HCV RNA Levels Research Articles

Spontaneous clearance of serum HCV-RNA after splenectomy in a patient with HCV-related liver cirrhosis and portal hypertension: a case report

BackgroundSpontaneous clearance of chronic hepatitis C virus (HCV) is rare in adults. A T-lymphocyte response is thought to be involved in HCV-RNA clearance. Splenectomy reportedly has a beneficial effect on T cell immune function in patients with cirrhosis. To the best of our knowledge, the present report is the first to describe spontaneous clearance of serum HCV-RNA within 1 year after splenectomy in a patient with cirrhosis.Case presentationA 55-year-old man with HCV cirrhosis was transferred to our institution with advanced pancytopenia, splenomegaly, and gastric varices. He had a 1-year history of ascites, edema, and general fatigue. The patient had a Child–Pugh score of 8 and serological type 1 HCV; the HCV-RNA level was 4.7 log IU/mL. Contrast-enhanced computed tomography showed gastric varices and marked splenomegaly (estimated spleen volume of 2175 mL). Esophagogastroduodenoscopy revealed enlarged gastric varices with no red color sign, and the varices were larger than those 1 year prior. He was diagnosed with decompensated HCV-related liver cirrhosis and portal hypertension. We considered direct-acting antiviral (DAA) therapy; however, DAA therapy was not approved in Japan for patients with decompensated cirrhosis at that time. Hand-assisted laparoscopic splenectomy was performed to improve the worsening portal hypertension. Further, we planned the initiation of DAA therapy after surgery, when such therapy would become available. DAA therapy was approved 1 year after splenectomy. At that time, we measured the HCV-RNA level before the initiation of DAA therapy; unexpectedly, however, serum HCV-RNA was not detectable, and the virus continued to disappear during the following 4 years. His liver function (total bilirubin, albumin, and prothrombin time) and pancytopenia improved during the 5 years postoperatively. The serum aspartate and alanine aminotransferase levels normalized between 1 and 5 years postoperatively. Esophagogastroduodenoscopy showed no change in the gastric varices during the 5 years after surgery. The patient remained asymptomatic and continued to do well.ConclusionsWe have presented a case of spontaneous clearance of HCV-RNA after splenectomy in a patient with cirrhosis and portal hypertension. Splenectomy may be associated with disappearance of HCV-RNA based on previous reports. More cases should be accumulated and evaluated.

Hospital-based screening outperforms primary care screening as a means of achieving hepatitis C virus micro-elimination

AimTo assess the respective performances of a HCV screening program in a hospital setting and a HCV screening model applied concomitantly in a primary care centre. MethodsAdult patients consecutively admitted to hospital for ambulatory surgery were screened for anti-HCV antibodies (hospital screening cohort, HPSC), as were patients receiving blood tests for medical reasons in a primary care centre (primary care screening cohort, PCSC). Serum anti-HCV and HCV RNA levels were tested by ELISA and real-time PCR, respectively. ResultsSeroprevalence of HCV infection was 2.2 % in the HPSC and 1.4 % in the PCSC (p = 0.044). All viraemic patients (0.2 % in HPSC and 0.1 % in PCSC) were treated with direct-acting antivirals and 85.7 % experienced a sustained virological response. ConclusionsHospital-based HCV screening outperformed primary care-centered screening, significantly increasing HCV case findings.

Hepatitis C virus-related hepatitis flare after immunochemotherapy in a patient with follicular lymphoma.

Reactivation of hepatitis viruses during chemotherapy can be problematic in the treatment of malignant lymphomas. However, studies on reactivation of chronic hepatitis C virus (HCV) infection are limited. A 43-year-old woman presented with generalized lymphadenopathy and multiple liver tumors, and she was diagnosed with follicular lymphoma (grade 3a; clinical stage IV). Chronic HCV infection was clinically diagnosed. Immunochemotherapy (ICT), including bendamustine and obinutuzumab, was initiated with close liver function monitoring without specific treatment for hepatitis C. However, liver dysfunction worsened 17 days after ICT initiation, and ICT was interrupted. HCV-RNA and transaminase levels continued to elevate. Liver biopsy results confirmed acute exacerbation of chronic hepatitis C. Direct active antiviral (DAA) therapy was started and effective. She has maintained a sustained virologic response since DAA therapy ended. With regard to lymphoma, complete metabolic response was maintained for 4 years without additional treatment. Physicians should be aware of HCV reactivation with hepatitis flare after ICT for lymphoma and consider the indication and timing of DAA therapy for hepatitis C in this setting.

