Revaccination for Hepatitis B in Previous Nonresponders Following Hepatitis C Eradication.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) do not respond to hepatitis B virus (HBV) vaccination as efficiently as the general population. We assessed if revaccination after HCV treatment resulted in improved response. METHODS: Previous HBV vaccine nonresponders were prospectively recruited for revaccination after HCV eradication. Hepatitis B surface antibody (HBsAb) testing was performed 1 month after series completion. RESULTS: Follow-up HBsAb testing was performed in 31 of 34 enrolled patients with 21 (67.7%) reactive results. There were no significant differences in HBsAb reactivity based on age, sex, race, or advanced fibrosis presence. CONCLUSIONS: HBV vaccine nonresponders should be considered for revaccination following HCV cure.

Long-term outcomes of a decentralized, nurse-led, statewide model of care for hepatitis C among people in prison in Victoria, Australia.

BACKGROUND: Prisons provide a key strategic opportunity to upscale hepatitis C testing and treatment in a high prevalence setting and are crucial for elimination efforts. METHODS: A decentralized, statewide nurse-led model of care offering hepatitis C treatment for people in prison was implemented in Victoria, Australia in 2015. The program provides hepatitis C care to all 14 adult prison sites in the jurisdiction. We prospectively evaluated treatment uptake between 1 November 2015 and 31 December 2021. Data on all people in prison treated were recorded in a clinical database. The primary outcomes were i) total number of people in prison with hepatitis C treated; ii) total number of DAA treatment courses. RESULTS: 3,133 DAA treatment courses were prescribed to 2,768 people in prison. The proportion of total Victoria DAA prescriptions the program was responsible for increased from 6% in 2016 to a peak of 23% in 2020. Of those treated, median age was 39 years, 91% were male and 9% had cirrhosis. Few (20%) had previously engaged in hepatitis C care in the community and at first treatment course in prison, only 6% had previously accessed hepatitis C treatment. Complete follow up data were available for 1,757/2,768 (63%) treated, with 1,627/1,757 (93%) achieving SVR12. CONCLUSIONS: A decentralized, nurse-led, statewide model of care was highly effective in treating large numbers of people in prison with hepatitis C and achieved high rates of SVR12. Nurse-led prison programs are playing a crucial role in eliminating hepatitis C as a public health threat in Australia.

Multivisceral transplantation utilizing hepatitis C virus-viremic donors for hepatitis C virus-negative recipients.

The advent of highly effective and well-tolerated direct-acting antiviral therapy has made it more feasible to transplant hepatitis C virus (HCV)-infected organs into HCV-negative recipients. This case report presents the outcomes of 4 patients who underwent multivisceral transplantation from HCV-nucleic acid test (NAT)-viremic donors, with 1 recipient also requiring a kidney transplant. All recipients received posttransplant direct-acting antiviral therapy with sofosbuvir/velpatasvir (SOF/VEL [Epclusa]). By the fourth week of therapy, none of the recipients exhibited detectable viral loads, and all achieved sustained virologic response at 12 weeks. Allograft function for HCV D+/R- recipients remained excellent throughout follow-up. One recipient died from posttransplant lymphoproliferative disorder and another developed end-stage renal disease; both outcomes were ostensibly unrelated to HCV-donor status. The other 2 patients are progressing well without any evidence of allograft rejection.

Outcomes of early vs late treatment initiation in solid organ transplantation from hepatitis C virus nucleic acid test-positive donors to hepatitis C virus-uninfected recipients: Results from the HCV-TARGET study.

