A Case Report of Ivermectin-Induced Liver Failure

Introduction: Ivermectin is an antiparasitic medication that is primarily metabolized by the liver. During the COVID-19 pandemic, researchers demonstrated that Ivermectin successfully inhibited the replication of SARS-COV-2 in vivo, but current research has failed to demonstrate clinical benefit for treatment of COVID-19. Despite this, misinformation campaigns have misled patients to ingest Ivermectin at concentrations meant for domestic animals. Here, we present a case of acute liver failure secondary to the use of Ivermectin. Case Description/Methods: A 61-year-old man with medical history of ischemic cardiomyopathy with last echocardiogram showing ejection fraction at 21%, atrial fibrillation on warfarin for oral anticoagulation, and previously treated Hepatitis C presented with generalized weakness and yellowish discoloration of the skin worsening over the last two weeks. The patient denied significant alcohol use, acetaminophen use, or illicit drugs. He admitted to injecting himself with two doses of weight-based horse ivermectin, for COVID prophylaxis, two weeks prior to his presentation. Physical exam was pertinent for scleral icterus and hepatomegaly with no abdominal tenderness. Initial labs revealed elevated liver chemistries in a mixed pattern (Figure 1). Acute hepatitis panel, HSV, and CMV were negative. Hepatitis C antibodies were positive, but the patient was in sustained virologic response. Full workup for chronic liver disease was unremarkable. Ultrasound revealed hepatosplenomegaly with patent portal and hepatic vasculature. Subsequently, the patient developed hepatic encephalopathy along with his coagulopathy, raising concern for acute hepatic failure. The patient was transferred to the ICU and started on NAcetylcysteine, rifaximin, and supportive care. The patient recovered well and fortunately did not require liver transplant. Discussion(s): While the FDA recommends against the use of Ivermectin for COVID-19, many continue to inappropriately consume it. Ivermectin-induced liver failure is a rare but deadly side effect. Given our patient's rapid onset of symptoms post-self injection of Ivermectin, his liver injury was presumed to be related to Ivermectin. The drug interaction between Ivermectin and warfarin had worsened the patients coagulopathy. Physicians should be aware of the ways Ivermectin overdose may clinically present to avoid delayed treatment. This case demonstrates the detriments of perpetuation of medical misinformation to care.

Is It Cancer Hepatic Inflammatory Pseudotumor: An Important Hepatic Mass Differential

Introduction: Hepatic inflammatory pseudotumor (HIP), albeit rare, is an important pathology to be included in differentials for hepatic masses. The benign nature and treatment of this disease process should be considered especially in comparison to malignant hepatic processes. Case Description/Methods: A 66-year-old male with pre-existing history of compensated Hepatitis C cirrhosis status post direct-acting antivirals with sustained virologic response presented in shock after a syncopal episode. Initial work up revealed leukocytosis, thrombocytopenia, acute renal injury, elevated liver enzymes, and COVID-19 positive test. Patient underwent initial liver ultrasound revealing intrahepatic and extrahepatic biliary ductal dilation. Subsequent MRCP demonstrated diffuse thickening of intra and extra hepatic bile ducts suggestive of cholangitis and several hepatic masses concerning for abscesses versus possible metastatic cholangiocarcinoma. Patient improved symptomatically with antibiotics and supportive care. A liver biopsy was performed with pathology showing lymphoplasmacytic inflammation and fibroblastic infiltration suggestive of hepatic inflammatory pseudotumor. A repeat MRCP one week later showed interval decrease in size of liver lesions and repeat liver function tests also showed improvement. Patient was discharged on a course of ciprofloxacin and metronidazole. Patient had repeat MRCP 3 months after discharge, with further significant improvement in size of liver lesions. After multi-disciplinary discussion the plan was for further surveillance with imaging and labs in 2 months. Discussion(s): Inflammatory pseudotumors are benign and non-neoplastic lesions that can occur in any organ. They can appear as a malignant lesion when they arise in the liver and an accurate identification can allow for conservative management and prevent unnecessary invasive procedures. Hepatic inflammatory pseudotumors are often seen with concomitant infection or inflammatory processes. Liver biopsies distinguish these tumors from other malignant processes as they demonstrate a characteristic dense inflammatory infiltrate interspersed in stroma of interlacing bundles of myofibroblasts. This case highlights the importance of maintaining HIP on the differential diagnosis. (Figure Presented).