Combining Selinexor with R-CHOP in the Treatment of Newly Diagnosed High-Risk (IPI 3-5) GCB Subtype DLBCL Patients: A Multicenter, Open Label Phase 2 Study

Background Diffuse large B-cell lymphoma (DLBCL) is an aggressive and highly heterogeneous lymphoma, and for high-risk group who has an International Prognostic Index (IPI) score of 3-5 it is more difficult to treat (Teras LR,2016; Ziepert M,2010). Under the standard R-CHOP-like immunochemotherapy, the 3-year overall survival (OS) rate of patients with IPI score of 0-1, 2, 3, 4-5 were 91%, 81%, 65% and 59%, respectively (Ziepert M,2010). The efficacy for high-risk population (IPI 3-5) was limited even after intensive chemotherapy, with an ORR of 74.5% and CR of 47.3% under R-CODOX-M/R-IVAC (McMillan AK,2020). Nonetheless, adding new agents to R-CHOP shows better efficacy in patients with IPI 3-5(Tilly H,2022; Nowakowski GS,2021). GCB subtype has better prognosis, but 20% of patients still relapsed after R-CHOP therapy (Nowakowski GS,2015), and no more benefit was achieved by modifying regimen with new agents like polatuzumab-R-CHP (Tilly H,2022), adding on lenalidomide (Nowakowski GS,2015) or ibrutinib (Wilson WH,2021). Selinexor is the only approved oral selective nuclear export inhibitor which demonstrated a 34% ORR in GCB subgroup as a monotherapy in relapsed/refractory DLBCL (Kalakonda N,2020). Selinexor combined with R-CHOP showed a CR rate of 58.8% and ORR of 94.1% in 17 high risk GCB DLBCL patients in a real-world setting (Zhiming Li,2023). This phase 2 study (NCT05422066) further explored the benefit and safety of Selinexor plus R-CHOP in the treatment of newly diagnosed (ND) GCB DLBCL patients with IPI 3-5. Methods This is a multicenter, open label, single arm phase 2 study enrolled 18~75 years old ND GCB DLBCL patients with IPI 3-5. Patients were administered selinexor 60mg QW in combination with standard R-CHOP therapy for 6 cycles (Rituximab 375 mg/m 2, cyclophosphamide 750 mg/m 2, doxorubicin 50 mg/m 2 IV, vincristine 0.5 mg/kg on day 1, prednisone 100 mg PO on days 1-5 in a 21-day cycle). The primary endpoint is complete remission (CR) rate. Secondary endpoints include objective response Rate (ORR), progression free survival (PFS), disease free survival (DFS), overall survival (OS), safety and tolerability. Results The median age of 15 patients was 59 years (range 25-71), with 10 males (66.7%). All patients were in advanced stage according to Ann Arbor staging system, with 13 patients in stage IV, and 2 in stage III. 11(73.3%) patients had ≥2 extranodal lesions and 9 (60%) patients had higher LDH level at baseline. 1 patient had TP53 mutation, and 6 patients (40%) had double expressor lymphoma (DEL) (Table 1). The overall best ORR and CR were 100% and 60%, respectively. The CR rate in 6 DEL patients were 50%; Patients with ≥2 extranodal lesions reached a CR of 54.5% (n=11), while 3 out of 4 patients with≤1 extranodal lesions completely responded. The CR rates of patients with Ki-67≥80% vs＜80% were 50% vs 62.5%, respectively. Median PFS and OS were not reached yet with a median follow-up of 8 months (range 2-11 months). 2 patients had progressive disease with 1 progressed after C4 and the other 1 after C6. 4 patients with viral hepatitis (3 HBV, 1 HCV) were administered both anti-tumor and antiviral therapy, and their HBV-DNA and HCV-RNA levels continuously declined (till undetectable) along with their tumor load (3 CR ,1 PR). Common treatment-relate adverse events (grade 3/4, all grades) included: leukopenia (80%, 93%), neutropenia (73%, 87%), anemia (27%, 93%), thrombocytopenia (27%, 67%), lymphopenia (20%, 27%), anorexia (13%, 40%), pneumonia (13%,40%), hypertriglyceridemia (7%, 40%), diarrhea (7%, 20%). All AEs were managed with appropriate supportive care and dose adjustments. 8 out of 15 patients had a dose reduction of selinexor to 40mg (initial dose 60mg QW) due to AE, 3 in C2 and the other 5 in C4-C5. All patients were continuously treated after dose reduction, and no treatment-related deaths occurred. Overall, 6 patients completed 6 cycles of selinexor+R-CHOP treatment with sustained remission, and 6 patients were still receiving therapy at time of writing this abstract (4 in C6, 2 in C3). 3 patients ended study, 2 PD and 1 withdrew informed consent after PR at the end of C4 (Figure 1). Conclusion Once weekly 60mg selinexor can be safely combined with R-CHOP in ND high risk (IPI 3-5) GCB subtype DLBCL patients with ORR of 100% and CR of 60%. No viral reactivation was observed in patients with viral hepatitis with simultaneous antiviral therapy.

