HCV Virus Research Articles

Glosa do wyroku Sądu Apelacyjnego w Szczecinie z dnia 29 grudnia 2014 r. I ACa 393/14 – wina organizacyjna zakładu leczniczego

The gloss refers to the judgment of the Court of Appeal in Szczecin dated December 29, 2014, in a case concerning the plaintiff’s infection with the HCV virus during a hospital stay. In this case, the courts had to address issues of the medical facility’s tort liability, based on medical records, expert opinions, and testimonies. The main issue was the possibility of infection occurring at the hospital and potential negligence by the medical staff. The Court of Appeal's ruling relied on the application of the so-called anonymous fault and the prima facie evidence doctrine. However, procedural analysis raises certain doubts regarding the establishment of the hospital's liability. The gloss highlights significant issues related to hospital-acquired infections, including the evidentiary difficulties that arise in medical cases. It criticizes the fact that the court largely relied on factual presumption, without concrete evidence of negligence by the medical staff.

Frequency of Hepatitis B and C Infections in Haemodialysis Patients

Background: Hepatitis B (HBV), and Hepatitis C viral HCV) infections are the major health problems worldwide. Patients undergoing hemodialysis (HD) are more vulnerable to acquired such infections than the general population. Objective: To evaluate the prevalence of HBV and HCV infection in hemodialysis patients and the association of number of dialysis and history of blood transfusion with risk of HBsAg and HCV infection. Methods: This cross-sectional observational study was conducted in inpatient and outpatient department of Nephrology and Medicine, Rangpur Medical College and Hospital, Rangpur, Bangladesh from December 2021 to May 2022. A total of 80 diagnosed case of End Stage Renal Disease (ESRD), who underwent dialysis during the study period were included in the study. Complete history was taken either from patient or accompanying attendants. Collected data were classified, edited, coded and entered the computer for statistical analysis by using SPSS version 23. Results: Out of 80 hemodialysis patients, mean age was found 42.6±8.6 years with range from 21 to 59 years. Male patients were predominant (72.50%) with male to female ratio was 2.6:1. The prevalence of HBV and HCV infection was found in 8.75% and 11.25% respectively. Frequency of dialysis and history of blood transfusion was not significantly associated with risk of HBsAg and HCV infection. Conclusion: The prevalence of HBV and HCV infection was found in 8.75% and 11.25% respectively. Frequency of dialysis and history of blood transfusion was not significantly associated with risk of HBsAg and HCV infection. J Rang Med Col. September 2024; Vol. 9, No. 2: 72-77

Use of HBsAg-positive donors in liver transplantation: An ILTS-EASL-AASLD multisociety survey.

The gap between organ supply and demand in liver transplantation remains large in most parts of the world. One strategy to increase the donor pool is to use grafts infected with HCV, HBV, and/or HIV viruses. We aimed to explore the current use of HBsAg-positive liver grafts worldwide. A prospective cross-sectional web-based survey was designed, with a total of 28 queries, assessing national and local regulations, center experience, and center-specific experience related to the topic, and sent to all members of International Liver Transplantation Society, European Association for the Study of the Liver, and American Association for the Study of the Liver, and promoted on social media. A total of 135 liver transplant centers answered the survey: 38% from WHO European Regions, 39% from American regions, and 9.7% from South-East Asian regions. Most of the participating centers (67.3%) had been performing liver transplantation for over 15 years, with a mean of 66.5 liver transplants per year, and 54% also performed living-donor liver transplants. HBV-related disease was the indication for liver transplantation in an average of 15% of all liver transplantation cases. Regarding national and/or regional regulations, 40% of the centers reported that the use of HBsAg-positive donors was permitted, and an additional 20% could use them under special circumstances. Thirty-two centers (31%) had previously used HBsAg-positive donors. Among these centers, 62.5% conducted living-donor liver transplants and showed an increased inclination toward the use of HBsAg-positive grafts in centers with elevated waitlist mortality. HBsAg-positive donors are underutilized worldwide. The use of HBsAg-positive liver grafts could help to increase the donor pool, particularly in highly endemic areas.

