Significant Liver Dysfunction Research Articles

Investigating the influence of molybdenum disulfide quantum dots coated with DSPE-PEG-TPP on molecular structures of liver lipids and proteins: An in vivo study

Molybdenum disulfide (MoS2) quantum dots (QDs) based therapeutic approaches hold great promise for biomedical applications, necessitating a thorough evaluation of their potential effects on biological systems. In this study, we systematically investigated the impact of MoS2 QDs coated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethyleneglycol)-2000](DPSE-PEG) linked with (3-carboxypropyl)triphenyl-phosphonium-bromide (TPP) on molecular structures of hepatic tissue lipids and proteins through a multifaceted analysis. The DSPE-PEG-TPP-MoS2 QDs were prepared and administered to the mice daily for 7 weeks. Liver tissues were subjected to a comprehensive examination using various techniques, including Fourier-transform infrared (FTIR) spectroscopy, UV–vis spectroscopy, and liver function tests. FTIR revealed subtle changes in the lipid composition of liver tissues, indicating potential modifications in the cell membrane structure. Also, the (CH stretching and amides I and II regions) analysis unveiled tiny alterations in lipid chain length and fluidity without changes in the protein structures, suggesting a minor influence of DSPE-PEG-TPP-MoS2 QDs on the liver’s cellular membrane and no effect on the protein structures. Further scrutiny using UV–vis spectroscopy demonstrated that DSPE-PEG-TPP-MoS2 QDs had no discernible impact on the absorbance intensities of aromatic amino acids and the Soret band. This observation implies that the treatment with SPE-PEG-TPP-MoS2 QDs did not induce significant alterations in helical conformation or the microenvironment surrounding prosthetic groups in liver tissues. The liver function tests, including ALP, ALT, AST, and BIL levels, revealed no statistically significant changes in these key biomarkers despite minor fluctuations in their values, indicating a lack of significant liver dysfunction. This study provides a detailed understanding of the effects of DSPE-PEG-TPP-MoS2 QDs on hepatic lipids and proteins, offering valuable insights into the biocompatibility and limited impact on the molecular and functional aspects of the liver tissue. These findings could be essential for the application of MoS2 QDs-based therapies.

Methionine-choline deficient diet deteriorates DSS-induced murine colitis through disturbance of gut microbes and infiltration of macrophages.

Ulcerative colitis (UC) is associated with changed dietary habits and mainly linked with the gut microbiota dysbiosis, necroptosis of epithelial cells, and mucosal ulcerations. Liver dysfunction and abnormal level of liver metabolism indices were identified in UC patients, suggesting a close interaction between gut and liver disorders. Methionine-choline deficient diet (MCD) has been shown to induce persistent alterations of gut microbiota and metabolome during hepatitis. In this study we further explored the disease phenotypes in UC patients and investigated whether MCD functioned as a trigger for UC susceptibility. After assessing 88 serum specimens from UC patients, we found significant liver dysfunction and dyslipidemia including abnormal ALT, AST, TG, TC, LDL-c and HDL-c. Liver dysfunction and dyslipidemia were confirmed in DSS-induced colitis mice. We fed mice with MCD for 14 days to cause mild liver damage, and then treated with DSS for 7 days. We found that MCD intake significantly exacerbated the pathogenesis of mucosal inflammation in DSS-induced acute, progressive, and chronic colitis, referring to promotion of mucosal ulcers, colon shortening, diarrhea, inflammatory immune cell infiltration, cytokines release, and abnormal activation of inflammatory macrophages in colon and liver specimens. Intraperitoneal injection of clodronate liposomes to globally delete macrophages dramatically compromised the pathogenesis of MCD-triggering colitis. In addition, MCD intake markedly changed the production pattern of short-chain fatty acids (SCFAs) in murine stools, colons, and livers. We demonstrated that MCD-induced colitis pathogenesis largely depended on the gut microbes and the disease phenotypes could be transmissible through fecal microbiota transplantation (FMT). In conclusion, this study supports the concept that intake of MCD predisposes to experimental colitis and enhances its pathogenesis via modulating gut microbes and macrophages in mice.

