A Case of Hepatic Tuberculosis in a Patient on Adalimumab for Ankylosing Spondylitis.

Hepatic tuberculosis (TB) is an uncommon extrapulmonary manifestation of tuberculosis. Hepatic TB is more common in immunocompromised patients, such as those on immunosuppressive medications or those with a human immunodeficiency virus (HIV) infection. Primary hepatic TB is rare, and liver involvement is often secondary to spreading from the lymphatics, portal vein, or hepatic artery. We report a case of hepatic TB in a patient on adalimumab for ankylosing spondylitis (AS).

Utilization of Immunotherapy as a Neoadjuvant Therapy for Liver Transplant Recipients with Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is widely recognized as the predominant type of primary liver malignancy. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for unresectable HCC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era to enhance outcomes in patients with HCC. Here, we report our experience with patients with HCC who had received Immune Checkpoint Inhibitors (ICPI) prior to curative OLT. Methods: This was a retrospective cohort that included patients with HCC who received ICPI prior to OLT at a single institution from January 2019 to August 2023. Graft rejection was assessed and reported along with the type of ICPI, malignancy treated, and the timing of ICPI in association with OLT. Results: During this cohort period, six patients with HCC underwent OLT after neoadjuvant ICPI. All patients were male with a median age of 61 (interquartile range: 59-64) years at OLT. Etiology associated with HCC was viral (N = 4) or Non-alcoholic steatohepatitis, NASH (N = 2). Tumor focality was multifocal (N = 4) and unifocal (N = 2). Lymphovascular invasion was identified in four patients. No perineural invasion was identified in any of the patients. All patients received ICPI including atezolizumab/bevacizumab (N = 4), nivolumab/ipilimumab (N = 1), and nivolumab as monotherapy (N = 1). All patients received either single or combined liver-directed/locoregional therapy, including transarterial chemoembolization (TACE), Yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 5 months. All patients responded to ICPI and achieved a safe and successful OLT. All patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT and one patient received prednisone as additional IS. No patient had clinical evidence of rejection. Conclusions: This cohort emphasizes the success of tumor downstaging by ICPI for OLT when employed as the neoadjuvant therapy strategy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, we believe that our study lays the groundwork for prospective trials to further examine the impact of ICPI prior to OLT.

Training Robust T1-Weighted Magnetic Resonance Imaging Liver Segmentation Models Using Ensembles of Datasets with Different Contrast Protocols and Liver Disease Etiologies.

Image segmentation of the liver is an important step in several treatments for liver cancer. However, manual segmentation at a large scale is not practical, leading to increasing reliance on deep learning models to automatically segment the liver. This manuscript develops a deep learning model to segment the liver on T1w MR images. We sought to determine the best architecture by training, validating, and testing three different deep learning architectures using a total of 819 T1w MR images gathered from six different datasets, both publicly and internally available. Our experiments compared each architecture's testing performance when trained on data from the same dataset via 5-fold cross validation to its testing performance when trained on all other datasets. Models trained using nnUNet achieved mean Dice-Sorensen similarity coefficients > 90% when tested on each of the six datasets individually. The performance of these models suggests that an nnUNet liver segmentation model trained on a large and diverse collection of T1w MR images would be robust to potential changes in contrast protocol and disease etiology.

Effect of a Hispanic outreach program on referral and liver transplantation volume at a single center.

BACKGROUND: Although Hispanic patients have high rates of end-stage liver disease and liver cancer, for which liver transplantation (LT) offers the best long-term outcomes, they are less likely to receive LT. Studies of end-stage renal disease patients and kidney transplant candidates have shown that targeted, culturally relevant interventions can increase the likelihood of Hispanic patients receiving kidney transplant. However, similar interventions remain largely unstudied in potential LT candidates. METHODS: Referrals to a single center in Texas with a large Hispanic patient population were compared before (01/2018-12/2019) and after (7/2021-6/2023) the implementation of a targeted outreach program. Patient progress toward LT, reasons for ineligibility, and differences in insurance were examined between the two eras. RESULTS: A greater proportion of Hispanic patients were referred for LT after the implementation of the outreach program (23.2% vs 26.2%, p = 0.004). Comparing the pre-outreach era to the post-outreach era, more Hispanic patients achieved waitlisting status (61 vs 78, respectively) and received a LT (971 vs 82, respectively). However, the proportion of Hispanic patients undergoing LT dropped from 30.2% to 20.3%. In the post-outreach era, half of the Hispanic patients were unable to get LT for financial reasons (112, 50.5%). CONCLUSIONS: A targeted outreach program for Hispanic patients with end-stage liver disease effectively increased the total number of Hispanic LT referrals and recipients. However, many of the patients who were referred were ineligible for LT, most frequently for financial reasons. These results highlight the need for additional research into the most effective ways to ameliorate financial barriers to LT in this high-need community.

