Alcohol-associated liver disease predicts increased post-liver transplant opioid use.

BACKGROUND: Alcohol-associated liver disease (ALD) is a rising indication for liver transplantation (LT). Prolonged opioid use after LT leads to increased graft loss and mortality. The aim is to determine if patients transplanted with a primary diagnosis of ALD had higher risk of post-LT opioid use (p-LTOU) compared to non-ALD patients. METHODS: This is a retrospective study of patients who underwent LT between 2015 and 2018 at Medstar Georgetown Transplant Institute. Patients with prolonged hospitalization post-LT (>90 days), death within 90 days post-LT, and re-transplants were excluded. RESULTS: Two hundred and ninety seven patients were transplanted, among 29% for indications of ALD. ALD patients were younger (52 vs. 56 years), more likely to be male (76% vs. 61%), Caucasian (71% vs. 44%), have higher MELD (28.8±8.8 vs. 25±8.8), and psychiatric disease than non-ALD patients (P < .05). There was no difference in pre-LT use of opioids, tobacco, marijuana, or illicit drugs between ALD and non-ALD patients. Pre-LT opioid use (OR = 11.7, P < .001), ALD (OR = 2.5, P = .01), and MELD score (OR = .95, P = .02) independently predicted 90-day p-LTOU. CONCLUSIONS: ALD, pre-LT opioid use, and MELD score independently predict p-LTOU. Special attention should be paid to identify post-LT prolonged opioid use in ALD patients.

Use of direct-acting antivirals for hepatitis C viral infection and association with intrahepatic cholangiocarcinoma: Is there a linkage?

Hepatitis C viral infection is recognized worldwide as a leading cause of cirrhosis and hepatocellular carcinoma. The goal of hepatitis C viral antiviral therapy is the permanent eradication of hepatitis C viral RNA, commonly referred to as a sustained virologic response - defined as "undetectable" RNA at 12 weeks following the completion of therapy. Hepatitis C viral treatment has dramatically advanced with the FDA approval of several new agents known as direct-acting antivirals. These drugs target specific nonstructural proteins of the virus, which disrupt viral replication, and therefore halt infection. However, recently, there has been a concern for increased risk of recurrence of treated hepatocellular carcinoma or denovo occurrence of hepatocellular carcinoma after treatment with direct-acting antivirals. We are now reporting three cases of intrahepatic cholangiocarcinoma that developed after sustained virologic response following hepatitis C viral treatment with direct-acting antivirals.

Ledipasvir/sofosbuvir is effective and well tolerated in postkidney transplant patients with chronic hepatitis C virus.

Patients with end-stage renal diseases on hemodialysis have a high prevalence of hepatitis C infection (HCV). In most patients, treatment for HCV is delayed until postrenal transplant. We assessed the effectiveness and tolerance of ledipasvir/sofosbuvir (LDV/SOF) in 32 postkidney transplant patients infected with HCV. The group was composed predominantly of treatment-naïve (75%) African American (68.75%) males (75%) infected with genotype 1a (62.5%). Most patients received a deceased donor kidney graft (78.1%). A 96% sustained viral response (SVR) was reported (27/28 patients). One patient relapsed. One patient with baseline graft dysfunction developed borderline rejection. No graft loss was reported. Six HIV-coinfected patients were included in our analysis. Five of these patients achieved SVR 12. There were four deaths, and one of the deaths was in the HIV group. None of the deaths were attributed to therapy. Coinfected patients tolerated therapy well with no serious adverse events. Serum creatinine remained stable at baseline, end of therapy, and last follow-up, (1.351±.50 mg/dL; 1.406±.63 mg/dL; 1.290±.39 mg/dL, respectively). In postkidney transplant patients with HCV infection with or without coinfection with HIV, a combination of LDV/SOF was well tolerated and effective.

Role of Stereotactic Body Radiation Therapy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC)is a common type of liver cancer with a poor prognosis, especially in patients with advanced stages or underlying liver disease. While surgical resection, liver transplantation, and ablation therapies have traditionally been the mainstay of treatment for HCC, radiation therapy has become increasingly recognized as an effective alternative, particularly for those who are not surgical candidates. Stereotactic Body Radiation Therapy (SBRT) is a highly precise form of radiation therapy that delivers very high doses of radiation to the tumor while sparing surrounding healthy tissue. Several studies have reported favorable outcomes with SBRT in HCC treatment. Moreover, SBRT can be used to treat recurrent HCC after prior treatment, offering a potentially curative approach in select cases. While SBRT has demonstrated its efficacy and safety in treating HCC, future studies are needed to further investigate the potential role of SBRT in combination with other treatments for HCC.