Curative hepatitis C virus (HCV) therapy has increased transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients (D+/R-). We evaluated outcomes of early and late HCV treatment among D+/R- nonliver organ transplants. Patients received HCV regimens per local standard (n = 10 sites). Outcomes were compared between early and late treatments. Early treatment regimens (ETR) (n = 56) were initiated pretransplantation to day 7 posttransplant. Late treatment regimens (LTRs) (n = 102) began median 31 (range, 8-114) days posttransplant. There were 79 kidney, 50 lung, 23 heart, and 6 mixed transplants, similar between groups. HCV RNA was quantifiable in 98% of LTR versus 44.6% of ETR recipients (P < .001). Mean (range) days on treatment were 28 (7-93) ETR and 81 (51-111) LTR (P < .0001). There were no virological failures with ETR, but relapse (n = 3) and nonresponse (n = 2) in LTR (P = .16), including fibrosing cholestatic hepatitis postrelapse (n = 1). Sustained virological response was 100% (95% confidence interval, 93.4-100.0) in ETR (n = 54) and 94.9% (95% confidence interval, 88.5-98.3) in LTR (n = 98). Acute rejection occurred in 11 (19.6%) ETR and 25 (24.5%) LTR. In total, 11 HCV-unrelated deaths occurred: 8 ETR and 3 LTR. Organ transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients was safe. ETR led to fewer virological failures with shorter treatment duration, supporting recommendations to initiate treatment promptly posttransplant.

Risk of de novo HCC in patients with MASLD following direct-acting antiviral-induced cure of HCV infection.

BACKGROUND & AIMS: Data are limited on the risk of de novo hepatocellular carcinoma (HCC) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) after achieving sustained virologic response (SVR12) using direct-acting antivirals (DAAs) for hepatitis C virus (HCV). METHODS: 1598 eligible patients received biannual alpha-fetoprotein (AFP) and liver imaging surveillance to detect de novo HCC beyond achieving SVR12. MASLD was defined as presence of controlled attenuation parameter (CAP) ≥ 248 dB/m and ≥ one cardiometabolic risk factor (CMRF). Cumulative HCC incidence was compared between patients with/without MASLD. We built univariable and multivariable Cox proportional hazards models to evaluate factors associated with HCC. Sensitivity analysis was performed using the Fine-Gray subdistribution hazards model. Additionally, we evaluated the mediation effect of MASLD on CMRFs and of CMRFs on MASLD for HCC using mediation analysis with bootstrapping. RESULTS: The incidence rate of HCC was 1.44 per 100 person-years of follow-up (PYFU) [95% confidence interval (CI): 1.19-1.74]. Patients with MASLD had a higher cumulative HCC incidence than those without MASLD (log-rank test, p < 0.001). Multivariable Cox regression analysis revealed that in addition to age, sex, LSM, platelet count, and AFP, MASLD (adjusted hazard ratio (aHR): 2.07 [95% CI:1.36-3.16], p < 0.001) was independently associated with HCC. This finding was confirmed by the Fine-Gray model, which showed a subdistribution HR (sHR) of 2.07 (95% CI: 1.34-3.19, p < 0.001) for MASLD. MASLD significantly mediated CMRFs for HCC development. CONCLUSION: After achieving SVR12, patients with MASLD exhibited an increased HCC risk compared to those without MASLD. Vigilant HCC surveillance and control of CMRFs to mitigate the effect MASLD on HCC remain crucial for this population. IMPACT AND IMPLICATIONS: The risk of de novo HCC among patients with MASLD, a novel nomenclature of steatotic liver disease (SLD), after the attaining of SVR12 using DAAs remains to be confirmed. In this study recruiting 1598 patients in Taiwan, individuals with MASLD exhibited approximately a two-fold increased risk of de novo HCC, compared to those without MASLD after achieving SVR12. MASLD significantly mediated CMRFs for HCC development. Our findings underscore the critical importance of pharmacological interventions and proactive lifestyle modifications to control CMRFs in patients with MASLD, as well as the need for vigilant HCC surveillance to ensure favorable outcomes following HCV eradication.

Single-cell atlas of the liver myeloid compartment before and after cure of chronic viral hepatitis.

