New window into hepatitis B in Africa: Liver sampling combined with single cell omics enables deep and longitudinal assessment of intrahepatic immunity in Zambia.

In Lusaka, Zambia, we introduced liver fine needle aspiration (FNA) into a research cohort of adults with treatment-naïve chronic hepatitis B virus (HBV) infection, with and without HIV coinfection, as well as with acute HBV infection. Over 117 enrollment and 47 longitudinal FNAs (at 1 year follow-up), we established participant acceptability and safety. We also demonstrated the quality of the material through single cell RNA sequencing of selected enrollment FNAs, which revealed a range of immune cells. This approach can drive new insights into HBV immunology, informing cure strategies, and can improve our understanding of HBV natural history in Africa.

Longitudinal Evaluation of Antibody Persistence in Mother-Infant Dyads After Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Pregnancy.

BACKGROUND: There are limited data on how coronavirus disease 2019 (COVID-19) severity, timing of infection, and subsequent vaccination impact transplacental transfer and persistence of maternal and infant antibodies. METHODS: In a longitudinal cohort of pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, maternal/infant sera were collected at enrollment, delivery/birth, and 6 months. Anti-SARS-CoV-2 spike immunoglobulin (Ig)G, IgM, and IgA were measured by enzyme-linked immunosorbent assay. RESULTS: Two-hundred fifty-six pregnant women and 135 infants were enrolled; 148 maternal and 122 neonatal specimens were collected at delivery/birth; 45 maternal and 48 infant specimens were collected at 6 months. Sixty-eight percent of women produced all anti-SARS-CoV-2 isotypes at delivery (IgG, IgM, IgA); 96% had at least 1 isotype. Symptomatic disease and vaccination before delivery were associated with higher maternal IgG at labor and delivery. Detectable IgG in infants dropped from 78% at birth to 52% at 6 months. In the multivariate analysis evaluating factors associated with detectable IgG in infants at delivery, significant predictors were 3rd trimester infection (odds ratio [OR] = 4.0), mild/moderate disease (OR = 4.8), severe/critical disease (OR = 6.3), and maternal vaccination before delivery (OR = 18.8). No factors were significant in the multivariate analysis at 6 months postpartum. CONCLUSIONS: Vaccination in pregnancy post-COVID-19 recovery is a strategy for boosting antibodies in mother-infant dyads.

Hepatitis C Guidance 2023 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection.

The Infectious Diseases Society of America and the American Association for the Study of Liver Diseases have collaboratively developed evidence-based guidance regarding the diagnosis, management, and treatment of hepatitis C virus (HCV) infection since 2013. A panel of clinicians and investigators with extensive infectious diseases or hepatology expertise specific to HCV infection periodically review evidence from the field and update existing recommendations or introduce new recommendations as evidence warrants. This update focuses on changes to the guidance since the previous 2020 published update, including ongoing emphasis on recommended universal screening; management recommendations for incomplete treatment adherence; expanded eligibility for simplified chronic HCV infection treatment in adults with minimal monitoring; updated treatment and retreatment recommendations for children as young as 3 years old; management and treatment recommendations in the transplantation setting; and screening, treatment, and management recommendations for unique and key populations.

Perspectives on Adherence From the ACTG 5360 MINMON Trial: A Minimum Monitoring Approach With 12 Weeks of Sofosbuvir/Velpatasvir in Chronic Hepatitis C Treatment.

BACKGROUND: With the advent of efficacious oral direct-acting antivirals (DAAs) for hepatitis C virus (HCV), identification of characteristics associated with adherence is critical to treatment success. We examined correlates of sub-optimal adherence to HCV therapy in a single-arm, multinational, clinical trial. METHODS: ACTG A5360 enrolled HCV treatment-naive persons without decompensated cirrhosis from 5 countries. All participants received a 12-weeks course of sofosbuvir/velpatasvir at entry. In-person visits occurred at initiation and week 24, sustained virologic response (SVR) assessment. Adherence at week 4 was collected remotely and was dichotomized optimal (100%, no missed doses) versus sub-optimal (<100%). Correlates of sub-optimal adherence were explored using logistic regression. RESULTS: In total, 400 participants enrolled; 399 initiated treatment; 395/397 (99%) reported completing at week 24. Median age was 47 years with 35% female. Among the 368 reporting optimal adherence at week 4 SVR was 96.5% (95% confidence interval [CI] [94.1%, 97.9%]) vs 77.8% (95% CI [59.2%, 89.4%]) P value < .001. In the multivariate model age <30 years and being a US participant were independently associated with early sub-optimal adherence. Participants <30 years were 7.1 times more likely to have early sub-optimal adherence compared to their older counterparts. CONCLUSIONS: Self-reported optimal adherence at week 4 was associated with SVR. Early self-reported adherence could be used to identify those at higher risk of treatment failure and may benefit from additional support. Younger individuals <30 years may also be prioritized for additional adherence support. Clinical Trials Registration. NCT03512210.

