Requiring Liver Transplantation Research Articles

Langerhans Cell Histiocytosis or Acute Cellular Rejection?

Langerhans cell histiocytosis (LCH) is a rare malignant disorder of epidermal antigen presenting cells. It is characterized by infiltration of various tissues with dendritic cells (Langerhans cells, LC) that express CD1a or CD207 (langerin), often leading to organ dysfunction. A patient with LCH required liver transplantation (LT) for LCH-associated biliary-tract disease. Cholangiopathy developed after LT. The question arose: In this patient, did LC in damaged liver-allograft biliary epithelium signify acute cellular rejection (ACR) or recurrent LCH? We evaluated immunohistochemical identification of LC (CD1a, CD207) in the proposita and in 14 ACR patient samples as distinguishing between ACR and recurrent LCH. Among 15 patient samples, 3 (20%) marked with neither antibody. Among the remaining 12 samples (80%), 4 (26.7%)-including that from the proposita-had cells marking for both antigens within bile-duct epithelium as well as in surrounding portal-tract connective tissue, 2 (13.3%) had cells marking for both antigens in one region or the other, but not in both, and 6 (40%) had cells marking for only one antigen in one region or the other. Immunostaining for CD1a and CD207/langerin in the setting of ACR without suspicion of LCH identifies LC in damaged bile ducts. This biomarker pairing proved not to be LCH-specific. Our findings indicate that the presence of these cells alone is insufficient to identify recurrent LCH in the allograft liver.

Natural course and outcomes of children with ubiquitin-specific protease 53 (USP53)-related genetic chronic cholestasis.

Ubiquitin-specific protease 53 (USP53) is essential for formation of cellular tight junctions and variations in this gene disrupt the tight junctions, resulting in cholestasis. We describe the clinical manifestations and outcomes of patients with USP53 mutations from the Indian progressive familial intrahepatic cholestasis registry. All 29 patients who harbored mutations in the USP53 gene either in the homozygous, compound heterozygous, or heterozygous state and presented with cholestasis were included. USP53 variants related to cholestasis had good outcomes, with native liver survival in 82.7%, whereas 17.3% required liver transplantation. Jaundice developed in 93% and within 3 months of age in 48.8%. Jaundice resolved in 21 (72.4%). Pruritus 76% at a median age of 7 months (severe in 10/22, 45% and refractory to medical therapy in 4, 18.1%). Majority of them (82.7%) had biallelic mutations. Protein-truncating mutations were present in 20 (69%) and missense mutations in 9 (31%). No correlation was found between the genotype and the outcome.

MicroRNA associated with hepatocyte injury and systemic inflammation may predict adverse outcomes in cirrhotic patients

As the global prevalence of chronic liver disease continues to rise, the need to determine which patients will develop end-stage liver disease and require liver transplantation is increasingly important. However, current prognostic models perform sub-optimally. We aim to determine microRNA profiles associated with clinical decompensation and mortality/transplantation within 1 year. We examined microRNA expression profiles in plasma samples from patients across the spectrum of cirrhosis (n = 154), acute liver failure (ALF) (n = 22), sepsis (n = 20) and healthy controls (HC) (n = 20). We demonstrated that a microRNA-based model (miR-24 and -27a) associated with systemic inflammation differentiated decompensated cirrhosis states from compensated cirrhosis and HC (AUC 0.77 (95% CI 0.69–0.85)). 6 patients within the compensated cirrhosis group decompensated the subsequent year and their exclusion improved model performance (AUC 0.81 (95% CI 0.71–0.89)). miR-191 (associated with liver injury) predicted risk of mortality across the cohort when acutely decompensated and acute-on-chronic-liver failure patients were included. When they were excluded miR-24 (associated with systemic inflammation) predicted risk of mortality. Our findings demonstrate that microRNA associated with systemic inflammation and liver injury predict adverse outcomes in cirrhosis. miR-24 and -191 require further investigation as prognostic biomarkers and therapeutic targets for patients with liver disease.

Evaluation of the therapeutic potential of novel nanoparticle formulations of glutathione and virgin coconut oil in an experimental model of carbon tetrachloride-induced liver failure.

