4 years of deucravacitinib treatment. Results suggest deucravacitinib treatment does not warrant routine laboratory testing for all patients, in contrast with the requirements for JAK1,2,3 inhibitors, reflecting its selectivity for TYK2.

Modulation of Serum Metabolic Profiles by Bifidobacterium breve BBr60 in Obesity: A Randomized Controlled Trial

Obesity, a prevalent metabolic disorder in youth, leads to complications and economic strain. Gut dysbiosis significantly contributes to obesity and metabolic issues. Bifidobacterium breve, a probiotic strain, may help regulate gut dysbiosis and benefit obese individuals. However, more research is needed on its effect on serum metabolism. A total of 75 overweight or obese young adults (aged 19–45) participated in the current study, and were randomly divided into probiotic and placebo groups using a random number table. Both groups received dietary guidance and underwent twelve weeks of intervention with either oral Bifidobacterium breve BBr60 (BBr60) or a placebo. After the intervention, collection and analysis of fasting serum samples were conducted using mass spectrometry coupled with liquid chromatography. Analyses of associations were conducted in order to determine the correlations between key serum metabolites and clinical obesity indicators, aiming to understand the influence of BBr60. Due to 10 participants dropping out for personal reasons, the study included 32 and 33 participants in the placebo and the BBr60 groups, respectively. The BBr60 intervention significantly regulated 134 serum metabolites and influenced crucial metabolic pathways in obesity management (p < 0.05), including ascorbate and aldarate metabolism for oxidative stress reduction, cholesterol metabolism for lipid regulation, parathyroid hormone synthesis, secretion and action for the endocrine system, oxidative phosphorylation for enhanced energy efficiency, and glycolysis/gluconeogenesis for glucose metabolism. Analysis showed a positive relationship between fasting blood glucose (FBG), aspartate aminotransferase (AST), total protein (TP), and the content of 5-Methyl DL-glutamate (p < 0.05). Similarly, body mass index (BMI), weight, and body fat percentage (BFP) were positively linked to serum metabolites (1-Hydroxycyclohexyl) acetic acid, and 5-Oxooctanoic acid (p < 0.05). Significant associations of AST levels with key serum metabolites in cholesterol metabolism pathways further suggest BBr60’s potential to improve liver function and overall metabolic health in overweight or obese individuals. These findings support BBr60’s effectiveness in modulating serum metabolic profiles and suggest it may improve liver function and BMI in overweight or obese individuals by regulating key serum metabolites.

The applications of Ursodeoxycholic acid in infant with cholestasis: A retrospective cohort analysis

Biliary atresia is the predominant etiology of cholestasis in early infancy. Impairment of bile fluid excretion results in elevated bilirubin levels, causing a yellowing of the skin. Ursodeoxycholic acid is well-established to enhance liver function when taken promptly. The application of ursodeoxycholic acid for treating cholestasis in pediatric patients remains contentious. The objective of this study is to assess the impact of ursodeoxycholic acid treatment on liver biomarkers in infant with cholestasis. This was retrospective cohort study in infant with cholestasis who underwent ursodeoxycholic acid treatment for two weeks. Secondary data including aspartate aminotransferase, alanine aminotransferase, total bilirubin, and direct bilirubin were extracted from the medical records of the outpatient clinic in the Department of Child Health at Dr. Soetomo General Hospital, Indonesia (January 2020 - December 2023). The data was devided into two groups based on biopsy and examined utilizing SPSS version 23. This study included 64 participants. Statistics show an equal gender ratio. Ursodeoxycholic acid treatment in paediatric cholestasis patients can lower liver biomarker level. Levels of total bilirubin and direct bilirubin diminished in individuals both groups. Notable levels were recorded in individuals with normal biopsy outcomes (p=0.007 and p=0.012). Administration of ursodeoxycholic acid markedly elevated ALT levels in both the normal and abnormal liver biopsy outcome groups (p=0.031 and p=0.006). Ursodeoxycholic acid has been shown to be effective in improving liver function in infant with cholestasis. In order to avoid negative effects, the medication must be carefully administered to people who already have liver fibrosis.

Persistent Liver Injury Following Avacopan Discontinuation in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Rare Case of Liver Biopsy in the Chronic Phase of Liver Injury.

Drug-induced liver injury (DILI) is a major concern associated with the use of avacopan, a new therapeutic agent for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Here, we report a rare instance of liver biopsy performed for persistent liver injury following discontinuation of avacopan in an elderly woman with microscopic polyangiitis (MPA). The patient developed cholestatic liver injury after 2 months of avacopan therapy, which led to drug cessation. Despite the discontinuation of avacopan followed by supportive care, the liver enzyme levels remained elevated, necessitating liver biopsy. Histological examination revealed residual inflammation and focal necrosis around the portal vein, indicating ongoing liver injury despite avacopan withdrawal. This case report highlights the hepatotoxic potential of avacopan, the importance of vigilant liver function monitoring, and the value of liver biopsy in the chronic phase of avacopan-induced liver injury. Further research is required to elucidate avacopan hepatotoxicity mechanisms and identify potential risk factors for DILI in patients with AAV.