Inflammatory pseudotumors in the liver associated with influenza: A case report.

BACKGROUND: Inflammatory pseudotumor (IPT) is a rare and benign lesion that mimics malignancy and can develop in any part of the body. The pathophysiology and etiology of these quasineoplastic lesions remain unclear. CASE SUMMARY: We report a case of a 65-year-old male who presented with fevers, night sweats, and unintentional weight loss following an influenza infection and was found to have multiple hepatic IPT's following an extensive work up. CONCLUSION: Our case highlights the importance of considering hepatic IPT's in the differential in a patient who presents with symptoms and imaging findings mimicking malignancy shortly following a viral infection.

Acute liver injury and IgG4-related autoimmune pancreatitis following mRNA-based COVID-19 vaccination.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disease that can affect multiple organs. Autoimmune pancreatitis type 1 is a manifestation of IgG4-RD and can often mimic tumor-like masses. Autoimmune phenomena following COVID-19 mRNA vaccination are being increasingly reported. Currently, there are no cases in which IgG4-RD involving the hepatobiliary system has been reported following the COVID-19 vaccination. We present the first case of IgG4-RD and AIP type 1 to be associated with the mRNA-based COVID-19 vaccination.

The Spontaneous Regression of Primary Gastrointestinal Malignancies: An Observational Review.

The spontaneous regression or remission (SR) of cancer, often described as the partial or complete disappearance of a malignant tumor in the absence of all medical treatment and therapy, is a well-documented phenomenon. With efforts ongoing to establish cancer treatments that limit undesirable outcomes and adverse effects, these uncommon occurrences of SR carry significant implications for novel therapies and warrant further investigation. While several case studies have reported instances of SR in gastrointestinal (GI) malignancies, a comprehensive review of previous manifestations of SR in the GI tract remains lacking. The inclusion criteria for the rare phenomenon are also in need of an appropriate update that takes recent scientific advancements and emerging new medical technologies into account. Our analysis of 390 cases of SR in the GI tract focuses primarily on neoplasms of the hepatobiliary system and proposes an updated version of the older inclusion criteria for spontaneous regression.

Postoperative Myocardial Injury and Outcomes in Liver and Kidney Transplant Patients.

BACKGROUND/PURPOSE: Myocardial injury after noncardiac surgery (MINS) is associated with major adverse cardiac events (MACE), but its significance post-liver and post-kidney transplantation is not well-defined. METHODS/MATERIALS: We retrospectively studied consecutive patients undergoing single-organ liver or kidney transplantation at a large tertiary transplant center. Liver and kidney transplant patients with troponins drawn within 30 days of transplantation were included. The primary exposure was MINS, defined as troponin elevation above the 99th percentile of the upper reference limit within 30 days of transplantation. The primary outcome was MACE, defined as death, myocardial infarction, revascularization, stroke, or heart failure hospitalization. RESULTS: Overall, 112 patients were included: 58 (51.7%) were liver transplant recipients, and 54 (48.3%) were kidney transplant recipients. Patients with MINS were significantly older (mean age 59 vs. 54 years, p = 0.01) and more likely to have diabetes (35% vs. 17%, p = 0.03). Other baseline characteristics were similar. Sixteen patients (14.2%) developed MACE, including 11 (9.8%) with 1-year MACE. MINS patients were significantly more likely to develop 1-year MACE (adjusted hazard ratio, 10.4; 95% confidence interval, 1.8-198). Kaplan-Meier cumulative MACE was significantly higher in the MINS group (p = 0.03). CONCLUSIONS: Liver and kidney transplant recipients with MINS are significantly more likely to develop 1-year MACE compared to those without MINS. Future prospective studies are needed to further delineate the cardiac risk and outcomes in transplanted patients.

Pre-Operative Cardiovascular Testing before Liver Transplantation.