BACKGROUND & AIMS: Chronic viral infections present serious public health challenges; however, direct-acting antivirals (DAAs) are now able to cure nearly all patients infected with hepatitis C virus (HCV), representing the only cure of a human chronic viral infection to date. DAAs provide a valuable opportunity to study immune pathways in the reversal of chronic immune failures in an in vivo human system. METHODS: To leverage this opportunity, we used plate-based single-cell RNA-seq to deeply profile myeloid cells from liver fine needle aspirates in patients with HCV before and after DAA treatment. We comprehensively characterised liver neutrophils, eosinophils, mast cells, conventional dendritic cells, plasmacytoid dendritic cells, classical monocytes, non-classical monocytes, and macrophages, and defined fine-grained subpopulations of several cell types. RESULTS: We discovered cell type-specific changes post-cure, including an increase in MCM7+STMN1+ proliferating CD1C+ conventional dendritic cells, which may support restoration from chronic exhaustion. We observed an expected downregulation of interferon-stimulated genes (ISGs) post-cure as well as an unexpected inverse relationship between pre-treatment viral load and post-cure ISG expression in each cell type, revealing a link between viral loads and sustained modifications of the host's immune system. We found an upregulation of PD-L1/L2 gene expression in ISG-high neutrophils and IDO1 expression in eosinophils, pinpointing cell subpopulations crucial for immune regulation. We identified three recurring gene programmes shared by multiple cell types, distilling core functions of the myeloid compartment. CONCLUSIONS: This comprehensive single-cell RNA-seq atlas of human liver myeloid cells in response to cure of chronic viral infections reveals principles of liver immunity and provides immunotherapeutic insights. CLINICAL TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT02476617). IMPACT AND IMPLICATIONS: Chronic viral liver infections continue to be a major public health problem. Single-cell characterisation of liver immune cells during hepatitis C and post-cure provides unique insights into the architecture of liver immunity contributing to the resolution of the first curable chronic viral infection of humans. Multiple layers of innate immune regulation during chronic infections and persistent immune modifications after cure are revealed. Researchers and clinicians may leverage these findings to develop methods to optimise the post-cure environment for HCV and develop novel therapeutic approaches for other chronic viral infections.

The role of treatment of hepatitis C with direct-acting antiviral agents on glycaemic control in diabetic patients: An updated systematic review and meta-analysis.

Recent studies suggested that successful clearance of chronic Hepatitis C Virus (HCV) by using direct-acting antiviral (DAA) agents could improve glycemic control in patients with diabetes; however, some studies failed to identify this benefit. We conducted a systematic review and meta-analysis to assess the impact of sustained virologic response (SVR) after treatment with DAA agents on glycemic control. Embase, Scopus and PubMed were searched through March 26th, 2023, for all studies evaluating whether eradication of HCV infection with DAAs is associated with an impact on glycemic control. Only studies with data on glycemic control, including haemoglobin A1c (HbA1c), fasting glucose, or Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), at least 12-week post-SVR were included. Sixteen studies met our eligibility criteria and were included in qualitative analysis. The mean HbA1c was 8.05% (95% CI: 7.79%-8.31%) before treatment and 7.19% (95% CI: 6.98%-7.39%) after treatment. There was a significant mean absolute reduction in HbA1c of 0.72% (95% CI: 0.52%-0.93%) with high heterogeneity between studies (I2 = 91.7%). The reduction in HbA1c remained significant in the subgroup analysis at 3 months follow up post SVR [0.74% (95% CI: 0.57%-0.91%)] and at least 6 months follow up [0.66% (95% CI: 0.23%-1.10%)]. We found a significant reduction in HbA1C after SVR in patients with type 2 diabetes mellitus, reflecting better glycemic control with HCV eradication. This data highlights an important extrahepatic benefit of HCV eradication.

Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving fixed-dose pangenotypic direct-acting antivirals.

Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving fixed-dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0-98.9) and 100% (95% CI: 66.4-100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed-dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9-100] vs. 97.1% [95% CI: 96.2-97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12 among patients with HCV who are treated with fixed-dose pangenotypic DAAs.

Hepatitis C virus-induced differential transcriptional traits in host cells after persistent infection elimination by direct-acting antivirals in cell culture.

Chronic hepatitis C virus infection (HCV) causes liver inflammation and fibrosis, leading to the development of severe liver disease, such as cirrhosis or hepatocellular carcinoma (HCC). Approval of direct-acting antiviral drug combinations has revolutionized chronic HCV therapy, with virus eradication in >98% of the treated patients. The efficacy of these treatments is such that it is formally possible for cured patients to carry formerly infected cells that display irreversible transcriptional alterations directly caused by chronic HCV Infection. Combining differential transcriptomes from two different persistent infection models, we observed a major reversion of infection-related transcripts after complete infection elimination. However, a small number of transcripts were abnormally expressed in formerly infected cells. Comparison of the results obtained in proliferating and growth-arrested cell culture models suggest that permanent transcriptional alterations may be established by several mechanisms. Interestingly, some of these alterations were also observed in the liver biopsies of virologically cured patients. Overall, our data suggest a direct and permanent impact of persistent HCV infection on the host cell transcriptome even after virus elimination, possibly contributing to the development of HCC.

Hepatitis C treatment outcome among people in prison: The SToP-C study.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) burden is higher among people in prison given high prevalence of injecting drug use. This study evaluated direct-acting antiviral (DAA) treatment outcome in prisons. METHODS: The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study enrolled individuals incarcerated in four Australian prisons (2017-2019). Participants with detectable HCV RNA were offered sofosbuvir-velpatasvir for 12 weeks. Sustained virological response (SVR) was assessed in intention-to-treat (ITT; participants commencing treatment and due for SVR assessment before study close) and per-protocol (PP; participants with documented treatment completion and SVR assessment) populations. RESULTS: Among 799 participants with HCV, 324 (41%) commenced treatment (94% male; median age, 32 years; median duration of incarceration, 9 months). In ITT population (n = 310), 201 had documented treatment completion (65% [95% CI: 59-70]), and 137 achieved SVR (ITT-SVR: 44% [95% CI: 39-50]). In PP population (n = 143), 137 achieved SVR (PP-SVR: 96% [95% CI: 91-98]). Six participants had quantifiable HCV RNA at SVR assessment from treatment failure (n = 2) or reinfection (n = 4). Release or inter-prison transfer was common reasons for no documented treatment completion (n = 106/109 [97%]) and no SVR assessment (n = 57/58 [98%]). In ITT analysis, longer incarceration was associated with increased SVR (adjusted OR per month 1.03 [95% CI: 1.01-1.04]). CONCLUSION: Among participants who completed DAA treatment and were assessed for SVR, treatment outcome was consistent with non-prison clinical studies. However, most individuals did not complete treatment or lacked study-documented treatment outcome due to release or transfer. Strategies to accommodate dynamic prisoner populations are required to ensure continuity of HCV care, including treatment completion and post-treatment care.

Viral eradication reduces all-cause mortality in patients with chronic hepatitis C virus infection who had received direct-acting antiviral therapy.