Met-Exo attenuates mitochondrial dysfunction after hepatic ischemia-reperfusion injury in rats by modulating AMPK/SIRT1 signaling pathway

Hepatic ischemia-reperfusion injury (IRI) results in significant postoperative liver dysfunction, and the intricate mechanism of IRI poses challenges in developing effective therapeutic drugs. Mitigating the damage caused by hepatic IRI and promoting the repair of postoperative liver injury have become focal points in recent years, holding crucial clinical significance. Adipose mesenchymal stem cell derived exosomes (ADSCs-Exo) and metformin (Met) can play a mitochondrial protective role in the treatment of hepatic IRI, but whether there is a synergistic mechanism for their intervention is not yet known. Combining the unique advantages of exosomes as drug carriers, the aim of this study was to investigate the protective effects and mechanisms of the constructed Met and ADSCs-Exo complex (Met-Exo) on the liver IRI combined with partial resection injury in rat and hypoxic reoxygenation injury of rat primary hepatocytes (HCs). In this study, firstly, we detected that mitochondrial morphology and function were severely affected in hepatic tissues after hepatic IRI combined with partial resection, and then verified by in vitro experiments that Met-Exo could promote mitochondrial biosynthesis and fusion-associated protein expression and inhibit mitochondrial fission-related protein expression by modulating the AMPK/SIRT1 signalling pathway. This indicates that ADSCs-Exo can not only play a targeting role as a drug carrier but also has a great potential to act as a vehicle to act synergistically with drugs in the treatment of tissue and organ damage, which provides a new therapeutic strategy and experimental basis for the treatment of liver injury in medical science and clinical veterinary.

Blood salvage and autotransfusion during orthotopic liver transplantation for hepatocellular carcinoma: A systematic review and meta-analysis.

Hepatocellular carcinoma (HCC) is a significant cause of oncologic mortality worldwide. Liver transplantation represents a curative option for patients with significant liver dysfunction and absence of metastases. However, this therapeutic option is associated with significant blood loss and frequently requires various transfusions and intraoperative blood salvage for autotransfusion (IBS-AT) with or without a leukocyte reduction filter. This study aimed to analyze available evidence on long-term oncologic outcomes of patients undergoing liver transplantation for HCC with and without IBS-AT. Per PRISMA guidelines, a systematic review of keywords "Blood Salvage," "Auto-transfusion," "Hepatocellular carcinoma," and "Liver-transplant" was conducted in PubMed, EMBASE, and SCOPUS. Studies comparing operative and postoperative outcomes were screened and analyzed for review. Twelve studies totaling 1704 participants were included for analysis. Length of stay, recurrence rates, and overall survival were not different between IBS-AT group and non IBS-AT group. IBS-AT use is not associated with increased risk of recurrence in liver transplant for HCC even without leukocyte filtration. Both operative and postoperative outcomes are similar between groups. Comparison of analyzed studies suggest that IBS-AT is safe for use during liver transplant for HCC.

Remdesivir inhibits the progression of glioblastoma by enhancing endoplasmic reticulum stress

Glioblastoma (GBM) is one of the most aggressive primary malignant brain tumors. The major challenge is the lack of effective therapeutic drugs due to the blood–brain barrier (BBB) and tumor heterogeneity. Remdesivir (RDV), a new member of the nucleotide analog family, has previously been shown to have excellent antiviral effects and BBB penetration, and was predicted here to have anti-GBM effects. In vitro experiments, RDV significantly inhibited the growth of GBM cells, with IC50 values markedly lower than those of normal cell lines or the same cell lines treated with temozolomide. Moreover, in multiple mouse models, RDV not only distinctly inhibited the progression and improved the prognosis of GBM but also exhibited a promising biosafety profile, as manifested by the lack of significant body weight loss, liver or kidney dysfunction or organ structural damage after administration. Furthermore, we investigated the anti-GBM mechanism by RNA-seq and identified that RDV might induce apoptosis of GBM cells by enhancing endoplasmic reticulum (ER) stress and activating the PERK-mediated unfolded protein response. In conclusion, our results indicated that RDV might serve as a novel agent for GBM treatment by increasing ER stress and inducing apoptosis in GBM cells.

