Seroprevalence of hepatitis B, C, and its associated risk factors among clinically suspected patients attending poly and Maraki Health Centers, Gondar City, North West Ethiopia.

Background: Hepatitis B and C viruses are major global health problems with a high mortality rate, mostly due to serious liver diseases such as liver cirrhosis, liver failure, and hepatocellular carcinoma. The objective of this study was to determine the prevalence of the hepatitis B and C viruses and associated risk factors among clinically suspected patients attending Poly and Maraki Health Centers in Gondar City. Methods: An institution-based cross-sectional study was conducted to recruit 422 clinically suspected patients attending Poly and Maraki Health Centers between June and August 2020. The blood sample was tested for hepatitis B surface antigen and anti-Hepatitis C virus antibodies using commercially available rapid test kits. We used logistic regression and chi-square analysis to assess factors associated with Hepatitis B virus and Hepatitis C virus infections. Results: The overall prevalence of hepatitis B surface antigen and anti-Hepatitis C virus antibodies was 29 (6.9%) and 5 (1.2%), respectively. The prevalence of Hepatitis B virus and Hepatitis C virus was found to be significantly higher at Maraki Health Center. Multiple sexual partners (adjusted odd ratio (AOR = 12.299; 95% CI = 2.515-60.142), history of delivery by traditional birth attendants (AOR = 6.284; 95% CI = 2.373-16.637), surgical history (AOR = 3.679; 95% CI = 1.009-13.417), previous hepatitis infections (AOR = 10.374; 95% CI = 1.128-95.444), and upper abdominal pain (AOR = 3.382; 95% CI = 1.215-9.414) were significantly associated with an increased risk of Hepatitis B virus infections. On the other hand, a history of blood transfusion (AOR = 43.132; 95% CI = 1.385-1343.176) and a history of kidney dialysis (AOR = 71.199; 95% CI = 2.074-2444.646) were significantly associated with Hepatitis C virus infection. Conclusions: According to the WHO endemicity classification, the prevalence of the hepatitis B virus was intermediate, while that of the hepatitis C virus was low. Therefore, it is necessary to strengthen the efforts to control and prevent Hepatitis B virus and Hepatitis C virus infections.

Assessment of hepatitis c core antigen in epithelial salivary gland neoplasms (ex-vivo study).

BACKGROUND: Salivary gland neoplasms (SGNs) pose a challenge to both pathologists and clinicians. Despite research, the etiology of these neoplasms remains unclear. This study aimed to identify any potential association between the presence of hepatitis C virus (HCV) at the protein or gene level and epithelial salivary gland neoplasms. METHODS: Formalin-fixed paraffin-embedded (FFPE) blocks of epithelial salivary gland neoplasms were retrieved from the archives of the Oral and Maxillofacial Pathology Department, Faculty of Dentistry, Cairo University within the 5-year period from 2016 to 2020. Immunohistochemistry was used to assess HCV core antigen, while reverse transcription polymerase chain reaction was employed for the evaluation of HCV RNA. RESULTS: A total of 44 specimens were collected, 28 of which were benign neoplasms and 16 were malignant neoplasms. There was a statistically significant difference in HCV positivity between the two groups (P-value = 0.036). Benign tumors showed a statistically significant lower percentage of positive cases than malignant tumors. The localization of staining was also evaluated, revealing various patterns of HCV core antigen expression, including diffuse cytoplasmic, patchy cytoplasmic, nuclear, and a combination of nuclear and cytoplasmic expression. There was no statistically significant difference between the expression patterns in benign and malignant tumors (P-value = 0.616). Given that Pleomorphic Adenoma and Mucoepidermoid Carcinoma were the predominant tumor types in this study, four cases were selected for RNA detection. HCV RNA was detected in all cases using RT-PCR. CONCLUSIONS: HCV core antigen is frequently detected in SGNs and is suggested to be a potential risk factor for the development of these neoplasms. Further studies are required to discover other biomarkers, their roles, and the pathways associated with HCV in SGNs.

High serum gamma-glutamyltransferase level after hepatitis C virus elimination is a risk factor for the development of hepatocellular carcinoma.

