It is not standard practice to treat patients with acute hepatitis C virus (HCV) infection. However, as the incidence of HCV in the United States continues to rise, it may be time to re‐evaluate ...acute HCV management in the era of direct‐acting antiviral (DAA) agents. In this study, a microsimulation model was developed to analyze the trade‐offs between initiating HCV therapy in the acute versus chronic phase of infection. By simulating the lifetime clinical course of patients with acute HCV infection, we were able to project long‐term outcomes such as quality‐adjusted life years (QALYs) and costs. We found that treating acute HCV versus deferring treatment until the chronic phase increased QALYs by 0.02 and increased costs by $483 in patients not at risk of transmitting HCV. The resulting incremental cost‐effectiveness ratio was $19,991 per QALY, demonstrating that treatment of acute HCV was cost‐effective using a willingness‐to‐pay threshold of $100,000 per QALY. In patients at risk of transmitting HCV, treating acute HCV became cost‐saving, increasing QALYs by 0.03 and decreasing costs by $3,655. Conclusion: Immediate treatment of acute HCV with DAAs can improve clinical outcomes and be highly cost‐effective or cost‐saving compared with deferring treatment until the chronic phase of infection. If future studies continue to demonstrate effective HCV cure with shorter 6‐week treatment duration, then it may be time to revisit current HCV guidelines to incorporate recommendations that account for the clinical and economic benefits of treating acute HCV in the era of DAAs. (Hepatology 2018;67:837–846)
BACKGROUNDAlcohol-related liver disease is the leading indication for liver transplantation in the USA. After remaining stable for over three decades, the number of deaths due to alcohol-related ...liver disease has been increasing as a result of increased high-risk drinking. We aimed to project trends in alcohol-related cirrhosis and deaths in the USA up to 2040 and assess the effect of potential changes in alcohol consumption on those trends. METHODSIn this modelling study, we developed a multicohort state-transition (Markov) model of high-risk alcohol drinking patterns and alcohol-related liver disease in high-risk drinking populations born in 1900-2016 in the USA projected up to 2040. We used data from the National Epidemiologic Survey on Alcohol and Related Conditions, National Institute of Alcohol Abuse and Alcoholism, US National Death Index, National Vital Statistics System, and published studies. We modelled trends in alcohol-related liver disease under three projected scenarios: the status quo scenario, in which current trends continued; a moderate intervention scenario, in which trends in high-risk drinking reduced to 2001 levels under some hypothetical moderate intervention; and a strong intervention, in which trends in high-risk drinking decreased by 3·5% per year under some hypothetical strong intervention. The primary outcome was to project deaths associated with alcohol-related liver disease from 2019 to 2040 for each pattern of alcohol consumption under the different scenarios. FINDINGSOur model closely reproduced the observed trends in deaths due to alcohol-related liver disease from 2005 to 2018. Under the status quo scenario, age-standardised deaths due to alcohol-related liver disease are expected to increase from 8·23 (95% uncertainty interval UI 7·92-9·29) per 100 000 person-years in 2019 to 15·20 (13·93-16·19) per 100 000 person-years in 2040, and from 2019 to 2040, 1 003 400 (95% CI 896 800-1 036 200) people are projected to die from alcohol-related liver disease, resulting in 1 128 400 (1 113 200-1 308 400) DALYs by 2040. Under the moderate intervention scenario, age-standardised deaths due to alcohol-related liver disease would increase to 14·49 (95% UI 12·55-14·57) per 100 000 person-years by 2040, with 968 100 (95% UI 845 600-975 900) individuals projected to die between 2019 and 2040-35 300 fewer deaths than under the status quo scenario (a 3·5% decrease). Whereas, under the strong intervention scenario, age-standardised deaths due to alcohol-related liver disease would peak at 8·65 (95% UI 8·12-9·51) per 100 000 person-years in 2024 and decrease to 7·60 (6·96-8·10) per 100 000 person-years in 2040, with 704 300 (95% CI 632 700-731 500) individuals projected to die from alcohol-related liver disease in the USA between 2019 and 2040-299 100 fewer deaths than under the status quo scenario (a 29·8% decrease). INTERPRETATIONWithout substantial changes in drinking culture or interventions to address high-risk drinking, the disease burden and deaths due to alcohol-related liver disease will worsen in the USA. Additional interventions are urgently needed to reduce mortality and morbidity associated with alcohol-related liver disease. FUNDINGAmerican Cancer Society and the Robert Wood Johnson Health Policy Research Fellowship.