Safety of Upfront Locoregional Therapy in Conjunction with Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma

<h3>Purpose/Objective(s)</h3> The use of atezolizumab and bevacizumab for advanced hepatocellular carcinoma (HCC) is a recently established standard of care. Addition of locoregional therapies (LRT) such as external beam radiotherapy (RT), radioembolization (Y90), transarterial chemoembolization (TACE), and/or radiofrequency ablation (RFA) may hold promise for further improving outcomes, but the safety of these approaches with atezolizumab/bevacizumab has not been established. This study assessed the safety of upfront LRT in conjunction with this immunotherapy regimen in HCC. <h3>Materials/Methods</h3> We reviewed all patients initiating atezolizumab with or without bevacizumab (IO) for HCC from July 2020 to January 2022 at a single institution. Patients receiving LRT (RT, Y90, TACE, and/or RFA) within 30 days of IO initiation (LRT+IO) were identified alongside a comparison arm of all patients initiating IO alone. Bevacizumab was typically held until after LRT. Treatment-related toxicities were recorded according to CTCAE definitions from the date of treatment initiation until discontinuation of IO or last follow up. Baseline, 1 month, and 3-month Child-Pugh (CP) score, ALBI score, transaminases, and total bilirubin were additionally recorded and analyzed using a repeated-measure mixed effects model. <h3>Results</h3> 50 HCC patients initiating atezolizumab were identified, 49 (98%) of these in combination with bevacizumab. Median follow up was 6.5 months (range 1.2-20), median age was 64 (34-79). 37 (74%) patients had BCLC stage C disease and 12 (34%) BCLC stage B. The majority of patients (86%) had CP class A liver function. Baseline characteristics were balanced between arms on univariate analysis (p>0.05). Of 27 (54%) patients in the LRT+IO arm, 9 received RT alone, 4 received RT combined with Y90 or TACE, 10 received Y90 alone, 3 received TACE alone, and 1 received RFA. The majority of the LRT+IO arm (63%) received LRT after the first infusion of atezolizumab. Grade 3 toxicities were observed in 2 (7.4%) patients in the LRT+IO arm, compared to 2 (8.6%) patients in the IO-only arm (p=0.87); grade 2 toxicity incidence was 63% in the LRT+IO arm versus 43% in the IO-only arm (p=0.17). The receipt of LRT+IO was associated with transient increase in CP and ALBI scores at 1 month relative to IO alone (median score increase 1 and 0.34, respectively, p<0.01); this association did not persist at 3 months. There was no treatment-related liver failure or grade 4/5 toxicity reported in either arm. LRT+IO was not associated with increased ALT, AST, or total bilirubin at 1 or 3 months. <h3>Conclusion</h3> In this single institution retrospective cohort study, upfront locoregional therapy with atezolizumab and bevacizumab for HCC was not associated with a significantly greater incidence of grade 2/3 toxicity or clinically significant liver dysfunction relative to the initiation of atezolizumab and bevacizumab alone. Further studies are needed to verify the safety of combination therapy and to assess clinical benefit.

S2691 A Rare Presentation of Gastric Plastocytomas in a Patient With Multiple Myeloma

Introduction: Multiple myeloma is an uncommon hematological neoplasm. This malignancy involves unchecked plasma cell growth in the bone marrow, but in a subset of often more advanced cases, these cells may migrate to soft tissues causing extramedullary plasmacytoma. This is unusual, and, in the literature, few cases of extramedullary plasmacytomas involve the gastrointestinal tract. Within this system, the more common locations are the stomach, the liver, the large bowel, and more rarely, the small bowel. Case Description/Methods: A 59-year-old male with a medical history of chronic hepatitis C, and Stage III multiple myeloma status post four cycles of chemotherapy presented with altered mental status. Upon evaluation, he had significant electrolyte abnormalities, remarkable anemia, severe renal and liver dysfunction, and a positive hemoccult test. Our patient received intravenous fluid, and multiple blood products. He was then admitted to the intensive care unit for a high level of care. On the second day of admission, he developed new onset hematemesis, and the gastroenterology team was consulted. The patient was started on a pantoprazole drip. Urgent esophagogastroduodenoscopy showed several polypoid appearing masses with overlying ulceration in the gastric fundus (Figure a &b), and tissue biopsies were obtained. Biopsy result of the polypoid fundal mass showed a large cell neoplasm with plasmocytic differentiation. Gastric tissue sections showed an ulcerated lesion with submucosal, tightly packed atypical large cells with multinucleation, prominent nucleoli and relatively identifiable mitoses (Figurec). A panel of immunohistochemical stains with plasma cell markers were positive for kappa, Multiple Myloma-1 nuclear protein, and CD138 (Figure d-f). The overall findings were compatible with gastric involvement by a plasma cell neoplasm. Discussion: This case highlights a complicated, yet a uniquely rare presentation of extramedullary plasmacytoma in a patient diagnosed with multiple myeloma. Although the gastrointestinal tract is rarely involved in patients with multiple myeloma, it should be considered as the differential diagnosis in patients with gastrointestinal bleeding especially with a known concurrent systemic hematological malignancy. The presence of gastrointestinal involvement and the malignant phase of multiple myeloma are associated with a poor prognosis despite aggressive therapy, and it is therefore paramount to establish an accurate diagnosis early to avoid any delays in treatment.Figure 1.: (a,b) EGD shows polypoid EMP in the gastric fundus. (c) Infiltration of plasmablasts with highly atypical nuclei and prominent nucleoli (hematoxylin-eosin 20x). (d) Granular positivity for kappa immunoglobulin light chain. (e) Positive immunostaining for MUM-1. (f) Positive CD138 immunostaining highlights the plasma cells in the lamina propria of the gastric fundus EMP.