Acute liver failure (ALF) is a critical condition characterized by rapid liver dysfunction, leading to high mortality rates. Current treatments are limited, primarily supportive, and often require liver transplantation. This study investigates the potential of a novel nanoparticle formulation of glutathione (GSH) and virgin coconut oil (VCO) alone and in combination to enhance therapeutic outcomes in a rat model of ALF induced by orogastric carbon tetrachloride (CCl4). The study employed adult male Albino rats divided into ten groups, with ALF induced via a single oral dose of CCl4. Various treatment regimens were administered over seven days, including conventional and nanoparticle forms of GSH and VCO and their combinations. The efficacy of treatments was evaluated through biochemical analysis of liver function markers, oxidative stress indicators, inflammatory biomarkers, and histopathological examinations. Nanoparticles were synthesized using established methods, and characterization techniques were employed to ensure their quality and properties. The nanoparticle formulations significantly improved liver function, as indicated by reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alongside decreased oxidative stress markers such as malondialdehyde. Furthermore, they reduced tumor necrosis factor alpha and interleukin-1 beta inflammatory markers. Histological analysis revealed reduced hepatocellular necrosis and inflammation in treated groups compared to controls. Also, decreased nuclear factor-kappa B was detected by immunohistochemical analysis. The findings show that the nanoparticle mixture of GSH and VCO effectively reduces liver damage in ALF. This suggests a promising drug-based approach for improving liver regeneration and protection. This innovative strategy may pave the way for new therapeutic interventions in the management of ALF.

Identification of necroptosis genes and characterization of immune infiltration in non-alcoholic steatohepatitis

BackgroundThe most common progressive form of non-alcoholic fatty liver disease (NAFLD) is non-alcoholic steatohepatitis (NASH), which is characterized by the development of cirrhosis, and requires liver transplantation. We screened for the differentially expressed necroptosis-related genes in NASH in this study, and analyzed immune infiltration through microarray and bioinformatics analysis to identify potential biomarkers, and explore the molecular mechanisms involved in NASH.MethodsThe GSE24807 microarray dataset of NASH patients and healthy controls was downloaded, and we identified the differentially expressed genes (DEGs). Necroptosis-related differential genes (NRDEGs) were extracted from these DEGs, and functionally annotated by enrichment analyses. The core genes were obtained by constructing gene co-expression networks using weighted gene co-expression network analysis (WGCNA). Finally, the transcription factor (TF) regulatory network and the mRNA-miRNA network were constructed, and the infiltrating immune cell populations were analyzed with CIBERSORT.ResultsWe identified six necroptosis-related genes (CASP1, GLUL, PYCARD, IL33, SHARPIN, and IRF9), and they are potential diagnostic biomarkers for NASH. In particular, PYCARD is a potential biomarker for NAFLD progression. Analyses of immune infiltration showed that M2 macrophages, γδ T cells, and T follicular helper cells were associated with the immune microenvironment of NASH, which is possibly regulated by CASP1, IL33, and IRF9.ConclusionsWe identified six necroptosis-related genes in NASH, which are also potential diagnostic biomarkers. Our study provides new insights into the molecular mechanisms and immune microenvironment of NASH.

Three consecutive cases of acute liver failure in young women due to acetaminophen overdose: insights into Japanese social issues and transplantation landscape.

Acetaminophen (APAP) is an over-the-counter (OTC) drug known worldwide for its safety and efficacy. However, in Japan, OTC drug overdose has become a prominent social problem in recent years due to stricter regulations for other drugs, especially among young people, and APAP is an increasing cause of acute liver injury due to overdose. This report describes three consecutive cases of acute liver failure in young women (22, 22 and 19years old) due to APAP overdose in December 2023. Despite severe liver injury, indicated by high ALT levels and coagulopathy, these cases recovered without requiring liver transplantation. This report discusses three cases of acute liver failure in young Japanese women following APAP overdose, reflecting a national increase in such cases due to increased misuse of OTC drugs and societal factors. Key findings include the need for early treatment with N-acetylcysteine (NAC) and the importance of mental health assessment in the management of overdose patients. The cases underscore the need for prompt team-based care to prevent serious outcomes and highlight the complexity of liver transplantation decisions in Japan, highlighting the need for comprehensive strategies to address the escalating problem of APAP overdose.