Summary
Background
The hepatitis C virus (HCV) care cascade has changed dramatically following the introduction of direct‐acting anti‐virals (DAAs). Up‐to‐date estimates of the cascade are needed to ...monitor progress, identify key gaps and inform policy.
Aim
To estimate the current and future HCV care cascade in the United States, nationally and in select subpopulations of interest.
Methods
We used a previously validated mathematical model to simulate the landscape of HCV in the United States from 2011 onwards, accounting for HCV screening policy updates, newer HCV treatments and rising HCV incidence.
Results
By the end of 2018, of 4.29 million HCV persons alive, 2.71 million (63%) were actively viremic, 2.24 million (52%) aware and 1.58 million (37%) cured. By 2030, under the status quo, of 3.65 million HCV persons alive, 1.88 million (51%) would be viremic, 2.25 million (62%) aware and 1.77 million (49%) cured. The HCV care cascade in 2018 differed substantially by subpopulation: of 1.34 million incarcerated HCV persons, 96% were viremic, 36% aware and 4% cured; of 0.87 million HCV persons in Medicare, 31% were viremic, 72% aware and 69% cured; and of 0.37 million HCV persons in Medicaid, 49% were viremic, 54% aware and 51% cured. Implementing universal screening, providing unrestricted treatment and controlling HCV incidence were factors found to have the largest effect on improving the HCV care cascade.
Conclusions
Since the launch of DAAs, the HCV care cascade has shifted towards higher awareness and treatment rates; however, additional interventions are needed to move towards HCV elimination.
Under current guidelines, hepatitis C virus (HCV)‐positive livers are not transplanted into HCV‐negative recipients because of adverse posttransplant outcomes associated with allograft HCV infection. ...However, HCV can now be cured post‐LT (liver transplant) using direct‐acting antivirals (DAAs) with >90% success; therefore, HCV‐negative patients on the LT waiting list may benefit from accepting HCV‐positive organs with preemptive treatment. Our objective was to evaluate whether and in which HCV‐negative patients the potential benefit of accepting an HCV‐positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov‐based mathematical model that simulated a virtual trial of HCV‐negative patients on the LT waiting list to compare long‐term outcomes in patients: (1) willing to accept any (HCV‐negative or HCV‐positive) liver versus (2) those willing to accept only HCV‐negative livers. Patients receiving HCV‐positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV‐negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV‐negative livers resulted in an increase in life expectancy when Model for End‐Stage Liver Disease (MELD) was ≥20, and the benefit was highest at MELD 28 (0.172 additional life‐years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV‐positive donor organ rates, that is, Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust. Conclusion: Transplanting HCV‐positive livers into HCV‐negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. (Hepatology 2018;67:2085‐2095).
Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective ...was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance.
We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance.
In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in ‘very early’/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in ‘very early’/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis.
Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis.
Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.
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•The value of lifelong surveillance for HCC in individuals after SVR is not known.•Ultrasound-based bi-annual surveillance for HCC appears to be cost-effective up to age 75 in those with cirrhosis.•This surveillance strategy was cost effective up to age 60 in those with stable advanced fibrosis.•Compared with no surveillance, surveillance detected 86 additional HCCs in ‘very early’/early stage per 1,000 patients with cirrhosis.