Increasing Living Liver Donor Pools: Liver Paired Exchange Versus ABO-incompatible Living Donor Liver Transplantation.

Increasing Living Liver Donor Pools: Liver Paired Exchange Versus ABO-incompatible Living Donor Liver Transplantation.

OXIDATIVE METABOLISM IN RATS WITH ACUTE HEPATIC INSUFFICIENCY

Liver failure is one of the most complex and unresolved problems in modern hepatology. The study aimed to study the parameters of oxidative metabolism in rats with acute hepatic insufficiency. Acute liver failure was induced by ingestion of 20% CCL4 oily solution. At the end of the experiment (3 weeks later), liver function tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, and bilirubin), antioxidant enzymes (catalase, superoxiddismutase (SOD)) nitric oxide (NO) were determined.The results of the study show that 3 weeks after the onset of CCL4-induced acute liver failure in rats, significant weight loss, liver dysfunction (increase in ALT, AST, bilirubin, total protein depletion) and oxidative stress (decreased NO content and activity of SOD and catalase).

Pediatric acute viral hepatitis with atypical variants: Clinical dilemmas and natural history.

Classical acute viral hepatitis (AVH) has an uncomplicated outcome. Acute liver failure has a grave prognosis. Atypical manifestations of AVH are a group of disorders that causes significant morbidity and dilemmas in children. These include prolonged cholestasis, relapsing hepatitis, ascitic form of AVH, late-onset hepatic failure (LOHF), intravascular hemolysis, and provoking an autoimmune trigger leading to autoimmune hepatitis. These entities cause significant liver dysfunction or worsening and are often difficult to differentiate from chronic liver disease (CLD). Ascitic form of AVH, LOHF, decompensated CLD and acute-on-chronic liver failure have significant overlapping features that need to be carefully dissected out. In many cases, only on long-term follow-up, these clinical entities can be separately identified. Intravascular hemolysis is usually caused by associated glucose-6-phosphate dehydrogenase deficiency. Rarely CLD such as Wilson disease and autoimmune hepatitis can also present with hemolysis in the initial presentation, which can mimic AVH with hemolysis. Identifying deviations from typical manifestations aid in avoiding unnecessary investigations, allowing focused therapy and alleviating anxiety.

Efficacy of local‐regional treatment plus sorafenib in intermediate‐stage hepatocellular carcinoma patients refractory to transarterial chemoembolization

AbstractSorafenib treatment is suggested for patients with intermediate‐stage hepatocellular carcinoma (HCC) refractory to transarterial chemoembolization (TACE). This study aimed to study if combining local‐regional treatment with sorafenib adds benefit to patients who had tumor progression after three sessions of TACE within 12 months. We retrospectively analyzed the treatment outcomes of sorafenib alone and combined treatment of sorafenib and local‐regional therapies in intermediate‐stage HCC patients after using inverse probability of treatment weighting (IPTW). Forty‐nine patients were enrolled; 28 patients were treated with sorafenib alone, whereas 21 patients received TACE or radiofrequency ablation (RFA) in addition to sorafenib. After IPTW, the two groups were well‐balanced for most baseline characteristics. The overall response rate (ORR) and disease control rate (DCR) were significantly higher in the sorafenib‐combination group than the sorafenib‐alone group (ORR: 41.3% vs 10.0%, P = .001; DCR: 44.6% vs 22.1%). The PFS was also significantly longer in the patients of the sorafenib‐combination group than the alone group (median 5.3 vs 3.0 months, HR, 0.55; 95% CI, 0.35‐0.88). The risk of extrahepatic metastases was significantly lower in the sorafenib‐combination group (HR, 0.04; 95% CI, 0.01‐0.50). The incidence of adverse events was comparable between sorafenib‐combination and sorafenib‐alone groups. Loco‐regional therapy may be still able to exert additional survival benefit to patients taking sorafenib for TACE‐refractory intermediate‐stage HCC showing a better PFS and lower risk of extrahepatic metastases without causing significant liver dysfunction. Further investigations to identify patients who will be more likely to benefit from the combination of sorafenib with local‐regional therapy are needed.

