A diterpene synthase from the sandfly Lutzomyia longipalpis produces the pheromone sobralene.

The phlebotomine sandfly, Lutzomyia longipalpis, a major vector of the Leishmania parasite, uses terpene pheromones to attract conspecifics for mating. Examination of the L. longipalpis genome revealed a putative terpene synthase (TPS), which-upon heterologous expression in, and purification from, Escherichia coli-yielded a functional enzyme. The TPS, termed LlTPS, converted geranyl diphosphate (GPP) into a mixture of monoterpenes with low efficiency, of which ß-ocimene was the major product. (E,E)-farnesyl diphosphate (FPP) principally produced small amounts of (E)-ß-farnesene, while (Z,E)- and (Z,Z)-FPP yielded a mixture of bisabolene isomers. None of these mono- and sesquiterpenes are known volatiles of L. longipalpis. Notably, however, when provided with (E,E,E)-geranylgeranyl diphosphate (GGPP), LlTPS gave sobralene as its major product. This diterpene pheromone is released by certain chemotypes of L. longipalpis, in particular those found in the Ceará state of Brazil. Minor diterpene components were also seen as products of the enzyme that matched those seen in a sandfly pheromone extract.

Downstaging hepatocellular carcinoma before liver transplantation: A multicenter analysis of the "all-comers" protocol in the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) consortium.

Patients with hepatocellular carcinoma meeting united network for organ sharing (UNOS)-downstaging (DS) criteria have excellent liver transplantation (LT) outcomes after DS. However, outcomes for "all-comers" (AC) patients with tumors initially exceeding UNOS-DS are poorly understood. Patients meeting AC (n = 82) or UNOS-DS (n = 229) at 7 LT centers in 4 UNOS regions were prospectively followed from 2015-2020. AC patients had a lower probability of successful DS (67% vs 83% within 12 months; P < .001). The 3-year survival was 69% for UNOS-DS vs 58% for AC (P = .05) and reduced to 30% in patients with Child-Pugh B/C cirrhosis or alpha-fetoprotein (AFP) ≥ 500. Five-year LT probability was 42% for AC vs 74% in UNOS-DS (P = .10). Thirty-eight percent were understaged on explant, with the increasing sum of the largest tumor diameter plus the number of lesions before LT (odds ratio 1.3; P = .01) and AFP ≥ 20 (odds ratio 5.9; P = .005) associated with understaging. Post-LT 3-year survival was 91% for AC vs 81% for UNOS-DS (P = .67). In this first prospective multiregional study of AC patients from the multicenter evaluation of reduction in tumor size before liver transplantation (MERITS-LT) consortium, we observed a 65% probability of successful DS. Three-year survival in AC was nearly 60%, though AC with Child-Pugh B/C or AFP ≥ 500 had poor survival. Explant pathology and 3-year post-LT outcomes were similar between cohorts, suggesting that LT is a reasonable goal in selected AC patients.

Downstaging Outcomes for Hepatocellular Carcinoma: Results From the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) Consortium.

BACKGROUND & AIMS: United Network of Organ Sharing (UNOS) has adopted uniform criteria for downstaging (UNOS-DS) of hepatocellular carcinoma (HCC) before liver transplantation (LT), but the downstaging success rate and intention-to-treat outcomes across broad geographic regions are unknown. METHODS: In this first multiregional study (7 centers, 4 UNOS regions), 209 consecutive patients with HCC undergoing downstaging based on UNOS-DS criteria were prospectively evaluated from 2016 to 2019. RESULTS: Probability of successful downstaging to Milan criteria and dropout at 2 years from the initial downstaging procedure was 87.7% and 37.3%, respectively. Pretreatment with lectin-reactive α-fetoprotein ≥10% (hazard ratio, 3.7; P = .02) was associated with increased dropout risk. When chemoembolization (n = 132) and yttrium-90 radioembolization (n = 62) were compared as the initial downstaging treatment, there were no differences in Modified Response Evaluation Criteria In Solid Tumors response, probability of or time to successful downstaging, waiting list dropout, or LT. Probability of LT at 3 years was 46.6% after a median of 17.2 months. In the explant, 17.5% had vascular invasion, and 42.8% exceeded Milan criteria (understaging). The only factor associated with understaging was the sum of the number of lesions plus largest tumor diameter on the last pre-LT imaging, and the odds of understaging increased by 35% per 1-unit increase in this sum. Post-LT survival at 2 years was 95%, and HCC recurrence occurred in 7.9%. CONCLUSION: In this first prospective multiregional study based on UNOS-DS criteria, we observed a successful downstaging rate of >80% and similar efficacy of chemoembolization and yttrium-90 radioembolization as the initial downstaging treatment. A high rate of tumor understaging was observed despite excellent 2-year post-LT survival of 95%. Additional LRT to reduce viable tumor burden may reduce tumor understaging.