AIM: Gamma-glutamyltransferase (GGT) is known as an oxidative stress marker, induced by alcohol consumption and metabolic disorders, and is reported as a predictor of hepatocellular carcinoma (HCC) development after hepatitis C virus (HCV) elimination. However, it is not clear whether GGT serves simply as a surrogate marker for overlapping metabolic diseases or reflects HCV-specific carcinogenicity. We investigated the association between GGT and hepatocarcinogenesis after achieving a sustained viral response (SVR), accounting for drinking habits or diabetes, and examined predisposing factors associated with GGT levels after SVR. METHODS: This is a prospective, multicenter, and observational study using the database of 1001 patients after HCV eradication with direct-acting antiviral agents. The association of GGT at SVR with cumulative HCC development was examined in a multivariate analysis using Cox proportional hazard models after adjustment for covariates including alcohol and diabetes. The association between oxidative stress markers or genetic factors and GGT levels was analyzed. RESULTS: High GGT levels at SVR were associated with HCC development (HR] 2.38, 95% CI 1.10-5.17). This association was also significant when restricted to patients without alcohol consumption or diabetes (HR 8.38, 95% CI 2.87-24.47). GGT levels were correlated with serum growth differentiation factor 15 levels, a marker of mitochondrial dysfunction. Single-nucleotide polymorphisms of ZNF827 and GDF15 were associated with high GGT levels. CONCLUSIONS: High GGT levels at SVR were associated with HCC development after accounting for alcohol consumption and diabetes. GGT levels are influenced by genetic predisposition and may reflect mitochondrial dysfunction after HCV eradication.

Analysis of Carcinogenic Involvement of MicroRNA Pattern in Peripheral Non-Cancerous Tissues and Chronic Viral Liver Injury.

Risk factors for hepatocarcinogenesis include chronic inflammation due to viral infection, liver fibrosis, and aging. In this study, we separated carcinogenic and non-carcinogenic cases due to hepatitis C virus (HCV) infection, aiming to comprehensively analyze miRNA expression in liver tissues by age, and identify factors that contribute to carcinogenesis. Total RNA was extracted from 360 chronic hepatitis C (CH), 43 HCV infected hepatocellular carcinoma (HCC), and surrounding non-tumor (SNT) tissues. MicroRNA (miRNA) expression patterns were analyzed using microarray. Using machine learning, we extracted characteristic miRNA expression patterns for each disease and age. There were no age-dependent changes in miRNA expression in the disease-specific comparisons; however, miRNA expression differed among the age groups of 50, 60, and 70 years of age between CH and SNT. The expression of miRNA was different between SNT and HCC only in patients in their 70s. Of the 55 miRNAs with significant differences in expression between CH and SNT, 34 miRNAs showed significant differences in expression even in the degree of liver fibrosis. The observation that miRNAs involved in hepatocarcinogenesis differ at different ages suggests that the mechanisms of carcinogenesis differ by age group as well. We also found that many miRNAs whose expression did not affect liver fibrosis were involved in carcinogenesis. These findings are expected to define biomarkers for detection of HCC at early stage, and develop novel therapeutic targets for HCC.

Trends in hepatitis C virus seroprevalence and associated risk factors among msm in Pakistan: insights from a community-based study.

Pakistan bears a substantial burden of hepatitis C virus (HCV) infection, with the second-highest prevalence globally. This community-based cross-sectional study, conducted from January to December 2022 in Punjab, Pakistan, investigates the seroprevalence of HCV among the men who have sex with men (MSM) population. The study identifies demographic and behavioral risk factors associated with HCV infection within this population group. Among the 501 participants, the study found an HCV seroprevalence of 14.86%. The association between demographic characteristics and seroprevalence is assessed by calculating the percentage of positive cases, revealing notable associations with age, education level, and self-identified sexual orientation. Furthermore, the study identified several behavioral risk factors positively associated with HCV seroprevalence, including sharing personal items such as razors and toothbrushes, histories of surgery, blood transfusion, dental procedures, intravenous drug use, and therapeutic injection histories. These risk factors were identified through structured interviews, and the prevalence of HCV seropositivity among the exposed groups was calculated accordingly. Interestingly, a lower HCV positivity rate was observed among self-reported HIV-positive individuals, contradicting previous research. The findings underscore the need for comprehensive, targeted prevention strategies such as risk factor awareness campaigns and educational programs tailored for the MSM population in Pakistan. Further research is warranted to validate these findings and better understand the complex interplay of factors contributing to HCV seroprevalence in this high-risk population.