Results of an Automatic Alert System from Microbiology to Link Diagnosis to Treatment in Patients with Chronic Hepatitis C

Introduction and Objectives: Strategies to simplify the care circuit for patients with the hepatitis C virus (HCV) are vital to achieving its eradication. To achieve this aim, we introduced an electronic system of HCV serology detection to link diagnosis with specialized assistance in order to minimize the loss of patients. Material(s) and Method(s): A retrospective single-center study of HCV patients developed by Microbiology Department from February 15th, 2020, to December 15th, 2021. In the event of a positive HCV antibody, the anti-HCV core was directly measured by the electronic system. If positive, an encrypted e-mail with the patient data was automatically sent to HCV specialized physicians, who, after evaluating the benefits of antiviral therapy in each patient, contacted them by phone for an appointment. In the first face-to-face consultation FibroScan, HCV genotype and viral load measurement were performed, and antiviral therapy was prescribed. Patient diagnosis origin and public health characteristics were recorded. We analyzed the association between antiviral therapy prescription and these variables. Statistical significance was set at p<0.005. Result(s): Of 171 patients identified, with a mean age of 59.6 +/- 15.9, 61.5 % of males and 81.2% of Spanish nationals. HCV origin from out-of-hospital settings predominated (50.9%, 87/171), particularly primary care (28.7%), penitentiary (11.6%) and addiction units (8.2%). In all, 43.3% (74/171) were aware of their diagnosis, but 64.9% (48/74) hadn't previously received antiviral therapy. Genotype 1 predominated. We recorded 19.4% (20/103) of patients F3 fibrosis and 27.2% (26/103) F4. Finally, 58.5% (100/171) attended a physician consultation. They were all treated with pangenotypic interferon-free therapy. A 100% rate of sustained viral response was achieved. The main reasons for not being treated were high comorbidity (43.7%,31/71), not located (23.9%, 17/71), patient refusal to treatment (23.9%,17/71) and death (8.5%,6/71). The sole association found between antiviral therapy and patient variables was that of comorbidities with being untreated (OR=7.14, p<0.001). Conclusion(s): Our alert system is simple and easily reproducible. It allows for minimizing the loss of HCV patients, even considering it was performed during the COVID-19 pandemic.Copyright © 2023

Progress in understanding of association between metabolic associated fatty liver disease and viral infectious diseases.

Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease with the highest incidence in the world, which affects 1/4-1/3 of the world population and has a serious effect on people's health. As is a multi-systemic disease, MAFLD is closely related to the occurrence and prognosis of many diseases. Studies have shown that MAFLD is associated with viral infectious diseases, and their interaction affects the prognosis of the disease. This paper reviews the research progress in this field in recent years.Copyright © The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With HIV-1: Week 48 Results From the Phase 3, Non-inferiority SALSA Randomized Trial.

BACKGROUND: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term non-inferior efficacy vs continuing tenofovir alafenamide-based regimens in treatment-experienced adults with HIV-1. The phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with continuing various 3-/4-drug current antiretroviral regimens (CAR). METHODS: Adults with HIV-1 RNA <50 copies/mL and no previous virologic failure were randomized (1:1, stratified by baseline third agent class) to switch to once-daily fixed-dose combination DTG/3TC or continue CAR (primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48; Snapshot, intention-to-treat-exposed population, 5% non-inferiority margin). RESULTS: Overall, 493 adults (39% women; 39% aged ≥50 years; 19% African American/African heritage; 14% Asian) were randomized to switch to DTG/3TC (n=246) or continue CAR (n=247). At Week 48, 1 (0.4%) participant in the DTG/3TC group and 3 (1.2%) in the CAR group had HIV-1 RNA ≥50 copies/mL (Snapshot), demonstrating non-inferiority (adjusted difference, -0.8%; 95% CI, -2.4%, 0.8%). Zero participants met confirmed virologic withdrawal criteria; therefore, no resistance testing was performed. Drug-related adverse events were more frequent with DTG/3TC (20%) than CAR (6%) through Week 48 but comparable post-Week 24 (5% vs 2%, respectively). Proximal tubular renal function and bone turnover biomarkers improved with DTG/3TC. Both groups had generally minimal changes in lipids and inflammatory biomarkers. CONCLUSIONS: Switching to DTG/3TC was non-inferior to continuing CAR for maintaining virologic suppression at Week 48 with no observed resistance, supporting the efficacy, good safety, and high barrier to resistance of DTG/3TC.