Stigmatising views towards individuals with eating disorders: trends and associations from 1998 to 2008 using a repeated cross-sectional design.

BACKGROUND: Eating disorders are stigmatised. Little is known about whether stigma has decreased over time and which groups hold more stigmatising beliefs. AIMS: To explore whether stigma towards eating disorders has changed between 1998 and 2008 and whether it varies by sociodemographic characteristics. METHOD: We used the Office for National Statistics Omnibus surveys 1998 and 2008. As outcomes, we selected four questions eliciting participants' views on issues of blame and ability to recover, and compared their mean scores across eating disorders, depression and alcohol dependence in both years. We used multivariable linear regressions to investigate associations between sociodemographic characteristics and each stigma domain. RESULTS: In total, 2720 participants had data on all variables of interest. Compared with 1998, in 2008 stigmatising views towards eating disorders improved. In both years, participants believed it was easier to recover from eating disorders than depression or alcohol dependence. Respondents believed people with eating disorders were more to blame for their condition than those with depression, but less than those with alcohol dependence. Men, those with less formal education, and those from ethnic minority backgrounds were more likely to place greater blame on individuals for their mental illness. Men were more likely than women to think it was possible to recover from an eating disorder. CONCLUSIONS: Stigmatising attitudes towards people with eating disorders have improved over time, but are still greater than those observed for other mental illnesses. Improving eating disorder mental health literacy could help to reduce these negative views and lead to improved quality of life, greater help-seeking and better prognosis.

Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection Is Associated With Increased Survival in Patients With a History of Hepatocellular Carcinoma.

BACKGROUND & AIMS: There is controversy regarding the benefits of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection for patients with a history of hepatocellular carcinoma (HCC). We performed a multicenter cohort study to compare overall survival between patients with HCV infection treated with DAAs and patients who did not receive DAA treatment for their HCV infection after complete response to prior HCC therapy. METHODS: We conducted a retrospective cohort study of patients with HCV-related HCC who achieved a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy, from January 2013 through December 2017 at 31 health care systems throughout the United States and Canada. We used Cox proportional hazards regression to determine the association between receipt of DAA therapy, modeled as a time-varying covariate, and all-cause mortality, accounting for informative censoring and confounding using inverse probability weighting. RESULTS: Of 797 patients with HCV-related HCC, 383 (48.1%) received DAA therapy and 414 (51.9%) did not receive treatment for their HCV infection after complete response to prior HCC therapy. Among DAA-treated patients, 43 deaths occurred during 941 person-years of follow-up, compared with 103 deaths during 526.6 person-years of follow-up among patients who did not receive DAA therapy (crude rate ratio, 0.23; 95% confidence interval [CI], 0.16-0.33). In inverse probability-weighted analyses, DAA therapy was associated with a significant reduction in risk of death (hazard ratio, 0.54; 95% CI, 0.33-0.90). This association differed by sustained virologic response to DAA therapy; risk of death was reduced in patients with sustained virologic response to DAA therapy (hazard ratio, 0.29; 95% CI, 0.18-0.47), but not in patients without a sustained virologic response (hazard ratio, 1.13; 95% CI, 0.55-2.33). CONCLUSIONS: In an analysis of nearly 800 patients with complete response to HCC treatment, DAA therapy was associated with a significant reduction in risk of death.

Direct-Acting Antiviral Therapy Not Associated With Recurrence of Hepatocellular Carcinoma in a Multicenter North American Cohort Study.