BACKGROUND AND AIMS: The impact of hepatitis C virus (HCV) eradication via direct-acting antiviral (DAA) therapy on overall mortality, particularly non-liver-related mortality, is understudied. METHODS: We recruited 4180 patients with chronic HCV infection who achieved sustained virological response (SVR) (HCV eradication) through DAA therapy (n = 2501, SVR group) or who did not receive antiviral therapy (n = 1679, non-SVR group); 1236 from each group were chosen using propensity score matching. Causes of death and all-cause mortality, including non-liver-related diseases, were investigated. RESULTS: Of the 4180 patients, 592 died during the follow-up period. In the SVR group, the mortality rates from liver-related and non-liver-related diseases were 16.5% and 83.5%, respectively. Compared to the non-SVR group, mortality rates from liver-related and non-liver-related diseases were 50.1% and 49.9%, respectively (p < .001). In non-cirrhotic patients, multivariable analysis revealed that SVR was an independent factor associated with both liver-related (hazard ratio [HR], .251; 95% confidence interval [CI], .092-.686) and non-liver-related (HR, .641; 95% CI, .415-.990) mortalities. In cirrhotic patients, multivariable analysis revealed that SVR remained an independent factor significantly associated with liver-related mortality (HR, .151; 95% CI, .081-.279). In propensity score-matched patients, the eradication of HCV (SVR group) decreased both liver-related (p < .001) and non-liver-related mortality (p = .008) rates compared to persistent HCV infection (non-SVR group). CONCLUSIONS: The elimination of HCV via DAA therapy reduced not only liver-related mortality but also non-liver-related mortality in patients with chronic HCV.

Exploring current and emerging therapies for porphyrias.

Porphyrias are rare, mostly inherited disorders resulting from altered activity of specific enzymes in the haem synthesis pathway that lead to accumulation of pathway intermediates. Photocutaneous symptoms occur when excess amounts of photoreactive porphyrins circulate in the blood to the skin, whereas increases in potentially neurotoxic porphyrin precursors are associated with neurovisceral symptoms. Current therapies are suboptimal and their mechanisms are not well established. As described here, emerging therapies address underlying disease mechanisms by introducing a gene, RNA or other specific molecule with the potential to cure or slow progression of the disease. Recent progress in nanotechnology and nanoscience, particularly regarding particle design and formulation, is expanding disease targets. More secure and efficient drug delivery systems have extended our toolbox for transferring specific molecules, especially into hepatocytes, and led to proof-of-concept studies in animal models. Repurposing existing drugs as molecular chaperones or haem synthesis inhibitors is also promising. This review summarizes key examples of these emerging therapeutic approaches and their application for hepatic and erythropoietic porphyrias.

The oncologic burden of hepatitis C virus infection: A clinical perspective.

Answer questions and earn CME/CNE Chronic hepatitis C virus (HCV) infection affects millions of people worldwide and is associated with cancer. Direct-acting antivirals (DAAs) have changed HCV treatment paradigms, but little is known about the management of HCV infection in patients with cancer. The substantial burden of HCV infection and the inconclusive evidence regarding its detection and management in patients with cancer prompted the authors to review the literature and formulate recommendations. Patients for whom HCV screening is recommended included all patients with hematologic malignancies, hematopoietic cell transplantation candidates, and patients with liver cancer. There is a lack of consensus-based recommendations for the identification of HCV-infected patients with other types of cancer, but physicians may at least consider screening patients who belong to groups at heightened risk of HCV infection, including those born during 1945 through 1965 and those at high risk for infection. Patients with evidence of HCV infection should be assessed by an expert to evaluate liver disease severity, comorbidities associated with HCV infection, and treatment opportunities. DAA therapy should be tailored on the basis of patient prognosis, type of cancer, cancer treatment plan, and hepatic and virologic parameters. HCV-infected patients with cancer who have cirrhosis (or even advanced fibrosis) and those at risk for liver disease progression, especially patients with HCV-associated comorbidities, should have ongoing follow-up, regardless of whether there is a sustained virologic response, to ensure timely detection and treatment of hepatocellular carcinoma. HCV infection and its treatment should not be considered contraindications to cancer treatment and should not delay the initiation of an urgent cancer therapy. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:411-431. © 2017 American Cancer Society.

Evaluation of patients treated with direct-acting anti-viral therapy for chronic hepatitis C and their risk of hepatocellular carcinoma in Hong Kong.