Investigating the efficacy of ergothioneine to delay cognitive decline in mild cognitively impaired subjects: A pilot study.

Dementia, particularly Alzheimer's disease, is a major healthcare challenge in ageing societies. This study aimed to investigate the efficacy and safety of a dietary compound, ergothioneine, in delaying cognitive decline in older individuals. Nineteen subjects aged 60 or above with mild cognitive impairment were recruited for this double-blinded, randomized, and placebo-controlled study (ClinicalTrials.gov identifier: NCT03641404, registration date: 19/08/2018). Subjects received either ergothioneine (25 mg per capsule) or a placebo, taken 3 times a week for one year. The whole blood profile, markers of renal and liver functions, neurocognitive performance, plasma levels of ergothioneine and its metabolites, and plasma biomarkers related to neurodegeneration were measured across the study. Ergothioneine intake did not alter clinical safety markers (blood counts, kidney and liver function) throughout the study, further validating its safety for human consumption. Subjects receiving ergothioneine demonstrated improved performance in assessment of learning ability and stabilized plasma levels of neurofilament light chain, compared with the placebo group, which saw no improvement in cognitive assessments and a significant increase in neurofilament light chain levels. Prolonged intake of ergothioneine showed no toxicity in elderly people. Enhanced Rey Auditory Verbal Learning Test performance and stabilized neurofilament light chain levels suggest improvements in memory and learning abilities and a deceleration of neuronal damage, respectively. Our results add to existing data that ergothioneine is safe for extended consumption and may hold the potential to delay cognitive decline in elderly adults.

GRK2 mediates cisplatin-induced acute liver injury via the modulation of NOX4.

The present study investigated the function of G protein-coupled receptor kinase 2 (GRK2) in acute liver injury (ALI) by cisplatin, and investigated the protective effect of pharmacological inhibition of GRK2. ALI models were generated in global adult hemizygous (ALI-Grk2±) mice and wild-type (WT) mice. Liver biochemistry parameters and histopathology were used to evaluate the severity of ALI and the protective effect of pharmacological inhibition of GRK2. GRK2-siRNA was used to knock down the expression of GRK2 in AML12 cells in vitro. ALI model mice exhibited increased blood levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and abnormal liver pathology accompanied by imbalanced L-glutathione (GSH) levels. Cisplatin administration upregulated GKR2, p-GRK2 and NADPH oxidase 4 (NOX4) expression in the liver tissues of ALI model mice. Compared to WT mice injected with cisplatin, Grk2± mice that received cisplatin showed significant improvements in liver function and pathological performance, decreased NOX4 levels, reduced endoplasmic reticulum (ER) stress, and diminished liver cell apoptosis. In vitro, the transfection of AML12 cells with siRNA significantly reduced NOX4 expression and inhibited cisplatin-induced reactive oxygen species production, ER stress (increased levels of GRP94, GRP78, p-elF2α and CHOP) and apoptotic death. Moreover, pharmacological treatment with drugs that inhibit GRK2 (CP-25 or paroxetine) significantly ameliorated cisplatin-induced ALI by improving liver pathological manifestations, inhibiting oxidative stress and ER stress, and reducing liver cell apoptosis. Similar results were observed in vitro. GRK2 mediates the development of cisplatin-induced ALI by modulating NOX4 and ER stress. Pharmacological inhibition of GRK2 with CP-25 or paroxetine effectively alleviated ALI. GRK2 can be used as a potential target for the prevention and treatment of liver injury.

Assessing the Impact of Ghee, Olive Oil and Margarine on Male Rabbit Fertility and Reproductive Hormones.

