Post-liver Transplant Setting Research Articles

NLRP3 Inflammasome in Acute and Chronic Liver Diseases.

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is an intracellular complex that upon external stimuli or contact with specific ligands, recruits other components, forming the NLRP3 inflammasome. The NLRP3 inflammasome mainly mediates pyroptosis, a highly inflammatory mode of regulated cell death, as well as IL-18 and IL-1β production. Acute and chronic liver diseases are characterized by a massive influx of pro-inflammatory stimuli enriched in reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs) that promote the assemblage and activation of the NLRP3 inflammasome. As the major cause of inflammatory cytokine storm, the NLRP3 inflammasome exacerbates liver diseases, even though it might exert protective effects in regards to hepatitis C and B virus infection (HCV and HBV). Here, we summarize the current knowledge concerning NLRP3 inflammasome function in both acute and chronic liver disease and in the post liver transplant setting, focusing on the molecular mechanisms involved in NLRP3 activity.

Liver Interventions in Children

AbstractThis review provides a comprehensive summary of the role of the interventional radiologist in managing liver disorders in children. Interventions are discussed with focus on indications for procedure, technical aspects, and patient management. Recommendations are supported by the most recent evidence and practice experience of the authors in the four subtopics, such as interventions in the post–liver transplant setting, for portal hypertension, for liver tumors, and for vascular anomalies of the liver, with emphasis on congenital portosystemic shunts.

S3037 Hepatocellular Carcinoma With Para-Celiac Lymph Node Metastasis Presenting as Unknown Primary Neoplasm in the Post-Liver Transplant Setting

Introduction: Metastatic HCC without primary liver lesion is an exceedingly rare clinicopathologic entity. Only a handful of case reports have been reported to date, mostly involving bony structures without primary liver cancer. To our knowledge, we hereby present the first case of metastatic HCC involving the para-celiac lymph nodes in the post-liver transplant setting. Case Description/Methods: A 73-year-old male who previously underwent liver transplant for non-alcoholic steatohepatitis was admitted to GI for the evaluation of a suspicious pancreatic tail cyst. He denied acute GI symptoms. Laboratory studies revealed normal liver enzymes. CT abdomen and pelvis showed a 2-cm lesion located under the right hemidiaphragm, posterior to the right hepatic lobe. Subsequently, the patient underwent diagnostic EUS with biopsy for both lesions. EUS revealed an irregularly shaped oval cyst in the tail, round cysts in the body and neck, and a complex of small cysts in the pancreatic head. The 45 x 55-mm para-celiac mass was irregularly shaped, hypoechoic, homogenous solid lesion, located lateral to the celiac axis. It had well-defined endosonographic borders. Immunostaining of the fine-needle biopsy (FNB) of the para-celiac mass was positive for Hep Par-1 and pancytokeratin, consistent with metastatic HCC (Figure 1; A&B). Fine-needle aspiration (FNA) of the pancreatic cysts was negative for malignancy. Alpha-fetoprotein level was 11.1 ng/mL. The diagnosis of HCC of unknown primary was finally made. The patient then underwent an uneventful surgical resection. Discussion: To our research, this is the first reported case of metastatic HCC without primary liver lesion involving the para-celiac lymph nodes in a post-transplant patient. With regard to pathogenesis, one theory implicates the presence of ectopic liver tissue that transforms into HCC. The presence of micro-HCC that regresses spontaneously or gets destroyed by the immune system can also be a plausible explanation. Standard diagnostic protocol for HCC consists of imaging (CT or MRI) and/or biopsy. Even in patients with cirrhosis, the diagnostic modality of choice is imaging and liver biopsy is less frequently performed. Biopsy is recommended for atypical hepatic lesions on imaging or nonclassical enhancement patterns or detection in the absence of cirrhosis. No standardized treatment exists for metastatic HCC with unknown primary. This report illustrates that clinicians should consider HCC while evaluating patients for the primary origin of metastatic carcinoma.Figure 1.: Immunostaining of the para-celiac mass. Endoscopic ultrasound-guided fine-needle biopsy (FNB) specimen indicating positive status for Hep Par-1 and pancytokeratin.