Transjugular Intrahepatic Portosystemic Shunt for Budd-Chiari Syndrome: A Single-Centre Experience.

Background: Despite several challenges in clinical management, there has been significant progress in understanding the aetiology, natural history and outcomes of Budd-Chiari syndrome (BCS) treatments. This study aims to evaluate the outcomes of transjugular intrahepatic portosystemic shunt (TIPS) using covered stent in management of BCS. Methods: We conducted a retrospective analysis of 70 BCS patients who underwent TIPS using covered stents between January 2010 and December 2022 at a single tertiary liver transplant centre. Patients' clinical features, laboratory parameters, and imagine findings were collected before and after TIPS. The primary endpoint was overall survival. Results: TIPS was performed on 70 patients with BCS out of a total of 88 patients. The remaining patients (18) underwent liver transplantation. The mean age was 37.7 ± 11.2 years at time of diagnosis and the majority were female (64.35). The most common symptoms and signs at presentation were abdominal pain, jaundice, ascites, and variceal bleeding. Over a median followup of 76 months, the survival rates at 1, 3, and 5 years were 98.8%, 97.9%, and 97.7%, respectively. Patients who underwent TIPS alone had better survival that patients with BCS who required liver transplantation (LTx) (p = 0.003). Conclusions: In our study TIPS provided a highly effective treatment option for BCS patients. The long-term favourability of the outcome was not impacted by the need for repeated TIPS revision. Use of covered stents was instrumental in reducing shunt dysfunction rates. Prospective and larger studies are needed to further optimize therapeutic strategies in this challenging population.

Drug Acute Liver Failure in Children Caused by Anthelmintic Agents (Albendazole): Treatment Strategy.

Drug-induced liver injury accounts for numerous clinically significant events each year and can cause severe injury, resulting in a need for liver transplant or fatality. Liver injury triggered by albendazole is relatively common, resulting in mild to moderate changes in liver enzymes and affecting ~16% of patients who use this medication. Albendazole-induced liver injury and jaundice have been previously documented, but a case of fulminant hepatic failure requiring liver transplant has not yet been described. Acute liver failure is a clinical syndrome that is potentially reversible. About 2% of liver transplants are performed because of acute liver failure. We reviewed drug-induced fulminant and subfulminant hepatic failures among pediatric patients transferred to the Batumi Center for Liver Diseases and Transplantation in Georgia. The 6 cases were children aged 2 to 14 years who were diagnosed in Georgia between 2018 and 2023. Of 6 children, patients N1 and N2 had reversible acute liver failure and treatment ended with recovery, patients N3 and N4 had successful transplant procedures performed at the peak of disease development, and patients N5 and N6 did not receive transplant procedures because of presence of irreversible brain damage. Although the Model for End-Stage Liver Disease Score (the model score for patients with end-stage liver disease) is useful for patients with chronic hepatocytic failure, the score does not apply for patients with acute liver failure. On the basis of our study, at the first signs of disease development, patients should be referred to the transplant center and the preparation of a living donor should be started immediately, so that organ transplant can be performed without a long elapse of time.

Amyloid precursor protein as a fibrosis marker in infants with biliary atresia.