Comparison of RT-PCR and ELISA Methods in the Diagnosis of Hepatitis C Virus in Patients

Background: Since HCV virus is the primary cause of liver cirrhosis and cancer, prompt diagnosis and timely treatment of this disease can prevent many complications. Due to the importance and necessity of this study, it aims to comparatively evaluate RT-PCR and ELISA methods in order to detect the presence of HCV infection in patients admitted to Baghiyatallah Hospital. Methods: Sera of 49 patients admitted to Baghiyatallah Hospital since September, 2019 to August, 2020, were tested for RNA detection of HCV virus using RT-PCR and for the presence of anti-HCV antibody at the same time. Results: In this study, the mean age of patients was approximately 38.3+6.3. The percentage of positive cases of HCV virus in the studied patients according to ELISA test and PCR test were 28.6% and 20.4%, respectively. Percentage of HCV positive cases had p = 0.001 based on PCR and ELISA tests by age group, number of sexual partners, history previous HCV infection, liver cirrhosis, addiction and treatment of previous HCV infection which was significantly different; However, it was not significant in terms of gender (p = 0.5232). According to Kappa coefficient, the percentage of agreement is 91.8 in both methods which indicates that the two models are consistent (P = 0.001) and the diagnostic value of ELISA versus PCR with sensitivity and specificity were 100% and 89.7%, respectively. Conclusion: ELISA susceptibility to anti-HCV antibody is more than 99%, but its specificity is low compared to RT-PCR method. On the other hand, these tests show only hepatitis C affection and does not distinguish between chronic acute or improved infection. It is not able to detect patients in the window phase, so the simultaneous application of ELISA and molecular methods is recommended to diagnose and follow the treatment of HCV virus.

How to better improve the treatment and outcomes of HCV in psychiatric patients: review of a Belgian monocentric psychiatric center.

Hepatitis C (HCV) is one of the major worldwide infections with 58 million infected persons in the world. HCV can lead to chronic liver disease, cirrhosis, and cancer. These past few years, clinical progress allowed a curative rate of 95% of the patients. There are still populations in which, treating the disease is more difficult, especially psychiatric patients, when substance abuse, psychiatric disorders are important risks factors for getting HCV. With the WHO organization establishing goals for clinical management and treatment of HCV, it is important to target where the difficulties lie in getting a better treatment program for those populations. Try to highlight the challenges of treating a certain group of patients compare to the general population. This is a cross sectional monocentric study. 79 patients from a mental facility were included between 2012 and 2022. Inclusion criteria were: >18 years old, an active viral HCV infection. 34.7% of patients with a positive PCR were treated with a significant difference between the closed psychiatric unit and the open one (66.5 vs 22.6%, p<.05). There was an 82.4% eradication rate (Sustained Viral Response at 3 months). There were significantly more schizophrenic disorders in the closed unit and significantly more alcohol abuse in the open one. Treatment of HCV in a psychiatric population is feasible with eradication rate equivalent at those in the general population. Patients with more severe mental illness are better treated in the configuration of a closed psychiatric unit.

Hepatitis C prediction using SVM, logistic regression and decision tree

Hepatitis C is an infection of the liver brought on by the HCV virus. In this condition, early diagnosis is challenging because of the delayed onset of symptoms. Predicting well enough can spare patients from permeant liver damage. The primary goal of this work is to use several machine learning methods to forecast this disease based on widely available and reasonably priced blood test data in order to diagnose and treat patients early on. Three machine learning techniques support vector machine (SVM), logistic regression, decision tree, has been applied on one dataset in this work. To find a suitable approach for illness prediction, the confusion matrix, precision, recall, F1 score, accuracy, receiver operating characteristics (ROC), performances of different strategies have been assessed. The SVM model's overall accuracy is 0.92, the highest among the three models.