Bariatric surgery, obesity and liver transplantation.

The obesity epidemic has profoundly impacted the epidemiology and trends of liver disease. In the current era, non-alcoholic fatty liver disease (NAFLD) progressing to non-alcoholic steatohepatitis (NASH) has emerged as the second leading indication for liver transplant (LT) and has been associated with the rising rates of hepatocellular carcinoma (HCC) with and without underlying cirrhosis. Obesity has been associated with poor post-transplant outcomes including lower patient and graft survival; higher risk of post-operative metabolic complications; poor wound healing; and higher infection rates. Bariatric surgery is currently the most effective management of morbid obesity and has been offered to patients both in the pre and post LT setting. The techniques attempted in LT recipients most commonly include sleeve gastrectomy (SG), gastric bypass surgery with few cases of gastric banding and biliopancreatic diversion. However, there is lack of evidence-based data on the optimal management for patients with obesity and who are liver transplant candidates and/or recipients. In the following discussion, we present the highlights from a review of the literature.

Comparable Survival for Hepatitis C–Related Hepatocellular Carcinoma After Liver Transplantation Irrespective of Viremic Status

Direct-acting antiviral (DAA) therapy for the treatment of chronic hepatitis C virus (HCV) infection is efficacious and well-tolerated in the post-liver transplant (LT) setting, prompting increased use of donors with HCV infection in patients waitlisted for LT.1,2 Although the incidence of nonviral hepatocellular carcinoma (HCC) is rising, HCV remains the most common risk factor for HCC among patients listed for LT in the United States.3 The use and outcomes of HCV-infected donors among patients with active HCV viremia waitlisted for (HCV-HCC) is lacking. Our aim was to evaluate post-LT survival among patients with HCV-HCC based on both recipient (active vs cured HCV) and donor (HCV+ vs HCV-) viremic status. Using the United Network for Organ Sharing (UNOS) registry, we analyzed all adult patients with HCV-HCC who underwent LT and had available recipient/donor HCV nucleic acid test (NAT) results from March 31, 2015 (date UNOS began reporting donor NAT) through June 30, 2021. Patients with acute liver failure, simultaneous organ transplant, previous LT, and those missing recipient and/or donor NAT results were excluded.

Hemophagocytic lymphohistiocytosis occurring after liver transplantation: A case series and review of the literature.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by excessive inflammation and tissue destruction due to a dysregulated immune response. Its secondary form is most commonly triggered by viral infection or malignancy. There have previously been 11 cases of acquired HLH described following liver transplantation in adult transplant recipients, most occurring within the first year following transplantation. Herein, we describe two cases of HLH in liver transplant recipients that both occurred remotely following transplantation. In the first case, HLH was thought to be triggered by the development of a post-transplant lymphoproliferative disorder in a patient who was initially diagnosed with recurrent autoimmune hepatitis. In the second, it was thought to be triggered by a newly acquired human herpesvirus-8 infection. In both cases, the syndrome was not recognized until treatment for the initial putative diagnoses was unsuccessful. Despite treatment, both patients unfortunately died from multiorgan failure. HLH in the post-liver transplant setting is likely under-recognized and has a high mortality; early diagnosis and intervention may lead to improved outcomes.

Sinusoidal dilatation and congestion in post-transplant liver biopsies from patients presenting with transaminitis

AimsSinusoidal dilatation and congestion (SDC) in liver biopsy may be obstructive (due to venous outflow impairment) or non-obstructive in nature. The significance of this finding in the post-liver transplant setting...

Posttransplant Hemophagocytic Lymphohistiocytosis in Pediatric Liver Transplant Recipients.

Hemophagocytic lymphohistiocytosis (HLH) refers to the life-threatening syndrome of pathologic immune activation, with a characteristic constellation of clinical findings comprising prolonged fever, splenomegaly, cytopenias, elevated inflammatory markers, and hemophagocytosis (HP).(1) It has been reported to occur after solid organ transplantation (SOT).(2) However, data are scarce regarding the incidence, characteristics, and long-term outcome of HLH in the post-liver transplantation (LT) setting, with only 5 pediatric and 18 adult cases reported in the literature.(3-7).