The Relationship Between Platelet-to-Lymphocyte Ratio (PLR) and HCV RNA Levels in HCV-HIV Coinfected Patients Before and After Receiving Direct-Acting Antiviral (DAA) Therapy at Dr. Mohammad Hoesin Hospital Palembang

The background described in the introduction section highlights the importance of studying the correlation between the platelet-to-lymphocyte ratio (PLR) and HCV RNA levels in these patients. This research follows an analytical correlational observational design with a cross-sectional approach. The study was conducted at the Internal Medicine Polyclinic of Dr. Mohammad Hoesin Hospital, Palembang. It involved 38 subjects who met the inclusion and exclusion criteria. The primary objective was to determine the correlation between PLR and HCV RNA levels in HIV-HCV coinfected patients receiving DAA therapy. The research findings concluded that there was a decrease in PLR and HCV RNA Viral Load levels in HIV-HCV coinfected patients after receiving DAA therapy compared to before receiving DAA therapy. The Platelet-to-Lymphocyte Ratio (PLR) was directly proportional to the quantitative HCV RNA Viral Load levels in HIV-HCV coinfected patients with a strong correlation value both before and after DAA therapy.

HIV RNA and HCV RNA Levels, and Mortality: The Japan Cohort Study of HIV Patients Infected through Blood Products

Background: Most hemophiliacs living with HIV are co-infected with HCV. In their clinical practice, the long-term effects of anti-HIV and anti-HCV therapies have not been sufficiently investigated. Objective: This study aimed to evaluate changes in HIV RNA and HCV RNA levels and the prognosis in hemophiliacs living with HIV over 24 years in Japan. Methods: We used cohort study data of 578 hemophiliacs living with HIV. We analyzed trends in HIV RNA levels between the fiscal years 1997 and 2008 (first follow-up), and trends in HIV RNA and HCV RNA levels between the fiscal years 2009 and 2020 (second follow-up). Mortality rates by HIV RNA and HCV RNA levels were calculated from 11,207 observed person-years and 194 deaths. Results: The percentage of HIV RNA levels <400 copies/mL rose in the first period of follow-up, and the percentage of HCV RNA-negative rose in the second period of follow-up. The participants with HIV RNA levels <400 copies/mL had a significantly lower mortality rate than the others, with a ratio of 0.46 in the first period. HCV antibody-positive participants who were HCV RNA-negative had a significantly lower mortality rate than those who were HCV RNA-positive, with a ratio of 0.47 in the second period. Conclusion: After the introduction of combination anti-HIV therapy over 24 years in hemophiliacs living with HIV, HIV RNA levels decreased in the first half of this period, resulting in decreased mortality. Additionally, HCV RNA levels decreased in the second half of this study period, resulting in even further decreased mortality.

Retrospective Investigation of Viral Hepatitis Seroprevalence in Patients Admitted at the Outpatient Clinics of Internal Medicine

ABSTRACT
 Aim: Viral hepatitis agents include Hepatitis B and Hepatitis C virus, which cause an important public health problem due to serious complications. Patients examined at the outpatient clinics of internal medicine are among main risk groups, as they have concomitant diseases and undergo various procedures. We aimed to investigate retrospectively the seroprevalence of viral hepatitis in outpatients in internal medicine in our region.
 Material and Methods: HBsAg and Anti-HCV parameters, and demographic data such as age and gender of patients admitted at the outpatient clinics of internal medicine at our hospital between January 2017 and July 2022 were retrospectively evaluated, with HBV-DNA and HCV-RNA levels of those who showed reactivity.
 Results: HBsAg test results of 2618 patients and Anti-HCV test results of 2943 patients were obtained in this study. The mean age of patients with HBsAg tests was 34.2±15.7, and mean age of patients with Anti-HCV test was 34.3±15.7 years. HBsAg reactivity rate was 0.9%; and the mean age of patients showing reactivity was 47.7±14.4 years. Anti-HCV reactivity rate was %0.1, with a mean age of 52.6±21.3 years. Both HBsAg and Anti-HCV reactivity was not present at the same patient in our study.
 Conclusion: Early diagnosis of Hepatitis B and Hepatitis C viruses decrease the risk of developing complications, easing treatment processes and decreasing the risk of contagion. Thus, increasing use of screening tests as part of preventive medicine is very important.

Efficacy and Safety of Sofosbuvir and Ledipasvir for Hepatitis C in Kidney Transplant Recipients: A Single-center Retrospective Observational Study.

Treatment using direct-acting antivirals provides high rates of sustained virologic response and a favorable safety profile for patients with chronic hepatitis C virus infection. However, data on the efficacy of direct-acting antivirals in kidney transplant recipients are still limited. We evaluated the safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination in kidney transplant recipients. Retrospective, observational, single-center study. Data of 29 kidney transplant recipients who received a fixed-dose safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination for 12 or 24 weeks with or without ribavirin were analyzed. The primary outcome was SVR12, which was defined as undetectable HCV-RNA levels 12 weeks after the treatment. Secondary outcomes were graft function, proteinuria, and calcineurin inhibitor trough level variability. The predominant hepatitis C virus genotype was 1b (n = 19, 65.6%). All patients achieved SVR12. No graft failures nor deaths were reported during the study period. Throughout and after the treatment, the levels of aspartate aminotransferase [21 (range: 18-29.5) to 16 (range: 14-20) U/l, p < 0.001] and alanine aminotransferase [22 (range: 15-34) to 14 (range: 12-17.5) U/l, p < 0.001] improved significantly, unlike bilirubin, hemoglobin, and platelet levels. Renal function remained stable. Dose adjustments for calcineurin inhibitors were required. Serious adverse events were not observed. Safety and efficacy of fixed-dose sofosbuvir/ledipasvir combination was effective and safe in kidney transplant recipients with hepatitis C virus. However, cautious monitoring of trough levels of calcineurin inhibitorss is needed due to potential drug-drug interactions during the treatment episode.