Diagnosis of human immunodeficiency virus associated disseminated intravascular coagulation.

Disseminated intravascular Coagulation (DIC) is a thrombotic microangiopathy which may complicate a number of severe disease processes including sepsis. Development of microvascular thromboses results in consumption of coagulation factors and platelets and ultimate bleeding. Patients with HIV infection (PWH) often present with baseline dysregulation of the coagulation system which may increase severity and derangement of DIC presentation. Previously, we have shown that HIV is a significant risk factor for development of DIC. We conducted a retrospective record review of all DIC screens submitted to our tertiary coagulation laboratory in Johannesburg, South Africa, over a one year period and compared the laboratory presentation of DIC in PWH with presentation of DIC in patients without HIV infection. Over the year, 246 patients fulfilled the International Society of Thrombosis and Haemostasis (ISTH) diagnostic criteria for DIC- 108 were confirmed HIV-infected and 77 were confirmed uninfected. PWH and DIC presented at a significantly earlier age (41 vs 46 years respectively, p<0.02). The prothrombin time was significantly more prolonged (30.1s vs 26.s), the d-dimer levels were substantially higher (5.89mg/L vs 4.52mg/L) and the fibrinogen (3.92g/L vs 1.73g/L) and platelet levels (64.8 vs 114.8x109/l) were significantly lower in PWH. PWH also showed significant synthetic liver dysfunction and higher background inflammation. PWH who fulfil the diagnostic criteria for DIC show significantly more dysregulation of the haemostatic system. This may reflect baseline abnormalities including endothelial dysfunction in the context of inflammation and liver dysfunction.

S2817 Glycopenic Hepatopathy in a Patient With Recurrent Diabetic Ketoacidosis: A Rare Complication of Poorly Controlled Type 1 Diabetes Mellitus

Introduction: Glycogenic hepatopathy (GH) is a rare condition predominately seen in patients with poorly controlled type 1 diabetes mellitus. This condition develops due to excessive accumulation of glycogen in the hepatocytes, leading to significant hepatomegaly and transient liver dysfunction with elevated liver enzymes. Case Description/Methods: A 24-year-old female with a history of poorly controlled type 1 diabetes mellitus complicated by multiple admissions for diabetic ketoacidosis (DKA) presented with acute onset abdominal pain, nausea and vomiting. Physical exam was significant for tender hepatomegaly. Admission laboratory results were significant for serum glucose 189 mg/dL, bicarbonate 5 mmol/L, anion gap 35 mmol/L, beta-hydroxybutyrate 6.5 mmol/L, and HbA1c 11.4%. Admission hepatic panel was significant for alanine aminotransferase 31 U/L, aspartate aminotransferase 56 U/L, alkaline phosphatase 138 U/L with normal bilirubin and prothrombin time. Patient was treated with insulin and intravenous fluids with resolution of her DKA. However, her clinical course was complicated by persistent abdominal pain with an acute rise in liver enzymes (alanine aminotransferase 216 U/L, aspartate aminotransferase 249 U/L, alkaline phosphatase 116 U/L with normal bilirubin and prothrombin time). Triglyceride level was elevated at 214mg/dL. Abdominal computed tomography was notable for hepatomegaly with liver size of 24 cm. Workup for hepatitis, HIV, COVID-19, autoimmune hepatitis, hemochromatosis, and Wilson's disease were negative. Patient underwent liver biopsy that demonstrated diffuse hepatocyte cytoplasmic clearing, consistent with GH. The patient was medically managed with strict glycemic control, diabetic diet and endocrinology input throughout admission. One week after hospital discharge, the patient remained asymptomatic and liver function tests returned to normal limits. Discussion: GH is a rare condition that should be considered in patients with poorly controlled diabetes mellitus who present with hepatomegaly and acute liver injury. While GH presents similarly to NAFLD, it can only be differentiated and definitely diagnosed by liver biopsy. This condition should not be overlooked as it is a favorable diagnosis with a good prognosis compared to other liver disease associated with diabetes mellitus. Further studies are needed to better understand the characteristics of this disease, and future development of non-invasive, rapid diagnostic testing could help avoid extensive and costly workups. (Figure Presented).