S2434 Post Liver Transplant Appendicitis: Be Vigilant for Appendiceal Tumors!

INTRODUCTION: De novo malignancies in post-transplant patients are a sequel of immunosuppression and have an incidence between 3 and 26%. They are one of the most common cause of morbidity and mortality in long term survival of liver transplant patients with risk almost four times greater than general population. While case reports of appendiceal tumors have been documented in renal transplant patients, there is not much literature for liver transplant patients. Also, fewer than 30 cases of appendicitis in post liver transplant setting have been reported in literature till date. We present a very rare case of mucinous appendiceal adenocarcinoma that presented as appendicitis within three years of liver transplant. CASE DESCRIPTION/METHODS: A 32-year-old Caucasian female with decompensated autoimmune cirrhosis underwent liver transplant in 2017 after detailed transplant evaluation. Post-transplant she was kept on protocol-based immunosuppression consisting of tacrolimus, mycophenolic acid and prednisolone with acceptable therapeutic drug monitoring. She presented in June 2019 with acute onset abdominal pain and was diagnosed with acute appendicitis on clinical examination and imaging. A laparoscopic appendicectomy was performed but complicated by intra-operative appendiceal rupture. Postoperative course was uneventful. Interestingly, final pathology revealed low-grade appendiceal mucinous neoplasm. Considering mandatory immunosuppressive state and peritoneal rupture of appendiceal malignancy, with extensive literature review and team discussions, patient underwent right hemicolectomy followed by intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) in July 2019. The patient recovered well with no disease recurrence till her last follow up on May 2020. DISCUSSION: Appendiceal malignancies are difficult to diagnose and found in 2% of appendectomy specimens. Mucinous appendiceal cancers are an even rarer subset with incidence of only 0.2%. The reported survival rate is <10% over 10 years. It is extremely rare for GI malignancy to present within 3 years of transplant since detailed cancer screening is part of transplant evaluation which includes abdominal imaging and colonoscopy. Here we report early presentation of a very rare appendiceal carcinoma in post liver transplant setting with excellent response to right hemicolectomy and HIPEC despite continued immunosuppression, which has never been reported. The case also stresses the need for detailed cancer screening in this special population.

Chronic Hepatitis E With Genotype 1—Masquerading as Allograft Rejection After LiverTransplantation

Hepatitis E is one of the leading causes of acute viral hepatitis worldwide. Chronic infection with hepatitis E is less common and limited to immunosuppressed patients and is usually due to genotype 3 of the virus. Genotype 1, the most prevalent strain in the South Asian region, is seldom known to be associated with chronic hepatitis. Here we describe a case of chronic hepatitis E with genotype 1 in a post-liver transplant setting. In the index case, previously compensated cryptogenic cirrhosis was decompensated by an acute hepatitis E infection, which necessitated liver transplantation because of acute chronic liver failure. This later progressed to chronicity. This case may have significant implications in management, especially in the post-liver transplant setting.

A review of the use of transient elastography in the assessment of fibrosis and steatosis in the post-liver transplant patient.

Liver biopsy is considered the gold standard method for diagnosing and staging liver disease, particularly in the post-liver transplant setting. Given the invasive nature of biopsy, alternate means for accurately assessing liver fibrosis and steatosis are preferred especially as the number of patients with fatty liver disease is increasing. Transient elastography has been validated as a useful tool for evaluation of liver fibrosis, as has controlled attenuation parameter index as a tool for assessing steatosis. It is a non-invasive, rapid, and highly reproducible approach to demonstrate the presence of fibrosis among non-transplant patients with chronic liver disease of various etiologies. However, it has not yet found wide acceptance in liver transplant recipients. There are few published studies evaluating the merits and applicability of transient elastography to assess allografts after liver transplantation. We review the published data on the use of transient elastography with concurrent controlled attenuation parameter in liver transplant recipients and recommend its greater use to follow allograft function over time.

Liver Transplantation for Nonalcoholic Steatohepatitis: Pathophysiology of Recurrence and Clinical Challenges.