BACKGROUND & AIMS: There is controversy over the effects of direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection on hepatocellular carcinoma (HCC) recurrence and tumor aggressiveness. We compared HCC recurrence patterns between DAA-treated and untreated HCV-infected patients who had achieved a complete response to HCC treatment in a North American cohort. METHODS: We conducted a retrospective cohort study of patients with HCV-related HCC with a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy from January 2013 through December 2017 at 31 health systems throughout the United States and Canada. Cox regression was used to examine the association between DAA therapy and time to recurrence after a complete response, with DAA therapy analyzed as a time-varying exposure. We also estimated the association between DAA therapy and risk of early HCC recurrence (defined as 365 days after complete response). RESULTS: Of 793 patients with HCV-associated HCC, 304 (38.3%) received DAA therapy and 489 (61.7%) were untreated. HCC recurred in 128 DAA-treated patients (42.1%; early recurrence in 52 patients) and 288 untreated patients (58.9%; early recurrence in 227 patients). DAA therapy was not associated with HCC recurrence (hazard ratio 0.90, 95% confidence interval 0.70-1.16) or early HCC recurrence (hazard ratio 0.96, 95% confidence interval 0.70-1.34) after we adjusted for study site, age, sex, Child-Pugh score, α-fetoprotein level, tumor burden, and HCC treatment modality. In DAA-treated and untreated patients, most recurrences were within the Milan criteria (74.2% vs 78.8%; P = .23). A larger proportion of DAA-treated than untreated patients received potentially curative HCC therapy for recurrent HCC (32.0% vs 24.6%) and achieved a complete or partial response (45.3% vs 41.0%) but this did not achieve statistical significance. CONCLUSION: In a large cohort of North American patients with complete response to HCC treatment, DAA therapy was not associated with increased overall or early HCC recurrence. HCC recurrence patterns, including treatment response, were similar in DAA-treated and untreated patients.

Excellent Outcomes of Liver Transplantation Following Down-Staging of Hepatocellular Carcinoma to Within Milan Criteria: A Multicenter Study.

BACKGROUND & AIMS: Single-center studies have reported excellent outcomes of patients who underwent liver transplantation for hepatocellular carcinoma (HCC) after successful down-staging (reduction of tumor burden with local-regional therapy), but multi-center studies are lacking. We performed a multi-center study, applying a uniform down-staging protocol, to assess outcomes of liver transplantation and performed an intention to treat analysis. We analyzed factors associated with treatment failure, defined as dropout from the liver transplant waitlist due to tumor progression, liver-related death without transplant, or recurrence of HCC after transplant. METHODS: We performed a retrospective multi-center study of 187 consecutive adults with HCC enrolled in the down-staging protocol at 3 liver transplant centers in California (Region 5), from 2002 through 2012. All patients underwent abdominal imaging 1 month after each local-regional treatment, and at a minimum of once every 3 months. The primary outcome was probability of treatment failure. RESULTS: Liver transplantation was performed after successful down staging in 109 patients (58%). Tumor explant from only 1 patient had poorly differentiated grade and 7 (6.4%) had vascular invasion. Based on Kaplan-Meier analysis of data collected a median 4.3 years after liver transplantation, 95% of patients would survive 1 year and 80% of patients would survive 5 years; probabilities of recurrence-free survival were 95% and 87%, respectively. There were no center-specific differences in survival in the intention to treat analysis (P = .62), in survival after liver transplantation (P = .95), or in recurrence of HCC (P = .99). Patients were removed from the liver transplantation waitlist due to tumor progression in (n = 59; 32%) or liver-related death without liver transplantation (n = 9; 5%). Factors associated with treatment failure, based on multivariable analysis, were pre-treatment levels of alpha-fetoprotein (AFP) >1000 ng/mL (hazard ratio, 3.3; P < .001) and Child Pugh class B or C (hazard ratio, 1.6; P < .001). The probability of treatment failure at 2 years from the first down-staging procedure was 100% for patients with levels of AFP >1000 and Child Pugh class B or C vs 29.4% for patients with neither risk factor (P < .001). CONCLUSIONS: In a retrospective, multi-center study on HCC down staging under a uniform protocol, we found patients to have excellent outcomes following liver transplantation, with no center-specific effects. Our findings support application of the down-staging protocol on a broader scale. Patients with Child Pugh class B or C and AFP >1000 are unlikely to benefit from down staging.

Hepatic artery and biliary complications in liver transplant recipients undergoing pretransplant transarterial chemoembolization.