End-stage liver disease (ESLD) is increasingly prevalent and shares many risk factors with coronary artery disease (CAD). No specific guidelines exist for pre-liver transplant evaluation of CAD, and pretransplant cardiovascular testing varies widely. The aim of this study is to characterize pre-transplant cardiac testing practices with post-transplant clinical outcomes. We retrospectively reviewed patients undergoing initial liver transplantation at our transplant center between January 2015 and March 2019. Patients with previous liver transplantation or multi-organ transplantation were excluded. Electronic medical records were reviewed for relevant demographic and clinical data. We included 285 patients with a mean follow-up of 2.4 years. Of 274 patients (96.1%) with pre-transplant transthoracic echocardiogram (TTE), 18 (6.6%) were abnormal. Non-invasive ischemic testing was performed in 193 (68%) patients: 165 (58%) underwent stress TTE, 24 (8%) underwent myocardial perfusion imaging, 3 underwent coronary computed tomography, and 1 underwent exercise electrocardiogram. Sixteen patients (6%) had left heart catheterization of which 10 (63%) were abnormal and 5 proceeded to revascularization before transplant. There were 4 (1.4%) deaths within 30 days of transplant and 23 deaths (8.1%) in total. ST-elevation myocardial infarction was seen in 1 patient within 30 days and 1 patient after 30 days (0.7% total). No cardiovascular deaths were observed. Among patients undergoing liver transplantation, pre-transplantation cardiovascular testing is exceedingly common and post-transplant cardiovascular complications are rare. Additional research is needed to determine the optimal testing and surveillance in this patient population.

Safety and efficacy of sofosbuvir/velpatasvir/voxilaprevir in post-liver transplant patients with previous direct-acting antiviral failure: Six case reports.

BACKGROUND: Direct-acting antiviral (DAA) therapy regimens are highly effective at eliminating hepatitis C virus (HCV) infection but rates of sustained virologic response (SVR) are lower in patients with decompensated cirrhosis or hepatocellular carcinoma. Since many of these patients will be referred for liver transplant, they will require retreatment after transplantation. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) is recommended by guidelines as the preferred regimen to treat HCV in DAA-experienced patients following liver transplant however there is limited data. CASE SUMMARY: We present the cases of six liver transplant recipients who had previous treatment failure with sofosbuvir-based DAA therapy prior to transplantation and who then received SOF/VEL/VOX after transplant. CONCLUSION: This case series demonstrate the real-world efficacy and safety of SOF/VEL/VOX in the post liver transplant setting. Treatment was successful with all patients achieving SVR, it was well tolerated, and there were minimal drug-drug interactions with their immunosuppressants.

Expression of WIF-1 in inflammatory bowel disease.

The WNT/ß-catenin cellular network has been extensively studied in numerous diseases including inflammatory bowel disease (IBD). IBD is a condition that increases the risk of developing colorectal cancer. WIF-1 is an inhibitory protein that acts by blocking the interactions of WNT with its receptor complex, thus leading to downregulation of end products of this pathway. While WIF-1 has been characterized in several cancers, its relationship with IBD has yet to be elucidated. In this study, the expression of WIF-1 in patients with IBD was analyzed in order to provide insights into the pathophysiology and rationale for alternative therapies. Biopsies of both normal and inflamed colonic mucosa from patients with Crohn's disease or ulcerative colitis were histologically examined for the degree of morphologic changes, immune cell infiltration and presence of WIF-1 through immunohistochemistry. No differences were observed in WIF-1 expression linked to a particular condition, but WIF-1 stain was significantly enhanced in the crypts and lamina propria as inflammation increased in biopsies from patients with both, ulcerative colitis and Crohn's disease. These findings could give guidance to new therapeutic applications of the WNT/ß-catenin system and WIF-1 in IBD.

Serum bilirubin as a prognostic marker in patients with acute decompensated heart failure.

BACKGROUND/AIMS: Several prognostic markers for heart failure (HF) have been determined but the importance of liver function tests (LFTs) remains unknown. The aim of this study was to determine the prognostic significance, if any, of abnormal LFTs in acute decompensated HF. METHODS: All adult patients (> 18 years of age) who were admitted to a community hospital with a diagnosis of acute decompensated HF during the period January 2008 to December 2009 were identified. Exclusion criteria included acute coronary syndrome, active hepatobiliary disease, renal failure (serum creatinine ≥ 2 mg/dL), and malignancy. The primary end point was readmission secondary to acute exacerbation of HF. The Cox proportional hazard model was used for statistical analyses. RESULTS: Univariate analysis showed that serum total bilirubin (TB, p < 0.01), serum B-type natriuretic peptide (p < 0.05), ejection fraction (EF, p < 0.05), and heart rate (p < 0.05) were significant predictors of hospital readmission secondary to acute decompensated HF. Multivariate analysis showed that high serum TB (> 1.3 mg/dL) on admission was an independent predictor (p < 0.05) of hospital readmission secondary to HF. The 'at-risk' group-patients with serum TB > 1.3 mg/dL and/or EF < 35% on admission-had a readmission rate that was 87% ± 20% (p < 0.05) higher than those with neither criterion. CONCLUSIONS: In patients with acute decompensated HF, elevated serum TB on admission with or without low EF (< 35%) predicts a worse prognosis and early future readmission, secondary to HF.