Real-World Data Analysis of Efficacy and Survival After Lutetium-177 Labelled PSMA Ligand Therapy in Metastatic Castration-Resistant Prostate Cancer.

Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA) radioligand therapy is emerging as a promising treatment for metastatic castration-resistant prostate cancer refractory to established therapies. While there is an increasing body of survival and other data from retrospective analyses and prospective trials, there is no clear understanding of how best to predict therapy response and survival outcomes. In this retrospective cohort analysis, we aimed to identify features that are associated with response to radioligand therapy and greater survival based on analysis of real-world data. 191 patients aged 70 ± 8 years with metastatic castration-resistant prostate cancer treated with radioligand therapy from November 2015 to February 2019 were included for analysis. Eligible patients had PSMA-expressing metastatic castration-resistant prostate cancer (confirmed by a 68Ga-PSMA-ligand positron emission tomography(PET)/computed tomography (CT)scan), an Eastern Cooperative Oncology Group performance status score ≤ 2 and no significant kidney, liver or bone marrow dysfunction (as characterised by kidney and liver function tests and a full blood count). Patients received one to five cycles of intravenous 177Lu-PSMA-ligand therapy. Endpoints included biochemical [prostate-specific antigen (PSA)] and radiologic (PSMA PET/CT) response, progression-free survival and overall survival, defined according to the Prostate Cancer Working Group 3 guidelines. Survival analysis was conducted by Kaplan-Meier estimation. Most individuals (89.5%) previously underwent first- and second-line systematic therapy. Of the 191 men treated with 452 cycles with mean injected activity of 6.1 ± 1.0 GBq per cycle, 159 patients were assessed for a biochemical response defined as a PSA decline ≥ 50% from baseline. A ≥ 50% PSA decline was observed in 89 (56%) patients, while any PSA decline occurred in 120 (75%) men. For the entire cohort, median values (interquartile range) of overall survival [n = 191], PSA progression-free survival [n = 132] and PET/CTprogression-free survival were 12 (5-18), 4 (3-8) and 6 (3-10) months, respectively. Survival analysis confirmed better outcomes in individuals who had demonstrated therapy response. Predominantly lymph node metastatic disease and chemotherapy-naïve status were significant pre-therapy factors associated with longer survival. Baseline PSA was significantly linked to survival outcomes: lower levels predicted a lower risk of death and disease progression. Treatment-related adverse events included grade 3 or 4 haematological (12%), grade 1 or 2 renal (4.5%), and grade 3 or 4 clinical events (5.7%). Our findings suggest that 177Lu-PSMA radioligand therapy provides a significant response rate with a low toxicity profile. The evidence promotes greater efficacy of radioligand therapy in predominantly lymph node metastatic castration-resistant prostate cancer, and in individuals with chemotherapy-naïve status and lower levels of baseline PSA.

Immunohistochemical detection of procalcitonin in fibrolamellar hepatocellular carcinoma

A 25-year-old woman with fever and epigastric pain was referred to our hospital. Blood examination showed significant liver dysfunction, markedly high C-reactive protein (CRP 19.1 mg/dL) and procalcitonin (48.3 ng/mL) levels. Dynamic computed tomography showed a tumor approximately 120 mm in size in the right lobe of the liver, but with no abscess formation. The patient was hospitalized and started on antibiotics; her CRP level improved, but the procalcitonin level did not decrease. Histopathological examination of the liver tumor biopsy revealed fibrolamellar hepatocellular carcinoma (FLC). Positive staining of the FLC with an anti-procalcitonin antibody suggested the production of procalcitonin.

Perioperative management of post-COVID-19 surgical patients: Indian Society of Anaesthesiologists (ISA National) Advisory and Position Statement.