Liver transplantation (LT) is the treatment of choice for patients with cirrhosis and hepatocellular carcinoma (HCC) not amenable to resection. Locoregional therapies for HCC are often used to reduce tumor burden, bridge patients to LT, and down-stage HCC so that patients are eligible for LT. We hypothesized that prior endovascular antitumor therapy may increase the risk of hepatic artery (HA) and biliary complications after LT. The aim of this study was to compare HA and biliary complications in LT recipients with HCC who received transarterial chemoembolization (TACE) before LT with complications in LT recipients with HCC who did not receive TACE before LT. This was a retrospective cohort study of HCC patients at two transplant centers. The prevalence of HA complications (HA thrombosis, stenosis, or pseudoaneurysm) and biliary complications (nonanastomotic stricture, bile leak, and diffuse injury) were compared between patients treated with or without TACE. There were 456 HCC patients with a median age of 61 years (77% were male, and 63% had hepatitis C virus), and 328 (72%) received TACE before LT. The overall prevalence of HA complications was 4.7% in the no-TACE group and 7.9% in the TACE group (P = 0.22). All HA stenosis complications (n = 14) occurred in the TACE group (P = 0.018 versus the no-TACE group). An older donor age and a lower albumin level significantly increased the odds of HA complications. There was a nonstatistically significant increased odds of HA complications in the TACE group versus the no-TACE group according to an adjusted analysis (odds ratio = 2.02, 95% confidence interval = 0.79-5.16, P = 0.14). The overall prevalence of biliary complications was 16.4% in the no-TACE group and 19.8% in the TACE group (P = 0.40). In conclusion, a lower pre-LT albumin level and an older donor age were significantly associated with higher odds of HA complications after LT. TACE was not associated with higher odds of overall HA complications but was associated with a higher prevalence of HA stenosis. Further studies are warranted to confirm the HA stenosis findings and elucidate the pathogenesis.

A sustainable dietetics bridging program: development and implementation in Atlantic Canada.

A provincial focus on immigration and improved foreign credential recognition has led to an investigation of best practices and subsequent recommendations for the development and implementation of a sustainable university-based bridging program for internationally educated dietitians in Atlantic Canada. Data were collected from various sources and used to inform program decisions and direction. An advisory framework was established through a core group representing dietetics education and regulation and internationalization. Subsequently, a key stakeholder group was formed. As a result of this collaboration and research, a dietetics bridging framework was developed and a program pilot tested. Lessons learned may inform similar endeavours and highlight the importance of collaborative leadership and collaboration among multiple stakeholders, and of creatively addressing program sustainability issues while keeping learners (internationally educated dietitians) at the centre.

You get us, so you like us: Feeling understood by an outgroup predicts more positive intergroup relations via perceived positive regard.

Intergroup felt understanding-the belief that outgroup members understand and accept ingroup perspectives-has been found to predict positive intergroup outcomes, but the mechanism through which it has its positive effects is unclear. Across eight studies, we tested the hypothesis that felt positive regard-the perception that outgroup members like and respect ingroup members-mediates the positive effects of felt understanding on outcomes like outgroup trust. Studies 1-6 (total N = 1,366) included cross-sectional and experimental designs and a range of intergroup settings such as Sunni-Shia relations in Lebanon, gender relations, and support for "Brexit" in the United Kingdom. Results of meta-analytic structural equation models across these studies provided evidence of the indirect effect of felt understanding via felt positive regard on outcomes including trust and positive relational emotions. Study 7 (N = 307) then tested the causal effect of felt positive regard through a direct manipulation. Findings confirmed that felt positive (vs. negative) regard did lead to more positive intergroup perceptions. Finally, Study 8 (N = 410) tested the indirect effect as a within-person change process using a year-long, two-wave study of the conflict in Chile between Indigenous Mapuche and Non-Indigenous Chileans: Change over time in felt understanding indirectly predicted change over time in trust via change in felt positive regard. We consider the theoretical implications of the findings for how intergroup relations may be improved and the possibilities presented by felt understanding for intervention development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update.