Biliary atresia (BA) is a rare condition of unknown origin in newborns with jaundice. In BA bile ducts are non-functional, causing neonatal cholestasis and following liver fibrosis and failure. This retrospective study included liver biopsies of 14 infants with BA aged [mean ± SD] 63 ± 23 days. Patients were grouped according to the clinical course (jaundice-free vs recurrent jaundice vs required liver transplantation or liver fibrosis (Ishak fibrosis score)) and followed for 1.61-5.64 years (mean 4.03). Transcriptome profiles were assessed using a panel of 768 fibrosis-specific genes, reanalyzed via qRT-PCR, and confirmed via immunostaining. Plasma from an additional 30 BA infants and 10 age-matched controls were used for amyloid precursor protein (APP) quantification by ELISA. Different clinical outcome groups showed a homogeneous mRNA expression. Altered amyloid-metabolism-related gene expression was found between cases with Ishak fibrosis score greater than 4. Immunostaining confirmed a distinct presence of APP in the livers of all BA subjects. APP plasma levels were higher in BA than in age-matched controls and correlated with the histological fibrosis grade. These results suggest that amyloidosis may contribute to BA and liver fibrosis, indicating that APP could serve as a potential liquid biomarker for these conditions. Biliary atresia patients with higher fibrosis scores according to Ishak have higher hepatic expression of amyloid-related genes while amyloid precursor protein accumulates in the liver and increases in the circulation. After a recent study revealed beta-amyloid deposition as a mechanism potentially involved in biliary atresia, we were able to correlate amyloid-metabolism-related transcript levels as well as amyloid precursor protein tissue and plasma levels with the degree of hepatic fibrosis. These findings suggest that amyloid precursor protein is a fibrosis marker in infants with biliary atresia, reinforcing the role of amyloid metabolism in the pathogenesis of this serious disease.

Chinese guidelines for the diagnosis and treatment of hereditary hemochromatosis

Hereditary hemochromatosis is an iron overload disease caused by mutations in iron-regulating genes, resulting in excessive iron deposition in organs such as the liver, heart, skin, pancreas, and gonads, leading to corresponding multi-system damage. This condition is relatively common in European and American populations, primarily caused by mutations in the HFE gene; however, it is rare in China and other Asian countries, almost exclusively due to mutations in non-HFE genes. Clinical features include unexplained chronic hepatitis or cirrhosis, accompanied by elevated serum ferritin and/or increased transferrin saturation. MRI shows iron deposition in the liver, liver biopsy reveals iron accumulation in hepatocytes, and genetic testing facilitate the diagnosis of this disease. Repeated phlebotomy is the first-line therapy for this condition. For those who cannot tolerate phlebotomy, iron chelation therapy may be used, and patients who progress to end-stage liver disease will require liver transplantation. To assist clinicians in making informed decisions on the diagnosis and treatment of hereditary hemochromatosis, the Chinese Society of Hepatology, Chinese Medical Association has invited experts from clinical medicine, molecular genetics, pathology, imaging, and methodology to systematically summarize the advancement in this field and collaboratively develop the current guidelines.

Current Landscape and Evolving Therapies for Primary Biliary Cholangitis

Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disorder characterized by progressive cholestatic that, if untreated, can progress to liver fibrosis, cirrhosis and liver decompensation requiring liver transplant. Although the pathogenesis of the disease is multifactorial, there is a consensus that individuals with a genetic predisposition develop the disease in the presence of specific environmental triggers. A dysbiosis of intestinal microbiota is increasingly considered among the potential pathogenic factors. Cholangiocytes, the epithelial cells lining the bile ducts, are the main target of a dysregulated immune response, and cholangiocytes senescence has been recognized as a driving mechanism, leading to impaired bile duct function, in disease progression. Bile acids are also recognized as playing an important role, both in disease development and therapy. Thus, while bile acid-based therapies, specifically ursodeoxycholic acid and obeticholic acid, have been the cornerstone of therapy in PBC, novel therapeutic approaches have been developed in recent years. In this review, we will examine published and ongoing clinical trials in PBC, including the recently approved peroxisome-proliferator-activated receptor (PPAR) agonist, elafibranor and seladelpar. These novel second-line therapies are expected to improve therapy in PBC and the development of personalized approaches.

Therapeutic Potential of Lactiplantibacillus plantarum FB091 in Alleviating Alcohol-Induced Liver Disease through Gut-Liver Axis.