Viral reactivation after hcv-positive renal allograft transplantation

Case Report: A 48y/o man with a history of ESRD secondary to FSGS was found to have hepatitis-C virus (HCV) reactivation after kidney transplantation (KT) with an HCV-positive allograft. The patient was HCV-negative before transplantation in July 2021. He was negative for hepatitis-B virus (HBV) core antibodies but had evidence of prior HBV vaccination and was negative for HIV 1/2. His induction therapy included thymoglobulin, and his maintenance immunosuppressive regimen included mycophenolate mofetil (MMF), tacrolimus, and prednisone. Aweek after KT, the patient tested positive for HCV genotype 1a, and he was started on sofosbuvir/velpatasvir in August 2021. Lab monitoring showed decreasing levels of HCV viral load (VL) until it was undetectable 2 months later. In January 2022, renal function remained stable, and urinalysis and hepatic function tests remained unremarkable. However, HCV viral load was positive in February 2022 and the HCV genotypewas 1a, as before. This result raised the possibility of reactivation of HCV from his allograft more than 6 months post KT. Additionally, despite negative BK polyoma VL initially, he was positive in January 2022 and discontinued his MMF. He was also positive for COVID-19 in January 2022 as well. Given his recurrence of HCV VL, he initiated sofosbuvir/velpatasvir/ voxilaprevir in April 2022 and completed therapy in July 2022, and maintained sustained viral response (SVR) as of October 2022. His BK VL was negative in May 2022. Recent guidelines on preventing HCV reactivation in allograft-positive KT recipients state that individuals should achieve SVR after 8-12 weeks of a course of direct-acting antiviral (DAA) therapy. The patient completed DAA therapy post-transplantation with a successful negative viral load 2 months later. However, he did not achieve SVR because his VL was again positive 3 months after completion of therapy. Reactivation of BKV, a DNA virus that establishes lifelong infection in renal tubular and uroepithelial cells, is common among KT recipients, but there is insufficient evidence to establish a causal association between BKV reactivation and HCV reactivation. There is no consensus on a chemotherapeutic maintenance regimen to prevent HCV reactivation. This case highlights the importance of close follow-up monitoring for HCV and BKV among KT recipients and the need to explore the relationship between BKV reactivation, HCV reactivation, and immunosuppression regimen. Copyright © 2023 Southern Society for Clinical Investigation.

Treatment-Experienced Patients on Third-Line Therapy: A Retrospective Cohort of Treatment Outcomes at the HIV Advanced Treatment Centre, University Teaching Hospital, Zambia.

Antiretroviral therapy (ART) uptake continues to increase across sub-Saharan Africa and emergence of drug-resistant HIV mutations poses significant challenges to management of treatment-experienced patients with virologic failure. In Zambia, new third-line ART (TLART) guidelines including use of dolutegravir (DTG) were introduced in 2018. We assessed virologic suppression, immunologic response, and HIV drug-resistant mutations (DRMs) among patients on TLART at the University Teaching Hospital (UTH) in Lusaka, Zambia. We conducted a retrospective review of patients enrolled at UTH on TLART for >6 months between January 2010 and June 30, 2021. CD4 and HIV viral load (VL) at TLART initiation and post-initiation were assessed to determine virologic and immunologic outcomes. Regression analysis using bivariate and multivariate methods to describe baseline characteristics, virologic, and immunologic response to TLART was performed. A total of 345 patients met inclusion criteria; women comprised 57.6% (199/345) of the cohort. Median age at HIV diagnosis was 30 (interquartile range: 17.3-36.8). In 255 (73.8%) patients with at least two VLs, VL decreased from mean of 3.45 log10 copies/mL (standard deviation [SD]: 2.02) to 1.68 log10 copies/mL (SD: 1.79). Common ARVs prescribed included DTG (89.9%), tenofovir disoproxil fumarate (68.7%), and darunavir boosted with ritonavir (66.4%); 170 (49.3%) patients had genotypes; mutations consisted of 88.8% nucleoside reverse transcriptase inhibitor, 86.5% non-nucleoside reverse transcriptase inhibitor, and 55.9% protease inhibitor. VL suppression to <1,000 copies/mL was achieved in 225 (78.9%) patients. DRM frequency ranged from 56% to 89% depending on drug class. Treatment-experienced patients receiving TLART in Zambia achieved high rates of suppression despite high proportions of HIV mutations illustrating TLART effectiveness in the DTG era.

Outcomes of Interferon-free Treatment of Hepatitis C Virus Infection Seven Years after Approval and Problems with Drop out during and after Treatment: A Retrospective, Single-center Study.