Seroprevalence of Hepatitis C Virus Among Blood Donors in a Tribal-Preponderant Region of India.

INTRODUCTION: Hepatitis C is a global health burden with significant morbidity and mortality. It primarily affects the liver and causes acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Common modes of transmission of hepatitis C virus (HCV) infection are blood transfusion, needlestick injury, and mother-fetus transmission, among which transmission, blood transfusion is one of the most important causes. Blood transfusion is one of the pillars in the management of patients that saves lives and improves morbidity. Blood donation in India is done by voluntary and replacement blood donors of both sexes. The aim of this study is to determine the seroprevalence of HCV among blood donors in the Jharkhand state, a tribal-preponderant region of India, and to see the trend over the years. MATERIAL AND METHODS: This is a nine-year retrospective observational study from 2015 to 2023 that screened for anti-HCV antibodies (third-generation kit: Abbott Diagnostics) using the chemiluminescence technique. RESULTS: In this study, in total, 249,461 units of blood were collected, of which the majority of donations were by male and replacement donors (RDs) comprising 230,757 (92.50%) and 188,047 (75.38%), respectively. The mean number of blood donations by replacement and male donors (MDs) was more than for voluntary donors (VDs) and female donors (FDs) (20894.11 ± 3041.71 RDs vs. 6823.77 ± 2332.96 VDs, p < 0.0001 and 25639.66 ± 2810.08 MDs vs. 2078.22 ± 828.16 FD, p < 0.0001), respectively. The overall prevalence of HCV was 0.63%, and all seropositive donors were male. CONCLUSION: Replacement blood donation contributes to the major part of blood donation and is primarily done by males in this tribal population-dominant region of India. Seroprevalence of HCV is high in the population of this part of India, and there is a constant or slightly upward trend in hepatitis C infection among individuals.

Evaluation of hepatic injury in chronic hepatitis B and C using APRI and FIB-4 indices compared to fibroscan results.

Background: Hepatitis B (HBV) and hepatitis C viruses (HCV) are significant causes of liver disease worldwide. Liver fibrosis (LF) is a complication of chronic liver damage caused by HBV and HCV due to our limited knowledge comparing the diagnostic performance of platelet to aspartate aminotransferase ratio index (APRI) and fibrosis-4 (FIB-4) index with fibroscan. Methods: This study evaluated liver damage in HBV and HCV using APRI, FIB-4, and fibroscan indices. This retrospective cohort descriptive-analytical study was conducted on patients with HBV and HCV. This study uses laboratory results and imaging to investigate liver damage in chronic HBV and HCV patients. APRI and FIB-4 were computed based on laboratory results. Results: A total of 185 patients (82 hepatitis B and 103 hepatitis C) were included in the study. Thirteen patients had liver cirrhosis. There was no statistically significant difference between the fibroscan results in the two groups (P=0.99). The HBV group's mean APRI and FIB-4 were lower than HCV, but no significant difference was observed (P>0.05). Our results in HBV and HCV patients showed that APRI and FIB-4 accomplished well anticipating cirrhosis with an area under the receiver operating characteristic curve (AUC) of 0.771-0.845 and 0.871-0.910, respectively. Conclusion: Fibroscan is a powerful tool superior to APRI and FIB-4 in predicting LF and cirrhosis. Nevertheless, APRI and FIB-4 are inexpensive and non-invasive indicators with acceptable efficacy in predicting advanced fibrosis or cirrhosis. However, these two measures are not reliable in low-grade fibrosis.

An Aggressive Case of Cryoglobulinemia and Membranoproliferative Glomerulonephritis: A Case Report.

