Chronic Cirrhosis Research Articles

The contribution of antinuclear antibodies in Primary Biliary Cholangitis (PBC): An experience from the immunology laboratory at University Hospital Center Hassan II, Fes, Morocco.

Patients older than 18 with chronic hepatitis or cirrhosis were recruited from September 2021 to January 2023. Clinical data were collected, including age, sex, symptoms, and biochemical parameters (ALT), (AST), (ALP), (GGT), (TB), (PT) and (PN), autoantibodies associated with hepatic autoimmune disorders: (AMA), anti-gp 210, anti-Sp100 and anti-F-actin antibodies were identified using HEp-2 cells as substrate (Fig. 1); and/or multiple Immunodot liver tests. HBsAg, anti-HCV, and HIV test results of the patients were found to be negative. 19 out of 71 had a confirmed diagnosis of PBC; 5 patients with AIH-PBC overlap (26.3%), and 14 patients with PBC (73.7%). Patients mainly were females with a 0.12-sex ratio. ANA patterns were dominated by cytoplasmic filamentous staining (AC-21) with punctuate nuclear envelope staining (AC-12). Multiple Immunodot tests were performed on all patients: AMA was present in 89.4%, anti-gp 210, and anti-Sp100 antibodies in 57.8% and 21.1%, respectively (Table 1).Patients were divided into groups depending on the positivity of AMA, anti-gp 210, and anti-Sp100 antibodies. 10.5% of PBC patients (2) had negatives AMA and positive anti-gp210. Almost half of PBC patients (11) had associated positive AMA and positive anti-gp210 and/or anti-Sp100, while 26.3% of them (5) had only positive AMA (Table 2). The findings in this work support the role of anti-gp 210 and anti-Sp100 in identifying patients with PBC and overlap syndromes. Moreover, Anti-gp 210 antibodies are found to be helpful for the diagnosis of PBC patients who are negative for AMAs.

Recent advances in the management of hepatocellular carcinoma.

Liver cancer remains a challenge of global health, being the 4th leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and is usually precipitated by chronic viral infections (hepatitis B and C), non-alcoholic steatohepatitis, heavy alcohol use, and other factors which may lead to chronic inflammation and cirrhosis of the liver. There have been significant advances in the systemic treatment options for HCC over the past decades, with several approvals of both immune checkpoint inhibitors and tyrosine kinase inhibitors in patients with preserved liver function. These advances have led to improvement in survival outcomes, with expected survival of greater than 18 months, in those with sensitive tumors, adequate liver function, and those functionally fit to receive sequential therapies. Several ongoing and promising trials are now evaluating combinational strategies with novel systemic agents and combinations of systemic therapy with locoregional therapy. In view of these trials, further advances in the treatment of HCC are foreseen in the near future.

Anti-Fibrotic Effects of <i>Calotropis procera</i> (Ait.) R.Br Roots Barks against Diethylnitrosamine-Induced Hepatic Fibrosis in Rats

Background: Liver diseases including chronic hepatitis, steatosis, fibrosis, cirrhosis and liver cancer are now a public health problem. In 2002, cirrhosis accounted for 27.63% of hepatobiliary diseases in Burkina Faso. In Africa and more particularly in Burkina Faso, the majority of the population (about 80%) uses medicinal plants for their primary health care. Calotropis procera (Ait.) R.Br (Apocynaceae) is a medicinal plant used in Burkina Faso in the treatment of liver problems. This work aims to evaluate the anti-fibrotic properties of Calotropis procera roots barks. Methods: The anti-fibrotic activity of the ethanolic extract of Calotropis procera roots barks was evaluated using diethylnitrosamine (DEN) to induce liver fibrosis in male Wistar rats. Serum biomarkers, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), Total protein, Albumin, Υ-Glutamyl transferase (GGT) were evaluated and the activities of antioxidant enzymes (Superoxide dismutase and catalase) as well as the level of malonedialdehyde (MDA) and that of nitric oxide (NO) were determined in the liver homogenate. Results: The treatment of rats suffering from hepatic fibrosis with the ethanolic extract leads to a significant restoration of the biomarkers of the hepatic function in particular, AST, ALP, GGT, Albumin. The extract also causes a reduction in oxidative stress in the liver through a significant increase in the activity rate of the antioxidant enzymes Superoxide dismutase (SOD) and catalase accompanied by a significant drop in the rate of MDA and NO suggesting the anti-oxidant effect of extract. Conclusion: The results of the study show that the ethanolic extract of the roots barks of Calotropis procera has anti-fibrotic properties.

