Faculty Bibliography

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

INTRODUCTION: Cystoisosporiasis is an underrecognized gallbladder infection of immunocompetent hosts due in part to subtle histopathologic findings and low index of suspicion during examination of routine cholecystectomy specimens. This case will highlight the importance of detecting the organism in order to gain understanding of its life cycle and to raise awareness of the potential symptoms for those who become immunosuppressed. CASE DESCRIPTION/METHODS: A 65-year-old male with compensated cirrhosis presented with complaints of intermittent right upper quadrant pain for three months. He denied symptoms of diarrhea, jaundice, fever, chills, recent travel and sick contacts. CBC, BMP and liver enzymes were unremarkable. A right upper quadrant ultrasound illustrated multiple gallstones within the gallbladder along with wall thickening measuring up to 4.8 mm. The patient underwent a laparoscopic cholecystectomy with resolution of symptoms. Pathologic evaluation of the resected gallbladder described elongated "banana-shaped" zoites of C. belliwithin parasitopherous vacuoles in the gallbladder columnar mucosa. DISCUSSION: Cystoisospora belli (C. belli) is an intracellular protozoan of the intestinal epithelium often associated with gastrointestinal (GI) disease in immunocompromised patients or those who travel to endemic areas. The infection is acquired by fecal-oral route through ingestion of infective oocysts in contaminated water. Symptoms of C. belli include watery diarrhea, abdominal pain, nausea, vomiting and weight loss due to malabsorption, whereas most infected immunocompetent patients remain asymptomatic. C. belli is known to reside within parasitophorous vacuoles in epithelial cells of the small intestine; however, incidence of gallbladder infection is on the rise as there becomes an increased awareness and recognition on the part of the pathologist. Previously, lack of recognition has stemmed from multiple factors including a low index of suspicion in patients without clinical symptoms or those who remain immunocompetent, the underwhelming appearance of infected gallbladders with lack of significant tissue reaction, as well as the sparse distribution of the organisms themselves. The unexpectedly high prevalence in gallbladder specimens has given rise to the idea that the gallbladder may be an anatomic reservoir for this commensal organism in the immunocompetent host. For this reason, C. belli infection should be considered in patients exhibiting typical GI symptoms following immunosuppression. (Figure Presented)

INTRODUCTION: Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the United States (U.S). The United States Drug-Induced Liver Injury Network (DILIN) reported that approximately 15-20% of DILI cases per year could be attributed to herbal and dietary supplements. Khat is a stimulant derived from the leaves of the shrub Catha edulis, which is native to North Yemen and other East African countries. Chewing khat, a drug of abuse, is an established social habit in areas endemic to the shrub. Khat has been associated with clinically relevant acute and chronic liver injury. We present a case of drug induced liver injury related to Khat. CASE DESCRIPTION/METHODS: A 47 year old Yemeni male with no medical history presented with jaundice. He denied prior liver disease, alcohol use or prescription drugs. He reported routine use of Khat. Labwork is shown in Figure 1. MRCP revealed mild hepatosplenomegaly. Viral workup revealed immunity to hepatitis A. The patient presented 3 months later with jaundice and persistently elevated liver enzymes. Abdominal ultrasound was unrevealing. Extensive workup revealed a positive antinuclear antibody 1:320, in homogeneous pattern and an elevated serum immunoglobulin G and was otherwise unrevealing. Liver biopsy revealed mild portal mononuclear infiltration associated with focal interface hepatitis and widespread lobular hepatitis with plasma cell prominence in the infiltrates (Figures 1 and 2). Subsequently the patient was started on a course of Prednisone and Ursodiol with complete resolution of liver injury. DISCUSSION: Liver injury related to Khat typically occurs after years of use and may present acutely with nausea, fatigue, and jaundice or chronically with evidence of portal hypertension. Biochemical injury is typically hepatocellular and liver enzymes may be significantly elevated. Autoantibodies can mimic autoimmune hepatitis. Resolution of liver injury typically occurs with cessation of khat use. Patients may require corticosteroid therapy however the response is typically partial. Liver transplantation due to Khat related liver failure has been reported. Given immigration of individuals from countries endemic to Khat, an extensive history including use of cultural drugs such as Khat and other herbal remedies is critical in making a diagnosis of unexplained liver toxicity. Our case highlights the importance of a complete drug and supplement history and maintaining a high index of suspicion for DILI in the appropriate clinical context. (Table Presented)

INTRODUCTION: The majority of "giant" hemangiomas remain asymptomatic with no cause for surgical intervention; however, this may not hold true for massive tumors. The following case will review the challenges facing both patients and physicians when managing these atypical tumors. CASE DESCRIPTION/METHODS: A 49-year-old male with no medical problems presented with complaints of post-prandial bloating, early satiety and mild epigastric discomfort. The bloating was intermittent for several years; however, symptoms have recently curtailed his eating habits. CBC, BMP and liver enzymes were unremarkable. An ultrasound highlighted a massively enlarged liver extending into the pelvis and displacing surrounding organs. The liver parenchyma appeared to be replaced with a homogenous, hyperechoic lesion. An MRI then illustrated a 29.5x20.1x19.4 cm, strongly hyperintense mass on T-2 weighted sequences consistent with the diagnosis of a hemangioma. He was referred to a hepatobiliary surgeon and an extended right hepatectomy was eventually performed. Histopathology results described vast endothelial lined channels supported by thin fibrous stroma without features of malignancy. The patient returned to clinic four weeks after surgery reporting complete resolution of his symptoms. DISCUSSION: Hemangiomas are the most common benign solid tumor of the liver with little to no risk of malignant transformation. Often discovered incidentally on imaging studies, the majority of these tumors remain indolent without the need for routine surveillance. Rarely these tumors become symptomatic, often correlating with tumor size. The definition of "giant" liver hemangioma remains controversial, with most authors assigning the label to tumors greater than 4cm or 5cm in size. It is for this reason that management of giant hemangiomas remains highly debated (i.e. observation versus resection). Recent studies have shown that tumors greater than 20cm in size pose a higher risk for GI symptoms related to mass effect on surrounding organs as well as causing a disturbance in the hematologic and coagulation systems. Surgical resection should be considered for symptomatic or complicated lesions, or when the diagnosis remains inconclusive. It is our belief that size classifications for giant hemangiomas requires further subgrouping to consider the danger of these massive tumors as well as the increased morbidity of surgery. Proper management of these tumors should be individualized to each patient and include [2259] Figure 1. a multidisciplinary team approach. (Figure Presented)

Article Title: ACG Clinical Guideline: Hereditary Hemochromatosis.