This case report describes a 66-year-old female with membranoproliferative glomerulonephritis (MPGN) with pulmonary involvement presumed secondary to Hepatitis C virus (HCV)-associated with mixed cryoglobulinemia. In this condition, pulmonary involvement is uncommon, and aggressive lung involvement can be associated with poor outcomes. Within eight weeks, the patient was hospitalized twice with acute pulmonary presentations and presented at a third hospitalization with dyspnea, chest pain, abdominal pain, and edema. Imaging revealed persistent and historically evolving lung consolidation, as well as a renal biopsy showing MPGN associated with mixed cryoglobulinemia. A lung biopsy revealed inflammation. Bronchoalveolar lavage did not show hemosiderin-laden macrophages and did not grow infectious agents. Serology revealed negative ANCAs and rheumatoid factor positive at 476 IU/ml (upper limit normal 14 IU/ml). Qualitative cryoglobulins were positive at 2 %ppt (reference range: negative %ppt) and Type II mixed cryoglobulinemia with IgM kappa plus polyclonal IgG. The treatment involved steroids and rituximab. The patient's clinical status deteriorated, and she elected to change her resuscitation status to comfort care measures. This case emphasizes that cryoglobulinemia can present with aggressive manifestations on a wide spectrum. Pulmonary manifestations are rare and were evident in this case (although without clear evidence of diffuse alveolar hemorrhage) and led to a complicated disease course and an unfavorable outcome. Overall, this case underscores the complexity of mixed cryoglobulinemia presentations and the challenges of managing severe cases with multi-organ involvement.

The Era of DAAs: Assessing the Patients' Characteristics, Clinical Impact, and Emergence of Comorbidities in HIV/HCV-Coinfected versus HIV-Infected Individuals.

Objective: To determine whether HIV-infected individuals versus individuals with HIV/HCV coinfection, in the era of interferon-free therapies, exhibit an increased incidence of comorbidities and non-AIDS-related events. Methods: A retrospective analysis was conducted by collecting data from clinical records of Spanish patients at a tertiary hospital involving HIV/HCV-coinfected and HIV-infected patients, all with effectively controlled HIV. Coinfected patients underwent HCV clearance using direct-acting antivirals (DAAs) and had no history of interferon treatment. The incidences of hypertension, diabetes mellitus, cardiovascular disease, kidney disease, liver disease, non-AIDS cancer, and death were compared between the groups. Multivariate adjustments for all factors potentially impacting outcomes were used to assess the risk of clinical event onset. Propensity score (PS) analyses were also conducted to support the multivariate model results. Results: Data were available from 229 HIV/HCV-coinfected patients and 229 HIV-infected patients. Both cohorts were comparable in terms of age, gender distribution, follow-up, and HIV-related characteristics. Multivariate models and PS showed that previous exposure to HCV was not associated with the onset of any clinical events studied. Significant differences between HIV/HCV-coinfected and HIV-infected were not found for survival according to the log-rank test (p = 0.402). Conclusions: Successful HCV elimination using DAAs improved the outlook regarding comorbidities and survival across HIV/HCV-coinfected cohorts. Early HCV detection and DAA therapy could enhance clinical results. These findings provide an optimistic perspective for those living with HIV/HCV coinfection and underscore the importance of continuing efforts toward early detection and DAA treatment initiation.

After the Storm: Persistent Molecular Alterations Following HCV Cure.

The development of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has revolutionized the management of this pathology, as their use allows viral elimination in a large majority of patients. Nonetheless, HCV remains a major public health problem due to the multiple challenges associated with its diagnosis, treatment availability and development of a prophylactic vaccine. Moreover, HCV-cured patients still present an increased risk of developing hepatic complications such as hepatocellular carcinoma. In the present review, we aim to summarize the impact that HCV infection has on a wide variety of peripheral and intrahepatic cell populations, the alterations that remain following DAA treatment and the potential molecular mechanisms implicated in their long-term persistence. Finally, we consider how recent developments in single-cell multiomics could refine our understanding of this disease in each specific intrahepatic cell population and drive the field to explore new directions for the development of chemo-preventive strategies.

