Subacute Liver Failure Research Articles

Risk factors for secondary infection after liver failure and effect of comprehensive nursing intervention.

In patients with liver failure (LF), the high rate of secondary infections, which are associated with poor prognosis, highlights the clinical significance of understanding the underlying risk factors and implementing targeted intervention programs. To investigate risk factors for secondary infections in patients with LF and evaluate the effectiveness of comprehensive nursing interventions. This retrospective study included 64 patients with LF, including 32 with and 32 without secondary infections. A questionnaire was used to collect data on age; laboratory parameters, including total and direct bilirubin, prothrombin time, blood ammonia, and other biochemical parameters; invasive procedures; and complications. Patients with secondary infections received comprehensive nursing intervention in addition to routine nursing care, whereas those without secondary infections received only routine nursing care to compare the effect of nursing intervention on outcomes. The infection rate, which was not associated with age or complications, was significantly associated with biochemical parameters and invasive procedures (P < 0.05). The infection rate was 61.6% in patients who had undergone invasive procedures and 32.1% in those who had not undergone invasive procedures during the hospital stay. The infection rate was also significantly associated with the type of LF (P < 0.05), with the lowest rate observed in patients with acute LF and the highest rate observed in those with subacute LF. The nursing satisfaction rate was 58.3% in the uninfected group and 91.7% in the infected group, indicating significantly higher satisfaction in the infected group (P < 0.05). In patients with LF, the rate of secondary infections was high and associated with biochemical parameters and type of LF. Comprehensive nursing intervention can improve patient satisfaction.

Human iPSC-liver organoid transplantation reduces fibrosis through immunomodulation.

Donor organ shortages for transplantation remain a serious global concern, and alternative treatment is in high demand. Fetal cells and tissues have considerable therapeutic potential as, for example, organoid technology that uses human induced pluripotent stem cells (hiPSCs) to generate unlimited human fetal-like cells and tissues. We previously reported the in vivo vascularization of early fetal liver-like hiPSC-derived liver buds (LBs) and subsquent improved survival of recipient mice with subacute liver failure. Here, we show hiPSC-liver organoids (LOs) that recapitulate midgestational fetal liver promote de novo liver generation when grafted onto the surface of host livers in chemical fibrosis models, thereby recovering liver function. We found that fetal liver, a hematopoietic tissue, highly expressed macrophage-recruiting factors and antifibrotic M2 macrophage polarization factors compared with the adult liver, resulting in fibrosis reduction because of CD163+ M2-macrophage polarization. Next, we created midgestational fetal liver-like hiPSC-LOs by fusion of hiPSC-LBs to induce static cell-cell interactions and found that these contained complex structures such as hepatocytes, vasculature, and bile ducts after transplantation. This fusion allowed the generation of a large human tissue suitable for transplantation into immunodeficient rodent models of liver fibrosis. hiPSC-LOs showed superior liver function compared with hiPSC-LBs and improved survival and liver function upon transplantation. In addition, hiPSC-LO transplantation ameliorated chemically induced liver fibrosis, a symptom of liver cirrhosis that leads to organ dysfunction, through immunomodulatory effects, particularly on CD163+ phagocytic M2-macrophage polarization. Together, our results suggest hiPSC-LO transplantation as a promising therapeutic option for liver fibrosis.

Epidemiological characteristics of inpatients with liver failure at the Beijing You'an Hospital from 2012 to 2021

