Ex-situ hepatectomy: Indications, Techniques and Results

Ex situ hepatectomy is a novel approach, used in treating complicated liver tumors, which are otherwise unresectable via conventional methods including organ perfusion, liver transplant, hemodynamic management, vascular reconstruction or even extended hepatic resection. The Ex situ hepatectomy technique denotes the entire removal of the infected liver, which is then perfused in a cold preservation solution, which allows the surgeon to remove tumors, which were otherwise unreachable when the liver is situated in the body. In so doing, the tumor is restricted ex situ on the surgeon stable, while the remaining liver is implanted orthotopically. Notably, the works on Ex situ hepatectomy techniques are credited to Pichlmary 1990, who proposed the surgical approach in the treatment of bilateral liver leiomyosarcoma. More to that, there are only a handful of successful Ex situ hepatectomy cases which have been recorded on a global scale, given the complexity of the operation. Secondary as well as primary liver tumors are some of the most commonly occurring liver tumors in humans.

Grazoprevir/Elbasvir treatment in liver or kidney transplant recipients with genotype-1b hepatitis C virus infection

More options regarding the choice of direct-acting antivirals (DAAs) are helpful for avoiding individual limitations in treating hepatitis C virus (HCV) infection. We aimed to assess the efficacy and tolerability of grazoprevir (GZR)/elbasvir (EBR) treatment in genotype-1b (GT-1b) HCV-infected liver or kidney transplant recipients. In this phase 4, single-arm, open-label, multicenter trial, patients received GZR 100mg/EBR 50mg daily for 12 weeks. Patients with any HCV infection other than genotype-1b (GT-1b), liver decompensation, human immunodeficiency virus or hepatitis B virus co-infection, a history of NS5A inhibitor exposure, or any severe drug-drug interactions (DDIs) were excluded. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12). Of the 14 patients (10 kidney and 4 liver transplant subjects) enrolled in this study, 9 (64%) were females; the median age was 64.0 (range: 43-73) years. The regularly used immunosuppressants were tacrolimus (93%), everolimus (29%), and sirolimus (7%), with patient blood levels easily managed and generally stable (all p > 0.05 in quantile regression analysis). The rate of SVR12 was 100% in intent-to-treat analysis. Only one patient discontinued GZR/EBR therapy at 6 weeks posttreatment due to a treatment-unrelated adverse event (AE); however, this patient remained achieving SVR12. Most AEs were mild in severity and deemed to be not treatment-related. No organ rejection episodes or deaths occurred during the study period. The single-tablet regimen of GZR/EBR for 12 weeks is highly effective and well tolerated in GT-1b HCV-infected liver or kidney transplant recipients, and its DDIs are generally easy to manage.

Absence of PEXEL-Dependent Protein Export in Plasmodium Liver Stages Cannot Be Restored by Gain of the HSP101 Protein Translocon ATPase

Host cell remodeling is critical for successful Plasmodium replication inside erythrocytes and achieved by targeted export of parasite-encoded proteins. In contrast, during liver infection the malarial parasite appears to avoid protein export, perhaps to limit exposure of parasite antigens by infected liver cells. HSP101, the force-generating ATPase of the protein translocon of exported proteins (PTEX) is the only component that is switched off during early liver infection. Here, we generated transgenic Plasmodium berghei parasite lines that restore liver stage expression of HSP101. HSP101 expression in infected hepatocytes was achieved by swapping the endogenous promoter with the ptex150 promoter and by inserting an additional copy under the control of the elongation one alpha (ef1α) promoter. Both promoters drive constitutive and, hence, also pre-erythrocytic expression. Transgenic parasites were able to complete the life cycle, but failed to export PEXEL-proteins in early liver stages. Our results suggest that PTEX-dependent early liver stage export cannot be restored by addition of HSP101, indicative of alternative export complexes or other functions of the PTEX core complex during liver infection.

ASSESSMENT OF FASCIOLA GIGANTICA INFECTION IN THE LIVER OF CATTLE SLAUGHTERED IN IKPOBA/OKHA AREA COUNCIL, EDO STATE, NIGERIA

This study investigated the prevalence and intensity of Fasciola gigantica infection in the liver of cattle slaughtered in three abattoirs located in Ikpoba/Okha Local Government Area of Edo State, Nigeria. It also estimated the economic implications of the condemned liver. A total of 17,325 cattle were examined in the three abattoirs over a period of 252 days (approximately 69 cattle/day) spanning over the wet and dry seasons; 1,683 cattle were infected with an overall prevalence of 9.71%. In Abattoir A, 11774 cattle were examined with 1069 (9.08%) prevalence. In Abattoirs B and C, 4352 and 1199 cattle, respectively, were examined and 563 (12.94%) and 51 (4.25%) were respectively infected. From the three abattoirs, 155 (0.89%) livers were considered unfit for human consumption due to F. gigantica infection. For the wet season, 1062 (10.89%) cattle livers were infected while 621 (8.20%) were infected during the dry season. The mean intensity of infection during the wet season was 37.80 and 30.42 during the dry season. The financial loss due to infected liver condemnation was at N803,160 (1,947.050USD) showing that liver condemnation arising from F. gigantica infection is a major cause of financial loss to cattle farmers and dealers. There is, therefore, need for adequate veterinary inspections for early detection and treatment of the disease. There should be more meat inspection, especially in private/individual abattoirs.