Objective This retrospective, single-center study assessed the effects of interferon (IFN)-free treatment of hepatitis C virus (HCV) infection, which has been approved for seven years; calculated the incidence of hepatocellular carcinoma (HCC) after achieving a sustained virologic response (SVR); and elucidated problems with follow-up for surveillance of post-SVR HCC, particularly the impact of the coronavirus disease 2019 (COVID-19) pandemic. Methods We summarized the SVR achievement rate of 286 HCV-infected patients who received 301 IFN-free treatments and analyzed the cumulative incidence of initial HCC and the cumulative continuation rate of follow-up after SVR in the 253 patients who achieved SVR and did not have a history of HCC. Results Among 286 patients who received IFN-free treatments, 14 dropped out, and the 272 remaining patients achieved an SVR after receiving up to third-line treatment. Post-SVR HCC occurred in 18 (7.1%) of the 253 patients without a history of HCC, with a cumulative incidence at 3 and 5 years after SVR of 6.6% and 10.0%, respectively; the incidence of cirrhosis at those time points was 18.2% and 24.6%, respectively.Of the 253 patients analyzed, 58 (22.9%) discontinued follow-up after SVR. Patients who had no experience with IFN-based therapy tended to drop out after SVR. Notably, the number of dropouts per month has increased since the start of the pandemic. Conclusion Currently, IFN-free treatment is showing great efficacy. However, the incidence of HCC after SVR should continue to be monitored. In this study, the COVID-19 pandemic did not affect treatment outcomes, but it may affect surveillance for post-SVR HCC.

Evaluation of Hepatitis C Positive Donor to Hepatitis C Negative Recipient Kidney Transplant in a Highly Sensitized Patient Population

Purpose: This study assessed outcomes of hepatitis C virus (HCV) donor positive to recipient negative (D+/R-) kidney transplants (KT) in high immunologic risk patients. Literature reports positive short-term outcomes in low immunologic risk patients, but limited data exists to support HCV D+/R- KT in high immunologic risk patients. Method(s): This retrospective cohort study included HCV antibody negative (-) recipients of a nucleic acid test (NAT) positive (+) KT who received HCV treatment with direct-acting antiviral therapy from 12/1/20 and 11/30/21. NAT+ KT recipients were matched 1:1 with NAT - KT recipients based on age, body mass index, and gender. All serologies were confirmed prior to study inclusion. The primary outcome was a composite of patient and graft survival 3 months post-KT. Secondary outcomes included percent of patients with sustained virologic response (SVR), time to HCV treatment initiation, incidence of cytomegalovirus (CMV) and BK viremia, presence of de novo donor specific antibody (DSA), rejection and HCV treatment related adverse drug reactions (ADRs). Descriptive statistics were used for baseline characteristics and a Log-Rank test was used for the primary outcome. Result(s): Eighteen HCV NAT+ KT recipients were matched with 18 HCV NAT- KT recipients. Study population was similar between groups and had end stage renal disease due to diabetes and/or hypertension, mean class I PRA >14%, pre-transplant DSA in 16% of patients in each cohort, and all received induction with rabbit anti-thymocyte globulin (Table 1). There was no difference in patient (p=0.32) and graft survival (p=0.99) between groups at 3 months post-KT. One death due to COVID-19 occurred in the NAT- group. There was no difference in estimated glomerular filtration rate (eGFR) at 1 (p=0.39) and 3 months (p=0.28), incidence of delayed graft function (DGF) (p= 0.67) or CMV (p=0.1) and BK viremia (p=1) between groups. (Table 2). HCV transmission occurred in all NAT+ KT recipients, and all who completed therapy achieved SVR. Treatment was initiated on average 8.5 weeks post-KT (Table 3). Notably, 33% of patients required financial assistance to obtain HCV treatment. Conclusion(s): Use of HCV D+/R- KT resulted in no difference in patient and graft survival at 3 months in this matched cohort. HCV NAT + KT patients should be connected with financial assistance programs early to promote timely treatment initiation. (Table Presented).

Aerosolized Hydrogen Peroxide Decontamination of N95 Respirators, with Fit-Testing and Viral Inactivation, Demonstrates Feasibility for Reuse during the COVID-19 Pandemic.

