Iodine-131 intervention in hyperthyroidism with hepatic insufficiency: Metabolomic evaluation.

Hyperthyroidism, often accompanied by hepatic insufficiency (HI), poses significant clinical challenges, highlighting the necessity for identifying optimal treatment strategies and early diagnostic biomarkers to improve patient outcomes. This study aimed to determine the optimal iodine-131 (131I) intervention dose for alleviating hyperthyroidism with HI and to identify serum metabolic biomarkers for early diagnosis using UPLC-Q/TOF-MS technology. A mouse model for early 131I intervention was established to monitor changes in physiological response, body weight, fur condition, thyroid, and liver function. Metabolite identification was achieved through UPLC-Q/TOF-MS and further analyzed via MetaboAnalyst. Six biomarkers were identified and subjected to ROC analysis. Early intervention with 80 µCi 131I per gram of thyroid tissue effectively controlled hyperthyroidism and improved liver function. Metabolomics analysis uncovered 63 differentially abundant metabolites, six of which (L-kynurenine, Taurochenodesoxycholic acid, Glycocholic acid, Phytosphingosine, Tryptamine, and Betaine) were identified as early warning biomarkers. Post-intervention, these biomarkers progressively returned to normal levels. This study demonstrates the efficacy of UPLC-Q/TOF-MS in identifying metabolic biomarkers for early diagnosis of hyperthyroidism with HI and highlights the therapeutic potential of early 131I intervention in normalizing these biomarkers.

Construction and validation of a prediction model for the risk of citrate accumulation in patients with hepatic insufficiency receiving continuous renal replacement therapy with citrate anticoagulation.

BACKGROUND: To construct and validate a prediction model of the risk of citrate accumulation in patients with hepatic dysfunction receiving continuous renal replacement therapy with regional citrate anticoagulation (RCA-CRRT), which reduces the risk of citrate accumulation. METHODS: All patients who received RCA-CRRT from 2021 to 2022 and were hospitalized in the First Affiliated Hospital of Zhejiang University were considered for study participation. Logistic regression analysis was used to identify the risk factors for citrate accumulation, based on which a nomogram model was constructed and validated in the validation group. RESULTS: Six factors were finally identified, from which a nomogram was created to predict the risk of citrate accumulation. The area under the curve of the prediction model was 0.814 in the training group and 0.819 in the validation group, and the model showed acceptable agreement between the actual and predicted probabilities. Decision curve analysis also demonstrated that the model was clinically useful. CONCLUSIONS: The model constructed from six factors reliably predicted the risk of citrate accumulation in patients with hepatic insufficiency who received RCA-CRRT.

POEMS syndrome characterized by bone lesions: A case report.

RATIONALE: POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal paraproteinemia, and skin changes) syndrome is a rare clinical syndrome characterized by multiple peripheral neuropathies, hepatosplenomegaly, endocrine disorders, monoclonal paraproteinemia, and dermatosis. The main manifestations of POMES were nerve and skin changes, and bone disease was not reported. Here, we report a case of POEMS syndrome with the main manifestation of bone lesions. PATIENT CONCERNS: POMES is rare and its clinical manifestations are complex, making it difficult for patients to find the department they should visit. It is easy to miss diagnosis and misdiagnosis, delay the treatment time of patients, and affect the prognosis. DIAGNOSIS INTERVENTIONS: The patient was admitted to the gastroenterology department due to hepatic insufficiency. Multiple osteogenic changes were found by improved enhanced CT due to screening for causes of hepatic insufficiency, and spleen enlargement was indicated by abdominal ultrasound. Due to the involvement of multiple system problems, and follow-up of medical history, it was found that there was a history of discoloration of the distal limb in cold weather in the past 5 years. All things considered, it may be POMES. Further refinement of the bone marrow examination revealed active proliferation of granulocytes and erythrocytes. Bone marrow biopsy showed active hyperplasia, dominated by granulocytes. IFE showed IgA (type λ) and monoclonal myeloma (M) protein bands. To sum up, POMES diagnosis is considered. OUTCOMES: After the diagnosis is clear and the informed consent of the patient and his family is obtained, prednisone acetate is anti-inflammatory, lenalidomide is used to regulate immune function, liver and stomach protection treatment and bile secretion promotion are given. The patient reported improvement in liver function, significant improvement in overall and limb stiffness, and was discharged with improvement. LESSONS: Although bone lesions are not typically the main manifestation of POEMS syndrome, this diagnosis should be considered when this manifestation is combined with organ enlargement, skin changes, and peripheral neuropathy. In addition, the collection of medical history is crucial, when there is a clinical manifestation and auxiliary examination does not match, the idea should be expanded according to the relevant evidence, and finally make the corresponding diagnosis.

