Management of pediatric liver failure with therapeutic plasma exchange and continuous renal replacement therapy: A retrospective observational study.

Liver failure represents a critical medical condition, marked by the rapid decline of hepatic functions. Emerging therapies, notably therapeutic plasma exchange (TPE) and continuous venovenous hemodiafiltration (CVVHDF), have demonstrated potential in mitigating these conditions through their roles in detoxification and hepatic support. The utility of these treatments, whether applied individually or in tandem, constitutes a significant area of research concerning the management of liver failure in pediatric patients. This study aims to evaluate the role and efficacy of TPE or TPE combined with CVVHDF in the treatment of liver failure among children. This retrospective study was conducted in a LTICU by reviewing the medical history of pediatric patients aged 1 month to 18 years. Patients were admitted between January 1, 2021 and December 1, 2023 due to acute liver failure or acute-chronic liver failure. The study evaluated those who received TPE or continuous renal replacement therapy combined with TPE. In statistical analyses, a P-value of <.05 was considered statistically significant. The study involved 24 patients with liver failure, comprising 13 males and 11 females. Sixteen patients (66.6%) received only TPE, while 8 patients (33.4%) were treated with TPE and CVVHDF. For patients treated only with TPE, the median INR reduced from 3.1 to 1.26, alanine aminotransferase from 1255 to 148, and aspartate aminotransferase from 2189 to 62. Similar significant reductions were observed in the TPE and CVVHDF group: INR from 3.9 to 1.26, alanine aminotransferase from 1749 to 1148, and aspartate aminotransferase from 1489 to 62. These changes were statistically significant with P-values of .01 for each parameter in both groups. Overall, 14 patients survived without requiring a liver transplant, while 4 patients underwent liver transplantation. Our study on pediatric liver failure treatment shows that both standalone TPE and its combination with CVVHDF are effective, especially as a bridge to transplantation. With 58% transplant-free survival, these therapies demonstrate significant clinical improvements. Future multicentric studies are needed for broader validation of these findings in liver failure management.

Successful results of early nucleos(t)ide analogue treatment for liver transplantation candidates with severe acute hepatitis B infection.

BACKGROUND: Early treatment of severe acute hepatitis B virus (HBV) infection with nucleos(t)ide analogues may prevent progression to acute liver failure (ALF). PATIENTS AND METHODS: The charts of 24 patients who were treated for severe acute HBV infection (either INR ≥ 1.5 or INR≥ 1.4 and total bilirubin ≥ 20 mg/dL at the referring institution or after admission) between April 2021 and May 2023 (inclusive) were evaluated retrospectively. Twelve patients were women; median [range] age: 48 [35-68]. Entecavir (0.5 mg/day) (n = 16) or tenofovir disoproxil fumarate (245 mg/day) (n =8) were used depending on availability. RESULTS: Two patients required liver transplant which was performed successfully in one (no suitable donor for the other). Deterioration to ALF was prevented in 22 of the 24 cases (92%); these patients could be discharged after median (range) 12 (5-24) days following initiation of the antiviral drug. There was no significant difference in efficacy between the two antiviral agents. The anti-HBsAg antibody became positive in 16 patients (73%); one other patient became HBsAg negative at 1 month after discharge but was lost to follow up. Five patients (23%) are still HBsAg positive but all except one have started treatment in the last 6 months. One of the recently treated 4 patients stopped taking the antiviral drug at his own will and one has become anti-HIV antibody positive during follow up. CONCLUSION: Early treatment of severe acute HBV infection with entecavir or tenofovir disoproxil fumarate prevents the need for liver transplant and consideration of living donors.

Single-center experience in 127 adult patients, mono or dual artificial liver support therapy, in patients with acute liver failure.

Background: Acute liver failure (ALF) is a serious condition characterized by sudden liver dysfunction, jaundice and hepatic encephalopathy. Its mortality rate of approximately 80% underscores the urgent need for effective treatments. Supportive extracorporeal therapies (SET), which temporarily support liver function and remove toxins, have shown promise in improving outcomes in acute liver failure (ALF). The aim of this study was to compare the outcomes of dual supportive extracorporeal therapy (SET) and mono supportive extracorporeal therapy in patients with acute liver failure. Methods: A total of 127 patients with acute liver failure were included in this retrospective, single-center study. Of these, 62 patients received dual supportive extracorporeal therapy and 65 patients received mono supportive extracorporeal therapy. Primary endpoints were survival without the need for liver transplantation and mortality. Secondary endpoints included resolution of encephalopathy and normalization of International Normalized Ratio (INR). Results: In the dual supportive extracorporeal therapy group, 59.6% of patients survived without the need for liver transplantation, while 27.4% achieved recovery with liver transplantation. The mortality rate in this group was 12.9%. Significant regression of encephalopathy grade was observed in 87% of patients, and the 1 year mortality rate for liver transplant recipients was 10.7%. In the mono supportive extracorporeal therapy group, 61.5% of patients experienced a successful recovery without the need for liver transplantation, with a mortality rate of 29.2%. Significant improvement in the grade of encephalopathy was observed in 70.7% of patients. Conclusion: Both dual supportive extracorporeal therapy (CVVHDF and PE) and mono supportive extracorporeal therapy (PE) were associated with significant improvements in renal and hepatic biochemical parameters, blood ammonia levels, and neurological status in patients with acute liver failure associated with grade III-IV hepatic encephalopathy. In particular, dual support was associated with improved hemodynamic stability, lactic acidosis and acid-base balance. Survival in acute liver failure in our retrospective cohort using a protocolized approach to extracorporeal therapies is higher compared to previously published large ALF studies. This protocolized approach warrants further prospective studies.