Efficacy of direct-acting antivirals in patients with hepatitis C virus-associated cryoglobulinemic vasculitis: Results of a long-term follow-up

Objective – to evaluate the long-term outcomes of HCV eradication with direct-acting antivirals (DAAs) in patients with hepatitis C-associated cryoglobulinemic vasculitis (HCV-CV)Materials and methods. We retrospectively assessed 48 patients with HCV-CV treated with DAAs. The activity of HCV-CV was assessed by using Birmingham Vasculitis Activity Score version 3 (BVAS v. 3). In patients with HCV-CV the rate of sustained virologic (defined as undetectable HCV-RNA levels 12 weeks after treatment cessation) and immunological (defined as absence of circulating cryoglobulins, rheumatoid factor and normal C4 level) response; and the rate of complete (defined by a BVAS v. 3 score of 0) and partial (defined as BVAS v. 3 score &lt;50% of the baseline score) clinical response were evaluated. Immunosupressants were given before or after DAAs therapy if clinically needed.Results. Median time of follow-up from treatment cessation were 26,5 (11,5–62,3) months. All 48 (100%) patients achieved sustained virologic response. Elimination of cryoglobulins were reported in 20 (41,7%) patients, complete immunological response-in 4 (8,3%) cases. Complete and partial clinical responses were observed in 13 (27,1%) and 19 (39,6%) patients, respectively. BVAS v. 3 score &lt;4 at baseline was independently associated with complete clinical response (ОR=7,58; 95% CI: 1,42–40,48; р=0,018). 3 (6,3%) patients demonstrated HCV-CV relapse.Conclusion. Patients with HCV-CV require a long-term follow-up period even after reaching the SVR. The use of BVAS v. 3 score before the DAAs therapy can facilitate the planning of therapeutic approach, particularly, when identifying the patients in whom the immunosupressive therapy should be considered after viral eradication.

Real-life Data of Glecaprevir/Pibrentasvir in Chronic Hepatitis C Patients: A Single-center Study

Background: Glecaprevir/pibrentasvir (G/P) is a pangenotypic direct-acting antiviral (DAA) drug with a high resistance barrier. It has been used in patients with chronic hepatitis C in Turkey since March 2019. This drug's efficacy and safety data in Turkey are very limited, and there are not enough studies on real-life data. Objectives: In this study, we aim to present real-life data, efficacy, and safety for our patients. Methods: In this retrospective, observational, single-center study, 116 patients who were started on G/P (100mg/40mg) oral therapy at the infectious diseases clinic between March 2019 and December 2021 due to HCV were included. Of the 116 patients included in the study, 92 were analyzed. Demographic data of the patients, previous treatment experience, drug use, viral load (HCV RNA levels at the 4th week of treatment and 12th week after treatment), and viral genotype data were obtained retrospectively from the automation system. Statistical analysis IBM SPSS version 21.0 statistical package program was used. Results: Seventy-one (77.2%) of the patients were male, and 21 (22.8%) were female, with a mean age of 47.4 (18 - 89). Genotype distribution of patients 8.7% (n = 8) type 1a, 31.5% (n = 29) type 1b, 26.1% (n = 24) type 2, 22.9% (n = 21) type 3, 10.9% (n = 10) were type 4, 8.7% (n = 8) of the patients were treatment-experienced. In our study, there were no patients with cirrhosis. SVR-12 could not be obtained from a patient infected with only genotype 1a. In addition, this patient was co-infected with Hepatitis B. No side effects were observed in any of the patients that required treatment discontinuation. The SVR-12 rate was 98.6% with patients per protocol analysis (PP), but the SVR-12 rate was 77.2% with intention to treat analysis (ITT). Conclusions: In conclusion, this study suggested that G/P therapy in Turkey is used in real life with very high efficacy and tolerability. In addition, a significant change was observed in the genotype distribution previously reported in Turkey in the patient group we treated.

