Downstaging Hepatocellular Carcinoma with Checkpoint Inhibitor Therapy Improves Access to Curative Liver Transplant.

PURPOSE: Liver transplantation is curative for hepatocellular carcinoma (HCC). Checkpoint inhibitor therapy (CPIT) has been used in unresectable HCC, but recent advances have demonstrated CPIT as an innovative method of downstaging advanced HCC with the caveat that CPIT prior to transplantation has risks including irreversible graft rejection. We report the outcomes of Mayo Clinic Arizona patients who underwent downstaging with CPIT. METHODS: This retrospective chart review was conducted for Mayo Clinic Arizona patients who were diagnosed with HCC who underwent downstaging with CPIT with the goal of meeting criteria for transplantation. RESULTS: We present nine cases with HCC outside Milan who underwent CPIT. Four received a transplant; one was delisted due to his exceptional therapeutic response. All received liver-directed therapy. Peak alpha-fetoprotein pre-CPIT ranged from 8-29,523 ng/mL, which decreased to 2.2-19.6 ng/mL on CPIT. CPIT included atezolizumab/bevacizumab, ipilimumab/nivolumab, nivolumab, and pembrolizumab; one patient received two regimens. CPIT was held prior to transplant at a median of 3 months. Three patients received methylprednisolone for immunosuppression induction; one received thymoglobulin. One patient developed acute cellular rejection at 5 weeks, 9 weeks, and 5 months post-transplant; given the late onset, these were not attributed to CPIT and were successfully treated. During an average follow-up of 16.5 months, no tumor recurrence has occurred. CONCLUSION: We describe nine patients with HCC outside Milan with inadequate response with liver-directed therapy, who achieved marked responses with CPIT, allowing for consideration of successful liver transplantation. Our case series supports the consideration of locoregional therapies and CPIT for downstaging to within transplant criteria.

Solid Organ Transplantation From SARS-CoV-2-infected Donors to Uninfected Recipients: A Single-center Experience.

BACKGROUND: The risk of donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in solid organ (heart, lung, liver, kidney, pancreas, and intestine) transplant recipients is poorly understood. Since hematogenous transmission of SARS-CoV-2 has not been documented to date, nonlung solid organs might be suitable for transplantation since they likely portend a low risk of viral transmission. METHODS: Abdominal solid organs from SARS-CoV-2-infected donors were transplanted into uninfected recipients. RESULTS: Between April 18, 2021, and October 30, 2021, we performed transplants of 2 livers, 1 simultaneous liver and kidney, 1 kidney, and 1 simultaneous kidney and pancreas from SARS-CoV-2-infected donors into 5 uninfected recipients. None of the recipients developed SARS-CoV-2 infection or coronavirus disease 2019, and when tested, allograft biopsies showed no evidence of SARS-CoV-2 RNA. CONCLUSIONS: Transplanting nonlung organs from SARS-CoV-2-infected donors into uninfected recipients demonstrated no evidence of virus transmission.

Expanding Treatment Access for Chronic Hepatitis C with Task-shifting in the Era of Direct-acting Antivirals.