Cytotoxic and Apoptotic Activities of Vernonia amygdalina Extract in HepG2 Cell Line

Liver cancer is a malignant tumor originating from the development of chronic hepatitis or cirrhosis and is responsible for damage to the shape and function of the liver. The loss of the ability of conventional chemotherapy to inhibit the growth of cancer cells is a major focus in the world. Natural ingredients are the solution to this problem, for example the use of Vernonia amygdalina leaves. Vernonia amygdalina contains flavonoids, cardiac glycosides, and steroids/triterpenoids which are reported to have anticancer properties. This study aims to examined the activity of these plants as anticancer liver through cytotocix and apoptotic activity. Vernonia amygdalina ethanol extract (VAEE), Vernonia amygdalina ethyl acetate extract (VAEAE), and Vernonia amygdalina n-hexane extract (VAHE) were obtained from a multistage maceration process. The extracts were tested for cytotoxic activity by the MTT method on HepG2 cells. VAEAE had the best inhibitory concentration 50 (IC50) value of 19.91 ± 0.24 µg/mL. Apoptosis test was performed using double staining method. Subjective observations were made using a fluorescence microscope. It was seen that Vernonia amygdalina ethyl acetate extract was able to trigger apoptosis in HepG2 cells.

Effects of chronic cirrhosis induced by intraperitoneal thioacetamide injection on the protein content and Michaelis-Menten kinetics of cytochrome P450 enzymes in the rat liver microsomes.

Chronic intraperitoneal injection of thioacetamide (TAA) in rats has been used as an animal model of human cirrhosis to study the effects of the disease on drug metabolism. However, TAA inhibits P450 enzymes directly and independently of cirrhosis. We investigated the effects of chronic cirrhosis in rats, induced by 10 weeks of intraperitoneal TAA, on the P450 enzymes after a 10-day washout period to eliminate TAA. Liver histology and serum biomarkers of hepatic function confirmed cirrhosis in all animals. Microsomal total P450 content, P450 reductase activity and ethoxycoumarin O-deethylase activity, a general marker of P450 activity, were significantly reduced by 30%-50% in cirrhotic animals. Additionally, the protein content and Michaelis-Menten kinetics of the activities of CYP2D, CYP2E1 and CYP3A were investigated. Whereas cirrhosis reduced the microsomal protein contents of CYP2D and CYP3A by 70% and 30%, respectively, the protein contents of CYP2E1 were not affected. However, the activities of all the tested isoenzymes were substantially lower in the cirrhotic livers. It is concluded that the TAA model of cirrhosis that incorporates a 10-day washout period after intraperitoneal injection of the chemical to rats produces isoenzyme-selective reductions in the P450 proteins or activities, which are independent of the direct inhibitory effects of TAA.

Prevalence and Risk Factors for Bleeding in Individuals with Hereditary Hemorrhagic Telangiectasia: A National Inpatient Sample Study