Alcoholic liver disease (ALD) poses a significant global health burden, often requiring liver transplantation and resulting in fatalities. Current treatments, like corticosteroids, effectively reduce inflammation but carry significant immunosuppressive risks. This study evaluates Lactiplantibacillus plantarum FB091, a newly isolated probiotic strain, as a safer alternative for ALD treatment. Using an in vivo mouse model, we assessed the effects of L. plantarum FB091 on alcohol-induced liver damage and gut microbiota composition. Alcohol and probiotics administration did not significantly impact water/feed intake or body weight. Histopathological analysis showed that L. plantarum FB091 reduced hepatocellular ballooning and inflammatory cell infiltration in liver tissues and mitigated structural damage in colon tissues, demonstrating protective effects against alcohol-induced damage. Biomarker analysis indicated that L. plantarum FB091 decreased aspartate aminotransferase levels, suggesting reduced liver damage, and increased alcohol dehydrogenase activity, indicating enhanced alcohol metabolism. Additionally, cytokine assays revealed a reduction in pro-inflammatory TNF-α and an increase in anti-inflammatory IL-10 levels in colon tissues of the L. plantarum FB091 group, suggesting an anti-inflammatory effect. Gut microbiota analysis showed changes in the L. plantarum FB091 group, including a reduction in Cyanobacteria and an increase in beneficial bacteria such as Akkermansia and Lactobacillus. These changes correlated with the recovery and protection of liver and colon health. Overall, L. plantarum FB091 shows potential as a therapeutic probiotic for managing ALD through its protective effects on liver and colon tissues, enhancement of alcohol metabolism, and beneficial modulation of gut microbiota. Further clinical studies are warranted to confirm these findings in humans.

Abcb4-defect cholangitis mouse model with hydrophobic bile acid composition by in vivo liver-specific gene deletion

Progressive familial intrahepatic cholestasis (PFIC) is a liver disease that occurs during childhood and requires liver transplantation. ABCB4 is localized along the canalicular membranes of hepatocytes, transports phosphatidylcholine into bile, and its mutation causes PFIC3. Abcb4 gene-deficient mice established as animal models of PFIC3 exhibit cholestasis-induced liver injury. However, their phenotypes are often milder than those of human PFIC3, partly because of the existence of large amounts of less toxic hydrophilic bile acids synthesized by the rodent-specific enzymes Cyp2c70 and Cyp2a12. Mice with double deletions of Cyp2c70/Cyp2a12 (CYPDKO mice) have a human-like hydrophobic bile acid composition. PFIC-related gene mutations were induced in CYPDKO mice to determine whether these triple-gene-deficient mice are a better model for PFIC. To establish a PFIC3 mouse model using CYPDKO mice, we induced abcb4 gene deletion in vivo using adeno-associated viruses expressing SaCas9 under the control of a liver-specific promoter and abcb4-target gRNAs. Compared to Abcb4-deficient wild-type mice, Abcb4-deficient CYPDKO mice showed more pronounced liver injury along with an elevation of inflammatory and fibrotic markers. The proliferation of intrahepatic bile ductal cells and hematopoietic cell infiltration were also observed. CYPDKO/abcb4-deficient mice show a predominance of taurine-conjugated chenodeoxycholic acid and lithocholic acid in the liver. In addition, phospholipid levels in the gallbladder bile were barely detectable. Mice with both human-like bile acid composition and Abcb4-defect exhibit severe cholestatic liver injury and are useful for studying human cholestatic diseases and developing new treatments.

Severe acute hepatitis of unknown origin in children: Is it still amystery? What role does adenovirus play?

On March 31, 2022, severe acute hepatitis of unknown origin was first reported from the Royal Glasgow Children's Hospital in Scotland. According to the criteria by WHO-ECDC, a probable case of unknown acute hepatitis in children is defined as a subject under 16 years of age, who tested negative for viral hepatitis and transaminases >500 U/L, starting from the 1st of October 2021. WHO invites Member States to participate in the global effort to collect anonymized clinical data on probable cases of severe acute hepatitis of unknown aetiology. As of May 26, 2021, 650 cases were already registered on the platform worldwide, of whom at least 38 cases have required liver transplants. Several hypotheses such as previous SARS-CoV-2 infection or coinfection or infection with another virus were examined and a strong association was found between adenovirus (41F) and acute hepatitis of unknown aetiology cases. This review article summarizes the global epidemiological evidences on acute hepatitis of unknown origin in children, analysing their incidence and characteristics.

