Clinician-Level Knowledge and Barriers to Hepatocellular Carcinoma Surveillance.

Importance: Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is underused. Identifying potentially modifiable factors to address barriers in HCC surveillance is critical to improve patient outcomes. Objective: To evaluate clinician-level factors contributing to underuse of HCC surveillance in patients with cirrhosis. Design, Setting, and Participants: This survey study included primary care clinicians (PCCs) and gastroenterology and hepatology clinicians at 5 safety-net health systems in the US. Clinicians were surveyed from March 15 to September 15, 2023, to assess knowledge, attitudes, beliefs, perceived barriers, and COVID-19-related disruptions in HCC surveillance in patients with cirrhosis. Data were analyzed from October to November 2023. Main Outcome and Measures: HCC surveillance knowledge was assessed with 6 questions querying the respondent's ability to correctly identify appropriate use of HCC surveillance. Attitudes, perceived barriers, and beliefs regarding HCC surveillance and perceived impact of the COVID-19 pandemic-related disruptions with HCC surveillance were assessed with a series of statements using a 4-point Likert scale and compared PCCs and gastroenterology and hepatology clinicians. Results: Overall, 347 of 1362 clinicians responded to the survey (25.5% response rate), among whom 142 of 237 (59.9%) were PCCs, 48 of 237 (20.3%) gastroenterology and hepatology, 190 of 236 (80.5%) were doctors of medicine and doctors of osteopathic medicine, and 46 of 236 (19.5%) were advanced practice clinicians. On HCC knowledge assessment, 144 of 270 (53.3%) scored 5 or more of 6 questions correctly, 37 of 48 (77.1%) among gastroenterology and hepatology vs 65 of 142 (45.8%) among PCCs (P < .001). Those with higher HCC knowledge scores were less likely to report barriers to HCC surveillance. PCCs were more likely to report inadequate time to discuss HCC surveillance (37 of 139 [26.6%] vs 2 of 48 [4.2%]; P = .001), difficulty identifying patients with cirrhosis (82 of 141 [58.2%] vs 5 of 48 [10.4%]; P < .001), and were not up-to-date with HCC surveillance guidelines (87 of 139 [62.6%] vs 5 of 48 [10.4%]; P < .001) compared with gastroenterology and hepatology clinicians. While most acknowledged delays during the COVID-19 pandemic, 62 of 136 PCCs (45.6%) and 27 of 45 gastroenterology and hepatology clinicians (60.0%) reported that patients with cirrhosis could currently complete HCC surveillance without delays. Conclusions and Relevance: In this survey study, important gaps in knowledge and perceived barriers to HCC surveillance were identified. Effective delivery of HCC education to PCCs and health system-level interventions must be pursued in parallel to address the complex barriers affecting suboptimal HCC surveillance in patients with cirrhosis.

Disparities in Hepatocellular Cancer Screening in Cirrhotic Patients With Psychiatric Disorders.

Background Patients with psychiatric disorders are at an increased risk of developing liver diseases, including hepatocellular carcinoma (HCC). HCC is a leading cause of cancer-related deaths in the United States. The aim of this study was to re-examine the association of psychiatric illness with HCC and assess its impact on screening practices and the outcomes of HCC. Materials and methods We performed a retrospective manual chart review of all patients diagnosed with HCC at a major safety-net hospital in Cleveland, Ohio, from January 2010 to December 2019. Patients were divided into two groups, those with and those without psychiatric illness. The patient characteristics recorded included psychiatric illnesses, etiology of liver disease, radiographic screening intervals, and tumor board recommendations upon initial diagnosis. We analyzed data using Statistical Product and Service Solutions version 26.0 (IBM Corp., Armonk, NY). We analyzed the qualitative and quantitative differences between the groups using the chi-square or Fisher's exact tests for categorical variables and t-test for continuous variables. Results There were a total of 393 patients with a diagnosis of HCC. Among them, 128 (32.5%) were diagnosed with at least one psychiatric illness. Fewer patients with psychiatric illness (33.6%) underwent screening within six months before being diagnosed with HCC compared to those without psychiatric illness (49.8%) (p = 0.002). Patients with psychiatric illness (71.1%) were more likely to have been seen by a gastroenterologist or hepatologist before their diagnosis of HCC compared to those without psychiatric illness (55.1%) (p =0.002). Patients with psychiatric illness were more likely to be offered systemic chemotherapy or hospice (39.1%) compared to those without psychiatric illness (29.1%) (p =0.039). Discussion A significant number of HCC patients in our study group have an underlying psychiatric illness. Patients with psychiatric disorders are prone to high-risk behaviors, likely predisposing them to chronic liver disease and HCC. Patients with psychiatric disorders are less compliant with screening practices. Our findings suggest that psychiatric illnesses tend to be diagnosed with more extensive HCC, which is less amenable to curative treatment. Significant efforts need to be made to identify barriers to HCC screening in cirrhotic patients with psychiatric disorders.