BACKGROUND & AIM: To evaluate the risk of early hepatocellular carcinoma (HCC) in chronic hepatitis C patients treated with direct-acting antivirals (DAAs) in Hong Kong, as it has not been studied before in this locality. METHODS: Three hundred thirty-three consecutive chronic hepatitis C patients treated with DAAs from two hospitals over the past 6 years were identified. Kaplan-Meier method was used to calculate cumulative HCC incidence. Cox regression was used to identify factors associated with HCC development. RESULTS: During a median follow-up of 23.4 months after DAA started, 15 (5.4%, 95% CI 3.3-8.7%) out of 279 total included patients developed HCC. The overall sustained virological response (SVR) rate was 98.9%. The 1-year cumulative incidence for de-novo HCC and HCC recurrence were 0.8 and 30.9%, respectively (log-rank test p < 0.001). The 1-year cumulative HCC incidence for patients without and with cirrhosis were 0.7 and 5.1%, respectively (log-rank test p = 0.036). Univariate analysis showed that significant factors associated with HCC after DAA were: history of treated HCC, cirrhosis, evidence of portal hypertension, higher AFP at the start or end of DAA therapy, higher bilirubin, lower platelets, lower albumin, and older age. From receiver operating characteristic curve analysis, the optimal cut-off level of AFP for predicting HCC was 10.5 ng/mL at the start and 5.6 ng/mL at the end of DAA therapy. CONCLUSIONS: The risk of early HCC recurrence remains high despite achieving SVR following DAA therapy, whereas the risk of early de-novo HCC occurence is low. AFP levels, both at the start and end of DAA therapy, can be useful in stratifying risks of HCC development.

Efficacy and safety of direct-acting antiviral regimen for patients with hepatitis C virus genotype 2: a systematic review and meta-analysis.

BACKGROUND: Direct-acting antivirals (DAAs) show high cure rates in treating chronic hepatitis C virus (HCV). However, the effect of DAAs on patients infected with genotype 2 (GT2) is difficult to determine despite the availability of several DAA regimens. METHODS: A systematic search of six databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Clinicaltrial.gov) was conducted through April 20, 2022. We considered the sustained virological response 12 weeks after treatment (SVR12) as the efficacy outcome, and adverse events (AEs) as the safety outcome. By calculating the mean SVR12 and the proportion of AEs among patients, we considered the intervention effect for each DAA regimen. The random effect model was then used in all meta-analyses. This systematic review and meta-analysis aimed to summarize the evidence on efficacy and safety of DAAs in patients infected with HCV GT2. The Bayesian Markov Chain Monte Carlo (MCMC) network metanalysis was used to indirectly compare regimen in GT2 patients. RESULTS: Among 31 articles included (2,968 participants), consisting of 1,387 treatment-naive patients and 354 patients with cirrhosis. The overall pooled SVR12 rate was 94.62% (95% CI: 92.43-96.52%) among the participants who received all doses of treatment. Meta-analysis results of AEs revealed that fatigue was the most common AE (14.0%, 95% CI: 6.4-21.6%), followed by headache (13.1%, 95% CI: 9.2-17.1%), whereas death and serious adverse events were uncommon. CONCLUSIONS: We compared DAA-based treatments indirectly using meta-analysis and found the combination of Sofosbuvir plus Velpatasvir and Glecaprevir plus Pibrentasvir, each administered over a 12-week period, were identified as the most effective and relatively safe in managing chronic hepatitis C virus genotype 2 (HCV GT2) infection. Both treatments achieved a SVR12 of 100% (95% CI 99-100%).

Hepatitis B transmission/reactivation associated with Hepatitis B core antibody and Hepatitis C nucleic acid testing positive organs: A report from the Organ Procurement and Transplantation Network Disease Transmission Advisory Committee.