Identification of new correctors for traffic-defective ABCB4 variants by a high-content screening approach

ABCB4 is located at the canalicular membrane of hepatocytes and is responsible for the secretion of phosphatidylcholine into bile. Genetic variations of this transporter are correlated with rare cholestatic liver diseases, the most severe being progressive familial intrahepatic cholestasis type 3 (PFIC3). PFIC3 patients most often require liver transplantation. In this context of unmet medical need, we developed a high-content screening approach to identify small molecules able to correct ABCB4 molecular defects. Intracellularly-retained variants of ABCB4 were expressed in cell models and their maturation, cellular localization and function were analyzed after treatment with the molecules identified by high-content screening. In total, six hits were identified by high-content screening. Three of them were able to correct the maturation and canalicular localization of two distinct intracellularly-retained ABCB4 variants; one molecule was able to significantly restore the function of two ABCB4 variants. In addition, in silico molecular docking calculations suggest that the identified hits may interact with wild type ABCB4 residues involved in ATP binding/hydrolysis. Our results pave the way for their optimization in order to provide new drug candidates as potential alternative to liver transplantation for patients with severe forms of ABCB4-related diseases, including PFIC3.

Biliary atresia.

Biliary atresia (BA) is a progressive inflammatory fibrosclerosing disease of the biliary system and a major cause of neonatal cholestasis. It affects 1:5,000-20,000 live births, with the highest incidence in Asia. The pathogenesis is still unknown, but emerging research suggests a role for ciliary dysfunction, redox stress and hypoxia. The study of the underlying mechanisms can be conceptualized along the likely prenatal timing of an initial insult and the distinction between the injury and prenatal and postnatal responses to injury. Although still speculative, these emerging concepts, new diagnostic tools and early diagnosis might enable neoadjuvant therapy (possibly aimed at oxidative stress) before a Kasai portoenterostomy (KPE). This is particularly important, as timely KPE restores bile flow in only 50-75% of patients of whom many subsequently develop cholangitis, portal hypertension and progressive fibrosis; 60-75% of patients require liver transplantation by the age of 18 years. Early diagnosis, multidisciplinary management, centralization of surgery and optimized interventions for complications after KPE lead to better survival. Postoperative corticosteroid use has shown benefits, whereas the role of other adjuvant therapies remains to be evaluated. Continued research to better understand disease mechanisms is necessary to develop innovative treatments, including adjuvant therapies targeting the immune response, regenerative medicine approaches and new clinical tests to improve patient outcomes.

Clinical characteristics and HLA associations of azithromycin-induced liver injury.

Azithromycin (AZ) is a widely used antibiotic. The aim of this study was to characterise the clinical features, outcomes, and HLA association in patients with drug-induced liver injury (DILI) due to AZ. The clinical characteristics of individuals with definite, highly likely, or probable AZ-DILI enrolled in the US Drug-Induced Liver Injury Network (DILIN) were reviewed. HLA typing was performed using an Illumina MiSeq platform. The allele frequency (AF) of AZ-DILI cases was compared to population controls, other DILI cases, and other antibiotic-associated DILI cases. Thirty cases (4 definite, 14 highly likely, 12 probable) of AZ-DILI were enrolled between 2004 and 2022 with a median age of 46 years, 83% white, and 60% female. Median duration of AZ treatment was 5 days. Latency was 18.5 days. 73% were jaundiced at presentation. The injury pattern was hepatocellular in 60%, cholestatic in 27%, and mixed in 3%. Ten cases (33%) were severe or fatal; 90% of these were hepatocellular. Two patients required liver transplantation. One patient with chronic liver disease died of hepatic failure. Chronic liver injury developed in 17%, of which 80% had hepatocellular injury at onset. HLA-DQA1*03:01 was significantly more common in AZ-DILI versus population controls and amoxicillin-clavulanate DILI cases (AF: 0.29 vs. 0.11, p = 0.001 and 0.002, respectively). Azithromycin therapy can lead to rapid onset of severe hepatic morbidity and mortality in adult and paediatric populations. Hepatocellular injury and younger age were associated with worse outcomes. HLA-DQA1*03:01 was significantly more common in AZ cases compared to controls.