In the United States, the fight to eradicate hepatitis C virus (HCV) infection has been ongoing for many years, but the results have been less than ideal. Historically, patients with chronic hepatitis C (CHC) were treated with interferon-based regimens, which were associated with frequent adverse effects, suboptimal response rates, and long durations of treatment - of up to 48 weeks. Expertise from specialist-physicians, such as hepatologists and gastroenterologists, was needed to closely follow patients on these medications so as to monitor laboratory values and manage adverse effects. However, the emergence of direct-acting antiviral (DAA) agents against HCV infection have heralded outstanding progress in terms of safety, tolerability, lack of adverse effects, efficacy, and truncated duration of therapy - 12 weeks or less - thereby making the need for close monitoring by specialist-physicians obsolete. With the recent approval of DAA agents by the Food and Drug Administration, the treatment model for CHC no longer relies on the limited number of specialist-physicians, which represented a major barrier to treatment access in the past, especially in underserved areas of the United States. We propose and share our experiences in adapting a task-shifting treatment model, one that utilizes a relatively larger pool of non-specialist healthcare providers, such as nursing staff (medical assistants, vocational licensed nurses, registered nurses, etc.) and advanced practice providers (nurse practitioners and physician assistants), to perform a variety of important clinical functions in an effort to make DAA-based antiviral therapy widely available against HCV infection. Most recently, task-shifting was implemented by the United States and World Health Organization in the fight against the human immunodeficiency virus and showed encouraging results. Based on our experiences in implementing this model at our outreach clinics, the majority of HCV-infected patients treated with DAA agents can be easily monitored by non-specialist healthcare providers and physician extenders. Task-shifting can effectively address one of the major rate-limiting factors in expanding treatment access for HCV infection.

Sofosbuvir-based Regimens with Task Shifting Is Cost-effective in Expanding Hepatitis C Treatment Access in the United States.

Background and Aims: The current paradigm of specialist physician-managed treatment of chronic hepatitis C virus infection (HCV) is inefficient in absorbing the approximately 3 million patients awaiting treatment in the United States. Task shifting-whereby specialist physicians screen patients for treatment eligibility but on-treatment monitoring is devolved to more abundant non-physician clinicians-achieves non-inferior treatment outcomes with second generation direct-acting antivirals (2nd Gen DAAs), may increase treatment capacity, and may facilitate greater treatment access. We determined the cost effectiveness of 2nd Gen DAAs with respect to interferon-based first-generation DAAs (1st Gen DAAs) within a task-shifted treatment model. Methods: Using a previously described decision-analytic Markov structure, we modeled a hypothetical cohort of 1,000 patients with HCV genotype 1 infection over a lifetime horizon, based upon our outreach clinic's HCV treatment protocol. Treatment-naïve and treatment-experienced HCV cohorts were modeled separately, based upon our outr8each clinic's demographics. Treatment response to 2nd Gen DAAs was modeled based on our outreach clinic's data. Adverse events, utility, costing, and transition probabilities were sourced from the literature. Results: Driven by improved effectiveness and safety, as well as an expected increase in treatment capacity, 2nd Gen DAAs treatment monitored by non-physician clinicians was projected to improve health outcomes and be dominant from a cost-effective perspective versus that of 1st Gen DAAs. Trends were consistent across all assessed patient subpopulations. Conclusions: Based on an assumption of increased treatment capacity accompanying a task-shifted treatment model, 2nd Gen DAAs-based treatment was cost effective and cost saving as compared to 1st Gen DAAs-based treatment for all HCV patient subgroups assessed.

The Role of e-Health in Optimizing Task-Shifting in the Delivery of Antiviral Therapy for Chronic Hepatitis C.

PURPOSE: Recently, we reported the successful application of task-shifting to improve the management of patients with chronic hepatitis C virus (HCV) infection receiving treatment with direct-acting antiviral (DAA) agents in underserved areas of California. We assessed the impact of e-health on task-shifting in our treatment model. METHODS: In a retrospective analysis, we reviewed the impact of e-health on optimizing the delivery of DAA-based regimen to HCV-infected patients in outreach clinics in medically underserved areas of California. A nonphysician healthcare provider worked in close conjunction with a hepatologist to monitor the patients during the course of antiviral therapy. We exclusively used our institution-based, secured e-health portal as the means of communication with the local staff and patients in outreach clinics. RESULTS: From January 2015 to June 2016, we treated over 100 HCV-infected patients with DAA-based regimens using the task-shifting model. During the study period, we did not experience any delay in the care of our patients undergoing treatment with DAA agents. Communication with the patient and staff using e-health was prompt, secured, and documented in electronic medical records. Due to the optimization of task-shifting by e-health and safety/tolerability of DAA, 95% patients did not need a follow-up clinic visit during the treatment. Return clinic visits during the treatment were unrelated to DAA use or associated with ribavirin-related anemia. In addition, we noted improvement in access and capacity of our outreach clinic. CONCLUSIONS: We report a positive impact of e-health in optimizing task-shifting for DAA in HCV-infected patients in underserved outreach clinics. More importantly, a secondary improvement in access and capacity of our clinic was noted.