[Systematic analysis of liver failure accompanied with hemophagocytic syndrome in adults].

Objective: To retrospectively analyze literature reports and summarize the clinical characteristics of liver failure in patients accompanied with adult hemophagocytic syndrome (HPS). Methods: The Wanfang, CNKI, VIP, PubMed, and Ovid databases were searched for relevant literature on liver failure patients accompanied with adult HPS published from January 1980 to May 2022. The final included literature was systematically reviewed after screening. Results: There were a total of 77 liver failure cases accompanied with adult HPS, with an average age of (41.8 ± 12.5) years. The most common clinical manifestations of these cases were persistent high fever, fatigue, gastrointestinal symptoms, and severe jaundice. The imaging changes were not specific, and the most common was hepatosplenomegaly. Laboratory examination showed a significant increase in serum total bilirubin, lactate dehydrogenase, triglycerides, and soluble interleukin-2 receptor levels, as well as serum ferritin, while there was a decrease in prothrombin activity, natural killer cell activity, and hemocytopenia of two or more lineages in peripheral blood. Myelogram examination showed hemophagocytosis. Adult HPS secondary to infection was more likely to be accompanied with liver failure (55.8%), with an overall case fatality rate of 84.4%. Conclusion: Patients with liver failure accompanied with adult HPS have an extremely high mortality rate and a poor prognosis. Early diagnosis and treatment are the keys to improving the prognosis.

Glucagon-like peptide-1 and glucagon-like peptide-2 regulation during human liver regeneration.

Accumulating evidence suggests that metabolic demands of the regenerating liver are met via lipid metabolism and critical regulators of this process. As such, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) critically affect hepatic regeneration in rodent models. The present study aimed to evaluate potential alterations and dynamics of circulating GLP-1 and GLP-2 in patients undergoing liver resections, focusing on post-hepatectomy liver failure (PHLF). GLP-1, GLP-2, Interleukin-6 (IL-6) and parameters of lipid metabolism were determined perioperatively in fasting plasma of 46 patients, who underwent liver resection. GLP-1 and GLP-2 demonstrated a rapid and consistently inverse time course during hepatic regeneration with a significant decrease of GLP-1 and increase of GLP-2 on POD1. Importantly, these postoperative dynamics were significantly more pronounced when PHLF occurred. Of note, the extent of resection or development of complications were not associated with these alterations. IL-6 mirrored the time course of GLP-2. Assessing the main degradation protein dipeptidyl peptidase 4 (DPP4) no significant association with either GLP-1 or -2 could be found. Additionally, in PHLF distinct postoperative declines in plasma lipid parameters were present and correlated with GLP-2 dynamics. Our data suggest dynamic inverse regulation of GLP-1 and GLP-2 during liver regeneration, rather caused by an increase in expression/release than by changes in degradation capacity and might be associated with inflammatory responses. Their close association with circulating markers of lipid metabolism and insufficient hepatic regeneration after liver surgery suggest a critical involvement during these processes in humans.

Biochemical and morphological responses to post-hepatectomy liver failure in rats.