Efficacy of Daclatasvir and Half Dose Sofosbuvir in the Treatment of Hepatitis –C Virus Infection in Patients of Maintanance Hemodialysis-3 Years Trial in A Tertiary Renal Center

Background: Hepatitis C virus (HCV) infection in end-stage renal disease (ESRD) heralds a bad outcome. Directly acting antiviral (DAA) drugs sofosbuvir along with daclatasvir are very effective in the management of HCV infection. Sofosbuvir is excreted mainly through the kidneys. There is sparse data worldwide on the use of sofosbuvir based drug regimens in ESRD patients having chronic hepatitis C (CHC) virus infection.This study was designed to evaluate the efficacy of half dose sofosbuvir in the management of HCV infection in ESRD patients on maintenance hemodialysis (MHD). Methods: This clinical trial was conducted among 125 ESRD patients on MHD at Gonoshasthaya dialysis center, Dhanmondi, Dhaka from July 2019 to June 2022. Total 125 HCV positive patient with ESRD on MHD were included in this study; all the patients underwent HCV-RNA PCR test. Patients with detectable HCV RNA were observed for six months without antiviral drugs to identify the occurrence of spontaneous clearance of virus. Patients who had detectable HCV-RNA after six months were treated with sofosbuvir(200 mg) and daclatasvir (60 mg), irrespective of genotype. The drugs were given daily for 12 weeks. All the patients were on regular follow up at two weeks interval. Blood counts, liver function, creatinine phosphokinase and serum amylase values were evaluated periodically; virological response was assessed by HCV-RNA after 12 weeks of antiviral treatment. Results: During the observation period, 29 (23.2%) patients had spontaneous virus clearance with an undetectable HCV-RNA. In the remaining 96 patients, the median HCV-RNA level was 2.76×104 (1.56 ×103– 1.89×106)I IU. Twelve weeks after the treatment, 91 (94.8%) patients achieved sustained virological response (SVR) with undetectable HCV-RNA. All patients tolerated the DAAs well and none of the patients reported any serious adverse events. No patient discontinued antiviral therapy due to side effects. Patients who attained SVR with DAA, after 6 months we repeated HCV-RNA in 30 patients, in majority of them (28, 93.3%), HCV-RNA were undetected but in 2 (6.7%) patients,HCV-RNA were detected again. Conclusion: Daclatasvir along with half-dose sofosbuvir are safe and effective in the treatment of CHC patients with ESRD on MHD. Half dose sofosbuvir regimen can reduce the cost of treatment of HCV in ESRD patients in developing countries like Bangladesh, where cost is a significant barrier to HCV treatment. J Bangladesh Coll Phys Surg 2023; 41: 102-107

Evaluation of Quantitative Hepatitis C Virus Core Antigen Testing as a Tool for Screening and Confirmation of HCV Infection.

Hepatitis C is a common viral infection worldwide. Finding the most effective diagnostic methods with low cost is always needed for laboratory improvement. In this study, we evaluated the performance of a quantitative chemiluminescent hepatitis C virus core antigen (HCV cAg) test by comparing it with the HCV confirmatory antibody line immunoblot assay (HCV Ab-LIA) test as well as the HCV quantitate reverse transcription-polymerase chain reaction (qRT-PCR) test. A total of 394 samples were enrolled in the retrospective study. Of these, 225 samples were tested using HCV Ab screening and confirmatory Ab-LIA along with chemiluminescent HCV core Ag testing, while 169 samples were tested using qRT-PCR for HCV RNA and chemiluminescent HCV core Ag testing. Out of these, 225 positive samples tested by HCV Ab screening test were analyzed using the confirmatory Ab LIA and HCV cAg assays, a total of 183 samples (81.3 %) were confirmed to be Ab-positive, and among those, 77 samples (42.1%) were also positive for HCV cAg. Thirty-eight samples (20.76%) were HCV Ab indeterminate, and all of them were HCV cAg negative. Four samples (1.8%) were HCV Ab LIA-negative and negative for HCV cAg. Moreover, 169 samples were measured for qRT-PCR HCV viral load and quantitative HCV cAg test. One hundred and three samples were positive for HCV RNA, while 66 were negative. Among the positives, 96/103 samples were HCV cAg positive and 7/103 samples were negative. Out of the negatives, 4/66 samples were HCV cAg positive but 62/66 samples were negative. The HCV cAg results were concordant with the qRT-PCR results in 158 samples (93.5%); however, 11 samples (6.5%) were found to be discrepant. The sensitivity, specificity, positive predictive value, and negative predictive value of the quantitative HCV cAg were found to be 93%, 94%, 96%, and 90%, respectively. The overall coefficient of correlation between the HCV RNA levels and HCV cAg data was determined to be r2 = 0.9. The HCV cAg test showed a high correlation with the HCV RNA levels and may potentially be used as a more cost-effective alternative to the HCV RNA qRT-PCR test.

Influence of hepatitis C viral parameters on pregnancy complications and risk of mother-to-child transmission.

