Considerations in gender-affirming hormone therapy in transgender and gender diverse patients undergoing liver transplantation.

Liver transplantation is lifesaving for patients with end-stage liver disease. Similar to the role of transplantation for patients with end-stage liver disease, gender-affirming hormone therapy (GAHT) can be lifesaving for transgender and gender diverse (TGGD) patients who experience gender dysphoria. However, management of such hormone therapy during the perioperative period is unknown and without clear guidelines. Profound strides can be made in improving care for TGGD patients through gender-affirming care and appropriate management of GAHT in liver transplantation. In this article, we call for the transplant community to acknowledge the integral role of GAHT in the care of TGGD liver transplant candidates and recipients. We review the current literature and describe how the transplant community is ethically obligated to address this health care gap. We suggest tangible steps that clinicians may take to improve health outcomes for this minoritized patient population.

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.

Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee.

BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.

White paper on antimicrobial stewardship in solid organ transplant recipients.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a "one-size-fits-all" style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Simultaneous Heart-Liver Transplantation for Congenital Heart Disease in the United States: Rapidly Increasing With Acceptable Outcomes.

BACKGROUND AND AIMS: There are more adults than children living with congenital heart disease (CHD) in the United States, with a growing proportion requiring heart-liver transplantation (HLT). Our aim was to ascertain the frequency, outcomes, and prognostic factors in this patient population. APPROACH AND RESULTS: United Network for Organ Sharing data on adult patients who underwent heart transplantation (HT) from 2009 through March 2020 were analyzed. The primary study outcome was patient survival. Cox proportional-hazards modeling assessed for mortality associations. There were 1,084 HT recipients: 817 (75.4%) CHD HTs only, 74 (6.8%) CHD HLTs, 179 (16.5%) non-CHD HLTs, and 14 (1.3%) heart-liver-kidney transplants. The number of CHD HLTs increased from a prior rate of 4/year to 21/year in 2019. Among patients with CHD, the 5-year survival rates were 74.1% and 73.6% in HTs only and HLTs, respectively (P = 0.865). There was a higher rate of allograft failure attributable to rejection in CHD HTs only compared with CHD HLTs (3.2% versus 0.4%; P = 0.014). Only 25 out of 115 HT-performing hospitals undertook CHD HLTs. Higher-volume centers (averaging one CHD HLT per year) had a 5-year patient survival rate of 83.0% compared with 61.3% in lower-volume centers (P = 0.079). Among HLT recipients, total bilirubin (hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.01-1.12) and diabetes (HR = 2.97, 95% CI = 1.21-7.31) were independently associated with increased mortality risk, whereas CHD and age were not. CONCLUSIONS: The rate of HLT for adult CHD in the United States is rising dramatically. The survival outcomes between CHD HT only and CHD HLT groups are comparable; however, the HLT group had lower rates of acute rejection. Among HLT recipients, diabetes and elevated bilirubin are associated with increased posttransplant mortality risk. An average of one CHD HLT per year could be considered a minimum quality metric at transplant centers.

Liver transplantation for alcoholic hepatitis in the United States: Excellent outcomes with profound temporal and geographic variation in frequency.

Medical-refractory severe alcoholic hepatitis (AH) has a high mortality. The national frequency, longer term outcomes and regional practices of AH liver transplantation (LT) in the United States are not well described, despite the increasing mortality from alcohol-associated liver disease. We analyzed the trends in frequency and outcomes of UNOS data on 39 455 adult patients who underwent LT from 2014 to 2019, including AH LT recipients. LTs for AH increased 5-fold, from 28 in 2014 to 138 in 2019, varying 8-fold between UNOS regions. Three transplant centers accounted for 50%-90% of AH LTs within each region. The number of transplant centers performing AH LTs increased from 14 in 2014 to 47 in 2019. AH patients were younger (mean = 39.4 years), had higher MELD scores (mean = 36.8), and were more often on dialysis (46.0%) and in ICU (38.4%), compared to other indications (all P < .05). One- and 5-year graft survivals for AH LT recipients were 91.7% and 81.9%, respectively. The frequency of AH LT is increasing rapidly, with excellent medium-term outcomes. An impact of AH recurrence on patient or graft survival is not apparent in this national analysis. There are marked geographic variations in practices, highlighting the lack of selection criteria standardization.

