Large Liver Research Articles

Endogenous Endophthalmitis From a Klebsiella pneumoniae Liver Abscess: The Incidence, Risk Factors, and Utility of Imaging

We investigated the rate of ophthalmologic examinations to detect endogenous endophthalmitis in patients with pyogenic liver abscesses (PLAs) and the incidence and risk factors of endophthalmitis from a PLA caused by Klebsiella pneumoniae (PLA-K). A retrospective case series METHODS: A total of 536 patients admitted to a university hospital in Korea, to treat PLAs during 2012-2022 were primarily included. The proportion of patients who were referred for ophthalmologic examinations was investigated and the incidence of endophthalmitis in 248 patients with PLA-K was calculated. Univariate and multivariate logistic regression analyses were performed to define risk factors including demographic characteristics, underlying diseases, radiological findings, and systemic conditions. A comprehensive ophthalmologic examination was performed in 73.7% of all patients with PLAs, and the incidence of endophthalmitis from a PLA-K was 7.3%. A liver abscess larger than 5 cm in size increased the incidence of endogenous endophthalmitis 4-fold compared to smaller abscesses (OR=4.01, 95% CI=1.02 - 15.78, P=.047), and portal or hepatic vein thrombophlebitis increased the incidence approximately 4-fold (OR=4.04, 95% CI=1.10 - 14.83, P=.036). Acute cholangitis was approximately 8-fold (OR=8.33, 95% CI=1.25 - 55.71, P=.029), and disseminated intravascular coagulation (DIC) was approximately 6-fold (OR=5.76, 95% CI=1.22 - 27.21, P=.027) more related to prevalence of endophthalmitis. Other extrahepatic infections increased the incidence approximately 43-fold (OR=43.06, 95% CI=10.14 - 182.90, P < .001). . Clinicians should consider the risk of endogenous endophthalmitis when PLA-K patients have large liver abscesses (> 5 cm), acute cholangitis, portal or hepatic vein thrombophlebitis, DIC, or other extrahepatic infections.

Autofluorescence-Raman Spectroscopy for Ex Vivo Mapping Colorectal Liver Metastases and Liver Tissue

IntroductionIdentifying colorectal liver metastases (CRLM) during liver resection could assist in achieving clear surgical margins, which is an important prognostic variable for both disease-free and overall survival. The aim of this study was to investigate the effect of auto-fluorescence (AF) and Raman spectroscopy for ex vivo label-free discrimination of CRLMs from normal liver tissue. Secondary aims include exploring options for multimodal AF-Raman integration with respect to diagnosis accuracy and imaging speed on human liver tissue and CRLM. MethodsLiver samples were obtained from patients undergoing liver surgery for CRLM who provided informed consent (15 patients were recruited). AF and Raman spectroscopy was performed on CRLM and normal liver tissue samples and then compared to histology. ResultsAF emission spectra demonstrated that the 671 nm and 775/785 nm excitation wavelengths provided the highest contrast, as normal liver tissue elicited on average around eight-fold higher AF intensity compared to CRLM. The use of the 785 nm wavelength had the advantage of enabling Raman spectroscopy measurements from CRLM regions, allowing discrimination of CRLM from regions of normal liver tissue eliciting unusual low AF intensity, preventing misclassification. Proof-of-concept experiments using small pieces of CRLM samples covered by large normal liver tissue demonstrated the feasibility of a dual-modality AF-Raman for detection of positive margins within few minutes. ConclusionsAF imaging and Raman spectroscopy can discriminate CRLM from normal liver tissue in an ex vivo setting. These results suggest the potential for developing integrated multimodal AF-Raman imaging techniques for intraoperative assessment of surgical margins.

Magnetic resonance imaging of organ iron before and after correction of iron deficiency in patients with heart failure.