Low Rates of Hepatitis B Virus Treatment Among Treatment-Eligible Patients in Safety-Net Health Systems.

BACKGROUND: Timely initiation of antiviral therapy in chronic hepatitis B virus (CHB) reduces risk of disease progression. We evaluate overall treatment rates and predictors of treatment among treatment-eligible safety-net CHB patients. METHODS: We retrospectively evaluated adults with CHB from 2010 to 2018 across 4 large safety-net health systems in the United States. CHB was identified with ICD-9/10 diagnosis coding and confirmed with laboratory data. Treatment eligibility was determined using American Association for the Study of Liver Diseases (AASLD) guidelines. Comparison of CHB treatment rates among treatment-eligible patients were performed using χ2 testing, Kaplan Meier methods and log-rank testing. Adjusted multivariate Cox proportional hazards models evaluated independent predictors of receiving treatment among eligible patients. RESULTS: Among 5157 CHB patients (54.7% male, 34.6% African American, 22.3% Asian), 46.8% were treatment-eligible during the study period. CHB treatment rates were 48.4% overall and 37.3% among CHB patients without human immunodeficiency virus. Significantly lower odds of treatment were observed in females versus males (odds ratio: 0.40, 95% confidence interval: 0.33-0.49, P<0.001) and patients age 65 years or above versus age below 45 years (odds ratio: 0.68, 95% confidence interval: 0.51-0.92, P=0.012). Conversely, significantly greater odds of treatment were observed in African American and Asians versus non-Hispanic whites, CHB patients with indigent care versus commercially insured patients, and non-English speaking versus English speaking patients. CONCLUSION: Among a large multicentered, safety-net cohort of CHB patients, 46.8% of treatment-eligible CHB patients overall and 37.3% of treatment-eligible CHB patients without human immunodeficiency virus received antiviral therapy. Improving CHB treatment rates among treatment-eligible patients represents "low hanging fruit," given the clear benefits of antiviral therapy in mitigating disease progression.

Antiviral Therapy Reduces Risk of Cirrhosis in Noncirrhotic HBV Patients Among 4 Urban Safety-Net Health Systems.

INTRODUCTION: To evaluate the impact of chronic hepatitis B virus infection (CHB) treatment on risk of cirrhosis, liver-related outcomes, and death among a diverse CHB cohort with a large proportion of African Americans. METHODS: Adults with noncirrhotic CHB without human immunodeficiency virus from 2010 to 2018 were retrospectively evaluated across 4 US safety-net health systems. CHB was identified with International Classification of Diseases, Ninth Revision/Tenth Revision diagnosis coding and confirmatory laboratory data. Propensity-score matching, Kaplan-Meier methods, and adjusted Cox proportional hazards models were used to evaluate impact of CHB treatment on risk of cirrhosis, hepatocellular carcinoma (HCC), death, and composite of cirrhosis, HCC, or death. RESULTS: Among 4,064 CHB patients (51.9% female, 42.0% age <45 years, 31.6% African American, 26.6% Asian, 26.7% Hispanic), 23.2% received CHB antiviral therapy and 76.8% did not. Among the propensity score-matched cohort (428 treated and 428 untreated), CHB treatment was associated with lower risk of cirrhosis (hazards ratio 0.65, 95% confidence interval 0.46-0.92, P = 0.015) and composite of cirrhosis, HCC, or death (hazards ratio 0.67, 95% confidence interval 0.49-0.94, P = 0.023). Females vs males and African Americans vs non-Hispanic whites had significantly lower risk of cirrhosis. When treatment effects were stratified by age, sex, and ethnicity, the benefits of antiviral therapies in reducing risk of cirrhosis were seen primarily in CHB patients who were females, age <45 years, and of Asian ethnicity. DISCUSSION: Our propensity score-matched cohort of noncirrhotic CHB patients demonstrated significant reductions in risk of cirrhosis due to CHB treatment.

