Faculty Bibliography

Chinese Americans experience cancer health disparities throughout the entire cancer continuum. Yet, they remain underrepresented in health research in part due to barriers in recruitment, engagement, and retention. This paper describes the strategies that we devised, by drawing upon our experiences with conducting two culturally sensitive cancer intervention studies, to help researchers improve their recruitment and retention rates of Chinese Americans in health research and address the gap in knowledge on intervention research with this population. The first study assessed the efficacy, adoption, and impact of an intervention, delivered by community health workers, to improve adherence to recommended stomach cancer prevention guidelines for at-risk Chinese Americans. The second study evaluated the feasibility and preliminary efficacy of a culturally adapted version of the Expressive Helping intervention for Chinese American cancer patients and survivors. Our main recruitment strategies revolved around building community relationships, developing culturally sensitive materials, and establishing good first impressions with participants. Our main engagement and retention strategies focused on attending to cultural sensitivity, fostering relationships, and using technology. Harnessing the community's inherent strengths and prioritizing cultural understanding is crucial for culturally sensitive health research with Chinese Americans.

INTRODUCTION/BACKGROUND:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS:We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS:Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION/CONCLUSIONS:Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

Article Title: Pregnancy Outcomes after Liver Transplantation: A Systematic Review and Meta-Analysis.

INTRODUCTION: Gaucher disease (GD) is an autosomal recessive, lysosomal storage disorder that results from a deficiency of the glucocerebrosidase enzyme, which is involved in the breakdown of the glycosphingolipid glucocerebroside. We present a rare and unusual case of HCC in a patient with Gaucher disease who was found to have a 5 cm liver tumor. CASE DESCRIPTION/METHODS: 65 yo M with PMH Gaucher's disease Type 1 on enzyme replacement therapy, GERD, OSA on CPAP, IBS, Anxiety, Appendectomy, Left hip replacement, Right knee replacement, was referred for evaluation of a 5 cm liver tumor. Patient denied fevers, chills, abdominal pain, nausea, vomiting, diarrhea, constipation, or any other associated symptoms. He denied alcohol use, herbal use, recent travel or other toxic habits. Family history consisted of a brother was also carried a diagnosis of Gaucher's disease. On presentation, VS were within normal limits and complete physical examination was unremarkable. Laboratory testing revealed TB 0.9, AST 22, ALT 22, ALP 91, INR 1.0, Plt 258, AFP 4.5, CEA 3.6, Ca19-9 of 21. The rest of laboratory work up including hepatitis panel has been unremarkable. MRI Abd showed a 5 cm segment 6 arterially enhancing lesion concerning for HCC. Upper and lower endoscopy were unremarkable. Presently patient is scheduled for a liver tumor resection surgery. DISCUSSION: The prevalence of GD is approximately 1 in 57-75 thousand births worldwide but it's more prevalent in Ashkenazi Jewish descent in whom the incidence is 1 in 800 births. GD was first described by Phillippe Gaucher in 1882, and in the 1900's Epstein and later Brandy et al, further described the disease. GD has been classified into 3 Types depending on age and presence of neurological deficit. It can present with hepatic fibrosis, hepatosplenomegaly, liver cirrhosis, pulmonary hypertension, cardiac or vascular anomalies, neurologic disease, lymphoma, itchyosis, and can have bone involvement which is usually painful. GD primarily leads to hematologic malignancies with solid organ tumors not far behind. Specific risk factors in GD leading to HCC have not been fully defined, although splenectomy has been considered. Our non cirrhotic patient with a healthy lifestyle and no splenectomy was found to have HCC based on imaging, and other similar cases have been reported. Therefore, close monitoring and HCC screening should be considered in any patient with Gauchers disease

INTRODUCTION: Hepatitis D virus, also known as the 'Delta virus' is a defective virus that requires hepatitis B virus for infection. About 257-291 million people are chronically infected with HBV worldwide, and of those up to 20 million had experienced HDV infection. We present unusual case with histological, serological, virological evidences of chronically active HDV infection which was initially thought to be medication induced. CASE DESCRIPTION/METHODS: A 34 yo M with PMH of Chronic hepatitis B infection diagnosed in 2013 has been on Tenofovir Disoproxil Fumarate (TDF) x4 years. After getting switched from TDF to Tenofovir Alfenamide (TAF) he had a rise in LFTs; Bilirubin 0.2, AST 126, ALT 327. He denied alcohol use, herbal use, recent travel or other toxic habits. On presentation, VS were within normal limits and complete physical examination was unremarkable. Patient was switched from TAF to TDF as it was thought to be possibly contributing to his abnormal LFTs and a complete liver disease work up was obtained. Laboratory testing revealed TB 0.9, AST 134, ALT 386, ALP 49, INR 1.1, Hepatitis B sAg+, sAb-, eAg-, eAb-, HBV DNA non detected, HDV Ag-, HDV Ab+, HDV PCR 133,000. Ultrasound showed hepatic steatosis. Despite switching back to TDF his LFTs remained elevated. Therefore, liver biopsy was performed showing features of portal and lobular inflammation consistent with hepatitis B & D infection and fatty liver disease. He was started on Pegylated Interferon-alpha treatment, and post-treatment, his LFTs have normalized, AST-28, ALT-43, HDV PCR 1050 IU/ml. DISCUSSION: HDV is a single stranded RNA that is composed of an outer HBsAg lipoprotein envelope, inner ribonucleoprotein structure and is complexed with the HDV encoded antigen. It can present as either acute HBV-HDV coinfection, acute HDV superinfection of a chronic HBV carrier, or as chronic HDV infection. HDV infection causes more severe viral hepatitis, increases risk of developing cirrhosis and hepatocellular carcinoma in comparison to HBV monoinfection. Prevalence of HDV Ab is highest in Africa, Turkey, Mongolia, Moldova, sex workers, IV drug users, HCV, HIV, etc. Clinically HDV infection manifests from asymptomatic carrier state to acute liver failure. Diagnosis of HDV is done with serologic testing. INF-a has been the only proven antiviral treatment against HDV. SVR to therapy, which is measured as undetectable serum HDV RNA levels is at around 25%. Although rare HDV should part of a differential diagnosis in all patients with HBV infection