Hepatitis C virus subtype diversity and transmission clusters characteristics among drug users in Zhuhai, South China

BackgroundHepatitis C virus (HCV) infection poses a major public health challenge globally, especially among injecting drug users. China has the world’s largest burden of HCV infections. However, little is known about the characteristics of transmission networks among drug user populations. This study aims to investigate the molecular epidemiology and transmission characteristics of HCV infections among drug users in Zhuhai, a bustling port city connecting Mainland China and its Special Administrative Regions.MethodsParticipants enrolled in this study were drug users incarcerated at Zhuhai’s drug rehabilitation center in 2015. Their sociodemographic and behavioral information, including gender, promiscuity, drug use method, and so forth, was collected using a standardized questionnaire. Plasmas separated from venous blood were analyzed for HCV infection through ELISA and RT-PCR methods to detect anti-HCV antibodies and HCV RNA. The 5’UTR fragment of the HCV genome was amplified and further sequenced for subtype identifications and phylogenetic analysis. The phylogenetic tree was inferred using the Maximum Likelihood method based on the Tamura-Nei model, and the transmission cluster network was constructed using Cytoscape3.8.0 software with a threshold of 0.015. Binary logistic regression models were employed to assess the factors associated with HCV infection.ResultsThe overall prevalence of HCV infection among drug users was 44.37%, with approximately 19.69% appearing to clear the HCV virus successfully. Binary logistic regression analysis revealed that those aged over 40, engaging in injecting drug use, and being native residents were at heightened risk for HCV infection among drug user cohorts. The predominant HCV subtypes circulating among those drug users were 6a (60.26%), followed by 3b (16.7%), 3a (12.8%), 1b (6.41%) and 1a (3.85%), respectively. Molecular transmission network analysis unveiled the presence of six transmission clusters, with the largest propagation cluster consisting of 41 individuals infected with HCV subtype 6a. Furthermore, distinct transmission clusters involved eight individuals infected with subtype 3b and seven with subtype 3a were also observed.ConclusionThe genetic transmission networks revealed a complex transmission pattern among drug users in Zhuhai, emphasizing the imperative for a targeted and effective intervention strategy to mitigate HCV dissemination. These insights are pivotal for shaping future national policies on HCV screening, treatment, and prevention in port cities.

Molecular characterization of plasma virome of hepatocellular carcinoma (HCC) patients

Hepatocellular carcinoma (HCC) stands as the most common cancer type, arising from various causes, and responsible for a substantial number of cancer-related fatalities. Recent advancements in viral metagenomics have empowered scientists to delve into the intricate diversity of the virosphere, viral evolution, interactions between viruses and their hosts, and the identification of viral causes behind disease outbreaks, the development of specific symptoms, and their potential role in altering the host’s physiology. The present study had the objective of “Molecular Characterization of HBV, HCV, anelloviruses, CMV, SENV-D, SENV-H, HEV, and HPV viruses among individuals suffering from HCC.” A total of 381 HCC patients contributed 10 cc of blood each for this study. The research encompassed the assessment of tumor markers, followed by molecular characterization of HBV, HCV, Anelloviruses (TTV, TTMV, and TTMDV), SENV-H and SENV-D viruses, HEV, CMV, and HPV, as well as histopathological examinations. The outcomes of this study revealed that majority of the HCC patients 72.4% (276/381) were male as compared to females. HCV infection, at 76.4% (291 out of 381), exhibited a significant association (p < 0.05) with HCC. Most patients displayed singular lesions in the liver, with Child Pugh Score Type B being the predominant finding in 45.2% of cases. Plasma virome analysis indicated the prevalence of TTMDV (75%), followed by TTMV (70%) and TTV (42.1%) among anelloviruses in HCC patients. Similarly, SENV-H (52%) was followed by SENV-D (20%), with co-infections at 15%. The presence of CMV and HEV among the HCC patients was recorded 5% each however 3.5% of the patients showed the presence of HPV. In conclusion, this study underscores that HCC patients serve as reservoirs for various pathogenic and non-pathogenic viruses, potentially contributing to the development, progression, and severity of the disease.

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights.

Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a‒g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a‒g) as inhibitors of HCV serine protease and as antibacterial agents against B. subtilis QB-928 and E. coli AB-274. Theophylline-1,2,4-triazoles were obtained in good to excellent yields (69%-95%) in a shorter time than conventional approach. 4-Chlorophenyl moiety containing theophylline-1,2,4-triazole 4c displayed significantly higher inhibitory activity against HCV serine protease enzyme (IC50 = 0.015 ± 0.25mg) in comparison to ribavirin (IC50 = 0.165 ± 0.053mg), but showed excellent binding affinity (-7.55kcal/mol) with the active site of serine protease, better than compound 4c (-6.90kcal/mol) as well as indole-based control compound 5 (-7.42kcal/mol). In terms of percentage inhibition of serine protease, 2-chlorophenyl compound 4b showed the maximum percentage inhibition (86%), more than that of the 3,4-dichlorophenyl compound 4c (76%) and ribavirin (81%). 3,4-Dimethylphenyl-based theophylline-1,2,4-triazole 4g showed the lowest minimum inhibitory concentration (MIC = 0.28 ± 0.50μg/mL) against the B. subtilis bacterial strain as compared to the standard drug penicillin (MIC = 1 ± 1.50μg/mL). The other 4-methylphenyl theophylline-1,2,4-triazole 4e (MIC = 0.20 ± 0.08μg/mL) displayed the most potent antibacterial potential against E. coli in comparison to the standard drug penicillin (MIC = 2.4 ± 1.00μg/mL). Molecular docking studies further helped in an extensive understanding of all of the interactions between compounds and the enzyme active site, and DFT studies were also employed to gain insights into the molecular structure of the synthesized compounds. The results indicated that theophylline-linked triazole derivatives 4b and 4c showed promise as leading contenders in the fight against the HCV virus. Moreover, compounds 4e and 4g demonstrated potential as effective chemotherapeutic agents against E. coli and B. subtilis, respectively. To substantiate these findings, additional in vivo studies and clinical trials are imperative, laying the groundwork for their integration into future drug design and development.

Antiviral Protein-Protein Interaction Inhibitors.

Continually repeating outbreaks of pathogenic viruses necessitate the construction of effective antiviral strategies. Therefore, the development of new specific antiviral drugs in a well-established and efficient manner is crucial. Taking into account the strong ability of viruses to change, therapies with diversified molecular targets must be sought. In addition to the widely explored viral enzyme inhibitor approach, inhibition of protein-protein interactions is a very valuable strategy. In this Perspective, protein-protein interaction inhibitors targeting HIV, SARS-CoV-2, HCV, Ebola, Dengue, and Chikungunya viruses are reviewed and discussed. Antibodies, peptides/peptidomimetics, and small molecules constitute three classes of compounds that have been explored, and each of them has some advantages and disadvantages for drug development.

A rapid and versatile reverse genetics approach for generating recombinant positive-strand RNA viruses that use IRES-mediated translation.

The lack of versatility of reverse genetics systems remains a bottleneck in viral research. Especially when (re-)emerging viruses reach pandemic levels, rapid characterization and establishment of effective countermeasures using recombinant viruses are beneficial in disease control. Indeed, numerous studies have attempted to establish and improve the methods. The circular polymerase extension reaction (CPER) method has overcome major obstacles in generating recombinant viruses. However, this method has not yet been examined for positive-strand RNA viruses that use cap-independent, internal ribosome entry site-mediated translation. Here, we engineered a suitable gene cassette to expand the CPER method for all positive-strand RNA viruses. Furthermore, we overcame the difficulty of generating recombinant viruses because of low transfection efficiency. Using this modified method, we also successfully generated reporter viruses and recombinant viruses from a field sample without virus isolation. Taking these findings together, our adapted methodology is an innovative technology that could help advance virologic research.

External quality control program in infectious diseases screening at laboratories and blood banks in Latin America: an analysis of the past 5 years.