Long-term hepatitis B and liver outcomes among adults taking tenofovir-containing antiretroviral therapy for HBV/HIV coinfection in Zambia.

BACKGROUND: Long-term outcomes of tenofovir-containing antiretroviral therapy (ART) for HBV/HIV coinfection were evaluated in Zambia. METHODS: A prospective cohort of adults with HIV and hepatitis B surface antigen (HBsAg)-positivity was enrolled at ART (included tenofovir DF + lamivudine) initiation. On therapy, we ascertained HBV viral load (VL) non-suppression, ALT elevation, serologic end-points, progression of liver fibrosis, based on elastography, and hepatocellular carcinoma (HCC) incidence. We also described a subgroup (low HBV VL and no/minimal fibrosis at baseline) that, under current international guidelines, would not have been treated in the absence of their HIV infection. RESULTS: Among 289 participants, at ART start, median age was 34 years, 40·1% were women, median CD4 count was 191 cells/mm3, 44·2% were hepatitis B e antigen-positive, and 28·4% had liver fibrosis/cirrhosis. Over median 5.91 years of ART, 13·6% developed HBV viral non-suppression, which was associated with advanced HIV disease. ALT elevation on ART was linked with HBV VL non-suppression. Regression of fibrosis and cirrhosis were common, progression to cirrhosis was absent, and no cases of HCC were ascertained. HBsAg seroclearance was 9·4% at 2 and 15·4% at 5 years, with higher rates among patients with low baseline HBV replication markers. DISCUSSION: Reassuring long-term liver outcomes were ascertained during tenofovir-based ART for HBV/HIV coinfection in Zambia. Higher than expected HBsAg seroclearance during ART underscores the need to include people with HIV in HBV cure research.

Prevalence and determinants of hepatitis delta virus infection among HIV/hepatitis B-coinfected adults in care in the United States.

Hepatitis delta virus (HDV) infection increases the risk of liver complications compared to hepatitis B virus (HBV) alone, particularly among persons with human immunodeficiency virus (HIV). However, no studies have evaluated the prevalence or determinants of HDV infection among people with HIV/HBV in the US. We performed a cross-sectional study among adults with HIV/HBV coinfection receiving care at eight sites within the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) between 1996 and 2019. Among patients with available serum/plasma specimens, we selected the first specimen on or after their initial HBV qualifying test. All samples were tested for HDV IgG antibody and HDV RNA. Multivariable log-binomial generalized linear models were used to estimate prevalence ratios (PRs) with 95% CIs of HDV IgG antibody-positivity associated with determinants of interest (age, injection drug use [IDU], high-risk sexual behaviour). Among 597 adults with HIV/HBV coinfection in CNICS and available serum/plasma samples (median age, 43 years; 89.9% male; 52.8% Black; 42.4% White), 24/597 (4.0%; 95% CI, 2.4%-5.6%) were HDV IgG antibody-positive, and 10/596 (1.7%; 95% CI, 0.6%-2.7%) had detectable HDV RNA. In multivariable analysis, IDU was associated with exposure to HDV infection (adjusted PR = 2.50; 95% CI, 1.09-5.74). In conclusion, among a sample of adults with HIV/HBV coinfection in care in the US, 4.0% were HDV IgG antibody-positive, among whom 41.7% had detectable HDV RNA. History of IDU was associated with exposure to HDV infection. These findings emphasize the importance of HDV testing among persons with HIV/HBV coinfection, especially those with a history of IDU.