The upper limit for partial hepatectomy (PH) in rats is 90%, which is associated with an increased risk of post-hepatectomy liver failure (PHLF), correlating with high mortality. Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further block randomization was performed to determine the time of euthanasia, whether 12, 24, or 48 h after surgery. A general distress score (GDS) was calculated to distinguish between rats with reversible (GDS < 10) and irreversible PHLF (GDS ≥ 10). At euthanasia, the liver remnant and blood were collected. Liver-specific biochemistry and regeneration ratio were measured. Hepatocyte proliferation and volume were estimated using stereological methods. All rats subjected to 90% experienced biochemical PHLF. The biochemical and morphological liver responses did not differ between the groups until 48 h after surgery. At 48 h, liver regeneration and function were significantly improved in survivors. The peak mean regeneration ratio was 15% for rats with irreversible PHLF compared to 26% for rats with reversible PHLF. The 90% PH rat model was associated with PHLF and high mortality. Irreversible PHLF was characterized by impaired liver regeneration capacity and an insufficient ability to metabolize ammonia.

Successful anesthesia management with inhalation anesthesia in Rosai-Dorfman disease: a case report.

Rosai-Dorfman disease (RDD) is a rare, benign, non-Langerhans cell histiocytic proliferative disease. RDD with central nervous system involvement is extremely rare. Surgical excision is generally regarded as the appropriate treatment of choice for this disease, especially when the lesion causes neurological compression. RDD can be accompanied by systemic symptoms, such as malaise, fever, weight change, leukocytosis, anemia, and hormonal disturbance, which may be challenging during general management. Little is known regarding peri-anesthesia management of this rare disease. We report a case of a patient in his 20s who had recurrent RDD and had general anesthesia with perioperative management. He was obese and hepatic insufficiency. This case report adds to the literature regarding the perioperative anesthetic management of RDD with central nervous system involvement.

External validation of the Japanese difficulty score for laparoscopic hepatectomy in patients undergoing robotic-assisted hepatectomy.

INTRODUCTION: The Japanese difficulty score (JDS) categorizes laparoscopic hepatectomy into low, intermediate, and high complexity procedures, and correlates with operative and postoperative outcomes. We sought to perform a validation study to determine if the JDS correlates with operative and postoperative indicators of surgical complexity for patients undergoing robotic-assisted hepatectomy. METHODS: Retrospective review of 657 minimally invasive hepatectomy procedures was performed between January 2008 through March 2019. Outcomes included operative time, estimated blood loss (EBL), blood transfusion, complications, post-hepatectomy liver failure (PHLF), length of stay, 30-day readmission, and 30-day and 90-day mortality. Patients were grouped based on JDS defined as: low (< 4), intermediate (4-6), and high (7 +) complexity procedures. Statistical comparisons were analyzed by ANOVA or χ2 test. RESULTS: 241 of 657 patients underwent robotic-assisted resection. Of these patients, 137 were included in the analysis based on JDS: 25 low, 58 intermediate, and 54 high. High JDS was associated with more major resections (≥ 4 contiguous segments) versus minor resections (median JDS 8 vs. 5, P < 0.0001). High JDS was associated with significantly longer operative times, higher EBL, and more blood transfusions. High JDS was associated with higher rates of PHLF at 16.7%, compared with 5.2% intermediate and 0.0% low, (P = 0.018). Complication rates, 30-day readmissions, and mortality rates were similar between groups. Median LOS was longer in patients with high JDS compared with intermediate and low (4 days vs. 3 days vs. 2 days; P = 0.0005). DISCUSSION: Higher JDS was associated with multiple indicators of operative complexity, including greater extent of resection, increased operative time, EBL, blood transfusion, PHLF, and LOS. This validation study supports the ability of the JDS to categorize patients undergoing robotic-assisted hepatectomy by complexity.

Pathology of Acute and Acute-on-Chronic Liver Failure.

Liver failure can develop as either acute liver failure in the absence of preexisting liver disease, or as acute-on-chronic liver failure in a patient with underlying chronic liver disease or cirrhosis. A timely liver biopsy is helpful to distinguish acute and chronic liver disease, identify precipitating factors, provide prognostic information based on pathologic changes, and aid in making appropriate decisions for patient management. This article will discuss the pathologic features of acute and acute-on-chronic liver failure. Developing an appreciation for the histopathologic patterns of injury observed in these entities is essential for a practical understanding of the diagnostic process.