To evaluate the screening of blood samples for infectious disease markers at laboratories and blood banks in Latin America per the findings of an External Quality Assessment Program (EQAP). This qualitative analysis used data from the EQAP coordinated by the Fundação Pro Sangue Hemocentro de São Paulo with the support of the Pan American Health Organization to assess the performance of blood screening for infectious diseases from 2014 to 2018 in Latin America. Each participating laboratory or blood bank received an identical blind panel with 24 blood samples with variable reactivity for all the screening parameters. Panels were processed at each participating facility and results were returned to the Fundação Pro Sangue Hemocentro de São Paulo for individual and joint analyses. Two types of discrepant results were potential failures: false positive results (FPRs) and false nonreactive results (FNRRs). A total of 23 136 samples were evaluated. Global rates of FPR, FNRR, and concordant results were 0.3%, 1.0% and 98.7%, respectively. Seven FNRRs were found for HBsAg (1.0%), 12 for syphilis (2.6%), and 21 for Chagas disease (2.9%). No FNRRs were found for the HIV, HCV, and HTLV viruses. The average accuracy of all the laboratories and blood banks participating in the EQAP during the study period was 99.5% (standard deviation, 0.5%). The findings of this qualitative analysis are positive for blood safety in Latin America, with an average accuracy of 99.5% among the participating laboratories and blood banks. This report reflects an important improvement in blood bank serological screening EQAP-PAHO report since the 2003.

General population knowledge, attitudes, and behaviors (KAB) on hepatitis c screening, Latium, Italy

Abstract Background In 2022, a free-of-charge screening to eliminate the HCV virus circulation was offered countrywide to the citizens born from 1969 to 1989. Recent studies reported low adherence rates to HCV screening campaigns, highlighting the need for policy makers to know the determinants of adherence, aimed to set up more effective communication campaigns. Methods A target population random sample answered by phone a questionnaire based on the Health Belief Model (HBF), containing 4 sections on perceived HCV susceptibility and severity, screening benefits and barriers. Each interviewed was finally invited to adhere to the screening. Prevalence was estimated using a 95% C.I., and association between sociodemographic characteristics, HBF attitudes, and screening adherence following the interview were assessed. Results Survey involved 641 participants. HCV susceptibility was perceived by 4.8% (C.I.95% 3,23-6,57) and HCV severity by 69,4% (I.C.95% 65,83-72,97), 95% (C.I.95% 93,3-96,6) acknowledged screening benefits and 88% (85,4-90,5) perceived no obstacles. It was found that 49.0% (C.I.95% 45,1-52,8) received no information. Perception of screening barriers was associated with low education level (OR 1.83, P = 0.02). In the 2 months following the interview, 17.6% (C.I.95% 14,6-20,5) carried out the HCV screening. Severity (OR 1.74, P = 0.03) and no barriers perception (OR 2.63, P = 0.01) were associated factors to post phone call adherence to UCV screening. Conclusions Insufficient communication campaign toward target population results in poor knowledge of HCV susceptibility and gravity and low adherence to HCV screening. Target population needs to acquire better awareness about HCV and HCV screening, through targeted and effective messages especially focusing on the susceptibility and gravity of HCV infection. Key messages • Target population does not feel susceptible to hepatitis c and has poor perception of severity. • It is necessary to improve communication through effective messages.

Clinical Practice Guidelines of the Russian Society for the Study of the Liver, the Russian Gastroenterological Association, the National Scientific Society of Infectious Disease Specialists for the Diagnosis and Treatment of Chronic Hepatitis C