Objective: To elucidate the epidemiological characteristics and changing trends of liver failure in order to provide evidence-based strategies for prevention and treatment. Methods: The epidemiological information of inpatients with liver failure admitted and treated at Beijing You'an Hospital from 2012 to 2021 was retrospectively collected. The trend test was used to analyze age, gender, as well as the year-by-year changes in the underlying acute and chronic etiology of acute liver failure (ALF), sub-acute liver failure (SALF), acute-on-chronic liver failure (ACLF), and chronic liver failure (CLF). Results: During the study period, information on a total of 8512 inpatients, aged 51.3±13.5 years and mainly male (71.9%) with liver failure, was collected. The highest to lowest proportions of liver failure types were ACLF 4 023 (47.3%), CLF 3 571(42.0%), SALF 670 (7.9%), and ALF 248 (2.9%). The top five causes of liver failure in the overall population, accounting for 87.6% of the total, were hepatitis B 3 199 (37.58%), alcoholic liver disease 2 237 (26.28%), cryptogenic liver disease 906(10.61%), hepatitis B + alcoholic liver disease 603 (7.08%), drugs 488 (5.73%), The top three etiologies of patients with different types of liver failure were acute etiologies for acute liver failure (ALF), followed by drugs 107 (43.1%), hepatitis B 47(19.0%), and unknown etiology 36 (14.5%); sub-acute liver failure (SALF), followed by drugs 381(56.9%), unknown etiology 106 (15.8%), and sepsis 56 (8.4%); and acute-on-chronic liver failure (ACLF), followed by drugs 2 092(52.0%), alcoholic liver disease 813(20.2%), and cryptogenic liver disease 398(9.9%); and chronic etiologies for chronic liver failure (CLF), followed by alcoholic liver disease 1 410(39.5%), hepatitis B 1 028(28.8%), and cryptogenic liver disease 364(10.2%). Longitudinal analysis showed that the average age of patients with liver failure increased year by year, but the sex ratio trend did not change significantly, with male patients predominating throughout. The proportion of drug-induced liver failure in patients with ALF and SALF increased year by year, and the difference in the trend test was statistically significant (P < 0.05). The proportion of patients with chronic etiologies of ACLF and CLF decreased year by year among hepatitis B, while the proportion of alcoholic liver disease, autoimmune liver disease, and cryptogenic liver disease increased year by year (the difference was statistically significant, P < 0.05). Conclusion: The etiological spectrum of liver failure is changing in our country. Although hepatitis B is still the main cause of liver failure, its proportion shows a decreasing trend year by year, with the exception of ACLF, which is no longer the primary etiology of other types of liver failure, while drug-induced liver disease, alcoholic liver disease, autoimmune liver disease, and cryptogenic liver disease are increasing year by year and will become the focus of liver disease prevention and treatment in the future.

Advances in hepatitis E epidemiology

Hepatitis E is a viral hepatitis that the hepatitis E virus (HEV) causes. In the early 1980s, the hepatitis E virus was first discovered and identified, and it is one of the important pathogens that cause acute viral hepatitis globally. HEV infection is usually self-limiting, but in some groups of populations, such as pregnant women, patients with chronic liver disease, and the elderly, the prognosis is poor and may result in acute or subacute liver failure or even death. In addition, HEV infection can occur in chronically immunocompromised populations. At present, some regions and countries are not paying enough attention to hepatitis E prevention, diagnosis, and treatment, which suggests that we should study the epidemiology of HEV infection.

Plex with Corticosteroids In Drug Induced Subacute Liver Failure.

Plex with Corticosteroids In Drug Induced Subacute Liver Failure.

Differential Diagnosis of Hyperferritinemia in Critically Ill Patients

Elevated serum ferritin is a common condition in critically ill patients. It is well known that hyperferritinemia constitutes a good biomarker for hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. However, further differential diagnoses of hyperferritinemia in adult critically ill patients remain poorly investigated. We sought to systematically investigate hyperferritinemia in adult critically ill patients without HLH. In this secondary analysis of a retrospective observational study, patients ≥18 years admitted to at least one adult intensive care unit at Charité-Universitätsmedizin Berlin between January 2006 and August 2018, and with hyperferritinemia of ≥500 μg/L were included. Patients with HLH were excluded. All patients were categorized into non-sepsis, sepsis, and septic shock. They were also classified into 17 disease groups, based on their ICD-10 codes, and pre-existing immunosuppression was determined. Uni- and multivariable linear regression analyses were performed in all patients. A total of 2583 patients were analyzed. Multivariable linear regression analysis revealed positive associations of maximum SOFA score, sepsis or septic shock, liver disease (except hepatitis), and hematological malignancy with maximum ferritin. T/NK cell lymphoma, acute myeloblastic leukemia, Kaposi's sarcoma, acute or subacute liver failure, and hepatic veno-occlusive disease were positively associated with maximum ferritin in post-hoc multivariable linear regression analysis. Sepsis or septic shock, liver disease (except hepatitis) and hematological malignancy are important differential diagnoses in hyperferritinemic adult critically ill patients without HLH. Together with HLH, they complete the quartet of important differential diagnoses of hyperferritinemia in adult critically ill patients. As these conditions are also related to HLH, it is important to apply HLH-2004 criteria for exclusion of HLH in hyperferritinemic patients. Hyperferritinemic critically ill patients without HLH require quick investigation of differential diagnoses.