With the World Health Organization plan for hepatitis C elimination by the year 2030, and recent guideline recommendations to screen all women during pregnancy for HCV, data on HCV in pregnancy are needed to determine the association of HCV viremia with adverse pregnancy outcomes and mother-to-child transmission (MTCT). This retrospective cohort study was performed in Ontario, Canada, using population-based administrative healthcare data. Individuals were stratified based on whether they had active HCV viremia during pregnancy or resolved viremia at time of pregnancy. Peak HCV viral load was determined. Logistic regression was used to determine the association of viremia with adverse pregnancy outcomes; maternal HCV RNA levels were evaluated as a predictor of MTCT. We identified a total of 2,170 pregnancies in 1,636 women who were HCV RNA positive prior to pregnancy; 1,780 (82%) pregnancies occurred in women who were HCV RNA positive during pregnancy. Patients who were HCV RNA positive during pregnancy were more likely to have preterm delivery (18% vs. 12%, p= 0.002), intrahepatic cholestasis of pregnancy (4% vs. <2%, p= 0.003), and post-partum hemorrhage (9% vs. 5%, p= 0.013), and less likely to have gestational diabetes (6% vs. 10%, p= 0.008) than those with resolved infection. Only 511 (29%) infants had screening consistent with guidelines after birth; there was an estimated 3.5% risk of MTCT. HCV RNA ≥6.0 log10 IU/ml was significantly associated with MTCT (exact odds ratio 3.4, p= 0.04). Active HCV viremia among individuals with a history of HCV infection significantly increases adverse pregnancy outcomes. Few infants are screened for MTCT. Higher HCV RNA is associated with increased risk of MTCT. The prevalence of hepatitis C has increased in women of child-bearing age and has important implications for women who become pregnant and their infants. We evaluated the effect that hepatitis C has on pregnancy outcomes as well as the rate of hepatitis C transmission to infants in a large database with linked mother-infant records. We found that active hepatitis C during pregnancy increased the risk of pregnancy complications. We also identified very low rates of testing of infants born to mothers with hepatitis C, but found higher rates of hepatitis C transmission to infants in mothers with higher virus levels.

The signal-to-cutoff ratios to predict HCV infection among people who inject drugs.

People who inject drugs (PWIDs) are primarily the high-risk population for HCV infection. This study aims to determine the optimal cut-off values for predicting HCV infection status based on the Signal-to-Cutoff (S/CO) ratio. In this study, a total of 719 PWIDs’ samples were collected, and performed for screening test by ELISA assay, and followed by RIBA assay and NAT assay to detect HCV antibody and HCV RNA levels, respectively. The findings revealed that the prevalence of HCV infection among PWIDs was 54.66% (393/719), and the false-positive rate of HCV antibody detection by ELISA assay among PWIDs was only 3.85% (16/416). In addition, when the optimal cut-off value for S/CO ratio was 2.0, the sensitivity and specificity of HCV antibody were 100.00% and 93.55%, respectively. And when the optimal cut-off value for S/CO ratio was 21.36, the sensitivity and specificity of HCV RNA positive were 89.90% and 72.73%, respectively. In conclusion, the status of HCV infection can be predicted based on the S/CO ratios of the ELISA assay, which can improve diagnosis and facilitate timely treatment to effectively prevent the spread of HCV infection.

Distribution of chronic hepatitis C genotype and evaluation of clinical factors affecting direct-acting antiviral treatment responses in the Western Black Sea Region, Turkey.

Chronic Hepatitis C (CHC) is a substantial global public health issue with significant variation between countries because of the genotypic differences. A sustained viral response (SVR) is essential to reduce the complications associated with CHC and can be achieved in most patients via direct-acting antivirals (DAAs). The present study aimed at determining the genotype distribution in patients with CHC in our region and the SVR in DAA therapy patients. The study was conducted retrospectively on 272 patients treated with DAA between September 2016 and 2021. Data including demographic and clinical characteristics of the patients (HCV RNA level, genotype, hepatitis B and HIV serology, cirrhosis and decompensation, presence of hepatocellular cancer, degree of hepatosteatosis, previous anti-HCV treatment experience, comorbidities) were recorded. The study's primary endpoint was to determine the SVR at week 24. Genotype 1 was the most common genotype (94.5%), with genotype 1b accounting for most patients (78%) among those. It was observed that the patients received Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir (OPRD) (47%), Ledipasvir/sofosbuvir (LDS) (38%), and Glecaprevir/pibrentasvir (GCP) (15%) as DAA treatment. SVR was observed in 92% (223) of the 240 patients at the end of 24 weeks. SVR-24 was significantly higher in the patient group with serum HCV RNA level ≤ 852.533 (p=0.002), in the hypertensive group (p=0.018), and without the psychiatric disease group (p<0.001). A high rate of SVR-24 was achieved by DAAs in CHC patients, most of whom were genotype 1 in the Western Black Sea Region, Turkey. Also, high viral load, hypertension, and psychiatric disease affected SVR-24, and clinical factors, such as cirrhosis, cirrhosis complications, hepatosteatosis, and other comorbidities did not.