Performance of an automated deep learning algorithm to identify hepatic steatosis within noncontrast computed tomography scans among people with and without HIV.

PURPOSE: Hepatic steatosis (fatty liver disease) affects 25% of the world's population, particularly people with HIV (PWH). Pharmacoepidemiologic studies to identify medications associated with steatosis have not been conducted because methods to evaluate liver fat within digitized images have not been developed. We determined the accuracy of a deep learning algorithm (automatic liver attenuation region-of-interest-based measurement [ALARM]) to identify steatosis within clinically obtained noncontrast abdominal CT images compared to manual radiologist review and evaluated its performance by HIV status. METHODS: We performed a cross-sectional study to evaluate the performance of ALARM within noncontrast abdominal CT images from a sample of patients with and without HIV in the US Veterans Health Administration. We evaluated the ability of ALARM to identify moderate-to-severe hepatic steatosis, defined by mean absolute liver attenuation <40 Hounsfield units (HU), compared to manual radiologist assessment. RESULTS: Among 120 patients (51 PWH) who underwent noncontrast abdominal CT, moderate-to-severe hepatic steatosis was identified in 15 (12.5%) persons via ALARM and 12 (10%) by radiologist assessment. Percent agreement between ALARM and radiologist assessment of absolute liver attenuation <40 HU was 95.8%. Sensitivity, specificity, positive predictive value, and negative predictive value of ALARM were 91.7% (95%CI, 51.5%-99.8%), 96.3% (95%CI, 90.8%-99.0%), 73.3% (95%CI, 44.9%-92.2%), and 99.0% (95%CI, 94.8%-100%), respectively. No differences in performance were observed by HIV status. CONCLUSIONS: ALARM demonstrated excellent accuracy for moderate-to-severe hepatic steatosis regardless of HIV status. Application of ALARM to radiographic repositories could facilitate real-world studies to evaluate medications associated with steatosis and assess differences by HIV status.

Predictive Algorithm for Hepatic Steatosis Detection Using Elastography Data in the Veterans Affairs Electronic Health Records.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) has reached pandemic proportions. Early detection can identify at-risk patients who can be linked to hepatology care. The vibration-controlled transient elastography (VCTE) controlled attenuation parameter (CAP) is biopsy validated to diagnose hepatic steatosis (HS). We aimed to develop a novel clinical predictive algorithm for HS using the CAP score at a Veterans' Affairs hospital. METHODS: We identified 403 patients in the Greater Los Angeles VA Healthcare System with valid VCTEs during 1/2018-6/2020. Patients with alcohol-associated liver disease, genotype 3 hepatitis C, any malignancies, or liver transplantation were excluded. Linear regression was used to identify predictors of NAFLD. To identify a CAP threshold for HS detection, receiver operating characteristic analysis was applied using liver biopsy, MRI, and ultrasound as the gold standards. RESULTS: The cohort was racially/ethnically diverse (26% Black/African American; 20% Hispanic). Significant positive predictors of elevated CAP score included diabetes, cholesterol, triglycerides, BMI, and self-identifying as Hispanic. Our predictions of CAP scores using this model strongly correlated (r = 0.61, p < 0.001) with actual CAP scores. The NAFLD model was validated in an independent Veteran cohort and yielded a sensitivity of 82% and specificity 83% (p < 0.001, 95% CI 0.46-0.81%). The estimated optimal CAP for our population cut-off was 273.5 dB/m, resulting in AUC = 75.5% (95% CI 70.7-80.3%). CONCLUSION: Our HS predictive algorithm can identify at-risk Veterans for NAFLD to further risk stratify them by non-invasive tests and link them to sub-specialty care. Given the biased referral pattern for VCTEs, future work will need to address its applicability in non-specialty clinics. Proposed clinical algorithm to identify patients at-risk for NAFLD prior to fibrosis staging in Veteran.

Using Serologic Testing to Assess the Effectiveness of Outbreak Control Efforts, Serial Polymerase Chain Reaction Testing, and Cohorting of Positive Severe Acute Respiratory Syndrome Coronavirus 2 Patients in a Skilled Nursing Facility.