COVID-19 in Chronic Liver Disease and Liver Transplantation: A Clinical Review.

The coronavirus disease 2019 (COVID-19) pandemic has brought challenges to clinicians caring for patients with chronic liver disease. In the past 6 months, COVID-19 has led to over 150,000 deaths in the United States and over 660,000 deaths around the world. Mounting evidence suggests that chronic liver diseases can have an adverse effect on the clinical outcomes of patients with COVID-19. We present a comprehensive review of the latest literature on preexisting liver diseases and its interrelationship with COVID-19 infection in cirrhosis, hepatocellular carcinoma, nonalcoholic fatty liver disease, autoimmune hepatitis, and viral hepatitis B. As social distancing and telemedicine gain new footing, we synthesize recommendations from 3 major hepatology societies [American Association for the Study of Liver Disease (AASLD), the European Association for the Study of Liver (EASL), and the Asian Pacific Association for the Study of Liver (APASL)] to present the best approaches for caring for patients with liver diseases as well as those requiring liver transplantation.

Clinical Considerations of Coagulopathy in Acute Liver Failure.

Acute liver failure (ALF) is the rapid onset of severe liver dysfunction, defined by the presence of hepatic encephalopathy and impaired synthetic function (international normalized ratio of ≥1.5) in the absence of underlying liver disease. The elevated international normalized ratio value in ALF is often misinterpreted as an increased hemorrhagic tendency, which can lead to inappropriate, prophylactic transfusions of blood products. However, global assessments of coagulopathy via viscoelastic tests or thrombin generation assay suggest a reestablished hemostatic, or even hypercoagulable, status in patients with ALF. Although the current versions of global assays are not perfect, they can provide more nuanced insights into the hemostatic system in ALF than the conventional measures of coagulopathy.

Mortality from Spontaneous Bacterial Peritonitis Among Hospitalized Patients in the USA.

BACKGROUND AND AIM: Spontaneous bacterial peritonitis (SBP) is a serious complication of cirrhosis and is associated with significant morbidity and mortality. In this study, we examined the clinical characteristics and risk factors associated with mortality in hospitalized patients presenting with SBP. METHODS: The Nationwide Inpatient Sample was queried for all hospitalizations involving SBP from 2006 to 2014 using the International Classification of Disease-9-CM Code. Logistic regression was performed to evaluate the association between SBP mortality and factors such as age, gender, race/ethnicity, and concomitant medical conditions at presentation (e.g., variceal hemorrhage, hepatic encephalopathy, acute renal failure, coagulopathy, and other infections including pneumonia). The lengths of stay (LOS) and total charges were also examined. RESULTS: From 2006 to 2014, there were 88,167 SBP hospitalizations with 29,963 deaths (17.6% in-hospital mortality). The mean age of patients who died in the hospital was higher (58.2 years vs. 55.8, p < 0.01) than those who survived the admission. Acute alcoholic hepatitis was noted among a higher proportion of patients who died (7.0 vs. 5.9%, p < 0.01), who were also likely to have more medical comorbidities. In multivariable analysis, older age, female gender, hepatic encephalopathy, coagulopathy, variceal hemorrhage, sepsis, pneumonia, and acute kidney injury were associated with increased in-hospital mortality. This group also had longer LOS (11.6 days vs. 9.1, p < 0.01) and higher total charges ($138,273 vs. $73,533, p < 0.01). CONCLUSION: SBP is associated with significant in-hospital mortality, especially in patients with concurrent risk factors. SBP remains a significant burden to the healthcare system.

Obstetricians' and gynecologists' knowledge, education, and practices regarding chronic hepatitis B in pregnancy.