Hepatic IFNL4 Gene Activation in Hepatocellular Carcinoma Patients with Regard to Etiology

Hepatocellular carcinoma (HCC) is a malignancy with a leading lethality. The etiology is quite diverse, ranging from viral infections to metabolic disorders or intoxications, and associates with specific somatic mutational patterns and specific host immunological phenotypes. Particularly, hepatitis C virus (HCV)-infected liver is featured by an activation of interferon (IFN)-stimulated genes (ISGs; IFN signature), which we suppose is driven by type III IFNL4. Taking advantage of the TCGA collection of HCC patients of various different etiologies, this study aimed at validating our previous findings on hepatic IFNL4 gene activation in HCV infection in an independent and larger cohort of patients with advanced liver disease. In a cohort of n = 377 cases, the entirety of the sequencing data was used to assess the IFNL genotypes, and the cases were stratified for etiology. The number of IFNL4 transcripts within nonmalignant and malignant tissues was found to be more abundant in patients with HCV or HCV/HBV infections when compared to other risk factors. Moreover, in patients with HCV infection as a risk factor, a close, positive relationship was found between ISG activation and the number of functional IFNL4 transcripts. Data on this independent TCGA sample support the concept of an IFNL4-dependent HCV-driven activation of hepatic ISGs. In addition to that, they add to the understanding of etiology-related host immunological phenotypes in HCC.

Clinical features and development of Sepsis in Klebsiella pneumoniae infected liver abscess patients: a retrospective analysis of 135 cases

Background Klebsiella pneumoniae is a primary pathogen of pyogenic liver abscess (PLA). However, little data are available on combination with sepsis. In this study, we aimed to evaluate the clinical characteristics and prognostic differences of PLA patients with sepsis. Methods This retrospective cohort study was conducted to investigate 135 patients with confirmed Klebsiella pneumoniae-caused liver abscesses (KPLA) from a tertiary teaching hospital, from 2013 to 2019. The patients were divided into two groups, KPLA with sepsis and KPLA without sepsis. The demographic characteristics, clinical features as well as laboratory and microbiologic findings were analyzed. Results A total of 135 patients with KPLA were analyzed. The mean age of patients was 60.9 ± 12.7 years, and the percentage of men was 59.3%. Among them, 37/135 (27.4%) of patients had sepsis and the mortality rate was 1.5%. The most common symptom was fever (91.1%). KPLA patients with sepsis had a significantly higher proportion of frailty, diarrhea, fatty liver, chronic renal insufficiency, and hepatic dysfunction compared to KPLA patients without sepsis (p < 0.05). Antibiotic therapy and percutaneous drainage were most frequently therapeutic strategy. Furthermore, the incidences of sepsis shock and acute respiratory distress syndrome were higher in the sepsis group compared to the non-sepsis group. As for metastatic infections, the lung was the most common site. In addition, KPLA patients with sepsis showed respiratory symptoms in 11 patients, endophthalmitis in 4 patients, and meningitis in 1 patient. Conclusion Our findings emphasize that KPLA patients combined with or without sepsis have different clinical features, but KPLA patients with sepsis have higher rates of complications and metastatic infections. Taken together, further surveillance and control of septic spread is essential for KPLA patients.

In vivo negative regulation of SARS-CoV-2 receptor, ACE2, by interferons and its genetic control

Background: Angiotensin I converting enzyme 2 (ACE2) is a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and differences in its expression may affect susceptibility to infection. Methods: We performed a genome-wide expression quantitative trait loci (eQTL) analysis using hepatitis C virus-infected liver tissue from 190 individuals. Results: We discovered that polymorphism in a type III interferon gene (IFNL4), which eliminates IFN-λ4 production, is associated with a two-fold increase in ACE2 RNA expression. Conversely, among genes negatively correlated with ACE2 expression, IFN-signalling pathways were highly enriched and ACE2 was downregulated after IFN-α treatment. Negative correlation was also found in the gastrointestinal tract where inflammation driven IFN-stimulated genes were negatively correlated with ACE2 expression and in lung tissue from a murine model of SARS-CoV-1 infection suggesting conserved regulation of ACE2 across tissue and species. Conclusions: We conclude that ACE2 is likely a negatively-regulated interferon-stimulated gene (ISG) and carriage of IFNL4 gene alleles which modulates ISGs expression in viral infection may play a role in SARS-CoV-2 pathogenesis with implications for therapeutic interventions.

Clinical Features and Development of Sepsis in Klebsiella Pneumoniae Infected Liver Abscess Patients: A Retrospective Analysis of 135 Cases

Background Klebsiella pneumoniae is a primary pathogen of pyogenic liver abscess (PLA). However, little data are available on combination with sepsis. In this study, we aimed to evaluate the clinical characteristics and prognostic differences of PLA patients with sepsis. Methods This retrospective cohort study was conducted to investigate 135 patients with confirmed Klebsiella pneumoniae-caused liver abscesses (KPLA) from a tertiary teaching hospital, from 2013 to 2019. The patients were divided into two groups based on comorbidity with sepsis. The demographic characteristics, clinical features as well as laboratory and microbiologic findings was analyzed. Results The 135 patients were analyzed, with a mean age of 60.9 ± 12.7 years, and 59.3% were men. Among them, 37/135 (27.4%) had comorbid sepsis and mortality rate was 1.5%. The most common symptom was fever (91.1%). KPLA patients with sepsis had a significantly higher proportion of frailty, diarrhea, fatty liver, chronic renal insufficiency, and hepatic dysfunction (p < 0.05). Antibiotic therapy and percutaneous drainage were most frequently used. The incidences of sepsis shock, acute respiratory distress syndrome was higher in the sepsis group compared to the non-sepsis group. As for metastatic infections, the lung was the most common site. Respiratory symptoms were found in 11 patients, and endophthalmitis coexisted in 4 patients, and meningitis occurred in 1 patient. Conclusion Our findings emphasize that KPLA patients combined with and without sepsis have different clinical features, but KPLA patients with sepsis have a high rate of complications and metastatic infections. Further surveillance and control of septic spread is essential in KPLA patients.