In response to the demand for N95 respirators by health care workers during the COVID-19 pandemic, we evaluated decontamination of N95 respirators using an aerosolized hydrogen peroxide (aHP) system. This system is designed to dispense a consistent atomized spray of aerosolized, 7% hydrogen peroxide (H₂O₂) solution over a treatment cycle. Multiple N95 respirator models were subjected to 10 or more cycles of respirator decontamination, with a select number periodically assessed for qualitative and quantitative fit testing. In parallel, we assessed the ability of aHP treatment to inactivate multiple viruses absorbed onto respirators, including phi6 bacteriophage, herpes simplex virus 1 (HSV-1), coxsackievirus B3 (CVB3), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For pathogens transmitted via respiratory droplets and aerosols, it is critical to address respirator safety for reuse. This study provided experimental validation of an aHP treatment process that decontaminates the respirators while maintaining N95 function. External National Institute for Occupational Safety & Health (NIOSH) certification verified respirator structural integrity and filtration efficiency after 10 rounds of aHP treatment. Virus inactivation by aHP was comparable to the decontamination of commercial spore-based biological indicators. These data demonstrate that the aHP process is effective, with successful fit-testing of respirators after multiple aHP cycles, effective decontamination of multiple virus species, including SARS-CoV-2, successful decontamination of bacterial spores, and filtration efficiency maintained at or greater than 95%. While this study did not include extended or clinical use of N95 respirators between aHP cycles, these data provide proof of concept for aHP decontamination of N95 respirators before reuse in a crisis-capacity scenario. IMPORTANCE The COVID-19 pandemic led to unprecedented pressure on health care and research facilities to provide personal protective equipment. The respiratory nature of the SARS-CoV2 pathogen makes respirator facepieces a critical protective measure to limit inhalation of this virus. While respirator facepieces were designed for single use and disposal, the pandemic increased overall demand for N95 respirators, and corresponding manufacturing and supply chain limitations necessitated the safe reuse of respirators when necessary. In this study, we repurposed an aerosolized hydrogen peroxide (aHP) system that is regularly utilized to decontaminate materials in a biosafety level 3 (BSL3) facility, to develop a method for decontamination of N95 respirators. Results from viral inactivation, biological indicators, respirator fit testing, and filtration efficiency testing all indicated that the process was effective at rendering N95 respirators safe for reuse. This proof-of-concept study establishes baseline data for future testing of aHP in crisis-capacity respirator-reuse scenarios.

SERVICE DEVELOPMENT -NURSE LED MULTIAGENCY HEPATITIS C MOBILE COMMUNITY OUTREACH SCREEN TEST TREAT SERVICE

Introduction Delivery of the World Health Organisation elimination agenda for Hepatitis C Virus (HCV) requires active case finding, to engage hard to reach risk groups. Surrey is a relatively affluent part of the country, but contains pockets of significant unmet need, which are a barrier to the HCV care cascade. In 2020 the Surrey HCV Operational Delivery Network (ODN) piloted 'pop up clinics' for housed homeless populations during the COVID 19 pandemic. Based on this experience the ODN lead successfully bid for NHS England funding for a Mobile Outreach Van (MOV). Methods Detailed mapping of the ODN was undertaken jointly with the Hepatitis C Trust to identify potential locations to screen e.g., Opiate Substation Therapy dispensing pharmacies, and areas with high numbers of homeless people. MOV procurement and governance obtained in accordance with Trust policy. Individuals complete a brief liver health questionnaire including Blood Bourne Virus (BBV) risk factors. HCV screening is undertaken using Oraquick point of care testing. Those screening HCV Antibody positive (Ab +ve) receive a Clinical Nurse Specialist (CNS) assessment for therapy including a BBV screen HCV PCR and Fibro Scan. Hepatitis C Trust peer support is available to all individuals. Other significant findings prompt onward referral e.g., cirrhosis surveillance. Results First six months of operation the team have undertaken 50 testing days in 16 venues. 761 individuals have accepted HCV Ab screening. 40 (5.2%) tested HCV Ab +ve. 10 individuals confirmed viraemic and eligible for treatment. Another 7 individuals were re-engaged to undertake end of treatment or Sustained Virologic Response 12/48 PCR. In addition, 1 HCV Ab +ve (PCR negative), patient was diagnosed with Human Immunodeficiency Virus and referred to the local sexual health team. 16 individuals identified with advanced fibrosis or cirrhosis were referred to hospital for Hepatocellular Carcinoma surveillance. Patients engaged through the MOV service have received their treatment in the community via this service delivered by a CNS. Conclusions Nurse led MOV screen test treat model has proven to be safe and effective in engaging difficult to reach populations. Hepatitis C Trust peers accessibility help to address the anxiety/stigma surrounding HCV. MOV wider benefits include engagement with drug and alcohol services, and harm reduction. The next phase of implementation, the team plan to deliver needle exchange and naloxone in a partnership agreement with Surrey County Council.