Perioperative management of post-COVID-19 surgical patients: Indian Society of Anaesthesiologists (ISA National) Advisory and Position Statement.

ISPD guidelines for peritoneal dialysis in acute kidney injury: 2020 update (adults)

(1) Peritoneal dialysis (PD) should be considered a suitable modality for treatment of acute kidney injury (AKI) in all settings (1B). (2.1) Flexible peritoneal catheters should be used where resources and expertise exist (1B) (optimal).(2.2) Rigid catheters and improvised catheters using nasogastric tubes and other cavity drainage catheters may be used in resource-poor environments where they may still be life-saving (1C) (minimum standard).(2.3) We recommend catheters should be tunnelled to reduce peritonitis and peri-catheter leak (practice point).(2.4) We recommend that the method of catheter implantation should be based on patient factors and locally available skills (1C).(2.5) PD catheter implantation by appropriately trained nephrologists in patients without contraindications is safe and functional results equate to those inserted surgically (1B).(2.6) Nephrologists should receive training and be permitted to insert PD catheters to ensure timely dialysis in the emergency setting (practice point). (2.7) We recommend, when available, percutaneous catheter insertion by a nephrologist should include assessment with ultrasonography (2C).(2.8) Insertion of PD catheter should take place under complete aseptic conditions using sterile technique (practice point).(2.9) We recommend the use of prophylactic antibiotics prior to PD catheter implantation (1B).(2.10) A closed delivery system with a Y connection should be used (1A) (optimal). In resource poor areas, spiking of bags and makeshift connections may be necessary and can be considered (minimum standard).(2.11) The use of automated or manual PD exchanges are acceptable and this will be dependent on local availability and practices (practice point). (3.1) In patients who are critically ill, especially those with significant liver dysfunction and marked elevation of lactate levels, bicarbonate containing solutions should be used (1B) (optimal). Where these solutions are not available, the use of lactate containing solutions is an alternative (practice point) (minimum standard).(3.2) Commercially prepared solutions should be used (optimal). However, where resources do not permit this, then locally prepared fluids may be life-saving and with careful observation of sterile preparation procedure, peritonitis rates are not increased (1C) (minimum standard).(3.3) Once potassium levels in the serum fall below 4 mmol/L, potassium should be added to dialysate (using strict sterile technique to prevent infection) or alternatively oral or intravenous potassium should be given to maintain potassium levels at 4 mmol/L or above (1C).(3.4) Potassium levels should be measured daily (optimal). Where these facilities do not exist, we recommend that after 24 h of successful dialysis, one consider adding potassium chloride to achieve a concentration of 4 mmol/L in the dialysate (minimum standard) (practice point). (4.1) Targeting a weekly K t/V urea of 3.5 provides outcomes comparable to that of daily HD in critically ill patients; targeting higher doses does not improve outcomes (1B). This dose may not be necessary for most patients with AKI and targeting a weekly K t/V of 2.2 has been shown to be equivalent to higher doses (1B). Tidal automated PD (APD) using 25 L with 70% tidal volume per 24 h shows equivalent survival to continuous venovenous haemodiafiltration with an effluent dose of 23 mL/kg/h (1C).(4.2) Cycle times should be dictated by the clinical circumstances. Short cycle times (1-2 h) are likely to more rapidly correct uraemia, hyperkalaemia, fluid overload and/or metabolic acidosis; however, they may be increased to 4-6 hourly once the above are controlled to reduce costs and facilitate clearance of larger sized solutes (2C).(4.3) The concentration of dextrose should be increased and cycle time reduced to 2 hourly when fluid overload is evident. Once the patient is euvolemic, the dextrose concentration and cycle time should be adjusted to ensure a neutral fluid balance (1C).(4.4) Where resources permit, creatinine, urea, potassium and bicarbonate levels should be measured daily; 24 h K t/V urea and creatinine clearance measurement is recommended to assess adequacy when clinically indicated (practice point).(4.5) Interruption of dialysis should be considered once the patient is passing >1 L of urine/24 h and there is a spontaneous reduction in creatinine (practice point).

Role of potato protein hydrolysate and exercise in preventing high-fat diet-induced hepatocyte apoptosis in senescence-accelerated mouse.