Background: Hereditary hemorrhagic telangiectasia (HHT) is the second most common hereditary bleeding disorder worldwide. Patients with HHT develop vascular anomalies in multiple organs that cause complications such as bleeding, thrombosis, anemia and high-output heart failure, resulting in poor quality of life. Few studies define the prevalence, risk factors, or screening tools for bleeding in HHT. Methods: We conducted a cross-sectional study of HHT patient discharges in the National Inpatient Sample (NIS) database from 2016-2018. Types of bleeding and other medical conditions were identified using ICD-10 codes. Analysis included NIS-provided discharge-level weights to reflect national estimates. NIS is the largest publicly available inpatient database in the U.S. developed by Healthcare Cost and Utilization Project (HCUP), containing a 20% stratified sample of U.S. hospital discharges. Categorical and continuous variables were assessed for association with HHT and bleeding status by Rao-Scott Chi-Square and weighted simple linear regression, respectively. Weighted multivariable logistic regression was performed to determine bleeding risk factors in HHT patients. Variables included gender, race, hypertension (HTN), chronic obstructive pulmonary disease (COPD), liver disease and cirrhosis, peptic ulcer disease (PUD), portal HTN, peripheral vascular disease (PVD), malignancy, hepatitis C (HCV), portal vein thrombosis (PVT) and Charlson Comorbidity Index (CCI). Results: Among 21,393,912 adult discharges, a total of 2591 discharges with HHT (0.012%) were identified. Compared with HHT without bleeding (HHT-NB), HHT discharges with bleeding (HHT-B) were more likely to be African American (15.8% vs 12.6%, p=0.046), male (44.4% vs 39.4%, p=0.03), have HTN (56.9% vs 51.0%, p=0.01); liver disease (21.6% vs 12%), cirrhosis (9.8% vs 5.4%), PUD (8.7% vs 1.0%), portal HTN (7.1% vs 3.0%), HCV (3.3% vs 1.3%), PVT (1.5% vs 0.3%), each p<0.001; PVD (6.9% vs 4.8%, p=0.03), and higher morbidity (CCI) (mean ± sd: 2.3 ± 0.09 vs 2.1 ± 0.05, p=0.03), while malignancy (3.9% vs 6.8%, p=0.008) was less common. Additionally, congestive heart failure (CHF) (26.1% vs 18.0%), gastroesophageal reflux disease (GERD) (25.5% vs 19.8%), liver disease (21.6% vs 12.3%), cirrhosis (9.8% vs 3.5%), portal HTN (7.1% vs 3.9%) and HCV (3.3% vs 1.3%), each p<0.001, were each more common in HHT-B than in non-HHT with bleeding (non-HHT-B). GI bleeding in HHT was as likely to occur in the upper GI tract as in non-HHT discharges (35.3% vs 36.7%, p=0.47), but significantly less likely in the lower GI tract (19.5% vs 29.8%, p<0.001). The most common type of bleeding in HHT were AV malformation (AVM) (32.1% vs 1.3%), epistaxis (17.7% vs 0.6%), and telangiectasia (2.3% vs 0.2%), each p<0.001, compared to non-HHT. Surgical/procedural bleeding (0.8% vs 4.2%), postpartum hemorrhage (PPH) (0.3% vs 6.5%), heavy menstrual bleed (HMB) (0.9% vs 5.9%), and malignancy (3.9% vs 10%) were less common in HHT vs non-HHT, each p<0.001, but iron deficiency anemia (IDA) was more common, 15.5% vs 7.5%, p<0.001, despite lower use of aspirin (4.7% vs 13.2%) or anticoagulants (5.1% vs 10.5%), each p<0.001, while mean length of stay (5.6 days vs 6.1 days, p=0.04) and inpatient mortality (1.8% vs 3.6%, p=0.01) were lower in the HHT group. In multivariable logistic regression, correlates of bleeding in HHT included PUD, adjusted odds ratio (AOR) 8.77 [95%CI 5.07 - 15.2]; PVT, AOR 3.81 [1.49 - 9.79]; and HCV, AOR 2.19 [1.17 - 4.08], while COPD, AOR 0.77 [0.61 - 0.98]; and malignancy, AOR 0.58 [0.36 - 0.94] were protective. Factors most commonly associated with HHT-B included CHF, AOR 2.57 [2.00 - 3.30]; and IDA, AOR 2.24 [1.82 - 2.77] compared to non-HHT-B. Conclusion: Among those with HHT, those with bleeding were more likely to be male, African American, and have HTN, PUD, and HCV than those without bleeding. GI tract AVM and angiodysplasia were the most common cause of bleeding in HHT. IDA was more common in HHT, but surgical and gynecological bleeding such as PPH and HMB were significantly less common compared to non-HHT. The presence of GI bleeding associated with AVM or angiodysplasia should raise the possibility of HHT. IDA was equally common in HHT with and without bleeding (15.5%) suggesting either lack of testing, poor response to therapy, or ongoing losses with unrecognized bleeding.

Extrahepatic Manifestations of Chronic HBV Infection and the Role of Antiviral Therapy.

The hepatitis B virus (HBV) infection leads to chronic hepatitis, cirrhosis, and hepatocarcinoma. However, about 20% of patients experience extrahepatic manifestations such as polyarteritis nodosa, non-rheumatoid arthritis, non-Hodgkin lymphoma, cryoglobulinemic vasculitis, and glomerulonephritis. These influence the patient's morbidity, quality of life and mortality. The treatment of an HBV infection is based on nucleotide analogues (NAs) which are safe and effective for the suppression of HBV-DNA in almost 100% of cases. A few studies have shown that NAs induce a viral response and an improvement of extrahepatic diseases. There is a lack of a thorough analysis of the available treatments for extrahepatic HBV manifestations. In 90% to 100% of cases, the NAs stop the HBV replication, and they produce a clinical response in the majority of patients with mild to moderate extrahepatic signs/symptoms. Arthritis can definitely disappear after the HBV elimination and, in some cases, the HBV eradication following NAs therapy appears to improve the renal function in HBV-related nephropathies. Plasma exchange can be used in subjects who are suffering from the most aggressive forms of cryoglobulinemic vasculitis and glomerulonephritis, progressive peripheral neuropathy, and life-threatening cases, and this can be combined with glucocorticosteroids and antiviral agents. In selected refractory patients, the use of rituximab in conjunction with NAs therapy can be considered. The review provides an update on extrahepatic conditions that are linked to HBV and the impact of treating HBV with NAs.