Drug-Induced Acute-on-Chronic Liver Failure: Challenges and Future Directions.

Drug-induced liver injury (DILI) is a global problem related to prescription and over-the-counter medications as well as herbal and dietary supplements. It can lead to liver failure with the risk of death and need for liver transplantation. Acute-on-chronic liver failure (ACLF) may be precipitated by DILI and is associated with a high risk of mortality. This review addresses the challenges in defining the diagnostic criteria of drug-induced ACLF (DI-ACLF). The studies characterizing DI-ACLF and its outcomes are summarized, highlighting geographic differences in underlying liver disease and implicated agents, as are future directions in the field.

Hidatidosis quística simulando una neoplasia hepática invasiva / Cystic hydatidosis simulating an invasive hepatic neoplasia

La hidatidosis/equinococosis quística es una infección zoonótica, endémica en muchos países de América del Sur, caracterizada por lesiones hepáticas que radiológicamente pueden simular neo-plasias malignas de aspecto quístico y que, dependiendo del tiempo de evolución y del grado de obstrucción de la vía biliar, pueden cursar con insuficiencia hepática, por lo cual es importante un diagnóstico oportuno. Presentamos el caso de un paciente masculino de 35 años, sin antecedentes patológicos de importancia, perteneciente a una comunidad indígena y residente de una zona rural de Colombia, quien presentó un cuadro clínico y pruebas de laboratorio sugestivos de obstrucción de la vía biliar, la cual fue confirmada con el hallazgo de una masa hepática quística infiltrante en los estudios imagenológicos, sospechándose inicialmente una etiología neoplásica maligna. El paciente finalmente falleció tras procedimiento quirúrgico, y su estudio histopatológico reveló una hidatidosis quística como diagnóstico definitivo.

Cystic echinococcosis/hydatidosis is a zoonotic infection, endemic in many South American coun-tries, characterized by liver lesions that radiologically can simulate malignant neoplasms with a cystic appearance, and depending on the time of progression and degree of obstruction of the bile duct, can present with liver failure, so a prompt diagnosis is important. We present the case of a 35-year-old male patient, with no significant pathological history, from an indigenous community and resident of a rural area in Colombia, who presented clinical symptoms and laboratory tests suggestive of bile duct obstruction, which was confirmed with the finding of an infiltrating cystic liver mass in imaging studies, initially suspecting a malignant neoplastic etiology. The patient developed a fulminant course after surgery, and the histopathological study revealed cystic hydatidosis as the definitive diagnosis.

Cambios fisiopatológicos y complicaciones de las resecciones hepáticas / Physiopathological changes and complications of liver resections / Alterações fisiopatológicas e complicações das ressecções hepáticas

Las modernas técnicas quirúrgicas y anestésicas han permitido ampliar el número de intervenciones quirúrgicas a nivel hepático por diversas patologías. Logrando disminuir su moralidad pero manteniendo al día de hoy elevados niveles de morbilidad. Durante la cirugía hepática se producen cambios hemodinámicos vinculados a la movilización del hígado, a los clampeos y a las pérdidas sanguíneas independientemente de la vía de abordaje. En el postoperatorio las complicaciones o cambios fisiopatológicos derivan de las lesiones producidas por los fenómenos de isquemia y reperfusión; y aquellas producidas por la regeneración hepática. Dicha capacidad depende no solo de la cantidad de hígado remanente sino también de la posible hepatopatía preexistente. La insuficiencia hepática postoperatoria es la complicación más temida y se manifiesta con ictericia, ascitis, encefalopatía y alteraciones en la paraclínica como la hiperbilirrubinemia y descenso del tiempo de protrombina. Las complicaciones quirúrgicas dependen del procedimiento realizado y se dividen principalmente en biliares y vasculares. Las secuelas de las hepatectomías dependen de factores como el estado general del paciente, la presencia hepatopatía, el acto quirúrgico y la cantidad y calidad del hígado remanente.

