Comparative Assessment of Liver Function During the Intensive Phase of Treatment of Respiratory Tuberculosis Patients Treated with First Line and Reserve Drugs

The objective: to compare liver function of respiratory tuberculosis patients during the intensive phase of treatment with first line drugs (chemotherapy regimen 1) and reserve drugs (chemotherapy regimens 4 and 5).Subjects and Methods: Data of 144 respiratory tuberculosis patients were analyzed, those patients were divided into 2 groups. Group 1 included 67 patients receiving chemotherapy regimen 1 and Group 2 included 77 patients treated with chemotherapy regimens 4 or 5. During the first 3 months of treatment, the frequency and severity of changes in the liver function were assessed.Conclusion: in patients with chronic viral hepatitis, parenchymal liver damage is more frequent and it improves slower. Transaminase levels returned to normal levels more frequently and rapidly with chemotherapy regimen 1, whereas with chemotherapy regimens 4 and 5, reduction of alanine aminotransferase level was observed only from the 2nd month of treatment.

Comparison of Two EUS-Guided Liver Biopsy Techniques (“Wet Heparin” and “Wet Saline”) For Benign Parenchymal Liver Disease

Background: Endoscopic ultrasound-guided liver biopsy (EUS-LB) has emerged as a viable mean to obtain core tissue. Different wet suction techniques using saline or heparin have been described. We aimed to compare tissue adequacy with the “wet saline” (WS) technique compared to the “wet heparin” (WH) technique.Methods: We conducted a retrospective review of patients who underwent EUS-LB and Percutaneous liver biopsy (PLB-LB) for benign parenchymal liver disease between May 2017 to October 2019. All procedures were performed at a single tertiary Veterans Affairs Medical Center (VAMC).Results: A total of 257 biopsies from 217 patients were included. Among the 102 EUS-LB specimens, 53 were obtained using WS technique and 49 were obtained using WH technique. Specimen adequacy was similar in the both groups. Median ASL and length of longest piece did not differ significantly between both groups. Clots were present more frequently in the WS group. Among patients who underwent EUS-LB of both right and left liver lobes, an adequate biopsy was obtained in 85% of patients in the WS group and 96% of patients in the WH group. EUS-LB showed lower risk of post procedural pain and complication rates when compared with percutaneous liver biopsy (PLB). To our knowledge, this is the first study to compare diagnostic accuracy between WH and WS EUS-LB techniques, and to compare post-procedure pain between EUS-LB and moderate sedation PLB. WH-EUS-LB may be preferable to WS because of fewer clots in the specimen. Prospective studies are needed to further verify these findings.

Single-Cell Transcriptomic Analysis of Livers During NLRP3 Inflammasome Activation Reveals a Novel Immune Niche

The NOD-like receptor protein 3 (NLRP3) inflammasome is a central contributor to human acute and chronic liver disease, yet the molecular and cellular mechanisms by which its activation precipitates injury remain incompletely understood. Here, we present single cell transcriptomic profiling of livers from a global transgenic Tamoxifen-inducible constitutively-activated Nlrp3A350V mutant mouse, and we investigate the changes in parenchymal and non-parenchymal liver cell gene expression that accompany inflammation and fibrosis. Our results demonstrate that NLRP3 activation causes chronic extramedullary myelopoiesis marked by an increase in proliferating myeloid progenitors that differentiate into neutrophils, monocytes, and monocyte-derived macrophages, results that were corroborated by flow cytometry and histological staining. We observed prominent neutrophil infiltrates with increased Ly6gHI and Ly6gINT cells exhibiting transcriptomic signatures of granulopoiesis typically found in the bone marrow. This was accompanied by a marked increase in Ly6cHI monocytes differentiating into Cd11bHITim4HIClec4fHI macrophages that express proinflammatory transcriptional programs similar to macrophages of non-alcoholic steatohepatitis (NASH) models. NLRP3 activation also downregulated metabolic pathways in hepatocytes and shifted hepatic stellate cells towards an activated pro-fibrotic state based on expression of collagen and extracellular matrix (ECM) regulatory genes. These results, which highlight abundant neutrophils and extramedullary granulopoiesis define an inflamed and fibrotic hepatic single cell microenvironment, precipitated solely by NLRP3 activation. Clinically, our data support the notion that neutrophils and NLRP3 should be explored as therapeutic targets in NASH-like inflammation.

Embossed topographic depolarisation maps of biological tissues with different morphological structures

Layered topographic maps of the depolarisation due to diffuse biological tissues are produced using a polarisation-holographic Mueller matrix method approach. Histological sections of myocardial tissue with a spatially structured optically anisotropic fibrillar network, and parenchymal liver tissue with a polycrystalline island structure are successfully mapped. The topography of the myocardium maps relates to the scattering multiplicity within the volume and the specific morphological structures of the biological crystallite networks. The overall depolarisation map is a convolution of the effects of these two factors. Parenchymal liver tissues behave broadly similarly, but the different biological structures present cause the degree of scattering multiplicity to increase more rapidly with increasing phase. Through statistical analysis, the dependences of the magnitudes of the first to fourth order statistical moments are determined. These moments characterise the changing distributions of the depolarisation values through the volume of biological tissues with different morphological structures. Parenchymal liver tissue depolarisation maps are characterised by larger mean and variance, and less skewness and kurtosis, compared to the distributions for the myocardium. This work demonstrates that a polarisation-holographic Mueller matrix method can be applied to the assessment of the 3D morphology of biological tissues, with applications in disease diagnosis.