Nonalcoholic fatty liver disease (NAFLD) is considered to be a serious clinical complication, which could cause significant liver dysfunction including fibrosis, cirrhosis, and cancer. Obesity could lead to NAFLD and contributes to liver disorder and related complicated liver diseases. Effect of exercise combined with alcalase treatment derived potato protein hydrolysate (APPH) on high-fat diet (HFD)-induced hepatic injury was investigated in senescence accelerated mouse-prone 8 (SAMP8) mice in the present study. Mice were divided into six groups (n=6): Group I-Control, Group II-HFD, Group III-Exercise, Group IV-HFD+APPH, Group V-HFD+Exercise, and Group VI-HFD+Exercise+APPH. Combined APPH treatment and exercise offer better cytoprotection in HFD-induced histological changes than APPH treatment and exercise alone. Further, APPH and exercise activate the cell survival proteins PI3K/Akt and prevent FasL/FADD-mediated apoptosis in HFD fed SAMP8 mouse. APPH with swimming exercise effectively modulate HFD-induced liver damage and apoptosis in aged mice through activation of PI3K/Akt protein. PRACTICAL APPLICATIONS: Exercise training is proven to reduce the health problems associated with aging and obesity, however, intensity and duration of the exercise differs between individuals. We used integrated pharmacological and nonpharmacological approach as a therapeutic strategy for preventing HFD-induced hepatic injury in aged subjects.

Acute Liver Failure Caused by Use of Fat Burner: A Case Report

Acute liver failure is a rare condition consisting of abrupt and extensive hepatocyte injury, leading to significant liver dysfunction associated with a high mortality. Liver transplantation is the most effective treatment in severe cases. The most common cause of acute liver failure in Western countries is drug-induced liver injury caused by prescription drugs and herbal and dietary supplements. Thermogenics, or fat burners, are a category of dietary supplements that claim to increase the resting metabolic rate, leading to weight loss. There are previous reports of acute liver failure associated with specific thermogenic formulations. We report the case of a 36-year-old male patient who developed jaundice 7 days after he started taking a thermogenic dietary supplement (Thermo Gun), with progressive deterioration of hepatic function and development of hepatic encephalopathy 19 days after the beginning of the symptoms. He had a Model for End-Stage Liver Disease score of 38 and fulfilled 4 of the King’s College Criteria for poor prognosis in patients with acute liver failure. He underwent liver transplantation, receiving a graft from a cadaveric donor, and is alive with good liver graft function 2 years after the transplant. No possible causes for acute liver injury were identified other than the use of the supplement, which contained N-acetyl-L-tyrosine; 1,3,7-trimenthylxanthine; white willow; and 1-hydroxypholedrine. We found no previous reports in the literature of acute liver failure associated with those particular substances. This manuscript is compliant with the Helsinki Congress and the Istanbul Declaration.

HMGB1-associated necroptosis and Kupffer cells M1 polarization underlies remote liver injury induced by intestinal ischemia/reperfusion in rats.

Reperfusion of the ischemic intestine often leads to drive distant organ injury, especially injuries associated with hepatocellular dysfunction. The precise molecular mechanisms and effective multiple organ protection strategies remain to be developed. In the current study, significant remote liver dysfunction was found after 6 hours of reperfusion according to increased histopathological scores, serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, as well as enhanced bacterial translocation in a rat intestinal ischemia/reperfusion (I/R) injury model. Moreover, receptor-interacting protein kinase 1/3 (RIP1/3) and phosphorylated-MLKL expressions in tissue were greatly elevated, indicating that necroptosis occurred and resulted in acute remote liver function impairment. Inhibiting the necroptotic pathway attenuated HMGB1 cytoplasm translocation and tissue damage. Meanwhile, macrophage-depletion study demonstrated that Kupffer cells (KCs) are responsible for liver damage. Blocking HMGB1 partially restored the liver function via suppressed hepatocyte necroptosis, tissue inflammation, hepatic KCs, and circulating macrophages M1 polarization. What's more, HMGB1 neutralization further protects against intestinal I/R-associated liver damage in microbiota-depleted rats. Therefore, intestinal I/R is likely associated with acute liver damage due to hepatocyte necroptosis, and which could be ameliorated by Nec-1 administration and HMGB1 inhibition with the neutralizing antibody and inhibitor. Necroptosis inhibition and HMGB1 neutralization/inhibition, may emerge as effective pharmacological therapies to minimize intestinal I/R-induced acute remote organ dysfunction.