Alcohol‐related liver disease (ALD) is the leading indication for liver transplantation worldwide. Since Mathurin et al. described their experience in providing early liver transplantation for ...patients with ALD in 2011, other centers have followed suit with generally favorable survival outcomes. This patient population poses a unique clinical challenge given the expedited nature of the evaluation and the lack of any significant sobriety period prior to transplantation. The SALT (Sustained Alcohol Use Post‐Liver Transplant) score is a standardized psychometric tool increasingly used to help stratify the risk of relapse and guide listing decisions for these challenging clinical situations. In 2018, our center introduced a protocol for early liver transplantation for acute alcohol‐related hepatitis (AAH). In this article, we offer a retrospective review of 26 patients transplanted between May 2018 and May 2021, including at least 1‐year follow‐up, and compare outcomes to initial SALT scores; we further identify additional factors that may impact post‐transplant success. As transplant committees continue to weigh the ethical dilemma of denying lifesaving treatment against the obligation to remain stewards of a limited resource, we aim to contribute to a more nuanced understanding of risk regarding early transplantation for ALD.
Early liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of ...sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH.
We developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease MELD and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant.
Patients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50–0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores.
In a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increase in life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate the benefits of early transplantation. Strategies are needed to prevent and treat posttransplantation use of alcohol.
Liver transplantation (LT) for alcohol-associated hepatitis (AH) is a relatively new practice and limited work exists surrounding the role social determinants of health may play in evaluation. This ...includes language that defines how patients interact with the healthcare system. We explored characteristics of patients with AH evaluated for LT within an integrated health system.
Using a system-wide registry, we identified admissions for AH from 1 January 2016 to 31 July 2021. A multivariable logistic regression model was developed to evaluate independent predictors of LT evaluation.
Among 1723 patients with AH, 95 patients (5.5%) underwent evaluation for LT. Evaluated patients were more likely have English as their preferred language (95.8% vs 87.9%, P = 0.020), and had higher INR (2.0 vs 1.4, P < 0.001) and bilirubin (6.2 vs 2.9, P < 0.001). AH patients who underwent evaluation had a lower burden of mood and stress disorders (10.5% vs 19.2%, P < 0.05). Patients with English preferred language had a greater than three times adjusted odds of LT evaluation compared with all others when adjusting for clinical disease severity, insurance status, sex, and psychiatric comorbid conditions (OR, 3.20; 95% CI, 1.14-9.02).
Patients with AH evaluated for LT were more likely to have English as their preferred language, more psychiatric comorbidities, and more severe liver disease. Despite adjustment for psychiatric comorbidities and disease severity, English preferred language remained the strongest predictor of evaluation. As programs expand LT for AH, it is vital to build equitable systems that account for the interaction between language and healthcare in transplantation.
Background
The demand for transplantable kidneys continues to outstrip supply, and the risk of donor‐derived infection limits utilization. The effect of donor or recipient HBV status, defined by ...surface antigen (HBsAg) positivity, on long‐term survival outcomes of kidney transplant (KT) is unknown.
Methods
We conducted a retrospective cohort study based on Organ Procurement and Transplantation Network (OPTN) data from 2000 to 2019. We identified three cohorts based on donor (D) or recipient (R) HBsAg status: D–R, D–R+, and D+R–. Pairwise comparisons of patient survival (PS) and all‐cause graft survival (GS) after propensity score matching were performed to assess the effect of HBV infection in KT recipients.
Results
Our findings showed that there were no statistically significant differences in PS and GS among D–R, D–R+, and D+R–groups, nor was the patient or GS different between donor and recipient HBsAg+ status. Finally, in 2019 kidney discard rates were 15% higher for HBsAg+ deceased donors compared to HBsAg– donors.
Conclusions
HBsAg+ status was not associated with worse PS or GS after KT. Prior to broadly advocating utilization of HbsAg+ kidneys, further studies assessing KT recipient morbidity and safety are necessary.
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