Viral hepatitis: Guidelines by the American Society of Transplantation Infectious Disease Community of Practice.

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of viral hepatitis in the pre- and post-transplant period. The current guidelines reflect the declining need for hepatitis B immunoglobulin following liver transplant, now replaced with nucleos(t)ide analogues that effectively suppress viral replication for the long term with minimal risk for drug resistance. It describes the limitations of pegylated interferon alpha in the treatment for chronic hepatitis D. The guidelines feature the paradigm shift in the treatment arena of chronic hepatitis C, now consisting of highly effective direct-acting antiviral (DAA) medications that effect a cure almost universally. Its safety profile and easy tolerance have permitted its use in patients with decompensated cirrhosis and/or end-stage renal disease. The high potency of the DAA's has fueled the rapidly expanding utilization of hepatitis C-exposed grafts in non-hepatitis C-infected liver, heart, or kidney recipients within structured protocols, followed by viral eradication with DAA therapy in the peri- or post-transplant period. Chronic hepatitis E has become more recognized in the solid-organ transplant recipients, and the therapeutic approach has been streamlined to start with reduction of immunosuppression, and if indicated afterward, ribavirin monotherapy.

Barriers to ideal outcomes after pediatric liver transplantation.

Long-term survival for children who undergo LT is now the rule rather than the exception. However, a focus on the outcome of patient or graft survival rates alone provides an incomplete and limited view of life for patients who undergo LT as an infant, child, or teen. The paradigm has now appropriately shifted to opportunities focused on our overarching goals of "surviving and thriving" with long-term allograft health, freedom of complications from long-term immunosuppression, self-reported well-being, and global functional health. Experts within the liver transplant community highlight clinical gaps and potential barriers at each of the pretransplant, intra-operative, early-, medium-, and long-term post-transplant stages toward these broader mandates. Strategies including clinical research, innovation, and quality improvement targeting both traditional as well as PRO are outlined and, if successfully leveraged and conducted, would improve outcomes for recipients of pediatric LT.

A Comparison Between Community and Academic Practices in the USA in the Management of Chronic Hepatitis B Patients Receiving Entecavir: Results of the ENUMERATE Study.

BACKGROUND AND AIMS: The management of chronic hepatitis B patients is not well characterized in real-world practice. We compared baseline characteristics of CHB patients on entecavir, the frequency of on-treatment monitoring, and the effectiveness of ETV treatment between academic and community practices. METHODS: Treatment-naïve CHB patients ≥18 years old, treated with ETV for ≥12 months from 2005 to 2013, in 26 community and academic practices throughout the USA were retrospectively evaluated. RESULTS: Of 841 patients enrolled, 658 (65% male, 83% Asian, median age 47, 9% with cirrhosis) met inclusion criteria. Half of the patients (52%) were from community practices. A lower percentage of patients in community practices had cirrhosis or liver cancer (5 vs. 14%). Community practices more often treated patients with baseline ALT < 2 × ULN. Over a median follow-up of 4 years, community practices were more likely to discontinue ETV with less frequent laboratory monitoring compared to academic practices. The 5-year cumulative probability of ALT normalization was greater among patients treated in community practices (70 vs. 50%, p < 0.001), but the 5-year cumulative probability of undetectable HBV DNA was lower (45 vs. 70%, p < 0.001) than those treated in academic practices. CONCLUSION: Academic practices saw CHB patients with more advanced liver disease, more often followed AASLD guidelines, and monitored patients on ETV treatment more frequently than community practices. While patients in community practices were less likely to achieve undetectable HBV DNA and more likely to achieve ALT normalization, the rates of HBeAg loss and seroconversion as well as HBsAg loss were similar.

Direct-acting antiviral regimens are safe and effective in the treatment of hepatitis C in simultaneous liver-kidney transplant recipients.