Fibrosis-4 index stratifies risks of hepatocellular carcinoma in patients with chronic hepatitis C.

BACKGROUND AND AIMS: Risk stratification for patients with a higher risk of hepatocellular carcinoma (HCC) is crucial. We aimed to investigate the role of the Fibrosis-4 (FIB-4) index in predicting chronic hepatitis C (CHC)-related HCC. METHODS: A retrospective cohort study consecutively included treatment-naive CHC patients receiving longitudinal follow-up at the National Taiwan University Hospital from 1986 to 2014. The clinical data were collected and traced for HCC development. Multivariable Cox proportional hazard regression analysis was used to investigate the predictors for HCC. RESULTS: A total of 1285 patients in the ERADICATE-C cohort were included. The median age was 54, 56% were females, and 933 had HCV viremia. There were 33%, 38%, and 29% of patients having FIB-4 index <1.45, 1.45-3.25, and ≥3.25, respectively. After a median of 9-year follow-up, 186 patients developed HCC. Multivariable analysis revealed that older age, AFP≥20 ng/mL, cirrhosis, and a higher FIB-4 index were independent predictors for HCC. Compared with patients with FIB-4 index <1.45, those with FIB-4 1.45-3.25 had a 5.51-fold risk (95% confidence interval [CI]: 2.65-11.46), and those with FIB-4 ≥ 3.25 had 7.45-fold risk (95% CI: 3.46-16.05) of HCC. In CHC patients without viremia, FIB-4 index 1.45-3.25 and FIB-4 ≥ 3.25 increased 6.78-fold and 16.77-fold risk of HCC, respectively, compared with those with FIB-4 < 1.45. CONCLUSION: The baseline FIB-4 index can stratify the risks of HCC in untreated CHC patients, even those without viremia. The FIB-4 index should thus be included in the management of CHC.

Study of behavioral and psychosocial factors relating to needle stick injuries in nursing staff of a tertiary care cancer hospital of Punjab, India.

Background and Objectives: Needle stick injury (NSI) is the most dreaded occupational health hazard affecting a healthcare worker (HCW) psychologically and physically. The risk of infection post needle stick injury ranges between 1.9% to greater than 40% for HBV infections, 2.7-10% for HCV and 0.2-0.44% for HIV infections. As per National AIDS Control Organisation (NACO) records, nursing staff is at highest risk (43%) followed by physicians (28%). The main objective of this study was to evaluate knowledge of nursing staff about needle stick injuries and to study factors leading to such incidents in their working areas, impart them knowledge regarding the same and fill gaps in knowledge. Materials and Methods: This is a cross-sectional retrospective analysis involving nursing staff and students. p values were calculated using SPSS software. Results: Overall NSI prevalence among nursing staff and students was 51.6% whereas in more exposed and less exposed group was 47.45% and 10.16% respectively (p=0.2056). The most common cause of NSI incident was recapping of needle (38.5%) followed by transferring needle to sharp container (35%). Conclusion: Consequences of NSI are serious and this study has tried to emphasize on the need to study the factors leading to NSI.

Opportunistic population screening as a hepatitis elimination strategy: the CRIVALVIR-FOCUS program.

OBJECTIVES: Hepatitis B (HBV) and hepatitis C (HCV) viruses are significant causes of primary liver cancer, responsible for over a million deaths annually. We aimed to develop a screening strategy for viral hepatitis elimination in Spain, aligned with WHO's 2030 objectives. DESIGN: The CRIVALVIR-FOCUS program, conducted at the Consortium General University Hospital of Valencia, aimed to identify individuals with active blood-borne viral infections through opportunistic population screening. The hospital's Health Department serves more than 280,000 adults. RESULTS: Of the 31,995 adults screened (52% women; 15% immigrants), HBV prevalence was 0.44%, with higher rates in men (0.57%) than women (0.32%), and notably higher in migrants (1.27%) compared to Spanish nationals (0.30%). The 45-64 age group had the highest HBV prevalence (0.65%). HCV prevalence was 0.35%, again higher in men than women (0.51% vs 0.20%) and in migrants compared to Spanish nationals (0.58% vs 0.31%), with the 45-64 age group showing the highest HCV prevalence (0.76%). From the positive tests, 78.0% (110/141) of HBV cases and 71.4% (80/112) of HCV cases were patients previously unaware of their infections. CONCLUSION: Opportunistic screening effectively identifies early cases, potentially enhancing prevention of new infections. Our study highlights the need for targeted interventions for individuals aged 45-64 and migrants. Designing specific screening programs, in collaboration with social workers and cultural mediators, is critical to improve access to care. Training and involving primary care professionals are vital actions for the program's success.