Intravenous iron therapy (IVIT) is known to improve functional status in chronic heart failure (CHF) patients. The exact mechanism is not completely understood. We correlated magnetic resonance imaging (MRI) patterns of T2* iron signal in various organs to systemic iron and exercise capacity (EC) in CHF before and after IVIT. We prospectively analysed 24 patients with systolic CHF for T2* MRI pattern of the left ventricle (LV), small and large intestines, spleen, liver, skeletal muscle, and brain for iron. In 12 patients with iron deficiency (ID), we restored iron deficit by IVIT using ferric carboxymaltose. The effects after 3months were analysed by spiroergometry and MRI. Patients with vs. without ID showed lower blood ferritin, haemoglobin (76±63 vs. 196±82μg/L and 12.3±1.1 vs. 14.2±1.1g/dL, all P<0.002), and in trend a lower transferrin saturation (TSAT) (19.1 [13.1; 28.2] vs. 25.1 [21.3; 29.1] %, P=0.05). Spleen and liver iron was lower as expressed by higher T2* value (71.8 [66.4; 93.1] vs. 36.9 [32.9; 51.7] ms, P<0.002 and 33.5±5.9 vs. 28.8±3.9ms, and P<0.03). There was a strong trend for a lower cardiac septal iron content in ID (40.6 [33.0; 57.3] vs. 33.7 [31.3; 40.2] ms, P=0.07). After IVIT, ferritin, TSAT, and haemoglobin increased (54 [30; 104] vs. 235 [185; 339] μg/L, 19.1 [13.1; 28.2] vs. 25.0 [21.0; 33.7] %, 12.3±1.1 vs. 13.3±1.3g/L, all P<0.04). Peak VO2 improved (18.2±4.2 vs. 20.9±3.8mL/min/kg-1 , P=0.05). Higher peak VO2 at anaerobic threshold was associated with higher blood ferritin, reflecting higher metabolic exercise capacity after therapy (r=0.9, P=0.0009). Increase in EC was associated with haemoglobin increase (r=0.7, P=0.034). LV iron increased by 25.4% (48.5 [36.2; 64.8] vs. 36.2 [32.9; 41.9] ms, P<0.04). Spleen and liver iron increased by 46.4 and 18.2%, respectively (71.8 [66.4; 93.1] vs. 38.5 [22.4; 76.9] ms, P<0.04 and 33.5±5.9 vs. 27.4±8.6ms, P<0.007). Iron in skeletal muscle, brain, intestine, and bone marrow remained unchanged (29.6 [28.6; 31.2] vs. 30.4 [29.7; 30.7] ms, P=0.7, 81.0±6.3 vs. 82.9±9.9ms, P=0.6, 34.3±21.4 vs. 25.3±14.1ms, P=0.2, 9.4 [7.5; 21.8] vs. 10.3 [6.7; 15.7] ms, P=0.5 and 9.8±1.5 vs. 13.7±8.9ms, P=0.1). CHF patients with ID showed lower spleen, liver, and in trend lower cardiac septal iron. After IVIT, iron signal of the left ventricle as well as spleen and liver increased. Improvement in EC was associated with increase in haemoglobin after IVIT. In ID, liver, spleen, and brain but not heart iron were associated with markers of systemic ID.

Validation of a Clinical Risk-based Classification System in a Large Nonalcoholic Fatty Liver Disease Real-world Cohort

There is an unmet need to validate simple and easily available methods that can be used in routine practice to identify those at risk of adverse outcomes from nonalcoholic fatty liver disease (NAFLD). A retrospective-prospective analysis of NAFLD patients enrolled in a longitudinal noninterventional study (TARGET-NASH) was performed to validate the prognostic utility of the following risk-categories: (A) Fibrosis-4 (FIB-4) <1.3 and/or liver-stiffness measurement (LSM) measured by Fibroscan <8 kp, (B) FIB-4 1.31‒2.6 and/or LSM 8.1-12.5 kp, and (C) FIB-4 >2.6 and/or LSM >12.5 kp. Those in class A with aspartate transaminase:alanine transaminase ratio >1 or platelets <150,000/mm3, or class B with aspartate transaminase:alanine transaminase ratio >1 or platelets <150,000/mm3 were upstaged by one class. Fine-Gray competing risk analyses were performed for all outcomes. A total of 2523 individuals (class A= 555, B= 879, C= 1089) were followed for a median duration of 3.74 years. Adverse outcomes increased from class A to C in all-cause mortality (0.07 vs 0.3 vs 2.5/100 person-years [PY], hazard ratio [HR], 3.0 and 16.3 class B and C vs A), liver-associated clinical events (0.2 vs 1 vs 8/100 PY, HR, 4.3 and 36.6 B and C vs A), major adverse cardiovascular events (0.69 vs 0.87 vs 2.02/100 PY, HR, 0.78 and 1.55 B and C vs A), hepatocellular carcinoma (0 vs 0.09 vs 0.88/100 PY, HR, 8.32 C vs B), and chronic kidney disease (1.24 vs 2.48 vs 3.51/100 PY). Those who were upstaged had outcome rates similar to the lower class defined by their FIB-4. These data support a FIB-4-based risk-stratification of NAFLD that can be used in routine clinical practice. gov Identifier: NCT02815891.