Proceedings of the 28th Annual Congress of the International Liver Transplantation Society.

The 2023 Joint International Congress of the International Liver Transplantation Society (ILTS), the European Liver and Intestine Transplant Association (ELITA), and the Liver Intensive Care Group of Europe (LICAGE) held in Rotterdam, the Netherlands, marked a significant recovery milestone for the liver transplant community after COVID-19. With 1159 participants and a surge in abstract submissions, the event focused on "Liver Disorders and Transplantation: Innovations and Evolving Indications." This conference report provides a comprehensive overview of the key themes discussed during the event, encompassing Hepatology, Anesthesia and Critical Care, Acute Liver Failure, Infectious Disease, Immunosuppression, Pediatric Liver Transplantation, Living Donor Liver Transplantation, Transplant Oncology, Surgical Approaches, and Machine Perfusion. The congress provided a platform for extensive discussions on a wide range of topics, reflecting the continuous advancements and collaborative efforts within the liver transplant community.

Pushing the limits of treatment for hepatocellular carcinoma.

PURPOSE OF REVIEW: We review existing and newer strategies for treatment and surveillance of hepatocellular carcinoma (HCC) both pre and postliver transplantation. SUMMARY: HCC is rising in incidence and patients are often diagnosed at later stages. Consequently, there is a need for treatment strategies which include collaboration of multiple specialties. Combinations of locoregional, systemic, and surgical therapies are yielding better postliver transplantation (post-LT) outcomes for patients with HCC than previously seen. Tumor biology (tumor size, number, location, serum markers, response to therapy) can help identify patients who are at high risk for HCC recurrence posttransplantation and may expand transplant eligibility for some patients.

Transplant Oncology: An Emerging Discipline of Cancer Treatment.

Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients' survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation.

Evidence to Date: Clinical Utility of Tremelimumab in the Treatment of Unresectable Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide and is associated with significant health care costs and burden. Management of HCC is guided based on the Barcelona Clinic Liver Cancer (BCLC) system and includes liver transplantation, surgical resection, and liver-directed and systemic therapies. In recent years, there have been significant advancements in understanding the immunogenicity of HCC and this has led to approval of different targeted agents as well as immunotherapy for advanced HCC. Tremelimumab is a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blocking antibody and has recently been approved in combination with durvalumab (a programmed death-ligand 1 [PDL1] inhibitor) as first-line therapy for advanced (Barcelona Clinic Liver Cancer Stage C) HCC. In this article, we review the different available systemic therapies for advanced HCC with special focus on the clinical utility of tremelimumab for the treatment of unresectable HCC.

Combined Hepatocellular Neuroendocrine Carcinoma: A Rare Tumor.

Neuroendocrine tumors originate from neuroendocrine cells primarily located in the gastrointestinal tract. These tumors often metastasize to the liver. Primary hepatic neuroendocrine carcinomas are uncommon, and combined hepatocellular neuroendocrine carcinomas are exceedingly rare. There is a lack of data on the management of these rare tumors. Most cases have very poor prognosis secondary to aggressive behavior of the neuroendocrine tumor component. It is important for clinicians to be aware of this rare carcinoma to allow for early diagnosis and optimize potential treatment options.

Pancreatic tuberculosis in a liver transplant recipient: a case report.

The pancreatic form of tuberculosis (TB) is rare and its diagnosis is challenging, since it manifests itself with non-specific symptoms and non-pathognomonic radiological findings, mimicking a neoplasia of the pancreas. Here, we report the case of a patient who had previously undergone liver transplantation and sought care for abdominal pain, weight loss, anorexia, hematochezia and postprandial fullness. Following an exploratory laparotomy and nucleic acid amplification testing on a pancreatic sample that had been collected, the patient was diagnosed with pancreatic TB. The patient received anti-tubercular pharmacological therapy and required percutaneous biliary drainage. Awareness of the possibility of a pancreatic TB diagnosis is important for clinicians. This attention should be even greater in patients who have undergone transplants, who are immunodeficient or who are from endemic areas.