Efficacy of Sofosbuvir and Velpatasvir Combination in the Treatment of Hepatitis C Virus (HCV) in Chronic Kidney Disease (CKD) Patients.

Background Hepatitis C virus (HCV) infection is still common in patients with chronic renal failure, even those on maintenance dialysis. A bidirectional association exists between HCV infection and chronic renal disease. Objective To assess the efficacy of sofosbuvir and velpatasvir combination in the treatment of chronic HCV in chronic kidney disease (CKD) patients. Methodology This descriptive, cross-sectional study was undertaken at the departments of Gastroenterology and Nephrology Lady Reading Hospital, Peshawar, from April 7, 2021, to October 7, 2021. Patients with chronic HCV and chronic renal disease at stage 4 or 5 were included while patients with decompensated cirrhosis liver, hepatoma, hepatitis B virus/HCV (HBV/HCV) coinfection, and post liver transplant patients were excluded. HCV infection was diagnosed based on detectable HCV ribonucleic acid (HCV RNA) by PCR (polymerase chain reaction). In contrast, CKD was diagnosed based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria for CKD. Sofosbuvir 400 mg orally daily and velpatasvir 100 mg orally with meals were given daily for 12 weeks. Effectiveness was defined as negative HCV RNA by PCR 12 weeks after treatment completion called sustained virological response rate 12 weeks after treatment completion (SVR12). Results A total of 73 patients including 67 (91.78%) males and six (8.22%) females between the ages of 20 years and 70 years were included in this study. The mean age of the participants was 48.77±8.0 years. Twelve weeks after the treatment completion, 69 (94.52%) had negative HCV RNA, whereas four (5.48%) patients had detectable HCV RNA. Conclusion It can be concluded from our study that a fixed-dose combination of sofosbuvir 400 mg and velpatasvir 100 mg is quite effective and recommended for treating chronic hepatitis C infection in patients with chronic renal disease in our local setup.

Evaluation of the risk of developing hepatocellular carcinoma in chronic Hepatitis C patients receiving antiviral treatment.

INTRODUCTION: Chronic HC leads to the development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The treatment of chronic HC with DAAs reduces mortality from LC and HCC. The study aimed to investigate the serological markers specific to HCC (PIVKA-II and AFP) in patients with chronic HC before and after DAA treatment. METHODOLOGY: The study involved 35 HCV patients (mean age: 56.23 ± 1.45) divided into two groups. Group 1 included 15 HCV + HCC patients and Group 2 included 20 HCV non-HCC patients. RESULTS: At the end of treatment all the patients were HCV RNA negative. Three months after the end of antiviral treatment, HCV RNA was undetectable in all patients, while a complete biochemical and virological response was observed in 66.7% of HCV + HCC patients and 85.0% of HCV non-HCC patients. PIVKA-II levels before the initiation of antiviral treatment were high in all patients. At the end of the treatment, in the HCV non-HCC group, normalization of PIVKA-II levels was observed only in 20.0% cases, and in 60.0% of cases 3 months after the treatment. Meanwhile, in patients with HCC and chronic HCV, PIVKA-II levels were within the normal range 3 months after treatment in only 13.3% of patients. CONCLUSIONS: It is necessary to monitor HCV patients with cirrhosis (F4) and severe fibrosis (F3) without HCC, who have high PIVKA-II and AFP levels and/or ALT activity despite obtaining sustained virologic response 3 months after treatment with DAAs.