Primary Hepatic Choriocarcinoma with Pregnancy: A Diagnostic and Therapeutic Challenge

Choriocarcinoma occurs mainly in the gonads, but an extragonadal origin has been reported, albeit infrequently. Primary hepatic choriocarcinoma (PHC) is a rare malignancy, with only 11 cases reported. Most cases reported were in males, with none reported in pregnant females. A 23-year-old primigravida presented with a large liver lesion involving the right lobe of the liver at 28 weeks of pregnancy. Preoperative imaging was suggestive of hepatocellular carcinoma. She underwent a non-anatomical resection of the liver lesion. Surprisingly, her postoperative histopathology revealed a diagnosis of PHC. Her blood workup showed elevated beta human chorionic gonadotrophin. She underwent a termination of her pregnancy at 32 weeks. Before initiating adjuvant chemotherapy four weeks after surgery, a whole-body PET scan revealed multiple bi-lobar liver and pelvic deposits. After a multidisciplinary team discussion, she was started on adjuvant chemotherapy. She is currently under regular follow-up, seven months post-surgery. PHC, one of the vascular lesions of the liver, poses a diagnostic and therapeutic challenge, warranting a multidisciplinary approach.

Key Issues and Novel Strategies of Stem Cell Intervention and Decellularized Scaffold Liver Tissue Engineer for End-Stage Liver Disease

End-stage liver disease (ESLD) is ultimation of all kinds of chronic liver diseases. It is highly morbidity and mortality disease and currently no effective treatment is available. Liver transplantation (LTx) is the only way for the treatment. However, the organ source limitation interferes with clinical application of LTx. For the goal of crossing liver source shortage barrier, researches attempt to explore techniques or methods like stem cells and tissue engineering, and recent years sounds developed rapidly and bright prospects, for example, artificial liver, tissue-engineered liver and xenotransplantation etc., in particular adult stem cells like bone marrow-derived mesenchymal stem cells (<SUB>BM</SUB>MSCs) and decellularized liver scaffold for large scale liver tissue engineer seems more eye-catching, and such decellularization / recellularization technology used has become the first strategy to build complex organs. We have previously discussed some points in the <Chinese Journal of Digestive Surgery > about optimizing bioscaffold materials that probably will be benificial for tissue engineer. In the present review, we would like to discuss some new developments based on research status and provide a little new thoughts, hopefully those can help people in this field in order to treat ESLD in the near future.

Intraoperative laparoscopic liver surface registration with preoperative CT using mixing features and overlapping region masks.

Laparoscopic liver resection is a minimal invasive surgery. Augmented reality can map preoperative anatomy information extracted from computed tomography to the intraoperative liver surface reconstructed from stereo 3D laparoscopy. However, liver surface registration is particularly challenging as the intraoperative surface is only partially visible and suffers from large liver deformations due to pneumoperitoneum. This study proposes a deep learning-based robust point cloud registration network. This study proposed a low overlap liver surface registration algorithm combining local mixed features and global features of point clouds. A learned overlap mask is used to filter the non-overlapping region of the point cloud, and a network is used to predict the overlapping region threshold to regulate the training process. We validated the algorithm on the DePoLL (the Deformable Porcine Laparoscopic Liver) dataset. Compared with the baseline method and other state-of-the-art registration methods, our method achieves minimum target registration error (TRE) of 19.9 ± 2.7mm. The proposed point cloud registration method uses the learned overlapping mask to filter the non-overlapping areas in the point cloud, then the extracted overlapping area point cloud is registered according to the mixed features and global features, and this method is robust and efficient in low-overlap liver surface registration.