In the present investigation, the impact of natural ghee, olive oil and synthetic margarine on the fertility parameters of male rabbits was evaluated by examining semen quality, fertility hormones, antioxidant markers, lipid profile, and liver and kidney functions. Eighty male rabbits were randomly allotted into four groups (20 rabbits each, four replicates/group). The basal diet supplemented the control group; the margarine group was fed a 10% margarine diet, the ghee group was fed a 10% ghee diet, and the olive oil group was fed a 10% olive oil diet. In the margarine group, the semen quality parameters, total testosterone levels, free testosterone, luteinizing hormone (LH) and antioxidant enzyme levels as catalase showed a significant reduction compared to other groups. At the same time, they were enhanced in ghee and olive oil groups. A substantial increase of triglyceride (TAG), low-density lipoprotein (LDL) and cholesterol, with a decrease of high-density lipoprotein (HDL) levels, were observed in the margarine group contrasted to ghee and olive oil groups. The ghee and the olive oil-treated group showed strong immunoreactions of androgen, FSH, LH receptors and mild caspase 3 in testicular tissue compared to the margarine-treated group. Finally, histopathological examination of rabbit testicular tissue showed proliferation of basal spermatogenic cells, increased luminal spermatid of seminiferous epithelium, and proliferation of interstitial cells in normal interstitial tissue in the ghee and olive oil treated group. Still, it showed severe vacuolation and necrosis in the basal luminal seminiferous epithelium and congestion of blood vessels in the margarine group. This present study revealed that the health influence of olive oil and ghee is better than margarine on male fertility parameters.

Promising PD-1 antagonists for liver cancer: an evaluation of phase II and III results.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a significant cause of cancer-related morbidity and mortality. Limited treatment options for advanced stages emphasize the need for effective therapies. This review examines immune checkpoint inhibitors (ICIs), specifically PD-1, PD-L1, and CTLA-4 inhibitors, as novel treatments for advanced HCC. The review includes data from phase II and III clinical trials that evaluate ICI combinations with tyrosine kinase inhibitors (TKIs) and anti-angiogenic agents, as well as locoregional treatments such as Transarterial Chemoembolization (TACE). Clinical outcomes, including progression-free survival and overall response rates, were analyzed along with the incidence and management of immune-related adverse events (irAEs). A systematic literature review method was applied to ensure the inclusion of comprehensive, high-quality studies. ICI-based therapies and their combinations are reshaping the treatment landscape for advanced HCC by providing improved outcomes and potentially extending patient survival. Although promising, these therapies require further refinement to optimize sequencing and treatment selection, especially for patients with different levels of liver function and disease stages. Managing adverse effects effectively is essential for maximizing the benefits of these therapies in clinical practice. Continued research is needed to support the development of personalized approaches that can better tailor these treatments to individual patient needs, ultimately enhancing the overall effectiveness and safety of HCC management.

Single-incision laparoscopic hepaticojejunostomy with selective ductoplasty for type IV-A Choledochal cysts in children: a retrospective study.

Type IV-A choledochal cyst (CDC) has been considered to have a poor prognosis due to the high incidence of postoperative anastomotic strictures and intrahepatic stones. This study aimed to evaluate the surgical outcomes of children with type IV-A CDC and to provide insights for clinical diagnosis and treatment. The study retrospectively analyzed patients from June 2015 to December 2018 at our center, 76 children were diagnosed with type IV-A CDC. All patients underwent single-incision laparoscopic choledochal cyst excision and Roux-en-Y hepaticojejunostomy. The decision to perform ductoplasty was made by comprehensively considering the intrahepatic duct dilatation (IHDD) and stricture. All patients were followed up 1, 3, and 6 months postoperatively, and then every 1 year thereafter. Patients were categorized into two groups based on IHDD changes postoperatively: the long-term group (LTG), with IHDD persisting for over a year, and the short-term group (STG), where IHDD normalized within a year. Single/multiple factor logistic regression was used to analyse the factors influencing postoperative IHDD. The median follow-up period was 80 months, with a range from 64 to 101 months. The decrease in postoperative liver function parameters, compared to preoperative levels, was statistically significant. Two patients (2.63%) developed bile leaks. One patient (1.32%) developed anastomotic stricture. All patients' IHDD returned to normal size. Fifty-six (73.7%) patients showed normalization of IHDD within one-year postoperatively. The median recovery time for IHDD in patients was 1.65 months, ranging from 3 days to 74 months postoperatively. There were significant differences in intrahepatic biliary sludge and stones and maximum diameter of IHDD between STG and LTG. Logistic regression was used to analyse the factors and found that intrahepatic biliary sludge and a wider maximum diameter of IHDD were risk factors for postoperative long-term IHDD in patients. Single-incision laparoscopic hepaticojejunostomy with selective ductoplasty are safe and effective for children with Type IV-A CDC. Long-term follow-up is recommended for children presenting with intrahepatic biliary sludge and larger IHDD.