Hepatitis B Reactivation and Liver Failure Because of COVID-19 Infection

ABSTRACT Coronavirus disease 2019 (COVID-19) has been associated with liver injury incidence reported between 15% and 53%. Viral binding to ACE2 receptors in hepatobiliary cells is believed to cause liver inflammation. The relationship between hepatitis B and COVID-19 is poorly understood, but patients treated with immunosuppressive therapy for COVID-19 are at higher risk of hepatitis B reactivation (HBVr). We present a case of a patient with HBVr because of COVID-19, in the absence of any immunosuppressive treatment, leading to fulminant liver failure and subsequent requiring liver transplantation. Given low incidence, limited data, and no current guidelines, further studies are needed to evaluate the benefit and cost-effectiveness of anti-HBV prophylaxis in a patient with chronic hepatitis B (CHB) and COVID-19. Meanwhile, the American Association for the Study of Liver Diseases guidelines for patients with CHB and immunosuppressant use can be considered for anti-HBV prophylaxis for patients with CHB and COVID-19 to prevent HBVr on a case-by-case basis.

Insuficiencia hepática aguda por adenovirus tratada con inmunoglobulina intravenosa

Background: Acute liver failure in pediatric age is a serious multisystem disease, characterized by a failure of the synthesis and detoxification function of the liver. Among the etiologies, viral infection should be investigated. Treatment is supportive and some cases require liver transplantation. Case report: A 2-year-old girl was admitted for acute liver failure. The PCR viral panel was positive for Adenovirus 41 and IgG antibodies to SARS-CoV-2 were also found. Supportive treatment was started without improvement, so intravenous immunoglobulin was administered, with resolution of the liver failure. Conclusion: Immunoglobulin has immunomodulatory mechanisms in children with severe acute hepatitis of infectious etiology, so in some cases, its administration can be considered as adjuvant therapy. Keywords: Acute liver failure, Hepatitis, Adenovirus, Immunoglobulin.

Transarterial embolization is an acceptable bridging therapy to hepatocellular carcinoma prior to liver transplantation.

Hepatocellular carcinoma (HCC) is an aggressive malignant neoplasm that requires liver transplantation (LT). Despite patients with HCC being prioritized by most organ allocation systems worldwide, they still have to wait for long periods. Locoregional therapies (LRTs) are employed as bridging therapies in patients with HCC awaiting LT. Although largely used in the past, transarterial embolization (TAE) has been replaced by transarterial chemoembolization (TACE). However, the superiority of TACE over TAE has not been consistently shown in the literature. To compare the outcomes of TACE and TAE in patients with HCC awaiting LT. All consecutive patients with HCC awaiting LT between 2011 and 2020 at a single center were included. All patients underwent LRT with either TACE or TAE. Some patients also underwent percutaneous ethanol injection (PEI), concomitantly or in different treatment sessions. The choice of LRT for each HCC nodule was determined by a multidisciplinary consensus. The primary outcome was waitlist dropout due to tumor progression, and the secondary outcome was the occurrence of adverse events. In the subset of patients who underwent LT, complete pathological response and post-transplant recurrence-free survival were also assessed. Twelve (18.5%) patients in the TACE group (only TACE and TACE + PEI; n = 65) and 3 (7.9%) patients in the TAE group (only TAE and TAE + PEI; n = 38) dropped out of the waitlist due to tumor progression (P log-rank test = 0.29). Adverse events occurred in 8 (12.3%) and 2 (5.3%) patients in the TACE and TAE groups, respectively (P = 0.316). Forty-eight (73.8%) of the 65 patients in the TACE group and 29 (76.3%) of the 38 patients in the TAE group underwent LT (P = 0.818). Among these patients, complete pathological response was detected in 7 (14.6%) and 9 (31%) patients in the TACE and TAE groups, respectively (P = 0.145). Post-LT, HCC recurred in 9 (18.8%) and 4 (13.8%) patients in the TACE and TAE groups, respectively (P = 0.756). Posttransplant recurrence-free survival was similar between the groups (P log-rank test = 0.71). Dropout rates and posttransplant recurrence-free survival of TAE were similar to those of TACE in patients with HCC. Our study reinforces the hypothesis that TACE is not superior to TAE as a bridging therapy to LT in patients with HCC.