We characterized serology following a nursing home outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) where residents were serially tested by reverse-transcription polymerase chain reaction (RT-PCR) and positive residents were cohorted. When tested 46-76 days later, 24 of 26 RT-PCR-positive residents were seropositive; none of the 124 RT-PCR-negative residents had confirmed seropositivity, supporting serial SARS-CoV-2 RT-PCR testing and cohorting in nursing homes.

Hepatotoxicity and Liver-Related Mortality in Women of Childbearing Potential Living With Human Immunodeficiency Virus and High CD4 Cell Counts Initiating Efavirenz-Containing Regimens.

BACKGROUND: Severe hepatotoxicity in people with human immunodeficiency virus (HIV) receiving efavirenz (EFV) has been reported. We assessed the incidence and risk factors of hepatotoxicity in women of childbearing age initiating EFV-containing regimens. METHODS: In the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, ART-naive pregnant women with HIV and CD4 count ≥ 350 cells/µL and alanine aminotransferase ≤ 2.5 the upper limit of normal were randomized during the antepartum and postpartum periods to antiretroviral therapy (ART) strategies to assess HIV vertical transmission, safety, and maternal disease progression. Hepatotoxicity was defined per the Division of AIDS Toxicity Tables. Cox proportional hazards models were constructed with covariates including participant characteristics, ART regimens, and timing of EFV initiation. RESULTS: Among 3576 women, 2435 (68%) initiated EFV at a median 121.1 weeks post delivery. After EFV initiation, 2.5% (61/2435) had severe (grade 3 or higher) hepatotoxicity with an incidence of 2.3 (95% confidence interval [CI], 2.0-2.6) per 100 person-years. Events occurred between 1 and 132 weeks postpartum. Of those with severe hepatotoxicity, 8.2% (5/61) were symptomatic, and 3.3% (2/61) of those with severe hepatotoxicity died from EFV-related hepatotoxicity, 1 of whom was symptomatic. The incidence of liver-related mortality was 0.07 (95% CI, .06-.08) per 100 person-years. In multivariable analysis, older age was associated with severe hepatotoxicity (adjusted hazard ratio per 5 years, 1.35 [95% CI, 1.06-1.70]). CONCLUSIONS: Severe hepatotoxicity after EFV initiation occurred in 2.5% of women and liver-related mortality occurred in 3% of those with severe hepatotoxicity. The occurrence of fatal events underscores the need for safer treatments for women of childbearing age.

Protease inhibitor-based direct-acting antivirals are associated with increased risk of aminotransferase elevations but not hepatic dysfunction or decompensation.

BACKGROUND & AIMS: Cases of acute liver injury (ALI) have been reported among chronic HCV-infected patients receiving protease inhibitor (PI)-based direct-acting antiviral (DAA) regimens, but no analyses have compared the risk of ALI in patients receiving PI- vs. non-PI-based DAAs. Thus, we compared the risk of 3 ALI outcomes between patients (by baseline Fibrosis-4 [FIB-4] group) receiving PI-based or non-PI-based DAAs. METHODS: We conducted a cohort study of 18,498 patients receiving PI-based DAA therapy (paritaprevir/ritonavir/ombitasvir±dasabuvir, elbasvir/grazoprevir, glecaprevir/pibrentasvir) matched 1:1 on propensity score to those receiving non-PI-based DAAs (sofosbuvir/ledipasvir, sofosbuvir/velpatasvir) in the 1945-1965 Veterans Birth Cohort (2014-2019). During exposure to DAA therapy, we determined development of: i) alanine aminotransferase (ALT) >200 U/L, ii) severe hepatic dysfunction (coagulopathy with hyperbilirubinemia), and iii) hepatic decompensation. We used Cox regression to determine hazard ratios (HRs) with 95% CIs for each ALI outcome within groups defined by baseline FIB-4 (≤3.25; >3.25). RESULTS: Among patients with baseline FIB-4 ≤3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR 3.98; 95% CI 2.37-6.68), but not severe hepatic dysfunction (HR 0.67; 95% CI 0.19-2.39) or hepatic decompensation (HR 1.01; 95% CI 0.29-3.49), compared to those receiving non-PI-based regimens. For those with baseline FIB-4 >3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR, 2.15; 95% CI 1.09-4.26), but not severe hepatic dysfunction (HR, 1.23 [0.64-2.38]) or hepatic decompensation (HR, 0.87; 95% CI 0.41-1.87), compared to those receiving non-PI-based regimens CONCLUSION: While risk of incident ALT elevations was increased in those receiving PI-based DAAs in both FIB-4 groups, the risk of severe hepatic dysfunction and hepatic decompensation did not differ between patients receiving PI- or non-PI-based DAAs in either FIB-4 group. LAY SUMMARY: Cases of liver injury have been reported among patients treated with protease inhibitor-based direct-acting antivirals for hepatitis C infection, but it is not clear if the risk of liver injury among people starting these drugs is increased compared to those starting non-protease inhibitor-based therapy. In this study, patients receiving protease inhibitor-based treatment had a higher risk of liver inflammation than those receiving a non-protease inhibitor-based treatment, regardless of the presence of pre-treatment advanced liver fibrosis/cirrhosis. However, the risk of severe liver dysfunction and decompensation were not higher for patients treated with protease inhibitor-based regimens.