Development of free 25-hydroxyvitamin D3 assay method using liquid chromatography-tandem mass spectrometry.

The free hormone hypothesis has triggered controversies regarding the measurement of free vitamin D metabolites, such as free 25-hydroxyvitamin D (25(OH)D), as a suitable indicator for total vitamin D for clinical use. This issue can be addressed by developing a precise and accurate method for free 25(OH)D measurement. In the present study, a novel assay method for free 25(OH)D3 based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. Sample preparation first involved ultrafiltration to remove vitamin D-binding protein-bound and albumin-bound 25(OH)D, followed by extraction with a column, derivatization, evaporation, dissolution, and injection into the LC-MS/MS system. The coefficient of variation of repeatability and reproducibility obtained were 3.8–4.5% and 4.8–5.9%, respectively. Satisfactory linearity (r=0.999) was obtained up to 80 pg/ml. The lower quantification limit was 0.97 pg/ml and the S/N ratio on the peak of 1.0 pg/ml sample was 24.8 (which is more than the acceptable value of 10). The recovery rate was between 84.5 and 92.4% with a negligible matrix effect (94.5–104.9%). Levels of free 25(OH)D3, but not total 25(OH)D3, in the serum of the patients with chronic kidney disease (CKD) and hepatic cirrhosis (HC) were substantially lower than those in healthy subjects. The correlation coefficient between total and free 25(OH)D3 was 0.738 in all samples, while the linear regression equations were different between the patients with CKD and HC. In conclusion, LC-MS/MS assay for free 25(OH)D3 might be useful to evaluate high-throughput methods, including ELISA.

Artificial Intelligence in the American Healthcare Industry: Looking Forward to 2030

Artificial Intelligence in the American Healthcare Industry: Looking Forward to 2030

A RARE CASE OF HUMAN PAPILLOMAVIRUS-ASSOCIATED TRACHEAL SMALL CELL CARCINOMA

A RARE CASE OF HUMAN PAPILLOMAVIRUS-ASSOCIATED TRACHEAL SMALL CELL CARCINOMA

S1824 Recurrent Shock in a 31-Year-Old Woman With Chronic Pancreatitis and Cirrhosis

S1824 Recurrent Shock in a 31-Year-Old Woman With Chronic Pancreatitis and Cirrhosis

Studies on the Anti-HBV Mechanism of Syringopicroside Based on Serum Metabolomics

Aims: Syringopicroside (SYR) is an iridoid monomer compound isolated from the leaves of clove. HBV is a hepatotropic virus that can cause severe liver diseases, including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Syringopicroside has a significant effect on anti-HBV, but its mechanism of action is still unclear. Methods: A metabolomics approach based on UPLC-G2-Si-HDMS was performed to analyze the serum biomarkers from HBV transgenic mice to find the biomarkers affected by syringopicroside. Through the analysis of metabolic pathways, the key pathways of syringopicroside involved in a therapeutic action were explored to study its potential mechanism. Using network pharmacology, the "component-target-pathway" network of syringopicroside in the treatment of hepatitis B was constructed and combined with the results of metabolomics. Furthermore, the mechanism of action of syringopicroside against HBV was also discussed. Results: Serum metabolomics identified a total of 42 HBV-related biomarkers, of which 8 returned to normal levels after syringopicroside treatment, involving a total of 6 metabolic pathways. Five biomarkers returned to normal levels after lamivudine treatment, involving 2 metabolic pathways. Network pharmacology analysis showed that syringopicroside in the treatment of hepatitis B mainly acts on 26 targets, including MMP9, MAPK1, and SLC29A1, involving 4 pathways. Conclusion: This study elucidates the multi-target and multi-channel integration mechanism of syringopicroside against HBV, lays a foundation for an in-depth study of the anti-HBV mechanism of syringopicroside, and also provides support for the development of innovative traditional Chinese medicines for the treatment of hepatitis B.