SUCCESSFUL IMPLEMENTATION OF CASE FINDING FOR HEPATITIS C IN PEOPLE DETAINED IN POLICE CUSTODY

Introduction As part of the national Hepatitis C (HCV) elimination strategy, NHS England aims to eliminate HCV by 2025. As part of this programme, identifying undiagnosed cases through HCV testing is critical. Unfortunately, the global COVID 19 pandemic led to a reduction in HCV testing in England, potentially slowing progress towards elimination. To mitigate the impact of this, innovative ways of increasing HCV testing are required. Individuals detained in police custody have higher rates of injecting drug use than the general population and may therefore be at risk of HCV transmission. Police custody suites may therefore provide an opportunity to offer HCV testing to 'at risk' individuals. In collaboration with local police custody healthcare staff, we developed a pilot of HCV testing for individuals in police custody. Here we describe the outcomes of this pilot Methods Since 01/07/2021, all individuals presenting to Northumbria police custody suites who were reviewed by a healthcare professional were offered Dried Blood Spot test (DBS) for HCV Antibody/RNA, HIV and HBsAg. Individuals were excluded if they were <16 years of age or alleged perpetrators of sexual violence. The Newcastle HCV team were responsible for informing people of their results and establishing those with a positive HCV result on a treatment pathway. Results Of the 3116 people in police custody identified as eligible to be offered BBV testing (See figure 1), 193 accepted (6%). A total of 19 were HCV Ab positive (10% of total individuals tested) and of these 12 were HCV RNA detected (63.0% of HCV Ab positive and 6% of total individuals tested). No cases of HIV or hepatitis B were identified. 137 (71.0%) individuals were negative for all BBV's. Unfortunately, 37 (19%) samples could not be processed by the lab due to insufficient samples (19.0%). This was identified as a training issue and addressed by senior custody suite staff. of the 12 cases of active HCV identified, 5 have commenced HCV antiviral treatment, 6 are awaiting treatment and 1 person is awaiting retesting as the result was 'weak positive'. of the 7 individuals who were HCV Antibody positive but RNA negative, 3 had self-cleared, 3 were known to have received antiviral treatment and achieved a sustained virological response and 1 patient was currently on treatment. Conclusions The pilot demonstrated that HCV screening can successfully be implemented into the police custody suites, leading to a diagnosis of active HCV in 6%. Wider implementation of this strategy could help progress towards HCV elimination.

Hepatitis C microelimination among people living with HIV in Taiwan.

To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39-7.12%) in 2018 to 2.09% (95% CI, 1.60-2.77%) in 2021 (decline by 66.4% [95% CI, 55.4-74.7%]); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44-32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14-17.44) (decline by 53.2% [95% CI, 27.3-70.6%]). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.

LESSONS FROM HEPATITIS C TREATMENT DURING THE COVID-19 PANDEMIC: DECREASED RESOURCE UTILIZATION LEADS TO SIMILAR EFFICACY IN BRITISH COLUMBIA, CANADA

Background: Early studies show that the COVID-19 pandemic has led to reduced prescription of direct-acting anti-viral (DAA) treatment for hepatitis C (HCV) infection. We sought to characterize HCV patients started on DAAs during the pandemic in British Columbia, Canada. Methods: A retrospective chart review of multiple sites was conducted using the British Columbia HCV Network. Patients initiated on DAA for HCV treatment from 09/17/2018- 09/17/2021 were included. Those treated for 18 months prior to 03/17/2020 were included as the pre-pandemic group (pre-PG) and those treated after 03/17/2020 comprised the pandemic group (PG). Results: A total of 393 patients were included, with 221 pre-PG patients and 172 PG patients, representing a 23% decline in HCV treatment during the pandemic. PG patients were significantly younger with mean age 55 years (vs 56 years pre- PG, p<0.01) and a higher proportion were on opioid agonist therapy (OAT) at 28% (vs 12% pre-PG, p<0.01). Rates of alcohol and active substance use were similar between both groups. Both groups had similar HCV genotypes, viral load, and FIB-4 scores. Pre-treatment transient elastography (TE) within 3 months of initiating treatment was completed in significantly fewer PG patients at 37% compared with 70% pre-PG (p<0.01). Of PG and pre-PG patients who completed TE, cirrhosis was found in 15 (9%) and 32 (14%) respectively, with mean liver stiffness measure of 8.69 kPa and 10.21 kPa, respectively. Beyond less utilization of TE, the pandemic also led to reduced total appointments at mean 3.1 visits per PG patient compared to 4.2 visits per pre-PG patient (<0.01). Considering the different types of appointments, PG patients had fewer office appointments at mean 1.6 per PG patient (vs 3.1 per pre-PG patient, p <0.01) but more telehealth appointments at mean 2.5 per PG patient (vs 2.1 per pre-PG patient, p <0.01). Treatment regimen was similar in both groups with predominant use of glecaprevir/pibrentasvir and sofosbuvir/velpatasvir. Treatment completion rate was 95% in PG patients compared to 89% pre-PG (p=0.03). Fewer PG patients completed lab work for sustained virologic response (SVR) at 61% (vs 88% pre-PG) however, SVR rate was similar between both groups (96% pre-PG and 99% PG, p=NS). Active drug use or OAT was not associated with treatment completion or SVR in either group. Conclusion: The COVID-19 pandemic has led to a decrease in HCV treatment rates. However, treatment completion and SVR rates remained high among those treated, suggesting minimal-pre-treatment investigations and use of telemedicine can optimize scarce resources with similar efficacy. (Figure Presented)