A 15-Year Retrospective Study of Supportive Extracorporeal Therapies Including Plasma Exchange and Continuous Venovenous Hemodiafiltration of 114 Adults with Acute Liver Failure Awaiting Liver Transplantation.

BACKGROUND Recently, there has been a recommendation to utilize a combination of supportive extracorporeal therapies, specifically plasma exchange and continuous venovenous hemodiafiltration, in patients with acute liver failure. This 15-year retrospective study aimed to evaluate supportive extracorporeal therapy, including plasma exchange and continuous venovenous hemodiafiltration, for 114 adults with acute liver failure awaiting liver transplant. MATERIAL AND METHODS In this retrospective study, the medical records of 1288 adult patients who underwent liver transplantation and 161 adult patients who received alternative therapy were analyzed; 114 patients who received combined supportive extracorporeal therapy for acute liver failure were included in the study. Biochemical laboratory data were compared before and after therapy. RESULTS The study included 50 male and 64 female patients. The first group (34 patients) recovered with liver transplantation, and 4 patients died in the first year after liver transplantation. In the second group (80 patients), 66 patients recovered without liver transplantation, while 14 patients died within the first 2 weeks after therapy. All patients showed significant reductions in serum hepatic function tests (alanine transaminase, aspartate transaminase, and total bilirubin), ammonia, and prothrombin time/international normalized ratio after discontinuation of combined supportive extracorporeal therapy (P<0.01). There was also a significant improvement in the hemodynamic parameter. CONCLUSIONS This combined extracorporeal therapy can be used as a supportive treatment for both recovery and bridge to liver transplantation in patients with acute liver failure. In addition, treatment can be continued until liver regeneration and until a usable donor is found.

Hyperammonemia and Hepatic Encephalopathy in Pediatric and Adult Liver Intensive Care Unit.

Objectives: The exact mechanism that causes the neurotoxicity of hepatic encephalopathy (HE) is still unknown. In this retrospective study, we aimed to define the frequency of hyperammonemia and its relationship with HE. Methods: The records of 190 patients who were followed up in the Organ transplantation and Hepato-pancreato-biliary surgery intensive care unit (ICU) between August 2021 and August 2022 were reviewed retrospectively. 111 adults and children whose ammonia levels were examined during their stay in the ICU were included in the study He was evaluated with West Haven Criteria. HE had grades 0-4 in the groups. Results: The median age (range) was 5 (0-16) children and 60 (20-104) adults. The median ammonia value (range) was 42,2 (16-314). Hyperammonemia was present in 39 patients (35%) of all patients. Patients with hyperammonemia and grade 0 encephalopathy were 16 (14%), grade 1-2 patients were 11(10%), and grade 3 patients were 12 (11%). Conclusion: While our findings and literature evidence strongly support the view that ammonia is the primary factor responsible for, HE development, it shows that factors other than ammonia can only exacerbate HE. In addition, we think that the increased ammonia value in patients with acute liver failure and acute on chronic liver failure is correlated with the increase in the degree of encephalopathy.

Value of extracorporeal artificial liver support in pediatric acute liver failure: A single-center experience of over 10 years.

Purpose: Acute liver failure (ALF) is a life-threatening disease characterized by rapid-onset liver dysfunction, coagulopathy, and encephalopathy in patients without chronic liver disease. Today, the combined application of continuous veno-venous hemodiafiltration (CVVHDF) and plasma exchange (PEX), which are forms of supportive extracorporeal therapy (SECT), with conventional liver therapy in ALF is recommended. This study aims to retrospectively analyze the effects of combined SECT in pediatric patients with ALF. Materials and Methods: We retrospectively analyzed 42 pediatric patients, followed in the liver transplantation intensive care unit. The patients had ALF and received PEX supportive therapy with combined CVVHDF. The biochemical lab values of the results for the patients before the first combined SECT and after the last combined SECT were analyzed comparatively. Results: Of the pediatric patients included in our study, 20 were girls and 22 were boys. Liver transplantation was performed in 22 patients, and 20 patients recovered without transplantation. After the discontinuation of combined SECT, all patients had significantly lower serum liver function test results (total bilirubin, alanine transaminase, aspartate transaminase), ammonia, and prothrombin time/international normalized ratio levels than the previous levels (p < 0.01). Hemodynamic parameters (i.e., mean arterial pressure) also improved significantly. Discussion and Conclusion: Combined CVVHDF and PEX treatment significantly improved biochemical parameters and clinical findings, including encephalopathy, in pediatric patients with ALF. PEX therapy combined with CVVHDF is a proper supportive therapy for bridging or recovery.