BACKGROUND: Better access to direct-acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation. AIM: To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy. METHODS: The number of HBcAb+ donors with delineated HCV NAT status was obtained from the Organ Procurement and Transplantation Network (OPTN) database. The number of unexpected HBV infections from transplanted organs adjudicated as "proven" or "probable" transmission was obtained from the OPTN Ad Hoc Disease Transmission Advisory Committee database. A chart review of the donors of "proven" or "probable" cases was conducted. RESULTS: From January 1, 2016, to December 31, 2021, 7735 organs were procured from 3767 HBcAb+ donors and transplanted into 7469 recipients; 545 (14.5%) donors were also HCV+. HBV transmission or reactivation occurred in seven recipients. The rate is not significantly different between recipients of HCV+ (0.18%, 2/1115) and the HCV NAT negative (HCV-) organs (0.08%, 5/6354) (p = 0.28) or between recipients of HCV+ and HCV- livers as well as non-liver organs. HBV transmission or reactivation occurred within a median of 319 (range, 41-1117) days post-transplant in the setting of missing, inadequate, or truncated prophylaxis. CONCLUSION: HBV reactivation associated with DAA therapy for HBcAb+ HCV+ organs is less frequent than reported in the non-transplant population, possibly due to the common use of HBV prophylaxis in the at-risk transplant population.

Real-world experience in treatment of donor-derived Hepatitis C virus in kidney transplant recipients with delayed initiation, shortened course glecaprevir/pibrentasvir versus standard of care.

BACKGROUND: There is limited literature describing the real-world practice of delayed initiation and shortened duration direct-acting antiviral (DAA) in kidney transplant recipients. We compared Hepatitis C virus (HCV) cure rates among kidney transplant recipients who received an HCV nucleic acid test positive (NAT +) kidney and were treated with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks or glecaprevir/pibrentasvir (G/P) for 8 weeks, a duration that is 4 weeks shorter than the guideline recommendation for treatment delay beyond 1-week post-transplant. METHODS: Retrospective study of HCV-negative adult patients who received a kidney transplant from an HCV NAT+ donor between April 2019 and April 2022 treated with either SOF/VEL for 12 weeks or G/P for 8 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy (SVR12). Secondary outcomes included time to DAA initiation, renal function, graft loss, patient death, liver function tests, and opportunistic infections. RESULTS: 102 kidney transplant recipients were included with 36 treated with G/P and 66 treated with SOF/VEL. All 36 (100%) treated with G/P achieved SVR12. One patient in the SOF/VEL group failed to achieve SVR12 but received additional therapy and was cured. Time to DAA initiation was similar with a mean of 4 weeks. There was no difference in AST/ALT > 3x ULN or renal function. One rejection occurred in each group. No patient death or graft loss was observed. There was no difference in cytomegalovirus and BK viremia between groups.  CONCLUSION: Delayed initiation of DAA therapy with 12 weeks of SOF/VEL or 8 weeks of G/P achieves SVR12 in kidney transplant recipients without significant adverse effects.

Natural history and clinical features of hepatitis C virus infection during childhood: A nationwide, observational survey in Japan.

AIM: Few data on spontaneous clearance rates of cases of mother-to-child transmission of hepatitis C viral (HCV) infection are available in Japan. Furthermore, the treatment courses of interferon-based and direct-acting antiviral agent (DAA) therapies for children are also unclear. Our aim was thus to clarify the long-term natural progression of HCV infection and the treatment outcomes of children in Japan. METHODS: We conducted a combined multicenter, observational survey involving 65 pediatric institutions in Japan. Pediatric HCV infection cases with patients born between 1973 and 2021 were collected over the 11-year period from 2012 to 2022. A total of 563 patients were enrolled, with 190 excluded for having insufficient laboratory data or treatment information, resulting in 373 eligible cases. RESULTS: Of 328 cases of mother-to-child infection, 34 (10.4%) had spontaneous clearance, with a median time to spontaneous clearance of 3.1 years (range 0.9-7.2 years). Of the total 373 eligible cases, 190 received antiviral therapy (interferon-based therapy, 158; DAA therapy, 32). Sustained virologic response rates after first-line treatment were 75.3% (119/158) and 100% (32/32) for interferon-based therapy and DAA therapy, respectively, with the DAA group showing a shorter time from therapy initiation to viral negativity (2.7 vs. 1.0 months; p = 0.0031). CONCLUSIONS: Approximately 10% of Japanese children infected by mother-to-child transmission achieve spontaneous resolution of HCV infection. Our findings indicate that DAA therapy is safe and highly effective in Japanese children, achieving higher sustained virologic response rates and shorter time to clearance of the virus compared with interferon-based therapy.