BACKGROUND: In pregnant women with high viral loads, third-trimester initiation of antiviral agents can reduce the risk of vertical transmission. We aimed to assess obstetricians' and gynecologists' (OB-GYN) knowledge and clinical practice when treating pregnant women with chronic hepatitis B virus (HBV). METHODS: All program directors (PDs) from 250 US OB-GYN residency programs were invited to anonymously complete an 18-item questionnaire. Descriptive statistics were calculated and analyzed. RESULTS: A total of 323 participants responded, including both PDs (n=51, response rate 21%) and residents (n=272, response rate 11%). Responding PDs (62% university-based vs. 32% community-based) came from various practice types. All PDs and 95.2% of residents reported screening for chronic HBV in pregnant patients on the first prenatal visit. A majority of PDs (85.5%) and residents (85%) correctly interpreted HBV serologies. Referral patterns showed that 66.7% of PDs and 65.5% of residents refer to a specialist regardless of viral load. A minority of respondents (19.6% PDs and 12.6% residents) knew that third-trimester antiviral therapy is recommended for women with high viral loads (>200,000 IU/mL). Few respondents had prescribed HBV antivirals (9.8% PDs and 6.0% residents), with residents more commonly prescribing tenofovir and less frequently lamivudine. Half the PDs believed trainees from their programs were comfortable managing HBV in pregnancy, but only 41.8% of residents reported being comfortable managing pregnant patients with HBV. CONCLUSION: OB-GYNs report screening almost all pregnant patients for chronic HBV, though significant gaps still exist in practitioner comfort and training regarding the management of HBV during pregnancy.

Chronic Gastric Ischemia Leading to Gastric Perforation.

A 69-year-old man with diabetes, peripheral vascular disease, and hypertension presented with 3 months of diffuse abdominal pain that worsened with meals, weight loss, and dysphagia. Esophagogastroduodenoscopy and computed tomography revealed findings consistent with chronic gastric ischemia secondary to atherosclerosis. Gastric ischemia eventually led to perforation. We discuss causes, symptoms, diagnosis, and management of gastric ischemia, an underdiagnosed and potentially fatal condition that requires urgent diagnosis and treatment.

Coding algorithms for identifying patients with cirrhosis and hepatitis B or C virus using administrative data.

BACKGROUND AND AIMS: Despite the use of administrative data to perform epidemiological and cost-effectiveness research on patients with hepatitis B or C virus (HBV, HCV), there are no data outside of the Veterans Health Administration validating whether International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes can accurately identify cirrhotic patients with HBV or HCV. The validation of such algorithms is necessary for future epidemiological studies. METHODS: We evaluated the positive predictive value (PPV) of ICD-9-CM codes for identifying chronic HBV or HCV among cirrhotic patients within the University of Pennsylvania Health System, a large network that includes a tertiary care referral center, a community-based hospital, and multiple outpatient practices across southeastern Pennsylvania and southern New Jersey. We reviewed a random sample of 200 cirrhotic patients with ICD-9-CM codes for HCV and 150 cirrhotic patients with ICD-9-CM codes for HBV. RESULTS: The PPV of 1 inpatient or 2 outpatient HCV codes was 88.0% (168/191, 95% CI: 82.5-92.2%), while the PPV of 1 inpatient or 2 outpatient HBV codes was 81.3% (113/139, 95% CI: 73.8-87.4%). Several variations of the primary coding algorithm were evaluated to determine if different combinations of inpatient and/or outpatient ICD-9-CM codes could increase the PPV of the coding algorithm. CONCLUSIONS: ICD-9-CM codes can identify chronic HBV or HCV in cirrhotic patients with a high PPV and can be used in future epidemiologic studies to examine disease burden and the proper allocation of resources.

Tobacco-related disease burden and preventive initiatives in China. Global health and the chronic diseases: perspective, policy and practice.

The burden of chronic diseases in global health is a surging area of research. The Global Health Initiative at the National Heart, Lung, and Blood Institute brings together investigators from developing countries with those from the developed world to study these diseases. In China, approximately 83 percent of all deaths in 2000 were attributed to chronic illnesses, which are the research focuses of the Chinese center of the Global Health Initiative. Tobacco use as well as passive smoking are modifiable risk factors in a large number of such chronic conditions. The prevalence of smoking in China is extensive and has inseparable ties to the economy, with tobacco taxes making up a large portion of government revenue in poorer provinces. Methods of smoking prevention have been piloted in some Chinese schools, which have mitigated the increase in smoking rate but have not resulted in a primary preventive effect. Efforts by the Yale Global Health Initiative and the Yale-China Association are bringing researchers together to address chronic disease in China as Yale School of Medicine enters its 200th year.

[CTLs induced by hTERT-related multiepitope peptide-sensitived mDCs specifically kill HLA-A24+ tumor cells].