Peripheral innate and adaptive immune cells during COVID-19: Functional neutrophils, pro-inflammatory monocytes, and half-dead lymphocytes.

BACKGROUND: A better understanding of innate and adaptive cells in COVID-19 is necessary for the development of effective treatment methods and vaccines. METHODS: We studied phenotypic features of innate and adaptive immune cells, oxidative burst, phagocytosis, and apoptosis. One hundred and three patients with COVID-19 were grouped according to their clinical features into the categories of mild (35%), moderate (40.8%), and severe (24.3%). RESULTS: Monocytes were CD16+ pro-inflammatory monocytes and tended to shed their HLA-DR, especially in severe cases (p < 0.01). Neutrophils were mature and functional, although a decline of their CD10 and CD16 was observed (p < 0.01). No defect was found in the reactive oxygen species production and their apoptosis. The percentage of natural killer cells was in the normal range, whereas the percentages of CD8+ NK and CD56+ T lymphocytes were found to be high (p < 0.01). Although the absolute numbers of all lymphocyte subsets were low and showed a tendency for a gradual decrease in accordance with the disease progression, the most decreased absolute number was that of B lymphocytes, followed by CD4+ T cells in the severe cases. The percentages of double-negative T cells; HLA-DR+ CD3+ and CD28- CD8+ subsets were found to be significantly increased. Importantly, we demonstrated the increased baseline activation of caspase-3 and increased lymphocyte apoptosis. CONCLUSION: We suggest that SARS-CoV-2 primarily affects the lymphocytes and not the innate cells. The increased baseline activation of Caspase-3 could make the COVID-19 lymphocytes more vulnerable to cell death. Therefore, this may interrupt the crosstalk between the adaptive and innate immune systems.

The role of plasma exchange in acute liver failure of autoimmune etiology.

BACKGROUND: Autoimmune hepatitis (AIH) is characterized by increased immunoglobulin G (IgG) levels, the presence of autoantibodies, and various degrees of lymphocyte predominant inflammation and fibrosis histologically. Immunosuppressive therapy induces remission in approximately 80% of those affected. However, liver transplantation is indicated in patients with acute liver failure with encephalopathy at presentation. Liver supporting systems, including plasma exchange (PE) allow bridging patients to transplantation or spontaneous recovery in the setting of liver failure. The role of these systems has not been assessed in children with liver failure of autoimmune etiology. CASE: Herein, we report three cases of AIH with fulminant presentation, with marked symptom resolution with PE as an adjunct therapeutic option to immunosuppressive treatment. CONCLUSION: In the setting of AIH, PE may have a special therapeutic role by removing autoantibodies and cytokines, therefore preventing further liver damage and decompensation, and allowing time for recovery.

Posthepatectomy liver failure

Liver surgery is one of the most complex surgical interventions with high risk and potential for complications. Posthepatectomy liver failure (PHLF) is a serious complication of liver surgery that occurs in about 10% of patients undergoing major liver surgery. It is the main source of morbidity and mortality. Appropriate surgical techniques and intensive care management are important in preventing PHLF. Early start of the liver support systems is very important for the PHLF patient to recover, survive, or be ready for a liver transplant. Nonbiological and biological liver support systems should be used in PHLF to prepare for treatment or organ transplantation. The definition of the state, underlying pathophysiology and treatment strategies will be reviewed here.

Management of Pediatric Acute Liver Failure in a Region With Insufficient Deceased Donor Support: A Single-Center Experience.

OBJECTIVES: Acute liver failure is a rapidly progressive and life-threatening disease in children, whose clinical features differ from those of adults. MATERIALS AND METHODS: This is a review of a single center's experience with pediatric acute liver failure in a region with insufficient deceased donor support. The study is a retrospective review and analysis of 22 pediatric patients with acute liver failure between January 2007 and May 2013. RESULTS: The cause of acute liver failure was indeterminate in 45.4% of cases. Listing for liver transplant was required in 72.7% of patients, whereas 27.3% developed spontaneous remission. In the patients placed on the liver transplant wait list, 75% underwent liver transplant and 25% died before undergoing liver transplant. The presence of ascites, high-grade encephalopathy, and laboratory findings including high lactate dehydrogenase and phosphorous levels and international normalized ratio were significant parameters in selecting patients needing liver transplants. All liver transplants were from living donors. One- and 3-year patient survival rates after liver transplant were 75% and 75%. No serious donor complications occurred. CONCLUSIONS: Living-donor liver transplant may be the only option to save the lives of pediatric patients with acute liver failure, especially in regions with insufficient deceased-donor support. Timely referral to a multidisciplinary transplant center, expedient evaluation of living donors, and appropriate timing of transplant are crucial for a successful outcome.