PURPOSE: To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to update the 2020 guideline on systemic therapy for HCC. The panel updated the systematic review to include randomized controlled trials (RCTs) published through October 2023 and updated recommendations. RESULTS: Ten new RCTs met the inclusion criteria and were added to the evidence base. RECOMMENDATIONS: Atezolizumab + bevacizumab (atezo + bev) or durvalumab + tremelimumab (durva + treme) may be offered first-line for patients with advanced HCC, Child-Pugh class A liver disease, and Eastern Cooperative Oncology Group performance status 0-1. Where there are contraindications to these therapies, sorafenib, lenvatinib, or durvalumab may be offered first-line. Following first-line treatment with atezo + bev, second-line therapy with a tyrosine kinase inhibitor (TKI), ramucirumab (for patients with alpha-fetoprotein [AFP] ≥400 ng/mL), durva + treme, or nivolumab + ipilimumab (nivo + ipi) may be recommended for appropriate candidates. Following first-line therapy with durva + treme, second-line therapy with a TKI is recommended. Following first-line treatment with sorafenib or lenvatinib, second-line therapy options include cabozantinib, regorafenib for patients who previously tolerated sorafenib, ramucirumab (AFP ≥400 ng/mL), nivo + ipi, or durvalumab; atezo + bev or durva + treme may be considered for patients who did not have access to these therapies in the first-line setting, and do not have contraindications. Pembrolizumab or nivolumab are also options for appropriate patients following sorafenib or lenvatinib. Third-line therapy may be considered in Child-Pugh class A patients with good PS, using one of the agents listed previously that has a nonidentical mechanism of action with previously received therapy. A cautious approach to systemic therapy is recommended for patients with Child-Pugh class B advanced HCC. Further guidance on choosing between options is included within the guideline.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Racial and ethnic disparities in untreated patients with hepatitis C virus-related hepatocellular carcinoma but not in those with sustained virologic response.

BACKGROUND: Racial and ethnic disparities exist for hepatitis C virus (HCV) treatment and hepatocellular carcinoma (HCC) survival. AIM: To evaluate the impact of HCV treatment on such disparities. METHODS: In a retrospective cohort study, we analysed 6069 patients with HCV-related HCC (54.2% Asian, 30.1% White, 8.5% Black, and 7.3% Hispanic) from centres in the United States and Asia. RESULTS: The mean age was 61, 60, 59 and 68, respectively, for White, Black, Hispanic and Asian patients. Black patients were most likely to have Barcelona Clinic Liver Cancer stage D, vascular invasion and distant metastasis (23% vs. 5%-15%, 20% vs. 10%-17% and 10% vs. 5%-7%, respectively; all p < 0.0001). Treatment rate with direct-acting antiviral agents (DAA) was 35.9% for Asian, 34.9% for White, 30.3% for Hispanic (30.3%), and 18.7% for Black patients (p < 0.0001). Among those untreated or without sustained virologic response (SVR), 10-year survival rates were 35.4, 27.5, 19.3 and 14.0, respectively, for Asian, Hispanic, White and Black patients (p < 0.0001). There were no statistically significant differences among those with SVR (p = 0.44). On multivariable analysis adjusted for relevant confounders, there was no statistically significant association between survival and being Hispanic (aHR: 0.68, p = 0.26) or Black (aHR: 1.18, p = 0.60) versus White. There was a significant association between being Asian American and survival (aHR: 0.24, p = 0.001; non-U.S. Asian: aHR: 0.66, p = 0.05), and for SVR (aHR: 0.30, p < 0.0001). CONCLUSION: DAA treatment rates were suboptimal. Racial and ethnic disparities resolved with HCV cure. Early diagnosis and improved access to HCV treatment is needed for all patients with HCV infection.

Acute liver failure caused by herpes simplex virus in a pregnant patient: is there a potential role for therapeutic plasma exchange?

A young woman presented with a febrile illness in the third trimester of pregnancy. Laboratory investigation revealed severe acute hepatitis with thrombocytopenia and coagulopathy. Liver injury progressed despite emergent caesarian section and delivery of a healthy infant. Therefore, therapeutic plasma exchange (TPE) was performed on three consecutive days post-partum for a presumed diagnosis of acute liver failure (ALF) associated with pregnancy due to hemolysis, elevated liver enzymes, and low platelets (HELLP) or acute fatty liver of pregnancy (AFLP). Treatment with TPE was followed by biochemical and clinical improvement but during her recovery herpes simplex virus type 2 (HSV-2) infection was diagnosed serologically and confirmed histologically. Changes in the immune system during pregnancy make pregnant patients more susceptible to acute HSV hepatitis, HSV-related ALF, and death. The disease is characterized by massive hepatic inflammation with hepatocyte necrosis, mediated by both direct viral cytotoxicity and the innate humoral immune response. TPE may have a therapeutic role in acute inflammatory disorders such as HSV hepatitis by reducing viral load and attenuating systemic inflammation and liver cell injury. Further investigation is needed to clarify this potential effect. The roles of vigilance, clinical suspicion, and currently accepted therapies are emphasized.

Evaluating the Effects of Ertapenem and Meropenem on Tacrolimus.