Women's health issues in solid organ transplantation: Breast and gynecologic cancers in the post-transplant population.

The success of solid organ transplant has steadily improved which has led to a unique set of post-transplant issues. The rates of de novo cancer in the solid organ transplant recipient population are higher than those in the general population. There is growing evidence that breast and gynecologic cancers may have a higher mortality rate in post-transplant patients. Cervical and vulvovaginal cancers specifically have a significantly higher mortality in this population. Despite this increased mortality risk, there is currently no consistent standard in screening and identifying these cancers in post-transplant patients. Breast, ovarian and endometrial cancers do not appear to have significantly increased incidence. However, the data on these cancers remains limited. Further studies are needed to determine if more aggressive screening strategies would be of benefit for these cancers. Here we review the cancer incidence, mortality risk and current screening methods associated with breast and gynecologic cancers in the post-solid organ transplant population.

Giant calyceal diverticulum with an extra-renal component: A case report.

Calyceal diverticula are urine-filled non-secretory cavities that result from outpouchings of the kidney's calyx or pelvis. These cavities lie in the renal parenchyma and are linked to the kidney's collecting system through a narrow channel. They are generally small in size and present without symptoms. Here, we report the case of a middle-aged patient who was diagnosed, following imaging exams, with a giant calyceal diverticulum presenting with an extra-renal component, a remarkably rare finding. The patient's condition was successfully treated through excision by laparoscopic surgery.

Impact of pre-operative transjugular intrahepatic portosystemic shunt on post-operative outcomes following non-transplant surgeries in patients with decompensated cirrhosis.

Background: Patients with cirrhosis have a high risk for morbidity and mortality in relation to abdominal surgery. Despite improvements in surgical techniques and intensive care, major abdominal surgery still remains a challenge. Major factors determining short- and long-term survival and perioperative complications in this patient population include severity of liver dysfunction, degree of portal hypertension (PHTN), and the presence of related complications such as ascites. Elective transjugular intrahepatic portosystemic shunt (TIPS) placement prior to surgery has been reported to improve perioperative outcomes, but available data is limited to case reports and small case series. We aimed to determine the impact of elective TIPS placement on perioperative outcomes after abdominal-pelvic surgeries in patients with cirrhosis. Methods: We performed a retrospective chart review of patients who underwent elective TIPS and compared these patients with a cohort of cirrhotic patients who underwent any abdominal surgeries without TIPS placement. The primary outcomes were mortality at 30 days and 1 year following surgery. Other post-operative outcomes compared between the two groups, included: blood loss, worsening ascites, wound leak, infections, encephalopathy, liver decompensation, and length of hospitalization. Results: Among 38 patients with cirrhosis who underwent abdominal surgery, 20 patients underwent pre-operative elective TIPS placement. Demographic characteristics of the two groups were comparable including age, gender, and body mass index (BMI). The median age was 62 years with a male predominance (62.5%). Both groups had similar etiologies of cirrhosis with hepatitis C virus (HCV) (34.2%) being most common. The most frequent indications for surgery were strangulated hernia (50%) in the TIPS group and acute cholecystitis (55.6%) in the non-TIPS group. Mean pre-TIPS hepato-venous portal gradient (HVPG) was 16.5 mmHg and mean post-TIPS HVPG was 7.0 mmHg. Mortality at 1 month was not statistically different between the groups (20% vs. 5.6%, respectively, P=0.19). The 1-year mortality was also not statistically different between the two groups (20% vs. 11.1%, P=0.36). Conclusions: We found no statistically significant difference in mortality or rate of post-operative complications between patients who received pre-operative TIPS and those who did not in our age-matched cohort.

Modern Outcomes After Liver Retransplantation: A Single-center Experience.

BACKGROUND: The need for liver retransplantation (reLT) has increased proportionally with greater numbers of liver transplants (LTs) performed, use of marginal donors, degree of recipient preoperative liver dysfunction, and longer survival after LT. However, outcomes following reLT have been historically regarded as poor. METHODS: To evaluate reLT in modern recipients, we retrospectively examined our single-center experience. Analysis included 1268 patients undergoing single LT and 68 patients undergoing reLT from January 2008 to December 2021. RESULTS: Pre-LT mechanical ventilation, body mass index at LT, donor-recipient ABO incompatibility, early acute rejection, and length of hospitalization were associated with increased risk of needing reLT following index transplant. Overall and graft survival outcomes in the reLT cohort were equivalent to those after single LT. Mortality after reLT was associated with Kidney Donor Profile Index, national organ sharing at reLT, and LT donor death by anoxia and blood urea nitrogen levels. Survival after reLT was independent of the interval between initial LT and reLT, intraoperative packed red blood cell use, cold ischemia time, and preoperative mechanical ventilation, all previously linked to worse outcomes. CONCLUSIONS: These data suggest that reLT is currently a safer option for patients with liver graft failure, with comparable outcomes to primary LT.