SYSTEMATIC REVIEW OF TELEHEALTH INTERVENTIONS IN PATIENTS WITH CHRONIC LIVER DISEASES

Background and aim Telehealth (TH) interventions may improve access to care, diseasespecific and general quality outcomes in chronic liver diseases (CLD). Given the current COVID-19 pandemic, TH interest has grown exponentially. We aimed to systematically evaluate outcomes of TH interventions in a variety of CLD. Methods We used key terms and searched PubMed/EMBASE from inception to 12/5/2020 for observational studies or clinical trials. Two authors independently screened s. We included any type of CLD, including post-transplant patients. Disagreements were solved by a third reviewer. We excluded s, case-reports, and reviews. We extracted the outcomes defined by the authors for each CLD (chronic hepatitis C or B, decompensated cirrhosis, hepatocellular carcinoma-HCC-, liver transplant referral and readmission/rejection after transplantation or weight loss in nonalcoholic fatty liver disease-NAFLD). No meta-analysis was planned due to the heterogeneity of the data. Results Of a total of 3567 studies screened, 29 met inclusion criteria (Table 1). Of these, 17 reported on HCV treatment outcomes [14 video telemedicine, 2 remote specialist consultation, and one texting based intervention]. All studies showed no statistically significant differences between sustained virological response (SVR) rates in telehealth intervention groups compared to control groups or historic general population. 4 retrospective studies examined decompensated cirrhosis/liver transplant referral, followup after transplant, and showed a reduction in time to transplant (138.8 days vs 249 day, P<0.01), mortality or readmission following transplant (28% vs 58%, P=0.004), and improved referral timing (0% immediate rejections of transplant referral vs 41%, P<0.001). Other important outcomes measured also demonstrated benefit in favor of telemedicine incorporation including autoimmune hepatitis remission (100% vs 77.3%, P=0.035). One study assessed chronic hepatitis B outcomes and had no difference in development of hepatocellular carcinoma, ALT fluctuation or cirrhosis over 2 years of follow-up. Finally, two studies assessed weight loss in nonalcoholic fatty liver disease: the prospective study showed no change in weight loss while the randomized clinical trial did. Conclusion TH interventions in patients with CLD shows consistent equivalent or improved clinical outcomes compared to traditional encounter. Similar SVR, decreased time to liver transplant referral and mortality outcomes were observed in the TH groups. In CHB, development of HCC, cirrhosis or biochemical remission was similar as well. In the NAFLD clinical trial, the TH group had 5%+ weight loss over 3 months compared to the control group. In the light of the ongoing COVID19 pandemic, TH in CLD should be the bridge to improve clinical outcomes when face-to-face encounters are not possible. (Table Presented) Abbreviations: DOC: Department of Corrections, TH: Telehealth, SVR: sustained virological response, SVR12: sustained virological response for 12 weeks, SVR24: sustained virological response for 24 weeks, GP: general practitioner, RCT: randomized controlled trial *Sterling et al, 2018 compared patients with private insurance in clinic vs indigent patients in clinic vs patients in the department of corrections using telemedicine. †Lepage et al, 2020 compared patients in outpatient clinic vs mixed delivery including clinic and telemedicine vs telemedicine only. ††These studies reported rates of SVR in their cohort and compared to historical rates of SVR in similar cohorts.