S3107 Successfully Treated Acute Liver Injury in Acute Hepatitis C With N-Acetyl Cysteine: A Case Report

Introduction: Significant liver injury related to acetaminophen overdose is more common in patients with preexisting liver disease. We present a patient with newly diagnosed acute hepatitis C infection with acute liver injury treated successfully with N-acetylcysteine despite negative acetaminophen levels. Case Description/Methods: A 29-year-old male with history of spontaneously cleared HCV two years ago and polysubstance use presented with abdominal pain, anorexia, and jaundice. He admitted to taking less than 2 g of acetaminophen for tooth ache and chronic back pain along with recent IV drug use, alcohol use, and marijuana use. Examination revealed scleral icterus and right upper quadrant tenderness. Labs revealed normal acetaminophen level, elevated bilirubin 9.4, transaminases AST 1,023; ALT 1,941; alkaline phosphatase (ALP) 202, and INR of 1.4. Hepatitis C antibody returned positive. Hepatitis C genotype was 1a or 1b with an HCV RNA level of 10,917. Evaluation for other etiologies for acute liver injury including alpha-1 antitrypsin, ceruloplasmin, autoimmune, and other infectious work up was negative. MRCP was normal without biliary pathology. He was given 140 mg/kg oral N-acetylcysteine for suspected acetaminophen overdose as the etiology for liver injury. His symptoms improved and liver tests showed an improvement in the next few days (total bilirubin 5.1, mg/dL, AST 100, ALT 731, ALKP 218). The patient was prescribed Sofosbuvir-Velpatasvir at discharge for the treatment of acute hepatitis C. Discussion: In patients with hepatitis C infection the rate of liver injury with acute or chronic infection is about 16.7%. This case highlights the importance of having a low threshold for treating patients for acetaminophen toxicity in acute hepatitis C patients based on history. This case also highlights further studies are needed to determine the incidence and implications of acute liver injury in acute hepatitis C patients as there are no studies in this group of patients so far. Table 1. - Liver Function Tests During Admission Liver Function Tests Initial Repeat Total Bilirubin (mg/dL) 9.4 5.1 ALT (IU/L) 1,941 731 AST (IU/L) 1,023 100 ALKP (IU/L) 202 218 INR 1.4 1.2

Efficacy of sofosbuvir and daclatasvir in compensated chronic hepatitis C infection

Aims and objectives: The advent of directly acting agents for the treatment of Hepatitis C infection has forever transformed our understanding and management of viral infections. With over 95 % patients achieving a sustained viral response at 12 weeks with some of these newly inducted agents, the prospect of eradicating the Hepatitis C virus seems like an achievable target, which makes this one of the most important discoveries in modern medicine. We studied the combination of Sofosbuvir and Daclatasvir in patients with chronic hepatitis C infection (Genotype 3) to assess the rates of sustained virological response at 12 weeks. Methods: We studied 67 treatment naive patients with compensated chronic hepatitis C infection (genotype 3). They were all started on Tab Sofosbuvir 400 mg daily and Tab Daclatasvir 60 mg once daily for 12 weeks and followed up for a total of 24 weeks, which includes a treatment duration and observation period of 12 weeks each. The patients were monitored with HCV RNA levels at one, three and six months, with as many evaluations of liver function and routine hemogram.

HCV inhibits M2a, M2b and M2c macrophage polarization via HCV core protein engagement with Toll-like receptor 2.

Hepatitis C virus (HCV) establishes a persistent infection in most patients, eventually leading to chronic hepatitis C (CHC), cirrhosis and hepatocellular carcinoma. Our previous study revealed that HCV core protein (HCVc) inhibited the differentiation of monocytes into M1 and M2 macrophages. However, it remains unclear as to whether HCVc affects the polarization of M2 macrophages, and if this effect promotes the progression of chronic disease. In the present study, peripheral blood mononuclear cells (PBMCs) from patients with CHC and healthy controls (HCs) were isolated, purified and polarized to M2a, M2b and M2c macrophages. Phenotypic expression, cytokine secretion and gene expression were analyzed using flow cytometry, ELISA and reverse transcription-quantitative polymerase chain reaction, respectively. Monocytes from HCs were cultured with HCVc to study the effect of HCVc on macrophage polarization. Plasma alanine transaminase and HCV-RNA levels were significantly higher, and albumin levels were significantly lower in the CHC group than those in the control group (P<0.05). M2a macrophages polarized from monocytes of patients with CHC expressed lower levels of CD209, IL-1 receptor antagonist (IL-1RA) and Fizz1 compared with those from HCs. M2b macrophages expressed lower levels of CD86 and TNF-α, and M2c macrophages expressed lower levels of CD163, TGF-β and sphingosine kinase 1 (SPHK1) in the CHC group compared with HCs (P<0.05). HCVc inhibited the expression levels of CD209, IL-1RA and Fizz1 in M2a macrophages; CD86 and TNF-α in M2b macrophages; and CD163, TGF-β and SPHK1 in M2c macrophages (P<0.05). HCVc significantly suppressed phagocytosis of all subtypes (P<0.05); however, this inhibition was restored by an anti-Toll-like receptor (TLR)2 antibody (P<0.05). In conclusion, HCVc inhibited monocyte-derived M2a, M2b and M2c subtype differentiation via the TLR2 signaling pathway, resulting in macrophages exhibiting reduced phagocytosis in patients with CHC. This may contribute to persistent HCV infection, thus suggesting that the blockade of HCVc may be a new therapeutic approach for the treatment of HCV infection.