Irritable Bowel Syndrome Symptoms in Nonalcoholic Fatty Liver Disease Patients Are an Indicator of Depression and Anxiety.

GOALS: Determine factors associated with Irritable bowel syndrome (IBS) in nonalcoholic fatty liver disease (NAFLD) patients. BACKGROUND: IBS affects 10% to 15% of the adult population worldwide and is linked to anxiety and depression. The impact of IBS-type symptoms in NAFLD patients is not well described. STUDY: A cross-sectional study of patients in the hepatology clinic at Houston Methodist Hospital was performed based on a respondent postal survey. IBS was defined by the Rome IV questionnaire, anxiety and depression were assessed with the Hospital Anxiety Depression scale. Patients with inflammatory bowel disease, colorectal carcinoma, or small bowel tumors were excluded. Patients were divided based on Rome IV diagnostic criteria for IBS and Hospital Anxiety Depression scale. RESULTS: 130 patients were included in the analysis, 38 satisfied Rome IV criteria for IBS (IBS group) versus 92 who did not (non-IBS group). Depression was more prevalent in the IBS group (18.4% vs 5.4%, P =0.01). Anxiety was also greater in the IBS group (31.6% vs 9.8%, P =0.002). Female sex, depression, and body mass index (BMI)>30 were independent predictors of IBS in NAFLD in 4 multiple logistic regression models. In newly diagnosed IBS patients, gamma-glutamyl transferase levels were lower (67.5 vs 28, P =0.04). Current abdominal pain was higher than 100% versus 81.3% ( P =0.045), as was pain associated with the change in stool frequency (96.3% vs 50%; P <0.001). CONCLUSION: Our study highlights the increased rate of IBS symptoms, depression, and anxiety in patients with NAFLD. Clinicians should be alert when IBS symptoms are reported by a NAFLD patient and be aware of the impact of these comorbidities on quality of life and response to therapy.

Hepatocellular Carcinoma Recurrence as Isolated Adrenal Metastasis.

Hepatocellular carcinoma is the sixth most common cancer in the Western world. The most frequent sites of metastasis are lungs, lymph nodes, and bones. Risk factors for extrahepatic metastasis are advanced intrahepatic lesions, vascular invasion, elevated tumor markers, and viral hepatitis. Isolated metachronous adrenal metastasis occurring after liver transplantation is exceedingly rare.

Pancreatic tuberculosis in a liver transplant recipient: a case report

ABSTRACT The pancreatic form of tuberculosis (TB) is rare and its diagnosis is challenging, since it manifests itself with non-specific symptoms and non-pathognomonic radiological findings, mimicking a neoplasia of the pancreas. Here, we report the case of a patient who had previously undergone liver transplantation and sought care for abdominal pain, weight loss, anorexia, hematochezia and postprandial fullness. Following an exploratory laparotomy and nucleic acid amplification testing on a pancreatic sample that had been collected, the patient was diagnosed with pancreatic TB. The patient received anti-tubercular pharmacological therapy and required percutaneous biliary drainage. Awareness of the possibility of a pancreatic TB diagnosis is important for clinicians. This attention should be even greater in patients who have undergone transplants, who are immunodeficient or who are from endemic areas.

Hepatocellular Carcinoma Due to Nonalcoholic Fatty Liver Disease: Current Concepts and Future Challenges.

Obesity has been labeled as the global pandemic of the 21st century, resulting from a sedentary lifestyle and caloric excess. Nonalcoholic fatty liver disease (NAFLD), characterized by excessive hepatic steatosis, is strongly associated with obesity and metabolic syndrome and is estimated to be present in one-quarter of the world population, making it the most common cause of the chronic liver disease (CLD). NAFLD spectrum varies from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The burden of NAFLD has been predicted to increase in the coming decades resulting in increased rates of decompensated cirrhosis, hepatocellular carcinoma (HCC), and liver-related deaths. In the current review, we describe the pathophysiology of NAFLD and NASH, risk factors associated with disease progression, related complications, and mortality. Later, we have discussed the changing epidemiology of HCC, with NAFLD emerging as the most common cause of CLD and HCC. We have also addressed the risk factors of HCC development in the NAFLD population (including demographic, metabolic, genetic, dietary, and lifestyle factors), presentation of NAFLD-associated HCC, its prognosis, and the issue of HCC development in non-cirrhotic NAFLD. Lastly, the problems related to HCC screening in the NAFLD population, the remaining challenges, and future directions, especially the need to identify the high-risk individuals, will be discussed. We will conclude the review by summarizing the clinical evidence for treating fibrosis and preventing HCC in those at risk with NAFLD-associated HCC.