Modern surgical and anesthetic techniques have made it possible to increase the number of liver surgeries for various pathologies. This has reduced morbidity but still maintains high levels of morbidity. During hepatic surgery, hemodynamic changes related to liver mobilization, clamping and blood loss occur independently of the approach route. In the postoperative period, complications or pathophysiological changes derive from the lesions produced by ischemia and reperfusion phenomena; and those produced by hepatic regeneration. This capacity depends not only on the amount of remaining liver but also on the possible pre-existing hepatopathy. Postoperative liver failure is the most feared complication and manifests with jaundice, ascites, encephalopathy and paraclinical alterations such as hyperbilirubinemia and decreased prothrombin time. Surgical complications depend on the procedure performed and are mainly divided into biliary and vascular. The sequelae of hepatectomies depend on factors such as the patient's general condition, the presence of liver disease, the surgical procedure and the quantity and quality of the remaining liver.

As modernas técnicas cirúrgicas e anestésicas tornaram possível aumentar o número de cirurgias hepáticas para várias patologias. Isto levou a uma diminuição da morbidade, mas ainda mantém altos níveis de morbidade. Durante a cirurgia hepática, ocorrem alterações hemodinâmicas ligadas à mobilização hepática, pinçamento e perda de sangue, independentemente da via de aproximação. No período pós-operatório, complicações ou alterações fisiopatológicas derivam de lesões causadas por fenômenos de isquemia e reperfusão, e aquelas causadas pela regeneração hepática. Esta capacidade depende não apenas da quantidade de fígado restante, mas também de uma possível doença hepática pré-existente. A insuficiência hepática pós-operatória é a complicação mais temida e se manifesta com icterícia, ascite, encefalopatia e alterações paraclínicas, tais como hiperbilirrubinemia e diminuição do tempo de protrombina. As complicações cirúrgicas dependem do procedimento realizado e são divididas principalmente em biliares e vasculares. As seqüelas de hepatectomias dependem de fatores como o estado geral do paciente, a presença de doença hepática, o procedimento cirúrgico e a quantidade e qualidade do fígado restante.

Screening of ferroptosis-related genes in sepsis-induced liver failure and analysis of immune correlation.

Purpose: Sepsis-induced liver failure is a kind of liver injury with a high mortality, and ferroptosis plays a key role in this disease. Our research aims to screen ferroptosis-related genes in sepsis-induced liver failure as targeted therapy for patients with liver failure. Methods: Using the limma software, we analyzed the differentially expressed genes (DEGs) in the GSE60088 dataset downloaded from the Gene Expression Omnibus (GEO) database. Clusterprofiler was applied for enrichment analysis of DEGs enrichment function. Then, the ferroptosis-related genes of the mice in the FerrDb database were crossed with DEGs. Sepsis mice model were prepared by cecal ligation and perforation (CLP). ALT and AST in the serum of mice were measured using detection kit. The pathological changes of the liver tissues in mice were observed by hematoxylin-eosin (H & E) staining. We detected the apoptosis of mice liver tissues using TUNEL. The expression of Hmox1, Epas1, Sirt1, Slc3a2, Jun, Plin2 and Zfp36 were detected by qRT-PCR. Results: DEGs analysis showed 136 up-regulated and 45 down-regulated DEGs. Meanwhile, we found that the up-regulated DEGs were enriched in pathways including the cytokine biosynthesis process while the down-regulated DEGs were enriched in pathways such as organic hydroxy compound metabolic process. In this study, seven genes (Hmox1, Epas1, Sirt1, Slc3a2, Jun, Plin2 and Zfp36) were obtained through the intersection of FerrDb database and DEGs. However, immune infiltration analysis revealed that ferroptosis-related genes may promote the development of liver failure through B cells and natural killer (NK) cells. Finally, it was confirmed by the construction of septic liver failure mice model that ferroptosis-related genes of Hmox1, Slc3a2, Jun and Zfp36 were significantly correlated with liver failure and were highly expressed. Conclusion: The identification of ferroptosis-related genes Hmox1, Slc3a2, Jun and Zfp36 in the present study contribute to our understanding of the molecular mechanism of sepsis-induced liver failure, and provide candidate targets for the diagnosis and treatment of the disease.