Hidden malignancy in large polycystic liver and kidney.

Hidden malignancy in large polycystic liver and kidney.

Identifying multiscale translational safety biomarkers using a network-based systems approach

Animal testing is the current standard for drug and chemicals safety assessment, but hazards translation to human is uncertain. Human invitro models can address the species translation but might not replicate invivo complexity. Herein, we propose a network-based method addressing these translational multiscale problems that derives invivo liver injury biomarkers applicable to invitro human early safety screening. We applied weighted correlation network analysis (WGCNA) toa large rat liver transcriptomic dataset to obtain co-regulated gene clusters (modules). We identified modules statistically associated with liver pathologies, including a module enriched for ATF4-regulated genes as associated with theoccurrence of hepatocellular single-cell necrosis, and as preserved in human liver invitro models. Within the module, we identified TRIB3 and MTHFD2 as a novel candidate stress biomarkers, and developed and used BAC-eGFPHepG2 reporters in a compound screening, identifying compounds showing ATF4-dependent stress response and potential early safety signals.

Robotic Left Trisectionectomy with Glissonian Approach (with Video)

BackgroundLeft hepatic trisectionectomy consists of the removal of liver segments 2, 3, 4, 5, and 8. This difficult surgical procedure may be required when the left liver and right anterior sector (segments 5 and 8) are involved. We present a video of a robotic anatomic left trisectionectomy with Glissonian approach to the left and right anterior sector pedicles. MethodsA 77-year-old man presented at a routine ultrasound with a large liver mass. Magnetic resonance imaging showed a bulky hepatocellular carcinoma occupying liver segments 2, 3, 4, 5, and 8, with a portal tumor thrombus in the right anterior sector. The patient had multiple comorbidities, including obesity, diabetes, hypertension, and coronariopathy. The multidisciplinary team decided to use immunotherapy with atezolizumab and bevacizumab. After 12 cycles, the patient showed an objective response, and left trisectionectomy was indicated. A robotic approach was proposed and consent was obtained. The Glissonian approach was used for anatomic control of the left and right anterior sector pedicles. ResultsThe operative time was 390 min with an estimated blood loss of 410 ml, and no transfusion was required during or after the procedure. Recovery was uneventful and the patient was discharged on postoperative day 8. No bile leak was observed, and the drain was removed on postoperative day 8. ConclusionsRobotic left trisectionectomy is safe and feasible. The Glissonian approach is useful for anatomic left liver trisectionectomy. This video can help gastrointestinal surgeons perform this complex procedure in a minimally invasive manner.

Tumor decellularization reveals proteomic and mechanical characteristics of the extracellular matrix of primary liver cancer

Tumor initiation and progression are critically dependent on interaction of cancer cells with their cellular and extracellular microenvironment. Alterations in the composition, integrity, and mechanical properties of the extracellular matrix (ECM) dictate tumor processes including cell proliferation, migration, and invasion. Also in primary liver cancer, consisting of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the dysregulation of the extracellular environment by liver fibrosis and tumor desmoplasia is pertinent. Yet, the exact changes occurring in liver cancer ECM remain uncharacterized and underlying tumor-promoting mechanisms remain largely unknown. Herein, an integrative molecular and mechanical approach is used to extensively characterize the ECM of HCC and CCA tumors by utilizing an optimized decellularization technique. We identified a myriad of proteins in both tumor and adjacent liver tissue, uncovering distinct malignancy-related ECM signatures. The resolution of this approach unveiled additional ECM-related proteins compared to large liver cancer transcriptomic datasets. The differences in ECM protein composition resulted in divergent mechanical properties on a macro- and micro-scale that are tumor-type specific. Furthermore, the decellularized tumor ECM was employed to create a tumor-specific hydrogel that supports patient-derived tumor organoids, which provides a new avenue for personalized medicine applications. Taken together, this study contributes to a better understanding of alterations to composition, stiffness, and collagen alignment of the tumor ECM that occur during liver cancer development.