Аim: diagnosis and treatment algorithms in the clinical recommendations intended for general practitioners, gastroenterologists, infectious disease specialists, hepatologists on the of chronic hepatitis C are presented.Summary. Chronic viral hepatitis C is a socially significant infection, the incidence of which in the Russian Federation remains significantly high. Over the past 10 years, great progress has been made in the treatment of hepatitis C — direct acting antiviral drugs have appeared. The spectrum of their effectiveness allows to achieve a sustained virological response in more than 90 % of cases, even in groups that were not previously considered even as candidates for therapy or were difficult to treat — patients receiving renal replacement therapy, after liver transplantation (or other organs), at the stage of decompensated liver cirrhosis, HIV co-infected, etc. Interferons are excluded from the recommendations due to their low effectiveness and a wide range of adverse events. The indications for the treatment have been expanded, namely, the fact of confirmation of viral replication. The terms of dispensary observation of patients without cirrhosis of the liver have been reduced (up to 12 weeks after the end of therapy). Also, these recommendations present approaches to active screening of hepatitis in risk groups, preventive and rehabilitation measures after the end of treatment.Conclusion. Great success has been achieved in the treatment of chronic hepatitis C. In most cases, eradication of viral HCV infection is a real task even in patients at the stage of cirrhosis of the liver, with impaired renal function, HIV co-infection, after solid organs transplantation.

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Tetraspanin CD81 plays major roles in cell-cell interactions and the regulation of cellular trafficking. This cholesterol-embarking transmembrane protein is a co-receptor for several viruses, including HCV, HIV-1 and Chikungunya virus, which exploits the large extracellular loop EC2 for cell entry. CD81 is also an anticancer target implicated in cancer cell proliferation and mobility, and in tumor metastasis. CD81 signaling contributes to the development of solid tumors (notably colorectal, liver and gastric cancers) and has been implicated in the aggressivity of B-cell lymphomas. A variety of protein partners can interact with CD81, either to regulate attachment and uptake of viruses (HCV E2, claudin-1, IFIM1) or to contribute to tumor growth and dissemination (CD19, CD44, EWI-2). CD81-protein interactions can be modulated with molecules targeting the extracellular domain of CD81, investigated as antiviral and/or anticancer agents. Several monoclonal antibodies anti-CD81 have been developed, notably mAb 5A6 active against invasion and metastasis of triple-negative breast cancer cells. CD81-EC2 can also be targeted with natural products (trachelogenin and harzianoic acids A-B) and synthetic compounds (such as benzothiazole-quinoline derivatives). They are weak CD81 binders but offer templates for the design of new compounds targeting the open EC2 loop. There is no anti-CD81 compound in clinical development at present, but this structurally well-characterized tetraspanin warrants more substantial considerations as a drug target.

Statistical optimization and characterization of fucose-rich polysaccharides extracted from pumpkin (Cucurbita maxima) along with antioxidant and antiviral activities

Biologically active phytochemicals from pumpkin reveal versatile medical applications, though little is known about their antiviral activity. The fucose-rich polysaccharide extraction conditions were optimized through Box-Behnken design and purified by column chromatography. The purified fucose-rich polysaccharide was characterized through SEM, FT-IR, 1H NMR, XRD, TGA, and GS-MS. The analysis results revealed an irregular and porous surface of the purified polysaccharide with high fucose, rhamnose, galactose, and glucose contents. The tested fucose-rich polysaccharides revealed significant antioxidant and anti-inflammatory activity at very low concentrations. The purified fucose-rich polysaccharides exerted a broad-spectrum antiviral activity against both DNA and RNA viruses, accompanied by high safety toward normal cells, where the maximum safe doses (EC100) were estimated to be about 3–3.9 mg/mL for both Vero and PBMC cell lines. Treatment of HCV, ADV7, HSV1, and HIV viruses with the purified polysaccharides showed a potent dose-dependent inhibitory activity with IC50 values of 95.475, 20.96, 5.213, and 461.75 μg/mL, respectively. This activity was hypothesized to be through inhibiting the viral entry in HCV infection and inhibiting the reverse transcriptase activity in HIV. The current study firstly reported the antioxidant, anti-inflammatory, and antiviral activities of Cucurbita maxima fucose-rich polysaccharide against several viral infections.

Neuropsychological profile of patients with infectious disease: characterization and comparison of patients with HIV, HTLV, and HCV.