Hepatitis C (HCV) remains the single most common etiology of end-stage liver disease leading to simultaneous liver/kidney transplant (SLKT) and has worse post-transplant survival compared to non-HCV patients. We aim to assess the effectiveness and tolerance of the all-oral direct-acting antiviral (DAA) agents with or without ribavirin (RBV) in the treatment of HCV recurrence post-SLKT. Thirty-four patients were studied retrospectively, composed predominantly of treatment-naïve (73.5%) non-Caucasian (61.8%) males (82.4%) infected with genotype 1a (64.7%). 94.1% reached a sustained virologic response (SVR) after 24 weeks (32/34 patients), without difference between 12 and 24 weeks of therapy. 64.7% had no clinical side effects. Three deaths occurred, all unrelated to treatment. One patient had liver rejection; tacrolimus was increased and prednisone was initiated while HCV treatment was continued and the patient ultimately achieved SVR. No liver graft losses. No kidney rejection or losses. We demonstrated that DAA combinations with or without RBV result in a remarkable SVR rate and tolerated in the majority of the studied SLKT patients. It is safe to wait to treat until post-kidney transplant and therefore increase the donor pool for these patients. Our cohort is ethnically diverse, making our results generalizable.

An interferon-free antiviral regimen for HCV after liver transplantation.

BACKGROUND: Hepatitis C virus (HCV) infection is the leading indication for liver transplantation worldwide, and interferon-containing regimens are associated with low response rates owing to treatment-limiting toxic effects in immunosuppressed liver-transplant recipients. We evaluated the interferon-free regimen of the NS5A inhibitor ombitasvir coformulated with the ritonavir-boosted protease inhibitor ABT-450 (ABT-450/r), the nonnucleoside NS5B polymerase inhibitor dasabuvir, and ribavirin in liver-transplant recipients with recurrent HCV genotype 1 infection. METHODS: We enrolled 34 liver-transplant recipients with no fibrosis or mild fibrosis, who received ombitasvir-ABT-450/r (at a once-daily dose of 25 mg of ombitasvir, 150 mg of ABT-450, and 100 mg of ritonavir), dasabuvir (250 mg twice daily), and ribavirin for 24 weeks. Selection of the initial ribavirin dose and subsequent dose modifications for anemia were at the investigator's discretion. The primary efficacy end point was a sustained virologic response 12 weeks after the end of treatment. RESULTS: Of the 34 study participants, 33 had a sustained virologic response at post-treatment weeks 12 and 24, for a rate of 97% (95% confidence interval, 85 to 100). The most common adverse events were fatigue, headache, and cough. Five patients (15%) required erythropoietin; no patient required blood transfusion. One patient discontinued the study drugs owing to adverse events after week 18 but had a sustained virologic response. Blood levels of calcineurin inhibitors were monitored, and dosages were modified to maintain therapeutic levels; no episode of graft rejection was observed during the study. CONCLUSIONS: Treatment with the multitargeted regimen of ombitasvir-ABT-450/r and dasabuvir with ribavirin was associated with a low rate of serious adverse events and a high rate of sustained virologic response among liver-transplant recipients with recurrent HCV genotype 1 infection, a historically difficult-to-treat population. (Funded by AbbVie; CORAL-I ClinicalTrials.gov number, NCT01782495.).

Gastrointestinal Manifestations of Autosomal-Dominant Polycystic Kidney Disease.

Autosomal-dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease, and the fourth most common cause of end-stage renal disease. ADPKD is a systemic disorder, associated with numerous extrarenal manifestations, including polycystic liver disease, the most common gastrointestinal manifestation, and diverticular disease, inguinal, and ventral hernias, pancreatic cysts, and large bile duct abnormalities. All of these gastrointestinal manifestations play a significant role in disease burden in ADPKD, particularly in the later decades of life. Thus, as ADPKD becomes more recognized, it is important for gastroenterologists to be knowledgeable of this monogenic disorder's effects on the digestive system.

Biopsy Specimens From Allograft Liver Contain Histologic Features of Hepatitis C Virus Infection After Virus Eradication.