Task-Shifting: An Approach to Decentralized Hepatitis C Treatment in Medically Underserved Areas.

BACKGROUND: Despite the availability of safe and effective direct-acting antiviral drugs (DAAs), the vast majority of patients with chronic hepatitis C (HCV) in the USA remain untreated, in part due to lack of access to specialist providers. AIMS: To determine the effectiveness of DAA-based treatment in medically underserved areas in California, in a healthcare model dependent on task-shifting--wherein a visiting hepatologist assesses patients for treatment eligibility, but subsequent routine follow-up evaluation of patients prescribed treatment is devolved to a part-time licensed vocational nurse under remote supervision of the hepatologist. METHODS: We retrospectively determined rates of sustained virologic response 12 weeks after treatment completion (SVR-12), adverse events, and treatment discontinuations in patients who received sofosbuvir-based DAA regimens between December 2013 and November 2014. RESULTS: Despite limited specialist provider involvement in medically underserved areas, all but two of 58 patients completed treatment, and 88 % of patients achieved the curative endpoint of undetectable HCV RNA 12 weeks after completing treatment (sustained virologic response, SVR-12). Almost 80 % of patients with cirrhosis and 85 % of patients with prior treatment experience achieved SVR-12. CONCLUSIONS: Treatment effectiveness with sofosbuvir-based regimens in medically underserved areas utilizing task-shifting from a specialist to a mid-level provider is comparable to those achieved in pivotal clinical trials for these regimens, and to "real-world" experiences of tertiary care centers in the USA.

Cholera toxin-specific memory B cell responses are induced in patients with dehydrating diarrhea caused by Vibrio cholerae O1.

BACKGROUND: Infection with Vibrio cholerae induces durable immunity against subsequent disease, a process hypothesized to reflect anamnestic immune responses at the intestinal mucosa. The presence of antigen-specific memory B cells may therefore be a more direct measure of protection than serum antibody responses. METHODS: We measured immunoglobulin (Ig) G memory B cells specific to cholera toxin B subunit (CTB) in 14 patients up to 90 days after V. cholerae O1 infection, by polyclonal stimulation of peripheral blood mononuclear cells followed by standard enzyme-linked immunospot assay. RESULTS: All patients generated CTB-specific IgG memory B cell responses by day 30 (mean, 0.10% of total circulating IgG memory B cells; range, 0.037%-0.28%), which persisted to day 90 (mean, 0.07%; range, 0.003%-0.27%). In contrast, circulating CTB-specific IgG antibody-secreting cells and serum vibriocidal and anti-CTB antibody responses peaked on day 7 and declined to undetectable or significantly lower levels by day 90. CONCLUSIONS: CTB-specific IgG memory B cell responses are detectable in the circulation at least 3 months after V. cholerae O1 infection and remain measurable even after serum antibody titers have declined to undetectable or considerably lower levels. This suggests that antigen-specific memory B cells may be an important long-term marker of the immune response to cholera.

Nutritional status of children under five in three state foster care institutions in Sri Lanka.

This study evaluated the prevalence of protein energy malnutrition (PEM) in children under five years (n = 52), in three randomly selected, State operated foster care institutions in Sri Lanka. The prevalence of PEM, was (51.9%), underweight (63.5%) and wasting (25.0%) was found to be considerably higher than the national prevalence (13.5%, 29.4%, 14.0%, respectively). Based on this preliminary evidence, it is recommended that a study representative of all institutionalised children in both State and private facilities be conducted to identify deficiencies and recommend improvements to institutional care in Sri Lanka.