Double pigtail tube drainage for large multiloculated pyogenic liver abscesses.

This study aims to investigate the efficacy and safety of double pigtail tube drainage compared with single pigtail tube drainage for the treatment of multiloculated pyogenic liver abscesses greater than 5 cm. This study retrospectively analyzed patients with pyogenic liver abscess admitted in the Affiliated Hospital of Chengde Medical College between May 2013 and May 2021. Patients with pyogenic liver abscess more than 5 cm in size, who underwent drainage of the abscess with either double pigtail or single pigtail tube, were included. A total of 97 patients with pyogenic liver abscesses larger than 5 cm were studied. These included 34 patients with double pigtail tube drainage and 63 patients with single pigtail tube drainage. The postoperative hospital stay (13.39 ± 4.21 days vs. 15.67 ± 7.50 days; P = 0.045), and time for removal of the catheter (17.23 ± 3.70 days vs. 24.11 ± 5.83 days; P = 0.038) were lower in the double pigtail tube group compared with the single pigtail tube group. The rate of reduction, in three days, of c-reactive protein levels was 26.61 ± 14.11 mg/L/day in the double pigtail tube group vs. 20.06 ± 11.74 mg/L/day in the single pigtail tube group (P = 0.025). The diameter of the abscess cavity at discharge was 3.1 ± 0.07 cm in the double pigtail tube group as compared with 3.7 ± 0.6 cm in the single pigtail tube group (P = 0.047). There was no bleeding in any of the patients despite abnormal coagulation profiles. There was no recurrence of abscess within six months of discharge and no death in the double pigtail tube group. Conclusion: Double pigtail tube drainage treatment in multiloculated pyogenic liver abscesses greater than 5 cm in size, is safe and effective.

T cell‐dependent bispecific antibodies alter organ‐specific endothelial cell–T cell interaction

Preclinical and clinical studies demonstrate that T cell‐dependent bispecific antibodies (TDBs) induce systemic changes in addition to tumor killing, leading to adverse events. Here, we report an in‐depth characterization of acute responses to TDBs in tumor‐bearing mice. Contrary to modest changes in tumors, rapid and substantial lymphocyte accumulation and endothelial cell (EC) activation occur around large blood vessels in normal organs including the liver. We hypothesize that organ‐specific ECs may account for the differential responses in normal tissues and tumors, and we identify a list of genes selectively upregulated by TDB in large liver vessels. Using one of the genes as an example, we demonstrate that CD9 facilitates ICAM‐1 to support T cell–EC interaction in response to soluble factors released from a TDB‐mediated cytotoxic reaction. Our results suggest that multiple factors may cooperatively promote T cell infiltration into normal organs as a secondary response to TDB‐mediated tumor killing. These data shed light on how different vascular beds respond to cancer immunotherapy and may help improve their safety and efficacy.

Combined CT-guided high-dose-rate brachytherapy (CT-HDRBT) and transarterial chemoembolization with irinotecan-loaded microspheres improve local tumor control and progression-free survival in patients with unresectable colorectal liver metastases compared with mono-CT-HDRBT.