Nonalcoholic steatohepatitis is the fastest-growing indication for the liver transplant and a leading cause of hepatocellular carcinoma among patients listed for liver transplantation in the USA. Post-transplant nonalcoholic hepatic steatosis and steatohepatitis are frequent complications of liver transplantation. Nonalcoholic steatohepatitis poses a significant challenge in both pre- and post-transplant period due to its association with metabolic syndrome, coronary artery disease, chronic kidney disease, and obstructive sleep apnea. While optimal therapy is not yet available in the post-liver transplant setting, lifestyle interventions continue to remain as the mainstay of therapy for post-transplant nonalcoholic steatohepatitis. Early recognition with protocol biopsies and noninvasive modalities, along with modification of known risk factors, are the most effective methods to curtail the progression of nonalcoholic steatohepatitis in the absence of FDA-approved pharmacologic therapy.

Obesity, dynapenia and high cardiovascular risk co-exist in post-liver transplant setting: results of a cross-sectional study

Cardiovascular disease is a major cause of death in post-liver transplantation (LT). The aim of this study was to evaluate LT patients as to the carotid intima-media thickness (CIMT) and its association with nutritional status, dietary intake, metabolic profile and cardiovascular risk factors. In this cross-sectional study, adult patients with more than 12 months of post-transplant follow-up underwent clinical, laboratory, functional and nutritional evaluation by 3-day-diet-record, anthropometry and dynamometry. CIMT was evaluated by Doppler ultrasonography. Sixty-nine post-LT patients [males 61%, median of age 59 (51-64) years were included; median time post-liver transplantation 2.8 (1.4-6.3) years]. High prevalence of malnutrition was found (45% of arm muscle area < p15 and 71% of handgrip strength < p30). Excess weight was present in 72% of patients, body mass index ≥ 30 kg/m2 in 35% and metabolic syndrome in 51%. Abnormal CIMT was found in 54% of the sample. Patients with abnormal CIMT presented higher cardiovascular risk Score, LDL cholesterol, higher prevalence of high-sensitive C-reactive protein ≥ 1 mg/L and higher intake of saturated and trans fatty acids (P < 0.05 for all). Abnormal IMT was commonly found in LT patients presenting at the same time with overweight and dynapemia. These results were associated with higher LDL-cholesterol levels, high-sensitive C-reactive protein ≥ 1 mg/L and higher intake of saturated and trans fatty acids. Preventive measures, including dietary advice, are required for all post-liver transplantation patients to minimize cardiovascular risk.

A 64-Year-Old Woman With Posttransplant Hepatitis

Abstract Abnormal liver function tests and nonspecific histopathologic findings are relatively common in the post–liver transplant setting. Whereas some cases remain idiopathic and many resolve spontaneously, some carry a risk of chronicity and long-term liver dysfunction including cirrhosis, graft loss, and death. Accurate assessment and follow-up of such findings are therefore crucial in this population. We report a case of a 64-year-old woman who underwent liver transplantation for chronic hepatitis C infection with cirrhosis. Several months after transplantation, she underwent a liver biopsy as part of a workup for abnormal serologic studies and transaminase elevation. The biopsy showed nonspecific hepatitis. Eventually, additional serologic testing demonstrated hepatitis E viral infection. Causes of hepatitis and other forms of posttransplant liver disease, including hepatitis E, are discussed.

Hepatitis B and liver transplantation

Chronic Hepatitis B (CHB) infection remains a common cause for liver cirrhosis and hepatocellular carcinoma. Orthotopic liver transplantation (OLT) has been a treatment modality for CHB patients with decompensated cirrhosis and or hepatocellular carcinoma. Previously early outcomes of transplantation for CHB patients were associated with rapid recurrence of the virus and loss of the allograft. Development of hepatitis B immunoglobulin (HBIG) and its use in prophylaxis of CHB patients after liver transplantation resulted in significant improvement in patient and allograft survival. Continued use of HBIG mono-therapy however has been complicated by development of viral resistance. With the development of nucleos(t)ide (NA) inhibitors for treatment of CHB, liver transplant outcomes continued to improve. One of the most important risk factors for viral recurrence in post liver transplant setting is the HBV DNA level. Use of NAs prior to liver transplantation to reduce the viral load has been an important way to prevent recurrence of CHB in post liver transplant patients. Addition of NAs to HBIG was the standard of therapy for liver transplant patients for many years and reduced the development of viral resistance. Long-term use of HBIG however is expensive and inconvenient for patients. Development of more potent NAs, with low viral resistance, has allowed for reduction and in some cases elimination of use of HBIG in post liver transplant prophylaxis of patients with CHB.