BACKGROUND & AIMS: Most patients, even those who have received a liver transplant, achieve a sustained virologic response (SVR) to therapy for hepatitis C virus (HCV) infection. Little is known about the histologic features of liver biopsy specimens collected after SVR, particularly in patients who have received a liver transplant. We aimed to better characterize the histologic features of allograft liver biopsy specimens from patients who achieved SVR to anti-HCV therapy after liver transplantation. METHODS: We performed a retrospective analysis of 170 allograft liver biopsy specimens from 36 patients who received a liver transplant for chronic HCV infection, had recurrent HCV infection after transplantation, and subsequently achieved SVR (collected from 1999 through 2015 at 4 medical centers). SVR was defined as an undetectable serum HCV RNA level 24 weeks after completion of HCV treatment. A total of 65 biopsy specimens were post-SVR (at least 1 post-SVR from each patient; some biopsy specimens were collected at later time points from a subset of patients). We performed polymerase chain reaction analysis for HCV RNA on a subset of the biopsy specimens (28 collected before SVR and 32 after SVR). RESULTS: Of the 65 post-SVR biopsy specimens, 45 (69%) had histologic features of active HCV infection. Of the initial post-SVR biopsy specimens collected from each of the 36 patients, 32 (89%) showed these changes. For patients with more than 1 post-SVR biopsy specimen, 6 (46%) had no change in fibrosis between biopsies, and fibrosis worsened for 3 patients (23%) based on their most recent biopsy. The HCV RNA level was undetectable in 31 of the 32 biopsy specimens analyzed by polymerase chain reaction. CONCLUSIONS: In a retrospective analysis of allograft liver biopsy specimens from patients who achieved SVR after a liver transplant for chronic HCV infection, histologic changes associated with active HCV were present in 69% and fibrosis continued to progress in 23%, despite the lack of detection of HCV RNA. Pathologists should be aware of patients' SVR status when analyzing liver biopsy specimens to avoid diagnoses of chronic HCV-associated hepatitis. Because of the persistent inflammatory activity and fibrosis after SVR, clinicians should continue to monitor patients carefully after SVR to anti-HCV therapy.

Novel educational interventions in residency increase knowledge of chronic liver disease and career interest in hepatology.

There is an increasing burden of chronic liver disease (CLD) in the United States but a significant shortage of hepatologists. Thus, it is necessary to develop new recruitment strategies to the field of hepatology as well as ensure that non-gastroenterology-trained physicians are able to capably assist in the care of CLD. We established a novel, nonelective, inpatient hepatology rotation that uses required modules in the American Association for the Study of Liver Diseases Curriculum and Training-First Hepatitis B and C curriculums as well as in LiverLearning. A paper-based anonymous assessment was distributed to the inaugural 25 postgraduate years 2 and 3 internal medicine residents before and after the 2-week rotation over the course of 1 year. Both the prerotation and postrotation assessments included validated multiple-choice questions and Likert-type questions, which evaluated self-perceived knowledge and comfort with managing CLD. The mean comfort level (1 = not at all comfortable/strongly disagree, 5 = very comfortable/strongly agree) of managing several common liver diseases increased significantly after completion of the rotation (i.e., cirrhosis 2.8 versus 3.8, P < 0.001; hepatitis B 2.4 versus 3.4, P = 0.001; hepatitis C 2.6 versus 3.7, P = 0.002; nonalcoholic steatohepatitis 3.0 versus 4.0, P < 0.001; liver transplant care 2.1 versus 3.4, P < 0.001). There was also a significantly increased interest in hepatology as a career (2.6 versus 3.0, P = 0.03). Finally, the mean percentage of multiple-choice questions answered correctly on the pretest was 62% and posttest was 77% (P = 0.02). CONCLUSION: Our novel curriculum and nonelective hepatology rotation has effectively demonstrated improvement in internal medicine residents' comfort with and knowledge of CLD, and increased career interest in hepatology was also observed after completion of the curriculum, which suggests that more exposure to CLD could positively impact recruitment to the workforce; larger, multicenter studies are needed to validate these results. (Hepatology 2016;64:2210-2218).

Accepting Hearts From Hepatitis C-Positive Donor: Can We Expand the Donor Pool?