Human liver organoid derived intra-hepatic bile duct cells support SARS-CoV-2 infection and replication and its comparison with SARS-CoV

BackgroundAlthough the main route of infection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory tract, liver injury is also commonly seen in many patients, as evidenced by deranged parenchymal liver enzymes. Furthermore, patients with severe liver disease have been shown to have higher mortality. Overall, the mechanism behind the liver injury remains unclear.Approach and resultsWe showed that intra-hepatic bile duct cells could be grown using a human liver organoid platform. The cholangiocytes were not only susceptible to SARS-CoV-2 infection, they also supported efficient viral replication. We also showed that SARS-CoV-2 replication was much higher than SARS-CoV.ConclusionOur findings suggested direct cytopathic viral damage being a mechanism for SARS-CoV-2 liver injury.

The morphological specifics of the stromal and parenchymal liver components of 6-12-months old children from hiv-mono-infected mothers

To determine the morphological specifics of the stromal and parenchymal liver components of 6-12-months old children from HIV-mono-infected mothers. Materials and methods. The morphometric investigation included 87 liver tissue biopsies of 6-12-months old dead children from HIV-mono-infected mothers. All morphometric parameters of the parenchymal and stromal liver components were calculated using the Avtandilov`s microscopic morphometric grid, which was consisted of 100 equidistant points. It was inserted into the microscope`s ocular tube with a total × 200 microscope magnification. The number of points that were found on the corresponding types of parenchymal and stromal liver components was calculated. In every case, it was selected 10 random microscopic areas and then all data were obtained, calculated and presented as percentages. Results. Morphometric parameters of hepatocytes: mononuclear hepatocytes – 90.2±7.6 % [control – 93.5±7.1], two-nuclear hepatocytes – 9.8±1.2 % [control – 6.5±1.2], TMHC (two-/mononuclear hepatocytes coefficient) – 0.10±0.02 [control – 0.06±0.01], hepatocytes with fat vacuoles – 19.6±2.1 % [control – 0.5±0.2]. Parenchymal and stromal liver components: parenchyma – 56.1±3.3 % [control – 74.2±4.3], stroma (including blood vessels and bile ducts) – 43.9±3.7 % [control – 25.8±2.6], SPI (stroma/parenchyma index) – 0.78±0.02 [control – 0.34±0.01]. Morphometric parameters of all of the liver components: hepatocytes – 56.1±3.3 % [control – 74.2±4.3], portal tracts – 26.4±2.1 % [control – 3.1±0.6], central veins – 8.1±1.2 % [control – 9.3±1.4], sinusoids – 7.3±1.2 % [control – 10.5±1.3], bile ducts – 2.1±0.1 % [control – 2.9±0.2]. Expression level parameters: fibronectin – 73.2±4.2 % [control – 17.3±2.5], collagen type I – 15.9±1.2 % [control – 9.7±1.9], collagen type III – 20.1±2.6 % [control – 10.1±0.9], collagen type IV – 7.3±0.2 % [control – 5.9±0.2]. Conclusions. It was established, that in the liver of 6-12-months old children from HIV-mono-infected mothers, the parenchymal component of the liver showed the signs of its significant reduction, increase of regenerative activity of hepatocytes, and fatty degeneration of hepatocytes with a certain sign of reactive steatohepatitis. Also, it was established, that the stromal component of the liver of children from HIV-infected mothers showed the signs of its progressive proliferation and collagenization due to increased production and accumulation of fibronectin, type I, type III collagens in the stroma of portal tracts and newly formed septa, and the signs of hepatic sinusoid capillarization due to type IV collagen accumulation in the space of Disse of the hepatic sinusoids.

A Single Cell Gene Expression Atlas of 28 Human Livers

ABSTRACTThe liver is the largest solid organ in the human body and is responsible for a multitude of essential functions for survival. Chronic liver injury affects over 1 billion people worldwide and therapeutic options other than liver transplantation are a critical unmet medical need. Thus, advances in molecular hepatology are essential to facilitate the discovery of new therapeutic targets. Here we describe the aggregation and integration of single cell RNA-sequencing in more than 36,000 cells from 28 human livers reported in five independent studies. Noteworthy, the merged data shows a high degree of overlap, demonstrating the robustness of liver gene expression at single cell level independent of age, gender, liver collection, processing and sequencing methods. Hence, this data allowed us to develop a user-friendly web browser for quick and easy interrogation and comparison of gene expression across a variety of parenchymal and non-parenchymal liver cell populations. Collectively, this study provides the largest human liver transcriptomic single cell atlas accessible for interactive visualization via an open-access web portal to the research community worldwide.

DNA Damage and Glutathione Peroxidase Activity in Liver and Kidney Cells in Wistar Rats Exposed to Terbuthylazine (TERB) for 28 Consecutive Days

The potential of low doses of the chloro-triazine herbicide terbuthylazine to induce DNA damage and impair activity of glutathione peroxidase (GPx) was evaluated in kidney and parenchymal and non-parenchymal liver cells of adult male rats. In a 28-day study, terbuthylazine was applied daily by oral gavage at doses: 0.004, 0.4 and 2.29 mg/kg bw/day. Tail Intensity (T Int) and Tail Length (TL) were used as descriptors of DNA damage. In the kidney, Tail Int was significantly different in all treated groups, while TL was different in 0.4 and 2.29 mg/kg bw/day groups, compared to controls. Significant differences in TL were recorded in parenchymal and non-parenchymal liver cells of all treated groups. Tail Int was significantly different from controls in non-parenchymal liver cells at all applied doses and in parenchymal cells at terbuthylazine doses of 0.004 and 2.29 mg/kg bw/day. A significant increase in GPx activity was observed only in the kidney at doses 0.4 and 2.29 mg/kg bw/day compared to the controls indicating its possible role in the protection of kidney from free radicals. It appears that repeated exposure to low doses of terbuthylazine could cause DNA instability in kidney cells and in parenchymal and non-parenchymal liver cells in rats.