Unraveling the non-fitness status of NK cells: Examining the NKp30 receptor and its isoforms distribution in HIV/HCV coinfected patients.

BACKGROUND: HIV/HCV coinfection is associated with a rapid progression to liver damage. Specifically, NK cell population dysregulation is of particular interest, as these cells have been shown to block HCV replication effectively and have an anti-fibrogenic activity. The NKp30 receptor is linked to tumor cell lysis and has a crucial role during viral infections. In the present study, we determined the subpopulations of NK cells based on CD56 and CD16 expression, NKp30 receptor expression, its isoforms A, B, and C, along with the cytotoxicity molecules in patients with HIV/HCV. RESULTS: evidenced by the APRI and FIB-4 indices, the HCV-infected patients presented greater liver damage than the HIV and HIV/HCV groups. The HCV group presented a decreased expression of NKp30 isoform A, and NK cell frequency was not different between groups; however, CD56brigth subpopulation, NKp30 receptor, and CD247 adaptor chain were decreased in HIV/HCV patients; further, we described increased levels of soluble IL-8, IL-10, IL-12, and IL-23 in the serum of HIV/HCV patients. CONCLUSIONS: HCV and HIV/HCV patients have multiple parameters of non-fitness status in NK cells; awareness of these dysfunctional immunological parameters in HIV/HCV and HCV patients can elucidate possible novel therapeutics directed towards the improvement of NK cell fitness status, in order to improve their function against liver damage.

The Combined Use of Dickkopf-1 and Soluble Axl Improves Hepatocellular Carcinoma Diagnostic Efficacy in Hepatitis C Patients.

BACKGROUND: Standard tools are not sensitive enough for hepatocellular carcinoma (HCC) early detection. This study aimed to evaluate the accuracy of dickkopf-1 (DKK1) and soluble Axl (sAxl) and their combined for early differentiating of HCC from premalignant benign liver diseases. METHODS: A total of 210 chronic hepatitis C (CHC) patients (55 fibrotic, 45 cirrhotic and 110 HCC) were enrolled. Both DKK1 and sAxl were tested using ELISA for all participants. RESULTS: HCC patients were accompanied by a significant increase (P<0.05) in DKK1 (5.38±2.05 ng/mL) and sAxl (178.02±49.39 ng/mL) compared to patients with fibrosis (2.16±0.6, 97.63±19.71 ng/mL, respectively) and cirrhosis (2.62±0.8, 121.84±34.66 ng/mL, respectively). Both DKK1 (AUC=0.852) and sAxl (AUC=0.882) had a good diagnostic accuracy in separating HCC from all non-HCC patients. Multiplying DKK1 with sAXL yielded values that significantly (P=0.0001) increased in patients who developed HCC (674.3 (434.2-1413.9)) versus fibrotic (204.9 (161.7-262)) and cirrhotic (254.4 (205.4-343.7)) patients. This model improves HCC diagnostic performances [AUC=0.921; sensitivity 90.9%, specificity 87%, PPV 88.5%, NPV 89.7% and efficiency 89.1%]. Elevated DKK1×sAxl values were associated with aggressive tumor features including multiple nodules, large size, Child-Pugh and BCLC late stages. CONCLUSIONS: combined use of DKK1×sAxl is simple and feasible HCC diagnostic model that could enhance HCC diagnostic accuracy and could replace AFP in follow up of patients with premalignant diseases.

Decentralised same day test and treatment of hepatitis C levering existing peer support networks among men who inject drugs: feasibility and effectiveness.