THE IMPACT of COVID-19 on HCV MICRO-ELIMINATION in MSM in GERMANY

Background: Men who have sex with men (MSM) have been identified as one subgroup with continuous HCV transmission and as a target for HCV micro-elimination efforts. We assess newly acquired HCV among MSM in Germany since the introduction of directly-acting antiviral agents (DAAs). Methods: The German NoCo cohort consists of patients from six German HIV and hepatitis treatment sites providing care for more than 8000 HIV-positive MSM, and serving as primary care providers and HIV pre-exposure prophylaxis (PrEP) sites. Patients who were diagnosed with recently acquired HCV infection since 2014 were enrolled and are followed-up. Virologic data, HIV and HCV treatment data, risk factors and behavior as well as liver disease assessment is acquired regularly. Results: Between January 2014, and October 2021, 237 MSM with recently acquired HCV infection were included. A majority were Caucasian (95%), and mean age was 45.3 years (standard deviation, SD, 9.57). At HCV diagnosis, median ALT level was 224 U/L (interquartile range, IQR, 86-521), and median HCV viral load was 475,000 IU/mL (IQR 66,955-3,005,882). The most prevalent HCV genotype were 1a (58.7%), and 4d (16%). The risk factors for HCV acquisition were as follows: MSM: 92.4%, intravenous drug use: 2.95%, intranasal drug use: 0.8%, other: 0.4%, unknown: 7.2%. A subgroup of 21 (8.9%) MSM were not co-infected with HIV, of whom 15 (71.4%) were using PrEP. Anti-HCV treatment with DAAs was documented in 165 patients (71.7%), 18 (7.8%) had a spontaneous clearance, and in 47 patients (20.4%) treatment was not started. DAAs were initiated a median 6.6 months (IQR 4 to 9.3) after diagnosis;all treated patients achieved a sustained virologic response (SVR), or treatment was still ongoing (16%). Between 2014-2019 27-36 patients were diagnosed with recently acquired HCV annually. In relation to all HIV-positive MSM under care, the incidence was 0.33-0.39% per year with no significant change over time. In 2020, a decline in HCV incidence to 0.28% was observed. In 2021 HCV incidence dropped to 0.02%. In the same period, the number of patients seen in the centers remained stable, and routine HCV testing returned to pre-pandemic levels by the end of 2020. Conclusion: The German NoCo cohort demonstrated stable HCV incidence rates despite a broad use of DAAs. In 2021, however, micro-elimination goals were met, possibly due to behaviour changes related to the SARS-CoV-2 pandemic and associated containment measures.

Impact of Multicomponent Support Strategies on Human Immunodeficiency Virus Virologic Suppression Rates During Coronavirus Disease 2019: An Interrupted Time Series Analysis.

BACKGROUND: After coronavirus disease 2019 (COVID-19) shelter-in-place (SIP) orders, viral suppression (VS) rates initially decreased within a safety-net human immunodeficiency virus (HIV) clinic in San Francisco, particularly among people living with HIV (PLWH) who are experiencing homelessness. We sought to determine if proactive outreach to provide social services, scaling up of in-person visits, and expansion of housing programs could reverse this decline. METHODS: We assessed VS 24 months before and 13 months after SIP using mixed-effects logistic regression followed by interrupted time series (ITS) analysis to examine changes in the rate of VS per month. Loss to follow-up (LTFU) was assessed via active clinic tracing. RESULTS: Data from 1816 patients were included; the median age was 51 years, 12% were female, and 14% were experiencing unstable housing/homelessness. The adjusted odds of VS increased 1.34 fold following institution of the multicomponent strategies (95% confidence interval [CI], 1.21-1.46). In the ITS analysis, the odds of VS continuously increased 1.05 fold per month over the post-intervention period (95% CI, 1.01-1.08). Among PLWH who previously experienced homelessness and successfully received housing support, the odds of VS were 1.94-fold higher (95% CI, 1.05-3.59). The 1-year LTFU rate was 2.8 per 100 person-years (95% CI, 2.2-3.5). CONCLUSIONS: The VS rate increased following institution of the multicomponent strategies, with a lower LFTU rate compared with prior years. Maintaining in-person care for underserved patients, with flexible telemedicine options, along with provision of social services and permanent expansion of housing programs, will be needed to support VS among underserved populations during the COVID-19 pandemic.

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

BACKGROUND: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. METHODS: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. RESULTS: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). CONCLUSION: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.

Impact of COVID-19 pandemic on surveillance of hepatocellular carcinoma: A study in patients with chronic hepatitis C after sustained virologic response.

Background: The current coronavirus disease 2019 (COVID-19) pandemic has strongly influenced many aspects of the medical care, including cancer surveillance. Aims: We investigated how the COVID-19 pandemic influenced surveillance for hepatocellular carcinoma (HCC), focusing on patients with hepatitis C virus infection who were receiving surveillance for HCC after sustained virologic response (SVR) in Japan. Methods: Patients who achieved SVR between 1995 and 2017 and continued receiving surveillance were compared by month in terms of the rate at which they kept their scheduled visits for HCC surveillance from July 2019 to May 2020. Results: The percentage of kept scheduled visits was above 97% before February 2020. By contrast, it declined sharply after March 2020 when COVID-19 became pandemic; the percentages were 75.5% in March, 63.0% in April and 49.1% in May 2020 (July 2019-February 2020 vs March-May 2020, P < 0.0001). Similar declines were observed in patients with cirrhosis or advanced fibrosis and in those with a history of HCC. Whereas most patients who cancelled a scheduled visit before February 2020 did not reschedule it, the majority of patients with cancellations after March 2020 did want to reschedule. Conclusions: The percentages of scheduled visits that were kept declined rapidly after COVID-19 became pandemic in Japan, although the spread of COVID-19 is relatively mild and the legal restriction of people's behaviour and movement is absent. Instituting measures to follow-up with cancelled patients and resume surveillance will be necessary in the future.