Metabolic management after sustained virologic response in elderly patients with hepatitis C virus: A multicenter study.

AIMS: Hepatocellular carcinoma (HCC) develops even in patients with hepatitis C virus (HCV) eradication by direct-acting antiviral agents. Fatty liver and metabolic dysfunction are becoming major etiologies of HCC. We aimed to evaluate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD), a new definition of steatotic liver disease, on the development of HCC after HCV eradication. METHODS: We enrolled 1280 elderly patients with HCV eradication and no history of HCC. We evaluated α-fetoprotein (AFP), Fibrosis-4 index and MASLD after 24 weeks of sustained virological response. Decision tree analysis was used to investigate factors associated with HCC development after HCV eradication. RESULTS: A total of 86 patients (6.7%) developed HCC during the follow-up period (35.8 ± 23.7 months). On multivariate analysis, serum AFP level (HR 1.08, CI 1.04-1.11, P = 0.0008), Fibrosis-4 index (HR 1.17, CI 1.08-1.26, P = 0.0007), and MASLD (HR 3.04, CI 1.40-6.58, P = 0.0125) at 24 weeks of sustained virological response were independent factors associated with HCC development. In decision tree analysis, the initial classifier for HCC development was AFP ≥7 ng/mL. However, in patients with AFP <7 ng/mL, MASLD, rather than Fibrosis-4 index, was the classifier for HCC development. No significant difference was observed in the cumulative incidence of HCC between patients with AFP ≥7 ng/mL and patients with AFP <7 ng/mL and MASLD. CONCLUSION: MASLD at 24 weeks of sustained virological response is a risk factor for HCC development in elderly patients with HCV eradication. Additionally, decision tree analysis revealed that MASLD was associated with HCC development, even in patients with serum AFP levels <7 ng/mL.

Magnetic resonance imaging-based risk factors of hepatocellular carcinoma after direct-acting antiviral therapy: A multicenter observational study.

AIM: To determine risk factors associated with hepatocellular carcinoma (HCC) development following direct-acting antiviral (DAA) therapy. METHODS: We enrolled patients with chronic hepatitis C who underwent direct-acting antiviral therapy and achieved sustained virologic response at 12 weeks between 2012 and 2018. Subsequently, patients were followed up. The primary endpoint was the development of HCC or the date of the last follow up when the absence of HCC was confirmed. Uni- and multivariate Cox proportional hazards models were used to identify factors contributing to HCC development, including gadoxetic acid-enhanced magnetic resonance imaging findings. The cumulative incidence rates of HCC development were calculated using the Kaplan-Meier method, and differences between groups were assessed using the log-rank test. RESULTS: The final study cohort comprised 482 patients (median age 70.5 years; 242 men). The median follow-up period was 36.8 months. Among 482 patients, 96 developed HCC (19.9%). The 1-, 3-, and 5-year cumulative rates of HCC development were 4.9%, 18.6%, and 30.5%, respectively. Multivariate analysis revealed that age, male sex, history of HCC, and hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were independent risk factors significantly associated with HCC development (p < 0.001-0.04). The highest risk group included patients with both a history of HCC and the presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement (the 1- and 3-year cumulative HCC development rates were 14.2% and 62.2%, respectively). CONCLUSION: History of HCC and presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were strong risk factors for HCC development following direct-acting antiviral therapy.