Investigation of Hepatitis C Virus (HCV) Genotypes by "Reverse Hybridisation Strip Assay" and DNA Sequence Analysis Methods

Hepatitis C Virus (HCV) is a virus that is estimated to infect approximately 185 million people worldwide and causes 350 000 deaths each year. The target in HCV treatment is the sustained virological response (SVR), and the most important virological factors determining SVR are genotype and baseline HCV-RNA levels. In this study, it was aimed to compare the HCV genotypes and subtypes detected by the "line probe assay (LIPA)" method with sequence analysis. HCV genotypes and subtypes were investigated by line probe assay (LIPA) (NLM analytica, Italy) and sequence analysis methods in 212 patients with chronic HCV diagnosis and with HCV RNA viral load of 10⁴ IU/ml and above. 5'UTR and core regions were studied in LIPA method and NS5B gene region was studied in the sequencing method. After amplifying 340 bp region in the NS5B gene region with the hemi-nested PCR method, sequence analysis (ABI 3500 Genetic Analyzer [Applied Biosystems, USA]) was performed. Statistical analysis of the study was determined by using TURCOSA Analytics program. In the study, HCV genotypes and subtypes that were determined in 212 patients by LIPA method were; 40 (18.8%) genotype 1a, 97 (45.75%) genotype 1b, 7 (3.3%) genotype 2, 12 (5.6%) genotype 2a/c, 2 (0.94%) genotype 2b, 19 (8.96%) genotype 3, 16 (7.55%) genotype 4, 1 (0.47%) genotype 4a, 15 (7.5%) genotype 4c/d, 1 (0.47%) genotype 4h and 2 (0.94%) genotype 5. The HCV genotypes and subtypes determined in 212 patients by sequence analysis were; 20 (9.43%) genotype 1a, 118 (55.6%) genotype 1b, 16 (7.55%) genotype 2a, 4 (1.89%) genotype 2b, 1 (0.47%) genotype 2k, 21 (9.91%) genotype 3a, 2 (0.94%) genotype 4a, 28 (13.21%) genotype 4d and 2 (0.94%) genotype 5a. The difference in results between the two methods was found to be statistically significant (p< 0.001). According to the viral load-genotype relationship, the highest viral load was detected in genotype 1a patients (p< 0.001). In conclusion, in order to determine HCV genotypes and subtypes in our study, LIPA and sequence analysis methods were compared and the genotype compatibility between the two methods were determined as 97.5% on the basis of genotype and 19% on the basis of subtype. Since the direct-acting antiviral (DEA) treatment protocol in chronic HCV patients is planned according to the genotype/subtype determination, the inconsistency of the results obtained in the LIPA method, which is routinely widely used, with the sequence analysis method is remarkable, and it was concluded that these results should be supported by studies containing more samples.

The role of vitamin D receptor polymorphisms in the course of chronic hepatitis C infection.

BackgroundVitamin D and its receptor (VDR) exert important immunoregulatory functions that contribute to liver homeostasis. The aim of this study was to investigate the influence of FokI, ApaI, BsmI and TaqI VDR polymorphisms on cirrhosis development and laboratory variables in patients with chronic hepatitis C (CHC).MethodsA total of 48 patients were enrolled in this retrospective, observational study and underwent genotype analysis; their medical records were examined to obtain relevant data.ResultsThe cumulative rate of progression to cirrhosis during the course of CHC was 31.3% after a median period of 11 years from diagnosis. Importantly, in multivariate analysis, FokI ff (adjusted hazard ratio [aHR] 13.6, 95% confidence interval [CI] 2.51-73.73; P=0.002) and ApaI aa (aHR 4.69, 95%CI 1.13-19.43; P=0.033) genotypes were independently associated with progression to cirrhosis. The presence of the aa genotype was also associated with higher liver stiffness measurements measured by transient elastography compared to the AA/Aa genotype (12.3kPa interquartile range [IQR] 9.6-17.3 vs. 7.1kPa IQR 5.6-11.1; P=0.012). In addition, higher HCV RNA and lower serum albumin levels were observed in patients with the tt genotype of the TaqI polymorphism compared to TT/Tt carriers, and in patients with the aa genotype compared to AA/Aa carriers. In haplotype analysis, no association was found between any haplotype and disease progression.ConclusionsIn patients with CHC, laboratory parameters are influenced by VDR polymorphisms and the development of cirrhosis is related to homozygosity for the dominant trait of ApaI and FokI variants.