BACKGROUND:A critical aspect of liver transplantation in hepatitis B patients is to prevent graft reinfection with hepatitis B virus. The use of hepatitis B immune globulin after transplant was a significant milestone, which allowed prolonged graft and patient survival by controlling hepatitis B reinfection in liver grafts. The development of anti-viral treatments with oral nucleos(t)ide analogues, led to a further reduction in graft reinfection and improvement in patient survival. The combination of the aforementioned two therapies has been widely used in hepatitis B-associated liver transplants. AIM/OBJECTIVE:To address the post-transplant management of hepatitis B and provide updates on preventing graft reinfection. METHODS:We performed a literature search on Ovid and PubMed for RCTs or cohort studies in English, which investigated the effectiveness of hepatitis B immune globulin and anti-viral therapy on hepatitis B-associated transplants (1/2000-1/2020). Studies that met pre-established criteria were reviewed. RESULTS:Based on currently available evidence, an algorithm for post-transplant management with anti-viral therapy is proposed. Also, the management of recipients who received grafts from hepatitis B core antibody-positive donors is discussed. CONCLUSIONS:The development of hepatitis B immune globulin and anti-viral treatments led to substantial improvement in graft and patient survival. The prevention of hepatitis B graft reinfection is complex and involves a broad interdisciplinary team.

PURPOSE/OBJECTIVE:To investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS/METHODS:This single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A-B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses. RESULTS:The median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6-11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1-3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9-23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6-26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2-7.2), and progression-free survival was 5.7 months (95% CI, 4.3-7.1). CONCLUSIONS:Radioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.

Article Title: Early Paracentesis in High-Risk Hospitalized Patients: Time for a New Quality Indicator.

Background: Standard of care nucleos(t)ide analogs (Nrtl) are effective in chronic HBV (CHB) infection, but achieve low rates of sustained responses off therapy. The combination of the HBV Core Inhibitor ABI-H0731 (731) with a Nrtl has demonstrated potent antiviral activity in prior clinical studies and is being evaluated in a long-term treatment study.
Method(s): Studies ABI-H0731-201 and ABI-H0731-202 were 24-wk double-blind, placebo (Pbo)-controlled studies in CHB patients (pts). After 24 wks of treatment, pts could enter the open-label extension study ABI-H0731-211 and receive 731+Nrtl for up to an additional 52 wks. The study diagram summarizes study design, patient flow and monitored parameters. This interim report summarizes data for HBeAg+ pts only.
Result(s): Final Wk 24 results confirmed greater mean Iog10 declines in HBV DNA (5.27 vs 3.99; p=0.017) and RNA (2.34 vs 0.61; p<0.001) are achieved with 731+ETV vs ETV in Study 202. By Wk 24 in Study 201, the proportion of pts on 731+Nrtl vs Nrtl achieving DNA "TND" was 69% vs 0% (p<0.001), and the proportion of pts achieving RNA <35 U/mL whose baseline RNA > 35 U/mL was 52% vs 0% (p=0.0013) respectively. There are 64 HBeAg+ pts currently on treatment in Study 211, having received an overall treatment duration of >32 wks. Among the 27 HBeAg+ pts receiving 731+Nrtl in Study 201, 41% (11/27) have now achieved DNA TND along with RNA <35 U/mL and HBeAg <1 lU/mL At their last timepoint, Study 202 (Rx naive) pts now in Study 211 (n=22) have demonstrated mean DNA and RNA declines of 6.1 and 3.0 logs, respectively, with observed mean log changes of >0.6 for HBeAg (11 pts >0.5, 4 pts >1.0), >0.8 log for HBcrAg (7 pts >1.0, 3 pts >2.0) and >0.4 log for HBsAg (7 pts >0.5, 3 pts >1.0). When, administered in combination with Nrtl for up to 1 year, 731 has been well-tolerated, with only mild/moderate adverse events and lab abnormalities, and only a single discontinuation due to a Grade 1 rash.
Conclusion(s): ABI-H0731 continues to exhibit a favorable safety and tolerability profile in pts treated for up to 1 yr. The combination of 731+Nrtl results in faster, deeper declines in HBV DNA and RNA than Nrtl alone, as well as subsequent declines in the surrogate markers of cccDNA (pgRNA, HBeAg and HBcrAg) predictive of cccDNA pool depletion, and HBsAg. The emergent data supports the continued development of ABI-H0731. Updated safety and efficacy data will be presented