Efficacy and safety of caspofungin for patients with hepatic insufficiency.

BACKGROUND: To observe the changes of hepatic function and efficacy of conventional dosage of caspofungin in the treatment of patients with different Child-Pugh scores. METHODS: In total, 200 patients (Child-Pugh A group: 66 patients, Child-Pugh B group: 83 patients, Child-Pugh C group: 51 patients) treated with caspofungin from May 2018 to March 2021 in the Second Affiliated Hospital of Chongqing Medical University were enrolled. Main investigation items were as follows: sex, age, weight, duration of treatment, dosage, department, underlying diseases, risk factors for fungal infection, albumin, liver enzyme, total bilirubin, serum creatinine, estimated glomerular filtration rate. To investigate the changes of liver, kidney function tests and efficacy during the treatments of caspofungin. Patients were divided into three groups according to the duration of treatment of caspofungin:1-week group, 2-week group and 3-week group, respectively. RESULTS: In the three groups, albumin, liver enzyme levels, total bilirubin and serum creatinine, estimated glomerular filtration rate had no significant difference (P > 0.05). The efficacy of different Child-Pugh scores and different duration of treatment was also significantly different (P > 0.05). CONCLUSIONS: Caspofungin is well tolerated and highly effective. And it will not exacerbate the hepatic and renal function when administered with the not-reducing dose, which indicate the clinical application value of caspofungin. Besides, extending the treatment duration has little effect on improving the efficacy of caspofungin. The drug should be withdrawn timely according to the patients' clinical condition in order to reduce the adverse reactions and economic burden.

Preeclampsia de presentación grave asociada a hígado graso agudo del embarazo / Severe preeclampsia associated with acute fatty liver of pregnancy / Pré-eclâmpsia grave associada a fígado gorduroso agudo da gravidez

La preeclampsia se puede asociar a una patología poco frecuente como es el hígado graso agudo del embarazo. Se reporta el caso clínico de una paciente de 35 años, tercigesta, cursando embarazo gemelar que presenta preeclampsia con elementos de gravedad, asociada a hígado graso agudo del embarazo. Se realiza diagnóstico y tratamiento precoz de ambas patologías, presentando buena evolución materno-fetal.

Preeclampsia can be associated with acute fatty liver of pregnancy, a rare disease. This report describes the case of a 35-year-old patient, gravida 3, pregnant with twins, who presented with severe pre-eclampsia associated with acute fatty liver of pregnancy. Early diagnosis and treatment of both pathologies was performed, resulting in good maternal-fetal evolution.

A pré-eclâmpsia pode estar associada a uma patologia rara, como o fígado gorduroso agudo da gravidez. Neste relato, apresentamos uma paciente de 35 anos, terciária, em gestação gemelar, apresentando pré-eclâmpsia grave, associada a esteatose hepática aguda na gestação. É realizado diagnóstico e tratamento precoces de ambas as patologias, apresentando boa evolução materno-fetal.

Establishment of a scoring model for early diagnosis of infection associated with liver failure.

INTRODUCTION AND OBJECTIVES: Infection is a common complication of liver failure. Serum inflammatory markers used to diagnose infection have sufficient diagnostic sensitivity but low specificity. This study aimed to improve the early diagnosis of infections in liver failure patients by developing a diagnostic model and evaluating its predictive ability. PATIENTS AND METHODS: A retrospective analysis of clinical data from liver failure patients. Cases were divided into infected and non-infected groups according to their clinical diagnosis. Nine infection-related predictors (age, body temperature, neutrophil ratio (NE%), procalcitonin (PCT), C-reactive protein (CRP), lactic acid (Lac), serum albumin (Alb), model of end-stage liver disease (MELD) score, and sequential organ failure assessment (SOFA) score) were included in multivariate logistic regression analysis. The diagnostic model was validated, and the receiver operating characteristic (ROC) curve was used to analyze its predictive accuracy. RESULTS: In the model group, multivariate logistic regression analysis showed that age, body temperature, PCT, CRP, Lac, and SOFA score were independent predictors of infection associated with liver failure (P < 0.05). The area under the ROC curve (AUC) of the model was 0.899 (95% confidence interval [CI] 0.846-0.939), and the sensitivity and specificity were 86.2% and 80.4%, respectively. The AUC for the validation group was 0.953 (95% CI 0.899-0.983), and the sensitivity and specificity were 91.7% and 84.2%, respectively. CONCLUSIONS: This study reports a model for early diagnosis of infection in liver failure patients. The model had high overall accuracy and showed good reproducibility and reliability in patients from different centers in the same region.