Barriers to hepatitis C direct-acting antiviral therapy among HIV/hepatitis C virus-coinfected persons.

BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have increased hepatitis C virus (HCV) treatment opportunities for vulnerable HIV/HCV coinfected persons. The aim of this study was to identify the frequency of and potential barriers to DAA prescription in HIV/HCV patients during the first few years of DAA availability in the United States. METHODS: The AIDS Healthcare Foundation electronic medical record system was queried to identify all HCV viremic HIV-infected patients in care at AIDS Healthcare Foundation Healthcare centers in January 2015-August 2017 and compare characteristics by receipt of a DAA prescription. Multivariate logistic regression analyses were conducted to examine factors associated with DAA prescription. RESULTS: Of 826 eligible patients, 355 (43%) were prescribed a DAA; among those not prescribed a DAA, 301 (64%) had well-controlled HIV (HIV RNA ≤ 200 copies per mL). In multivariate logistic regression analysis, patients with a history of substance use (odds ratio [OR], 0.51 [95% confidence interval 0.35-0.73]) or on select HIV antiretroviral regimens were less likely to be prescribed a DAA. Those who had well-controlled HIV (OR, 5.03 [3.06-8.27]), CD4 + T cell count >200 cells per mm3 (OR, 1.85 [1.04-3.30]), estimated glomerular filtration rate >60 mL/min/1.73 m2 (OR, 3.32 [1.08-10.15]), or established care prior to January 2015 (OR, 1.57 [1.08-2.29] were more likely to be prescribed a DAA. CONCLUSIONS: In addition to lack of HIV suppression, select antiretroviral regimens, substance use, and kidney disease appeared to limit DAA prescription in the early interferon-free DAA era. Many were not prescribed DAAs despite HIV suppression. Further research is needed to determine if the observed associations persist today.

High Rates of Hepatitis B Virus (HBV) Functional Cure Among Human Immunodeficiency Virus-HBV Coinfected Patients on Antiretroviral Therapy in Zambia.

Among 284 human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected adults starting tenofovir-based antiretroviral therapy (ART) in Zambia, median baseline CD4+ count was 202 cells/mm3 and 41.6% were hepatitis B e-antigen positive. Within 2 years of therapy, 29 (10.2%) participants experienced HBV functional cure (confirmed loss of hepatitis B surface antigen). In multivariable analysis, baseline CD4 count <350 cells/mm3, female sex, and lower baseline HBV deoxyribonucleic acid were associated with increased odds of functional cure. Immune recovery during HIV-HBV treatment with ART may drive higher rates of functional cure than during HBV monoinfection treatment. Understanding the mechanisms underlying this phenomenon could inform immunomodulatory therapies for HBV cure.

Hepatitis C Virus (HCV) Direct-Acting Antiviral Therapy in Persons With Human Immunodeficiency Virus-HCV Genotype 1 Coinfection Resulting in High Rate of Sustained Virologic Response and Variable in Normalization of Soluble Markers of Immune Activation.