Proceedings of the 26th Annual Virtual Congress of the International Liver Transplantation Society.

After a 1-y absence due to the coronavirus disease 2019 pandemic, the 26th Annual Congress of the International Liver Transplantation Society was held from May 15 to 18, 2021, in a virtual format. Clinicians and researchers from all over the world came together to share their knowledge on all the aspects of liver transplantation (LT). Apart from a focus on LT in times of coronavirus disease 2019, featured topics of this year's conference included infectious diseases in LT, living donation, machine perfusion, oncology, predictive scoring systems and updates in anesthesia/critical care, immunology, radiology, pathology, and pediatrics. This report presents highlights from invited lectures and a review of the select abstracts. The aim of this report, generated by the Vanguard Committee of International Liver Transplantation Society, is to provide a summary of the most recent developments in clinical practice and research in LT.

Gemcitabine Plus Cisplatin Versus Non-Gemcitabine and Cisplatin Regimens as Neoadjuvant Treatment for Cholangiocarcinoma Patients Prior to Liver Transplantation: An Institution Experience.

Background: Cholangiocarcinoma management is constantly being updated in view of existing evidence in order to establish practice guidelines and consensus statements. However, the available treatment guidelines to optimize outcomes for cholangiocarcinoma patients who require liver transplantation are still controversial. This study contributing to the cholangiocarcinoma care field by investigating a new promising neoadjuvant therapy that might be help to grant the liver transplant option to the patients with cholangiocarcinoma. Here, we evaluate and compare the potential efficacy of chemotherapy combination of Gemcitabine plus Cisplatin versus non- Gemcitabine and Cisplatin regimens as a neo-adjuvant treatment for cholangiocarcinoma patients prior to liver transplantation. Methods: In this retrospective study, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with either the combination of neo-adjuvant Gemcitabine plus Cisplatin with no radiation or other standard options of neo-adjuvant treatment. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center in collaboration with the same institution's transplant center according to an open-labeled, and centers-approved clinical management protocol. Patients were listed for liver transplantation if they had a minimum of six months of scans showing response or confirmation of disease stability. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. This report, which was censored on March 18, 2022. Results: Out of a total of 707 liver transplant recipients were screened, 37 patients were confirmed with a diagnosis of cholangiocarcinoma and only 18 patients (11 males and 7 females) with a median age of 61.83 [interquartile range: 58.27-68.74] met inclusion criteria. Of the 18 patients enrolled, 10 received Gemcitabine/Cisplatin, while 8 patients received either Gemcitabine monotherapy or Capecitabine or FOLFIRI. Months for recurrence after transplantation was 20.1 (IRQ: 20.1-20.1) in the Gemcitabine/Cisplatin group and 9.5 (8.9-12.47) months in the non-Gemcitabine/Cisplatin group (p-value=0.18). Median months of follow-up in the Gemcitabine/Cisplatin group was 28.35 (27.1-32.23) months versus 40.12 (20.6-56.22) months in the non-Gemcitabine/Cisplatin group (p-value=0.33). In non-Gemcitabine/Cisplatin patients, overall survival was 75% (95% CI 31-93%) at both years 1 and 2; 63% (95% CI 23-86%) at years 3 to 5. In Gemcitabine/Cisplatin patients, overall survival was 100% (95% CI 100-100%) at both years 1 and 2; 75% (95% CI 13-96%) at years 3 to 5. Three non-Gemcitabine/Cisplatin patients died at 328 days, 340 days, and 896 days, respectively. One Gemcitabine/Cisplatin patient died at 885 days. Conclusion: Our findings suggest improved overall survival outcomes with Gemcitabine plus Cisplatin as neo-adjuvant treatment with no concomitant radiation compared to non-Gemcitabine/Cisplatin regimens in patients with cholangiocarcinoma prior to liver transplantation.