S1338 The Prevalence of Protein-Calorie Malnutrition Among Patients With Alcoholic, Non-Alcoholic and Chronic Viral Cirrhosis in the United States: A Population-Based Study

S1338 The Prevalence of Protein-Calorie Malnutrition Among Patients With Alcoholic, Non-Alcoholic and Chronic Viral Cirrhosis in the United States: A Population-Based Study

Frequency distribution of hepatitis B virus (HBV) genotypes in Iraqi patients

Infection with the hepatitis B virus can lead to asymptomatic carrier status, developing into severe chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Ten genotypes (A-J) and 46 sub-genotypes have been discovered. As a result, the current study was conducted to determine HBV genotypes in Iraqi patients. RT-PCR was used to determine the highest viral load in infected subjects and then used for screening HBV genotyping. The results showed that HBV genotype distribution among HBV infected patients was as follows: genotypes C, A, B, and D (8.5%, 5%, 4.3%, and 2.1%, respectively). In addition, the value of the viral load was higher with genotype C compared to A, B, and D HBV genotyping. This study concluded that mono-genotypes prevalent in patients infected with HBV and genotype C were more prevalent. In addition to the existence of a relationship between viral load and genotyping.

Management of patients with chronic hepatitis and cirrhosis during the periooperative period of ophthalmic surgery

Aim. To study the frequency and structure of hepatitis and cirrhosis among ophthalmic surgery patients.Material and methods. Among 1706 ophthalmic surgery patients, 43 patients with chronic hepatitis and cirrhosis were selected. A clinical assessment of the etiology and severity of their condition was carried out and the possibility of performing ophthalmic surgery was determined.Results. The average age of the patients included in the study comprised 64.1 ± 9.7 years, with 72.1% of the patients belonging to the elderly age group. 88.4%, 9.3%, and 2.3% (one patient) of the patients suffered from viral hepatitis (B, C, chronic HBV and HCV coinfection), toxic hepatitis, and autoimmune hepatitis, respectively. Among hepatitis patients, HCV monoinfection prevailed (55.4%). The majority (97.7%) of patients demonstrated minimal disease activity. Although violations of the hemostatic system were detected in nine patients, signs of significant hypocoagulability were observed in three patients (6.9%). Following a 3-day course of intramuscular vitamin K injections 2 to 3 times per day, these three patients underwent successful ophthalmic surgery. Out of 97.7% of patients admitted to surgery, 39 people were operated in a planned manner and 3 people required medical preparation. In one patient with suspected acute viral hepatitis B, planned surgical treatment was postponed.Conclusions. The share of patients with hepatitis and cirrhosis in the general structure of ophthalmic surgery patients comprised 2.5%. Among them, viral hepatitis B and C prevailed (88.4%) with dominated HCV monoinfection (55.4%). The vast majority of patients (97.7%) showed minimal hepatitis activity; 6.9% had signs of significant hypocoagulability, thus requiring preoperative medical preparation.

Effects of co-infection with Clonorchis sinensis on the sex hormones levels in male patients with chronic hepatitis B.

ObjectiveWe evaluated the levels of sex hormones in male hepatitis B patients co‐infected with Clonorchis sinensis (C. sinensis).MethodsA total of 136 male individuals were enrolled in this study, including 27 healthy controls, 28 patients with C. sinensis mono‐infection, 19 patients with only chronic hepatitis B, 18 patients with post‐hepatitis B liver cirrhosis, 26 chronic hepatitis B patients co‐infected with C. sinensis, and 18 post‐hepatitis B liver cirrhosis patients coinfected with C. sinensis. Serum levels of progesterone (P), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), and follicle stimulating hormone (FSH) in these groups were measured.ResultsThe results showed that compared with the LC group, the LC+ C. sinensis co‐infected group had an increase in E2 but decrease in T and FSH. The levels of E2 in CHB+ C. sinensis co‐infected patients were significantly higher than those in CHB mono‐infected patients, but the significantly lower levels of T were observed. Compared with HCs group, the LC group showed significant increase in all terms of sex hormones, except PRL. By contrast, the CHB mono‐infected group presented an apparent decrease in E2, T, and PRL than the HCs group. However, there were no significant differences in sex hormone levels between the C. sinensis mono‐infected patients and HCs.ConclusionThis study suggests that C. sinensis co‐infection aggravates the sex hormone disturbance in HBV patients at both chronic hepatitis and cirrhosis stages, providing evidences for potential strategies in disease prevention and treatment.

Early risk stratification of mortality in the geriatric patients who are at high risk for bleeding and fall from a ground level: an analysis of the national data.