BACKGROUND: Hepatitis C virus (HCV) direct-acting antivirals are highly effective. Less is known about changes in markers of immune activation in persons with human immunodeficiency virus (HIV) in whom a sustained virologic response (SVR) is achieved. METHODS: We conducted a nonrandomized clinical trial of 12 or 24 weeks of paritaprevir-ritonavir-ombitasvir plus dasabuvir (PrOD) with or without ribavirin in persons with HCV-1/HIV coinfection suppressed with antiretroviral therapy. Plasma HCV, soluble CD14 (sCD14), interferon-inducible protein 10, soluble CD163 (sCD163), interleukin 6 (IL-6), interleukin 18, monocyte chemoattractant protein (MCP-1), autotaxin (ATX), and Mac2-binding protein (Mac2BP) were measured over 48 weeks. RESULTS: Participants were treated with PrOD for 12 (n = 9) or 24 (n = 36) weeks; the SVR rate at 12 weeks was 93%. At baseline, cirrhosis was associated with higher ATX and MCP-1, female sex with higher ATX and IL-6, older age with higher Mac2BP, higher body mass index with higher ATX, and HIV-1 protease inhibitor use with higher sCD14 levels. In those with SVR, interferon-inducible protein 10, ATX, and Mac2BP levels declined by week 2, interleukin 18 levels declined by the end of treatment, sCD14 levels did not change, and sCD163, MCP-1, and IL-6 levels changed at a single time point. CONCLUSIONS: During HIV/HCV coinfection, plasma immune activation marker heterogeneity is in part attributable to age, sex, cirrhosis, body mass index, and/or type of antiretroviral therapy. HCV treatment with paritaprevir-ritonavir-ombitasvir plus dasabuvir is highly effective and is associated with variable rate and magnitude of decline in markers of immune activation. CLINICAL TRIALS REGISTRATION: NCT02194998.

Opiate Dependence: A Risk Factor for Hepatitis B Virus Exposure in Homeless Adults.

The prevalence of hepatitis B virus (HBV) in the homeless population is underestimated despite multiple behavioral risks. Data from a sample of 534 homeless adults from downtown Los Angeles were analyzed to examine the prevalence and predictors of HBV infection in this community. The prevalence of HBV was 7 to 10 times higher than in the US general population rate. Opiate dependence, injection and noninjection use, was an independent predictor of HBV exposure. Testing and counseling occurred at significantly lower rates for HBV than for human immunodeficiency virus. Findings emphasize the need to enhance screening and counseling in homeless communities and other populations with opiate use.

Universal Screening of Pregnant Women for Hepatitis C: The Time Is Now.

The epidemiology of hepatitis C virus (HCV) has changed significantly over the last decade. Once most prevalent among older adults, the current burden has disproportionately affected young adults including women of childbearing age (WOCA). The Society for Maternal-Fetal Medicine recently issued guidelines that made no change in the recommendation to screen pregnant women based on risk factors. The current burden in young adults including WOCA supports a change in strategy away from risk-based screening to universal HCV screening in pregnancy. Universal screening offers several advantages that position us for a future where HCV treatment in pregnancy can happen and offers us progress toward the elimination of HCV.

Significance and Management of Isolated Hepatitis B Core Antibody (Anti-HBc) in HIV and HCV: Strategies in the DAA Era.

PURPOSE OF REVIEW: The purpose of this review is to summarize the prevalence and clinical implications of the isolated anti-HBc serologic profile in HIV-infected individuals. We highlight the rare but important issue of HBV reactivation in the setting of HCV therapy and describe an approach to management. RECENT FINDINGS: The isolated anti-HBc pattern, a profile that most often indicates past exposure to HBV with waning anti-HBs immunity, is found commonly in HIV-infected individuals, particularly those with HCV. Some large cohort studies demonstrate an association with advanced liver disease, while others do not. Conversely, meta-analyses have found an association between occult HBV infection (a component of the isolated anti-HBc pattern) and advanced liver disease and hepatocellular carcinoma in HIV-uninfected individuals. In HIV-uninfected individuals with anti-HBc positivity, HBV reactivation has been reported in patients receiving HCV therapy. This phenomenon is likely the result of disinhibition of HBV with HCV eradication. In HIV-infected patients, the long-term liver outcomes associated with the isolated anti-HBc pattern remain to be fully elucidated, supporting the need for large cohort studies with longitudinal follow-up. HBV reactivation during HCV DAA therapy has been well-described in HIV-uninfected cohorts and can inform algorithms for the screening and management of the isolated anti-HBc pattern in this population.