Purpose: Further elucidate the potential drug interaction between tacrolimus and carbapenems in order to appropriately maintain the balance between infection treatment and therapeutic immunosuppression. Methods: This study was a retrospective evaluation of solid organ transplant recipients on a stable dose of tacrolimus who received either ertapenem or meropenem. Patients were excluded if they had acute kidney injury, acute liver failure, concomitant initiation of medications that interact with tacrolimus, or were pregnant. The primary endpoint was the change in the median daily tacrolimus dose after meropenem or ertapenem administration. The secondary endpoint was the change in serum tacrolimus levels after meropenem or ertapenem administration. Results: A total of 28 patients on tacrolimus were included in the study, 12 received ertapenem and 16 received meropenem. The median daily tacrolimus dose was 4.5 mg [IQR 3.0 mg - 8.8 mg] prior to and 3.4 mg [IQR 2.3 mg - 8.8 mg] after ertapenem administration. The median daily tacrolimus dose was 3.0 mg [IQR 1.6 mg - 5.5 mg] before and 3.0 mg [IQR 1.6 mg - 5.5 mg] after meropenem administration. No statistically significant difference in regard to the change in the median daily tacrolimus dose after ertapenem (P =.173) or meropenem administration (P =.755) was observed. There was no statistically significant difference found after ertapenem (P =.583) or meropenem (P =.317) administration when comparing pre- and post-administration median serum tacrolimus levels. Conclusion: The administration of ertapenem or meropenem did not affect serum tacrolimus levels or daily tacrolimus dose suggesting against empiric dose adjustments with co-administration.

Multidisciplinary management of hepatocellular carcinoma.

Hepatocellular carcinoma is a leading cause of death in patients with cirrhosis. Management algorithms continually are increasing in sophistication and involve application of single and multimodality treatments, including liver transplantation, hepatic resection, ablation, transarterial chemoembolization, radioembolization, and systemic chemotherapy. These treatments have been shown to increase survival times. As many as 75% of patients with limited-stage disease who are given curative therapies survive 5 years, whereas less than 20% of untreated patients survive 1 year. Treatment can be optimized based on the patient's tumor stage, hepatic reserve, and functional status. However, because of the heterogeneity in presentation among patients, a multidisciplinary approach is required to treat hepatocellular carcinoma, involving hepatologists, surgeons, interventional radiologists, and oncologists. We present each specialist's viewpoint on controversies and advances in the management of hepatocellular carcinoma.

Reduced effectiveness of standard recruitment for deceased organ donor registration: the need for population-specific recruitment materials.

BACKGROUND: The low rate of deceased donor organ donation limits the availability of life-saving transplants. Transplant candidate caregivers are an under-utilized but potentially devoted pool of advocates who themselves may be recruited to register for deceased organ donation. AIMS: To compare the effectiveness of recruitment materials in Transplant Candidate Caregivers (TCC) and San Francisco Bay Area Health Fair Attendees (HFA). METHODS: Each subject was given a California Transplant Donor Network educational pamphlet and cohort-coded registration materials. The primary outcome was the number of new registrations per recruitment packet distributed. RESULTS: A total of 232 recruitment packets were distributed; 116 to each of the two cohorts. The TCC group was more likely to be older (49 vs. 45, p = 0.05), female (71 vs. 63%, p = 0.2), Hispanic (21 vs. 5%, 0.001), married (75 vs. 33%, p < 0.0001), and less educated (p = 0.007). Despite demographic differences, the two groups had similar prior donor registration rates (40% TCC vs. 50% HFA, p = 0.11). However, with a minimum 2-week follow-up, the number of new registrations was only nine in the TCC cohort as compared to 38 in the HFA cohort (0.33 vs. 0.80 new registrations/packet, p < 0.0001). CONCLUSIONS: The effectiveness of standard deceased donor registration recruitment materials is reduced in Transplant Candidate Caregivers as compared to Health Fair Attendees. This reduced efficacy may be due to dissimilar demographics, psychosocial status at time of recruitment, and beliefs about organ donation. Development of audience specific recruitment materials may improve efforts to register Transplant Candidate Caregivers for deceased organ donation.

Hepatitis B and hepatocellular carcinoma screening among Asian Americans: survey of safety net healthcare providers.