BACKGROUND: Prevalence of hepatitis C virus (HCV) infection among people who inject drugs in the state of Manipur, India, is 43%; however, access to care is poor. We piloted a Community-led and comprehensive hepatitis care model that included same-day HCV treatment at drug treatment centres. METHODS: Screening was conducted through venipuncture samples collected by community peer PWID, using HCV antibody (HCV Ab) rapid screening and hepatitis B virus (HBV) surface antigen (HBsAg) rapid diagnostic tests. Reactive HCV Ab samples were tested for HCV RNA using near point-of-care Truenat® HCV on Truelab® Quattro. Eligible HCV RNA-positive participants were treated on the same day using direct-acting antivirals and followed for sustained virologic response (SVR). HBsAg-negative participants received rapid HBV vaccination regimen while those positive for HBsAg were tested for DNA and referred for treatment. RESULTS: Between November 2021 and August 2022, 643 individuals were approached and 503 consented and were screened. All screened were males with history of injection drug use, and a median age of 27 years (IQR 23-32). Of the 241 (47.9%) HCV Ab reactive all underwent RNA testing and 156 (64.7%) were RNA detectable. Of those with viraemia, 155 (99.4%) were initiated on treatment with 153 (98.1%) on same day, with 2 (1.2%) HBsAg positive and waiting for HBV DNA results. Among those 153, median time from HCV Ab screening to treatment was 6 h 38 min (IQR 5 h 42 min-8 h 23 min). In total 155 (100%) completed HCV treatment, of those 148 (95.5%) completed SVR testing and 130 (87.8%) achieved SVR12. 27 (5%) participants were HBsAg-positive, 3 (11.1%) were also living with HCV viraemia; 443 (97.6%) were eligible for vaccination and 436 (98.4%) received all 3 vaccine doses. CONCLUSION: Community-led hepatitis care incorporating same day "test and treat" for HCV was feasible and effective. HBV screening identified a large proportion who were unvaccinated. Peer support extended resulted in ensuring compliance to care and treatment cascade and completing all the three doses of HBV vaccination. As the screening, diagnostics infrastructure and vaccine are available in most countries with national viral hepatitis programs also in place, our model can be adapted or replicated to progress towards global elimination targets.

Successful Cardiac Surgical Management in a Trisomy 21 Child After Long-Term Hospitalization Associated With Bronchopneumonia and Hepatitis C Virus Seropositivity: A Case Report.

A 31-month-old girl with trisomy 21 (Down syndrome) was seen in the emergency department of pediatrics because of oxygen desaturation associated with features of lower respiratory tract infections. She was born at full term and diagnosed with congenital heart disease (CHD) having ventricular septal defect (VSD), and patent ductus arteriosus (PDA); consequently, she underwent corrective surgery after adequate optimization of treatment. Incidentally, she was detected to have the presence of anti-hepatitis C virus (HCV) antibodies. In this case report, we mainly focus on the multi-modal approach to medical and surgical management.

Hepatitis C Virus E1E2 Structure, Diversity, and Implications for Vaccine Development.

Hepatitis C virus (HCV) is a major medical health burden and the leading cause of chronic liver disease and cancer worldwide. More than 58 million people are chronically infected with HCV, with 1.5 million new infections occurring each year. An effective HCV vaccine is a major public health and medical need as recognized by the World Health Organization. However, due to the high variability of the virus and its ability to escape the immune response, HCV rapidly accumulates mutations, making vaccine development a formidable challenge. An effective vaccine must elicit broadly neutralizing antibodies (bnAbs) in a consistent fashion. After decades of studies from basic research through clinical development, the antigen of choice is considered the E1E2 envelope glycoprotein due to conserved, broadly neutralizing antigenic domains located in the constituent subunits of E1, E2, and the E1E2 heterodimeric complex itself. The challenge has been elicitation of robust humoral and cellular responses leading to broad virus neutralization due to the relatively low immunogenicity of this antigen. In view of this challenge, structure-based vaccine design approaches to stabilize key antigenic domains have been hampered due to the lack of E1E2 atomic-level resolution structures to guide them. Another challenge has been the development of a delivery platform in which a multivalent form of the antigen can be presented in order to elicit a more robust anti-HCV immune response. Recent nanoparticle vaccines are gaining prominence in the field due to their ability to facilitate a controlled multivalent presentation and trafficking to lymph nodes, where they can interact with both the cellular and humoral components of the immune system. This review focuses on recent advances in understanding the E1E2 heterodimeric structure to facilitate a rational design approach and the potential for development of a multivalent nanoparticle-based HCV E1E2 vaccine. Both aspects are considered important in the development of an effective HCV vaccine that can effectively address viral diversity and escape.