To compare the effectivity and toxicity of monotherapy with computed tomography-guided high-dose-rate brachytherapy (CT-HDRBT) vs. combination therapy of transarterial chemoembolization with irinotecan (irinotecan-TACE) and CT-HDRBT in patients with large unresectable colorectal liver metastases (CRLM) with a diameter of > 3 cm. Forty-four retrospectively matched patients with unresectable CRLM were treated either with mono-CT-HDRBT or with a combination of irinotecan-TACE and CT-HDRBT (n = 22 in each group). Matching parameters included treatment, disease, and baseline characteristics. National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0) were used to evaluate treatment toxicity and the Society of Interventional Radiology classification was applied to analyze catheter-related adverse events. Statistical analysis involved Cox regression, Kaplan-Meier estimator, log-rank test, receiver operating characteristic curve analysis, Shapiro-Wilk test, Wilcoxon test, paired sample t-test, and McNemar test. P-values < 0.05 were deemed significant. Combination therapy ensued longer median progression-free survival (PFS: 5/2 months, p = 0.002) and significantly lower local (23%/68%, p < 0.001) and intrahepatic (50%/95%, p < 0.001) progress rates compared with mono-CT-HDRBT after a median follow-up time of 10 months. Additionally, tendencies for longer local tumor control (LTC: 17/9 months, p = 0.052) were found in patients undergoing both interventions. After combination therapy, aspartate and alanine aminotransferase toxicity levels increased significantly, while total bilirubin toxicity levels showed significantly higher increases after monotherapy. No catheter-associated major or minor complications were identified in each cohort. Combining irinotecan-TACE with CT-HDRBT can improve LTC rates and PFS compared with mono-CT-HDRBT in patients with unresectable CRLM. The combination of irinotecan-TACE and CT-HDRBT shows satisfying safety profiles.

Case Report of a 45-year-Old Female Patient with a Large Cystic Liver Lesion with Imaging Features of Hydatid Cyst, which Was Found to Be Cystadenocarcinoma. A Challenge

Case Report of a 45-year-Old Female Patient with a Large Cystic Liver Lesion with Imaging Features of Hydatid Cyst, which Was Found to Be Cystadenocarcinoma. A Challenge

Acute management of pneumonia in adult patients.

Acute management of pneumonia in adult patients.

HEPATECTOMIA PARCIAL EMPREGANDO GRAMPEADOR LINEAR CORTANTE: HÁ VANTAGENS?

ABSTRACT BACKGROUND: Morbidity of liver resections is related to intraoperative bleeding and postoperative biliary fistulas. The Endo-GIA stapler (EG) in liver resections is well established, but its cost is high, limiting its use. The linear cutting stapler (LCS) is a lower cost device. AIMS: To report open liver resections, using LCS for transection of the liver parenchyma and en bloc stapling of vessels and bile ducts. METHODS: Ten patients were included in the study. Four patients with severe abdominal pain had benign liver tumors (three adenomas and one focal nodular hyperplasia). Among the remaining six patients, four underwent liver resection for the treatment of colorectal liver metastases, three of which had undergone preoperative chemotherapy. The other two cases were one patient with metastasis from a testicular teratoma and the other with metastasis from a gastrointestinal neuroectodermal tumor. RESULTS: The average length of stay was five days (range 4–7 days). Of the seven patients who underwent resections of segments II/III, two presented postoperative complications: one developed a seroma and the other a collection of abdominal fluid who underwent percutaneous drainage, antibiotic therapy, and blood transfusion. Furthermore, the three patients who underwent major resections had postoperative complications: two developed anemia and received blood transfusions and one had biloma and underwent percutaneous drainage and antibiotic therapy. CONCLUSIONS: The use of the linear stapler in hepatectomies was efficient and at lower costs, making it suitable for use whenever EG is not available. The size of the LCS stapler shaft is more suitable for en bloc transection of the left lateral segment of the liver, which is thinner than the right one. Further studies are needed to evaluate the safety of LCS for large liver resections and resections of tumors located in the right hepatic lobe.