AIM: To study the antigen specific anti-tumor effect of cytotoxic T lymphocytes(CTLs), which was induced by human telomerase reverse transcriptase (hTERT)-related multiple epitope peptides impulsed myeloid dendritic cells(mDCs), against human leukocyte antigen (HLA)-A24(+) tumor cells. METHODS: Four branches of multiple antigen peptides (MAPs) of hTERT epitopes and three separate peptides were solid-phase artificially synthesized, phlebotomize peripheral blood from HLA-A24(+) healthy volunteers, sorted the blood through MACS MicroBeads and cultured mDCs, Nylon fiber column purified T lymphocytes, mDCs impulsed with each type of peptides were co-cultured with T lymphocytes to induce CTLs specifically killing effect, and the resultant CTLs were used as effector cells, SMMC-7721 with hTERT and HLA-A24 positive and SKOV3 which are hTERT-positive but HLA-A24-negative tumor cells were used as target cells. The level of human IL-12, TNF-α in the culture supernatant was determined by ELISA. Flow cytometry assay was used to assess the killing ability of CTLs against tumor cells. RESULTS: MAPs of hTERT epitopes including I540 (ILAKFLHWL), V461 (VYGFVRACL), L766 (LTDLQPYMRQFVAHL) and three separate peptides could impulse mDCs and then induce CTLs to specifically kill SMMC-7721, CTLs induced by MAPs had stronger cytotoxic effect compared with three separate peptides mixed(P < 0.05). CONCLUSION: mDCs-impulsed with hTERT-associated MAPs can induce production and proliferation of allogenic CTLs, which show antigen specific anti-tumor effect against HLA-A24(+) tumor cells. This result has significantly meaning in tumor immunotherapy.

Therapeutic potential of stem cell in liver regeneration.

Liver transplantation is the only life-saving procedure for patients with end-stage liver disease. However, its potential benefits are hampered by many disadvantages, such as the relative shortage of donors, operative risks, and high costs. These issues have prompted the search for new alternative therapies for irreversible liver disease. Stem cell therapy, with the ability for self-renewal and potential for multilineage differentiation, is a promising alternative approach. Several studies have demonstrated that transplantation of hepatic stem/progenitor cells or hepatocyte-like cells derived from multipotent stem cells leads to donor cell-mediated repopulation of the liver and improved survival rates in experimental models of liver disease. However, a registered clinical application based on stem cell technology will take at least an additional 5 to 10 years because of some limitations; e.g. the lack of suitable cell sources and risk of teratoma formation. This review summarizes the general understanding of the therapeutic potentials of stem cells in liver disease, including the sources, mechanisms, and delivery methods of hepatic stem cells in liver regeneration, and discusses some challenges for their therapeutic application.

Reproducibility of oxygen saturation monitoring during six-minute walk test and exercise stress test in patients with pulmonary arteriovenous malformations associated with hereditary hemorrhagic telangiectasia.

Patients with pulmonary arteriovenous malformations (PAVMs) are at risk for multiple complications and require close follow-up. We investigated the reproducibility of the 6-minute walk test (6MWT) and exercise stress test (EST) for the evaluation of low oxygen saturation in patients with PAVMs. Twenty-two patients with PAVMs, most of whom had hereditary hemorrhagic telangiectasia (HHT), participated in a Human Investigations Committee-approved protocol. Patients ranged from 9 to 74 years of age (mean 28) and had a broad spectrum of anatomic subtypes of PAVMs, including focal and diffuse. Standard 6MWT and cycle ergometry EST were both performed twice with adequate rest between tests. Heart rate (HR) and oxygen saturation were measured at the beginning and end of each test. Distance walked and maximum resistance was also recorded. The intraclass correlation coefficients (r(i)) at the end of 6MWT were as follows: HR (r(i) = 0.940; 95% confidence interval [CI] 0.863-0.975), oxygen saturation (r(i) = 0.973; 95% CI 0.933-0.989), and distance (r(i) = 0.942; 95% CI 0.867-0.975). The r(i)s at the end of EST were as follows: HR (r(i) = 0.941; 95% CI 0.865-0.975), oxygen saturation (r(i) = 0.993; 95% CI 0.982-0.997), and maximum resistance (r(i) = 0.941; 95% CI 0.864-0.975). 6MWT and EST were reproducible measures of exercise capacity and oxygen saturation and are potential adjunct tests in the follow-up assessment for patients with PAVMs.