BACKGROUND: Until recently, transplantation from hepatitis C-positive donors was relatively contraindicated as eradication of active hepatitis C previously required an interferon-based regimen that has been associated with rejection in solid organ transplantation. New interferon-free treatment regimens for hepatitis C have fewer adverse events and higher cure rates than interferon-based regimens. Interferon-free regimens have been shown to be safe in the liver transplantation literature, but little is known about the safety and efficacy of treatment in heart transplantation. CASE DESCRIPTION AND DISCUSSION: Here we report a case of successful eradication of hepatitis C with a non-interferon-based regimen using ledipasvir-sofosbuvir following combined orthotopic heart and liver transplantation. Based on the prevalence of hepatitis C in the general population, inclusion of hepatitis C-positive donors for heart transplantation can expand this component of the donor pool 3- to 6-fold. CONCLUSIONS: In carefully selected patients and recipients, inclusion of hepatitis C-positive donors may allow for expansion of the donor pool.

Opioid and opioid substitution therapy in liver transplant candidates: A survey of center policies and practices.

This national survey sought to determine the practices and policies pertaining to opioid and opioid substitution therapy (OST) use in the selection of liver transplant (LT) candidates. Of 114 centers, 61 (53.5%) responded to the survey, representing 49.2% of the LT volume in 2016. Only two programs considered chronic opioid (1 [1.6%]) or OST use (1 [1.6%]) absolute contraindications to transplant, while 63.9% and 37.7% considered either one a relative contraindication, respectively. The majority of programs did not have a written policy regarding chronic opioid use (73.8%) or OST use (78.7%) in LT candidates. Nearly half (45.9%) of centers agreed that there should be a national consensus policy addressing opioid and OST use. The majority of responding LT centers did not consider opioid or OST use in LT candidates to be absolute contraindications to LT, but there was significant variability in center practices. These surveys also demonstrated a lack of written policies in the assessment of the candidacy of such patients. The results of our survey identify an opportunity to develop a national consensus statement regarding opioid and OST use in LT candidates to bring greater uniformity and equity into the selection of LT candidates.

A case of Q fever after liver transplantation.

Coxiella burnetii, the causative agent of Q fever, is a zoonosis that causes both acute and chronic disease in humans. Few cases have been reported in solid organ transplant recipients, and this case highlights the need to include Q fever in the differential diagnosis for fever of unknown origin in solid organ transplant hosts.

Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study.

OBJECTIVES: Data from the United States are lacking regarding the impact of entecavir (ETV) on the risk of hepatocellular carcinoma (HCC). Our aim is to determine whether treatment with ETV is associated with a reduced HCC risk by calculating the expected HCC incidence based on the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model and comparing it with the observed HCC incidence. METHODS: The incidence of HCC in US patients treated with ETV between 2005 and 2013 in a retrospective cohort was obtained. The predicted HCC incidence was calculated using the REACH-B model. The standardized incidence ratios (SIRs) were calculated as a ratio of observed over predicted HCC cases. RESULTS: Of 841 patients, 646 (65% male, 84% Asian, median age 47 years, 36% hepatitis B e antigen positive, 9.4% with cirrhosis) met the inclusion criteria. Over a median follow-up of 4 years, 17 (2.6%) cases of HCC were diagnosed, including 8 out of 61 (13.1%) patients with cirrhosis and 9 out of 585 (1.5%) without cirrhosis. Compared with those without HCC, the 17 patients with HCC were older at 53 years vs. 47 years and more likely to have cirrhosis at 47.1% vs. 8.4%. Among patients without cirrhosis, the observed HCC incidence was significantly lower than predicted by the fourth year (SIR, 0.37; 95% confidence interval: 0.166-0.82). A sensitivity analysis that comprised all patients, including those with cirrhosis, showed that at the maximum follow-up time of 8.2 years, a significantly lower than predicted HCC incidence was noted with an SIR of 0.56 (95% confidence interval: 0.35-0.905). CONCLUSIONS: Based on the REACH-B model, long-term ETV therapy was associated with a lower than predicted HCC incidence. However, the risk of HCC persisted, and careful HCC surveillance remains warranted despite the anti-viral treatment.