Intrahepatic quantification of HBV antigens in chronic hepatitis B reveals heterogeneity and treatment-mediated reductions in HBV core-positive cells

Patterns of liver HBV antigen expression have been described but not quantified at single-cell resolution. We applied quantitative techniques to liver biopsies from individuals with chronic hepatitis B and evaluated sampling heterogeneity, effects of disease stage, and nucleos(t)ide (NUC) treatment, and correlations between liver and peripheral viral biomarkers. Hepatocytes positive for HBV core and HBsAg were quantified using a novel four-plex immunofluorescence assay and image analysis. Biopsies were analysed from HBeAg-positive (n= 39) and HBeAg-negative (n= 75) participants before and after NUC treatment. To evaluate sampling effects, duplicate biopsies collected at the same time point were compared. Serum or plasma samples were evaluated for levels of HBV DNA, HBsAg, hepatitis B core-related antigen (HBcrAg), and HBV RNA. Diffusely distributed individual HBV core+ cells and foci of HBsAg+ cells were the most common staining patterns. Hepatocytes positive for both HBV core and HBsAg were rare. Paired biopsies revealed large local variation in HBV staining within participants, which was confirmed in a large liver resection. NUC treatment was associated with a >100-fold lower median frequency of HBV core+ cells in HBeAg-positive and HBeAg-negative participants, whereas reductions in HBsAg+ cells were not statistically significant. The frequency of HBV core+ hepatocytes was lower in HBeAg-negative participants than in HBeAg-positive participants at all time points evaluated. Total HBV+ hepatocyte burden correlated with HBcrAg, HBV DNA, and HBV RNA only in baseline HBeAg-positive samples. Reductions in HBV core+ hepatocytes were associated with HBeAg-negative status and NUC treatment. Variation in HBV positivity within individual livers was extensive. Correlations between the liver and the periphery were found only between biomarkers likely indicative of cccDNA (HBV core+ and HBcrAg, HBV DNA, and RNA). HBV infects liver hepatocyte cells, and its genome can exist in two forms that express different sets of viral proteins: a circular genome called cccDNA that can express all viral proteins, including the HBV core and HBsAg proteins, or a linear fragment that inserts into the host genome typically to express HBsAg, but not HBV core. We used new techniques to determine the percentage of hepatocytes expressing the HBV core and HBsAg proteins in a large set of liver biopsies. We find that abundance and patterns of expression differ across patient groups and even within a single liver and that NUC treatment greatly reduces the number of core-expressing hepatocytes.

A new insight into genetic structure of Danube and Italian foci of fascioloidosis

Human induced translocation and introduction of species have reshaped parasite fauna on a global scale. The introduction of the large American liver fluke Fascioloides magna from North America to Europe is an example of an invasive alien parasite causing significant ecological and economic damage. Recent genetic studies have shown that F. magna was introduced to Europe on multiple occasions forming three permanent foci of infection. This study primarily focuses on the poorly researched genetic structuring of F. magna flukes originating from Croatia and Serbia. Additional samples from USA and Italy are also included, thereby providing novel insights into F. magna’s biogeography. Partial cox1 and nad1 genes were amplified from 216 F. magna flukes extracted from red deer, roe deer, fallow deer, white-tailed deer and wild boar. Seven cox1 and nine nad1 haplotypes were identified, of which two cox1 and four nad1 haplotypes have not been not previously found. Our analysis has expanded the knowledge about possible sources of F. magna introduction to Europe, by identifying a cox1 haplotype shared by flukes from the north-eastern parts of the USA and Italy and another cox1 haplotype shared by flukes also from north eastern parts of the USA and the Danube floodplains.

Comparison of mitochondrial cox1 gene in Fascioloides magna from different host species

Large American liver fluke (Fascioloides magna) was introduced to Europe at least twice, via invaded North American deer species. These imports resulted in formation of three permanent foci of fascioloidosis - Italian, Czech and Danube floodplain forests. Molecular analysis revealed that flukes in Italian foci represent separate genetic group, and that flukes from Czech and Danube foci are genetically identical. Since previous studies of genetic structure of F. magna from Croatia were based on samples collected from red deer in one limited area (Baranja), the aim of this study was to analyse genetic diversity of 111 fluke samples collected from various hosts (red, roe and fallow deer, wild boar) and geographic locations in Croatia. On 355 base pair long cytochrome oxidase subunit 1 sequence, three haplotypes were identified - previously published CO1-Ha3 and CO1-Ha4, and one new haplotype named CO1-Ha36. Results obtained in our study confirmed as expected, that F. magna in Croatia has a Danube origin and that haplotypes are shared among different final host species.