Understanding the effect of the HIV, HTLV-1, and HCV viruses on cognitive aspects can help in the better characterization of dementia, as well as the best conducts to be suitable for rehabilitation. Thus, the present study aimed to characterize and compare the neuropsychological profile of 3 groups of patients with infectious diseases: HIV, HTLV, and HCV. The results of neuropsychological assessments and depression assessment of 325 people treated at a referral hospital for infectious diseases were analyzed, being 120 HIV carriers (74 (61.7%) men) with an average age of 47.5years (SD = 10.3), 65 patients with HTLV-1 (16 (24.6%) men) with a mean age of 49.9years (SD = 12.9), and 87 HCV patients (47 (54%) men) with a mean age of 55.5years (SD = 11.2). In addition, 54 people (26 (48.1%) men) with negative serology who made up the control group were evaluated. The results of the statistical evaluation of the sociodemographic factors of the four groups (HIV, HTLV-1, HCV, and control) showed that in addition to age, schooling was a significant factor among them and may have a strong influence on the performance of cognitive tests. The HTLV-1 group had the lowest neurocognitive performance and also the highest rate of depressive symptoms.

IMPACTO DE LA ANCESTRÍA GENÉTICA EN LA DISTRIBUCIÓN DEL POLIMORFISMO DE INTERFERÓN-λ4 RS12979860 EN UNA POBLACIÓN GLOBAL DE BUENOS AIRES, ARGENTINA

Human interferon-λ4 is a cytokine involved in early stages of antiviral responses. Strikingly, some allelic variants with diminished antiviral activity reduce the susceptibility to viral infections, thus they would have suffered a positive selection pressure throughout the evolutionary history of the genus Homo. An intronic variant within the IFNλ4 locus (rs12979860, T˃C) emerged as one of the main gene determinants of the response to HCV and other viruses. The rs12979860-C allele has a differential frequency in African, European and Native American populations, though South American data are scarce. Here we characterize for the first time the distribution of rs12979860 genotypes in a sample of the global population of Buenos Aires, Argentina, assessing its association with European, Native American and African parental components. The rs12979860 genotypes were determined by PCR-RFLP in DNA samples from donors of a blood banks of Buenos Aires (n=96), whose genetic individual ancestry (European, African or Native American) had been previously determined using molecular markers. The distribution of rs12979860-CC, CT and TT was 29.17%, 50.0% and 20.83%, respectively. A significant increase in the frequency of CC among donors with a strong European contribution and a greater impact of the Native American component among donors carrying the T allele were observed. Native American and European components were associated to the rs12979860 distribution in a sample of the global population of Buenos Aires, while no differences were directly attributable to the African ancestry. Considering interferon´s key role in antiviral responses, our results may contribute to both bioanthropological and immunogenetic studies associated with infectious diseases. Key words: ancestry, Buenos Aires, IFNλ4 polymorphism, rs12979860 distribution.

A Case Report of ABO-Incompatible Kidney Transplant in Human Immunodeficiency Virus-Positive Patient Coinfected with Both Hepatitis B and Hepatitis C Viruses

Individuals with human immunodeficiency virus (HIV) are at increased risk for end-stage kidney disease (ESKD). Kidney transplantation is the best treatment for HIV-positive ESKD patients. There are many challenges such as interactions between antiretroviral drugs and immunosuppressants, coinfection with hepatitis B (HBV) or/and C (HCV) viruses, and a higher risk of posttransplant infections and malignancies. We should not defer HIV-positive kidney transplants perceiving these medical complexities, instead employ a multidisciplinary approach to achieve successful transplantation. For HIV-positive ESKD patients, ABO-incompatible (ABOi) kidney transplantation and considering HIV-positive kidney donors are successful strategies for increasing the donor pool. We report a case of an HIV-positive ESKD patient who had coinfection with both HBV and HCV viruses and successfully underwent an ABOi live-related kidney transplant.