The purpose of the study is to identify the risk factors of mortality early in patients who have history of using of anticoagulants or coagulopathy and sustained a ground level fall (GLF). The American College of Surgeons Trauma Quality Improvement Program (ACS-TQIP) dataset of the calendar year 2013 through 2016 was accessed for the study. All elderly patients ≥ 65 years old, who were taking an anticoagulant and suffered from a GLF, were included in the study. Other patient characteristics included: sex, race, initial systolic blood pressure (SBP), hypotension (SBP less than 110 mmHg), Injury Severity Score (ISS), Glasgow Coma Scale (GCS) Score, comorbidities such as hypertension (HTN), congestive heart failure (CHF), chronic renal failure (CRF), chronic pulmonary obstructive disease (COPD) and cirrhosis. Multivariable analysis was performed to develop the risk model. A total of 10,368 patients qualified for the study. Of this total, 788 (7.6%) patients died. The median [IQR] age of the patients was 80 [75-85] years. More than 90% of the patients were white. Fifty-four percent of the patients were female. Approximately 8% of the patients presented with hypotension at the time of hospital arrival. Multivariable analysis showed advanced age, male gender, high ISS, low GCS, presence of hypotension, CHF, CRF, COPD and cirrhosis were highly significant for odds of mortality. Approximately 8% of the patients, who took an anticoagulant or had a history of coagulopathy and sustained a GLF, died. Certain demographics, higher injury severity and a few comorbidities were highly associated with in-hospital mortality.

Risk Factors for Cancer Mortality in Spain: Population-Based Cohort Study.

Background: Cancer is considered a major public health problem due to its increasing incidence and high mortality. This study aims to identify risk factors for cancer mortality in Spain. Methods: Retrospective population-based cohort study in 20,397 participants of the 2011/2012 National Health Survey in Spain. Risk factors associated with mortality due to neoplasm from 2011 to 2017 were analyzed, and hazard ratios were calculated with a multivariate Cox model with competing risks for mortality from other causes. Results: Myocardial infarction, chronic obstructive pulmonary disease, cirrhosis, and mental disorders were associated with an increased risk of mortality due to neoplasm. Male sex, age over 50 years, history or current smoking habit, negligible intake of legumes, and poorer self-perceived health were also associated with increased cancer mortality. Conclusions: Comorbidities, tobacco use, poor diet, and worse self-perceived health were the main risk factors for cancer mortality in Spain.

Drug-drug interactions between antithrombotics and direct-acting antivirals in hepatitis C virus (HCV) patients: A brief, updated report.

Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease affecting over 71 million people worldwide. An increased incidence of atherothrombotic events [e.g. coronary artery disease (CAD), atrial fibrillation (AF)] has been observed in HCV seropositive patients. On the other hand, an increased bleeding risk is another clinical issue, particularly in subjects with liver cirrhosis, gastroesophageal varices, portal hypertension, thrombocytopenia and alcohol consumption. The introduction and progressively greater use of direct-acting antivirals (DAAs) (instead of protease and polymerase inhibitors) during the last decade has enabled a sustained virological response to be achieved in a significant percentage of patients. However, due to the high cardiovascular risk profile in HCV-infected patients, the concomitant use of antithrombotic therapies is often required, bearing in mind the possible contraindications. For example, despite better pharmacokinetic and pharmacodynamic properties compared with vitamin K-antagonists, plasma level fluctuations of direct oral anticoagulants (DOACs) due to pathological conditions (e.g. chronic kidney diseases or hepatic cirrhosis) or drug-drug interactions (DDIs) may be of great importance as regards their safety profile and overall clinical benefit. We aimed to examine and briefly summarize the significant DDIs observed between antithrombotic and HCV antiviral drugs.

First identification of bovine hepacivirus in wild boars

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma in humans. Humans were long considered the only hosts of Hepacivirus. Recently HCV-like sequences have been found in several animal species. Hepaciviruses are considered species-specific but a wider host range and a zoonotic role has been hypothesized. We report the first detection of bovine hepacivirus (BovHepV) sequences in wild boars. A total of 310 wild boars hunted in Campania region were investigated with a pan-hepacivirus nested-PCR protocol for the NS3 gene. Hepacivirus RNA was detected in 5.8% of the animals. Sequence and phylogenetic analysis showed high homology with BovHepV subtype F, with nucleotide identity of 99%. The positive wild boars were georeferenced, revealing high density of livestock farms, with no clear distinction between animal husbandry and hunting areas. These findings might suggest the ability of BovHepV to cross the host-species barrier and infect wild boars.