THU-428 - Pregnancy outcomes in the post liver transplant setting: The Irish experience

THU-428 - Pregnancy outcomes in the post liver transplant setting: The Irish experience

Use of everolimus in liver transplantation.

In recent years, the use of mammalian target of rapamycin inhibitors has gained traction in their use as alternative or adjunct immunosuppressants in the post-liver transplantation (LT) setting. The efficacy of everolimus (EVR) in de novo LT is established and a reasonable time to initiate EVR is 30 d from LT surgery. Initiating EVR early post-LT allows for calcineurin inhibitor (CNI) reduction, thus reducing nephrotoxicity in LT recipients. However, data is inadequate on the appropriate timing for conversion from CNI to EVR maintenance in order to achieve optimal renoprotective effect without compromising drug efficacy. Adverse effects of proteinuria, hypercholesterolemia and hyperlipidemia are significantly higher as compared to standard CNI and long-term implications on graft and patient survival in LT is still unclear. Future research to explore strategies to minimise EVR adverse effects will be crucial for the success of EVR as an important alternative or adjunct immunosuppressive therapy in LT.

Can FRAX Help Portuguese Men?

Hepatitis E is one of the leading causes of acute viral hepatitis worldwide. Chronic infection with hepatitis E is less common and limited to immunosuppressed patients and is usually due to genotype 3 of the virus. Genotype 1, the most prevalent strain in the South Asian region, is seldom known to be associated with chronic hepatitis. Here we describe a case of chronic hepatitis E with genotype 1 in a post-liver transplant setting. In the index case, previously compensated cryptogenic cirrhosis was decompensated by an acute hepatitis E infection, which necessitated liver transplantation because of acute chronic liver failure. This later progressed to chronicity. This case may have significant implications in management, especially in the post-liver transplant setting.

Hepatitis C following liver transplantation: current approach and future research opportunities.

The treatment of hepatitis C virus infection (HCV) in liver transplant recipients was very limited until direct-acting antivirals became widely available. We review the current approach to HCV treatment following liver transplantation and future research opportunities. Current treatment of HCV infection with all oral new direct-acting antivirals in the postliver transplant setting is easier, shorter, tolerable, and more effective with high-sustained virological response rates. However, some challenges remain, including the optimal timing of therapy, drug-drug interactions, renal insufficiency, and HIV coinfection. Patients with recurrent HCV following liver transplant will significantly benefit from all oral new direct acting antivirals. Ongoing studies will determine the optimal timing and combination in this unique population.

Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Indications for Treatment

The landscape of treatment for HCV infection has evolved substantially with the advent of highly effective direct-acting antiviral agents (DAA). The Korean Association for the Study of the Liver updated guideline for managemnt of hepatitis C in accordance with the introduction of DAA into practice in late 2015. Due to high effectiveness and few side effects of DAA, indications for treatment has been widened to include patients who had been contraindicated for the combination treatment of peginterferon-α and ribavirin, i.e. decompensated cirrhosis and pre- and post-liver transplant setting. As succeesul treatment of HCV can reduce complications of cirrhosis, development of hepatocelluar carcinoma and liver-related mortality, and improve extrahepatic manifestions, all HCV-infected patients with no contraindication should be considered for treatment. Considering the risk for morbidity and mortality and benefit of treatment, patients with advanced fibrosis ≥F3 including compensated and decompensated cirrhosis, those in the pre- and post-tranplasnt setting, and those with severe extrahepatic manifestations including HCV-related mixed cryoglobulinemia and glomerulonephritis should be given priority for treatment.