S1203 When Is Suspected Drug Induced Liver Injury (DILI) Not DILI? An Analysis of Unlikely Cases from the U.S. Drug Induced Liver Injury Network (DILIN)

Introduction: The diagnosis of drug induced liver injury (DILI) is difficult as it is largely a clinical diagnosis of exclusion. To aid in diagnostic decision making, we reviewed cases enrolled in DILIN with an initial diagnosis of DILI that were ultimately adjudicated as unlikely with alternative etiologies accounting for the abnormal liver tests. Methods: The DILIN is an ongoing NIH observational trial in which hepatologists enrolled patients from 2004 to the present with a high suspicion of DILI. Cases were adjudicated by a panel of experts through a structured process and scored from 1 (definite DILI) to 5 (unlikely DILI). Cases that were scored at least probable DILI (1-3) were compared to unlikely DILI (5). Unlikely cases were further reviewed for salient features and trends over time. Results: From 9/04 to 12/21, 1916 cases were adjudicated; 134 (7%) were unlikely DILI. There were no demographic features to distinguish at least probable cases from unlikely cases. Unlikely cases more often had renal disease (18% vs 9%, p=0.005), HIV (7% vs 2% p< 0.001), hepatitis C (HCV) (12% vs 3% p< 0.001), and hepatitis B (5% vs 1 % p< 0.001). Unlikely DILI vs. true DILI was higher for brief latency between drug use and liver injury (< 1 week 9% vs 5%) or very long latency ( >24 weeks 28% vs 16%) p=0.002 overall. The most common alternative diagnoses for unlikely cases were autoimmune hepatitis (AIH) (20%) and HCV (20%) (Table). Among white patients, carriage frequency of two copies of HLA-DQA1*03:01 was greater among those with AIH (13%) compared to DILI (3%) and population controls (1%). Patients with unlikely DILI had greater all-cause (16% vs 7%, p< 0.001) and liver related mortality (10% vs 3%, p< 0.001). Unlikely DILI cases died within six months at a higher rate (14% vs 6%, p=0.004). Transplant rates, hospitalization, and duration of illness were similar. Conclusion: DILI is difficult to diagnose, even among experienced hepatologists. Demographic factors are not helpful in the initial diagnosis. Very short or very long latency between suspect drug and initial liver injury decreases likelihood of true DILI. HCV PCR testing is critical in presumed DILI. Genetic testing in white patients with AIH vs. DILI may be useful. Longitudinal follow up of patients with DILI is essential to refine the diagnosis, treat an alternative disease, and potentially absolve a medication presumed to have caused DILI. Table 1. - Alternative Diagnoses in 134 Unlikely DILI cases Diagnosis N % Comments Autoimmune hepatitis 27 20.1 The most common incorrectly implicated class of medications were antibiotics (9/27) followed by HDS products (8/27). Nearly all had a liver biopsy, but findings were neither diagnostic for DILI nor classic for AIH. Other common themes included 1) prevalent systemic immune mediated disease (systemic lupus erythematous, hypothyroidism, inflammatory bowel disease, etc.) in 8/27 cases; 2) negative or relatively low antinuclear antibody titers (< 1:80) which increased on follow up; 3) a response to steroids in 14/27 with six of these having a flare in enzymes after immunosuppression titration or withdrawal. Hepatitis C 27 20.1 Of the 24 that were acute cases, 17 were enrolled prior to 2011 and none since 2017. Most of these cases had negative HCV antibodies and were discovered to have a positive HCV viral load later in their clinical course. Three patients had prevalent detectable HCV virus which later cleared spontaneously on follow up. Gallstones/BiliaryDisease 18 13.4 Eight cases with biliary tract malignancy.Three cases with primary sclerosing cholangitis. Normal imaging in some patients who acutely passed a stone.No differences in the presence of stones (3.3% vs. 6.7% p=0.32), or ductal dilation (3.3% vs. 2.5% p=0.89) between unlikely DILI and probable and higher DILI cases. Hepatitis E 11 8.2 Diagnosis often delayed as test is a send-out in most centers. Sepsis 7 5.2 Frequently in Intensive Care Unit on multiple drugs and hypotensive. Other ( >20 diverse etiologies) 44 32.8 Etiologies included alcohol, myopathy, Epstein Barr virus, cytomegalovirus, nonalcoholic steatohepatitis, metastatic cancer, and granulomatous liver disease.