[Research advances in the treatment of liver failure with mesenchymal stem cell-derived exosomes].

Liver failure is a serious clinical syndrome in which multiple pathogenic factors exceed the liver's self-repair capability, resulting massive hepatocellular necrosis, rapid disease progression and high mortality. Liver transplantation is the most effective method for the treatment of liver failure, but it has disadvantages, such as insufficient liver donor and high cost. The clinical efficacy of mesenchymal stem cells in liver failure have been validated, but its application has been limited to certain extent. Cell-free-based therapies, especially mesenchymal stem cell-derived exosomes, has become a research hotspot in recent years. This paper reviews the research advances in the treatment of liver failure with the use of mesenchymal stem cell-derived exosomes.

A case of HBV-induced liver failure in the REEF-2 phase II trial: Implications for finite treatment strategies in HBV 'cure'.

Nucleoside analogues are the mainstay of treatment for patients with chronic HBV infection but have no direct effect on covalently closed circular DNA. Long-term HBV viral suppression is now routine, but the desirable endpoint of functional cure is rarely achieved. Newer therapies, targeting other aspects of the replicative life cycle of HBV, present opportunities to deliver finite therapy and HBV 'cure'. This is an area of keen focus for the HBV community. We describe a severe case of hepatitis B reactivation, occurring shortly after the withdrawal of a nucleoside analogue within the protocol of a clinical trial (REEF-2). Despite best supportive care and prompt re-introduction of tenofovir, the patient developed subacute liver failure, requiring emergency orthotopic liver transplantation. As we strive to achieve HBV cure, this case highlights the potential risks of finite therapy and highlights the need for improved biomarker-driven strategies and re-evaluation of study protocols.

Prognostic significance of hyperammonemia in neuroendocrine neoplasm patients with liver metastases.

Neuroendocrine neoplasms (NENs) are rare, usually slow-growing tumors, often presenting with extensive liver metastases. Hyperammonemia due to insufficient hepatic clearance has been described in NEN cases; however, no systematic evaluation of risk factors and outcomes of NEN-associated hyperammonemia exists so far. This case report and retrospective review of NEN patients developing hyperammonemia from the years 2000 to 2020 at the Erasmus Medical Center in Rotterdam, the Netherlands, aimed to describe these patients and determine prognostic factors to improve evaluation and treatment. Forty-four NEN patients with documented hyperammonemia were identified. All patients had liver metastases with 30% (n = 13) showing signs of portal hypertension. Patients who developed encephalopathy had higher median ammonia levels, but there was no association between the severity of hyperammonemia and liver tumor burden or presence of liver insufficiency. Eighty-four percent (n = 37) of patients died during follow-up. The median (IQR) time from diagnosis of hyperammonemia to death was 1.7 months (0.1-22.7). Hyperbilirubinemia, hypoalbuminemia, elevated international normalized ratio, presence of liver insufficiency, encephalopathy and ascites were associated with worse outcomes. Their role as independent risk factors for mortality was confirmed using the Child-Pugh score as a summary factor (P < 0.001). No difference was seen concerning overall survival between our hyperammonemia patients and a propensity score-matched control stage IV NEN cohort. In conclusion, hyperammonemia comprises a relevant and potentially underdiagnosed complication of NEN liver metastases and is associated with worse outcomes. Assessment of signs of encephalopathy, risk factors and the Child-Pugh score could be helpful in selecting patients in whom ammonia levels should be measured.