REVISÃO DE LITERATURA: MANEJO DO PACIENTE COM COLANGITE ESCLEROSANTE PRIMÁRIA

The primary sclerosing cholangitis (PSC) is a progressive, idiopathic, immune mediated disease, characterized by intra or extrahepatic cholestasis, Inflammation and fibrosis of the bile ducts, which may progress to liver cirrhosis or cholangiocarcinoma (CCA) in the vast majority of patients. Objective: Analyze what the current literature discusses about the management of PSC. Method: A systematic review was carried out using the PubMed and SciELO database, applying the descriptors "Primary Sclerosing Cholangitis" AND "Cholangite" AND "Clinical management" AND Cholangiocarcmoma. Discussion: It is more common in men, with an average diagnosis at 35 years old. The PSC has a wide range of symptoms and stages of the disease. In the beginning, symptoms are rare and patients may be asymptomatic. The most commonly found symptoms are pruritus, fatigue, right upper quadrant abdominal pain, jaundice, fever, and weight loss. In about 75% of patients with PSC, liver function tests are chronically abnormal and fluctuating with a most commonly found pattern of cholestatic condition with elevation of alkaline phosphatase (AF) and yglutamyl transferase (GGT). Although endoscopic retrograde cholangiopancreatography (ERCP) is conventionally considered the gold standard test for the diagnosis of PSC, the main modality of choice currently for Imaging diagnosis in patients with suspected PSC is magnetic resonance cholangiopancreatography (CPRM). Due to the absence of effective medical therapy for PSC, liver transplantation (LT) remains the only curative option. There is little evidence for the use of medications as a way to inhibit the progression of the disease. Still several new drugs are under investigation, representing the potential to improve survival and clinical outcomes in PSC. Final considerations: We conclude that it is extremely important to approach the management of PSC. The diagnosis is a great challenge since its clinical, laboratory and imaging aspects overlap, as it was portrayed during this exposure. Nevertheless, due to the various differential diagnoses ofjaundice with cholestatic pattern, the etiological search is crucial and the absence of effective medical therapy, with several new drugs under analysis, should guide further studies to improve the survival and clinical outcomes of these patients. Another point to be considered is that there is a scarcity of data in the literature that address the PSC in the Brazilian population.

Understanding the Role of Alcohol in Metabolic Dysfunction and Male Infertility

Purpose: Over the past 40–50 years, demographic shifts and the obesity epidemic have coincided with significant changes in lifestyle habits, including a rise in excessive alcohol consumption. This increase in alcohol intake is a major public health concern due to its far-reaching effects on human health, particularly on metabolic processes and male reproductive function. This narrative review focuses on the role of alcohol consumption in altering metabolism and impairing testicular function, emphasizing the potential damage associated with both acute and chronic alcohol intake. Conclusion: Chronic alcohol consumption has been shown to disrupt liver function, impair lipid metabolism, and dysregulate blood glucose levels, contributing to the development of obesity, metabolic syndrome, and related systemic diseases. In terms of male reproductive health, alcohol can significantly affect testicular function by lowering testosterone levels, reducing sperm quality, and impairing overall fertility. The extent of these effects varies, depending on the frequency, duration, and intensity of alcohol use, with chronic and abusive consumption posing greater risks. The complexity of alcohol’s impact is further compounded by individual variability and the interaction with other lifestyle factors such as diet, stress, and physical activity. Despite growing concern, research on alcohol’s effects remains inconclusive, with significant discrepancies across studies regarding the definition and reporting of alcohol consumption. These inconsistencies highlight the need for more rigorous, methodologically sound research to better understand how alcohol consumption influences metabolic and reproductive health. Ultimately, a clearer understanding is essential for developing targeted public health interventions, particularly in light of rising alcohol use, demographic changes, and the ongoing obesity crisis.

Aging, ROS, and cellular senescence: a trilogy in the progression of liver fibrosis.

Ageing is an inevitable and multifaceted biological process that impacts a wide range of cellular and molecular mechanisms, leading to the development of various diseases, such as liver fibrosis. Liver fibrosis progresses to cirrhosis, which is an advanced form due to high amounts of extracellular matrix and restoration of normal liver structure with failure to repair damaged tissue and cells, marking the end of liver function and total liver failure, ultimately death. The most important factors are reactive oxygen species (ROS) and cellular senescence. Oxidative stress is defined as an impairment by ROS, which are by-products of the mitochondrial electron transport chain and other key molecular pathways that induce cell damage and can activate cellular senescence pathways. Cellular senescence is characterized by pro-inflammatory cytokines, growth factors, and proteases secreted by senescent cells, collectively known as the senescence-associated secretory phenotype (SASP). The presence of senescent cells, which disrupt tissue architecture and function and increase senescent cell production in liver tissues, contributes to fibrogenesis. Hepatic stellate cells (HSCs) are activated in response to chronic liver injury, oxidative stress, and senescence signals that drive excessive production and deposition of extracellular matrix. This review article aims to provide a comprehensive overview of the pathogenic role of ROS and cellular senescence in the aging liver and their contribution to fibrosis.