BACKGROUND: Physician patterns of screening for hepatitis B (HBV) and hepatocellular carcinoma (HCC) among Asian Americans are not well described. AIMS: To describe HBV and HCC screening practices among providers with large Asian American populations. METHODS: Providers within San Francisco's safety net system were surveyed with respect to HBV and HCC screening practices as well as knowledge, attitudes, and barriers to HCC screening. RESULTS: Among the 109 respondents (response rate = 72%), 62% were aged >40, 65% female, 24% Asian, 87% primary care providers, and 48% had >25% Asian patients. Only 76% had screened >50% of their Asian patients for HBV and 43% had vaccinated >50% of eligible patients against HBV. Although 94% knew Asians were disproportionately affected by HCC, only 79% had screened for HCC in >50% of their Asian patients with chronic hepatitis B (CHB). A majority believed that HCC screening in CHB reduces HCC mortality (70%) and is cost-effective (57%). The most common HCC screening modality was AFP with abdominal ultrasound every 6-12 months (63%). Factors associated with HBV screening were familiarity with AASLD guidelines (OR 6.4, 95% CI 1.3-30.1, p = 0.02) and having vaccinated >50% of eligible patients against HBV (OR 2.2, 95% CI 1.1-4.5, p = 0.03). Factors associated with HCC screening using abdominal ultrasound every 6-12 months were having >25% Asian patients (OR = 4.5, 95% CI 1.3-15.3, p = 0.02) and higher HCC knowledge score (OR = 1.9 per item, 95% CI 1.01-3.6, p = 0.045). CONCLUSIONS: HBV and HCC screening rates and HBV vaccination among Asians from physician report is suboptimal. HCC screening is associated with having more Asian patients and higher provider knowledge. Provider education is essential in increasing rates of HBV and HCC screening among Asian Americans.

Effects of Cirrhosis and Diagnosis Scenario in Metabolic-Associated Fatty Liver Disease-Related Hepatocellular Carcinoma.

Metabolic-associated fatty liver disease (MAFLD) is a major cause of liver-related complications, including hepatocellular carcinoma (HCC). While MAFLD-related HCC is known to occur in the absence of cirrhosis, our understanding of MAFLD-related HCC in this setting is limited. Here, we characterize MAFLD-related HCC and the impact of cirrhosis and screening on survival. This was a multicenter, retrospective, cohort study of MAFLD-related HCC. MAFLD was defined based on the presence of race-adjusted overweight, diabetes, or both hypertension and dyslipidemia in the absence of excess alcohol use or other underlying cause of liver disease. The primary outcome of interest was overall survival, and the primary dependent variables were cirrhosis status and prior HCC screening. We used Kaplan-Meier methods to estimate overall survival and Cox proportional hazards models and random forest machine learning to determine factors associated with prognosis. This study included 1,382 patients from 11 centers in the United States and East/Southeast Asia. Cirrhosis was present in 62% of patients, but under half of these patients had undergone imaging within 12 months of HCC diagnosis. Patients with cirrhosis were more likely to have early stage disease but less often received curative therapy. After adjustment, cirrhosis was not associated with prognosis, but the presence of cancer-related symptoms at diagnosis was associated with poorer prognosis. Conclusion: Cirrhosis was not associated with overall survival in this cohort of MAFLD-related HCC, while diagnosis in the presence of symptoms was associated with poorer prognosis. The HCC surveillance rate in patients with MAFLD-related HCC was disappointingly low in a multicenter cohort.

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline.

PURPOSE: To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to conduct a systematic review of published phase III randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and provide recommended care options for this patient population. RESULTS: Nine phase III randomized controlled trials met the inclusion criteria. RECOMMENDATIONS: Atezolizumab + bevacizumab (atezo + bev) may be offered as first-line treatment of most patients with advanced HCC, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1, and following management of esophageal varices, when present, according to institutional guidelines. Where there are contraindications to atezolizumab and/or bevacizumab, tyrosine kinase inhibitors sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC, Child-Pugh class A liver disease, and ECOG PS 0-1. Following first-line treatment with atezo + bev, and until better data are available, second-line therapy with a tyrosine kinase inhibitor may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with α-fetoprotein ≥ 400 ng/mL), or atezo + bev where patients did not have access to this option as first-line therapy. Pembrolizumab or nivolumab are also reasonable options for appropriate patients following sorafenib or lenvatinib. Consideration of nivolumab + ipilimumab as an option for second-line therapy and third-line therapy is discussed. Further guidance on choosing between therapy options is included within the guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.