The properties and health hazards from early nuclear weapon fallout: The Castle Bravo incident revisited

Early fallout is defined as the fallback to the earth’s surface of radioactive particles shortly after a nuclear detonation (often arbitrarily defined within 24 h). At the difference of wide spreading global fallout, early fallout mainly consists of larger particles that are often visible. The initial mixture is rich in short- and very short-lived radionuclides associated with a very high initial activity that decreases rapidly (in 7 h, the dose rate is reduced by 90%). The main danger of early fallout results from external irradiation by highly penetrating gamma-radiation that may cause acute radiation sickness. Only in the case of the thyroid, internal irradiation by the incorporation of radioiodine may prevail. The bombings of Hiroshima and Nagasaki are examples of airbursts with many fatalities by prompt effects (blast, burns, and initial ionizing radiations), but they produced little fallout. The nuclear test code-named Castle Bravo on the Marshall Islands (1954) did not have casualties by its blast, thermal or initial radiation effects, but the inhabitants of the nearby islands and the crew of a Japanese fisherboat (Lucky Dragon) were affected by large amounts of fallout. For the inhabitants of the Rongelap Atoll, the average dose from external irradiation was assessed at 1.6 Gy. From a clinical point of view, based on hematological data using the METREPOL classification system, the acute radiation syndrome can be categorized as mild (H1). Blood transfusions were not required, and antibiotics were not administered for prophylaxis or therapy of infections related to irradiation. The equivalent dose received by the thyroid resulted mainly from internal irradiation with 7.6 Gy. The major late effects were thyroid abnormalities, including thyroid failure, nodules, and malignant tumors. The 23 Japanese crewmen seem to have been irradiated by higher doses (2.9 Gy). Compared to the hematological data of the Rongelap victims, the evolution pattern over time is quite similar. Still, the absolute values of the cell counts are lower, and on average, the acute radiation syndrome can be categorized as rather moderate (H2). Considering the individual cases, data show a large interindividual variability, and the clinical severity category ranges from “no alterations” (H0) to severe (H3). Victims were treated with repeated blood transfusions and antibiotics. Several of them developed jaundice, and one of them died six months after the incident showing symptoms compatible with subacute liver failure. A radiochemical organ analysis revealed that only the bones were clearly contaminated with fission products. In the 1990s, many surviving crewmen were diagnosed with hepatitis C, incurred probably from blood transfusions that were often contaminated at the time, and died from hepatocellular carcinomas. Thyroid dysfunctions were not reported. The Castle Bravo case permits to study the health hazards resulting from early fallout independently from the prompt effects of a nuclear detonation. The prevailing external irradiation was confirmed, except for the thyroid with a higher dose resulting from radioiodine incorporation mainly caused by ingestion. As shown for the Japanese fishermen, the risks incurred by medical treatments must be carefully weighed against the benefits of the therapeutic intervention. The cause of death of the only short-term fatality is not fully elucidated, but is consistent with liver failure due to transfusion hepatitis rather than radiation effects.

Clinical Significance of Detection of Serum CA125 and CA199 in Patients with Chronic and Acute (Subacute) Liver Failure of Hepatitis B

Clinical Significance of Detection of Serum CA125 and CA199 in Patients with Chronic and Acute (Subacute) Liver Failure of Hepatitis B

Risk factors and prognostic model for HBV-related subacute liver failure

BackgroundThe prognosis for patients with chronic hepatitis B virus (HBV)-related subacute liver failure is poor. Thus, accurate prognostication would facilitate management and optimize liver allocation. This study aimed to explore the risk factors for HBV-related subacute liver failure and establish a risk model.MethodsA total of 192 patients with HBV-related subacute liver failure treated at the First Affiliated Hospital of Xi’an Jiaotong University during January 2018 to January 2019 were selected and divided into the survival group (n=113) and the death group (n=79) based on their status within 6 months. Patient information were collected, including age, sex, body mass index, complications, hepatitis B e antigen (HBeAg), hepatic encephalopathy, hepatorenal syndrome, infections, ascites, HBV-DNA, Model for End-Stage Liver Disease (MELD), liver function tests, international normalized ratio (INR), serum creatinine and total cholesterol. Binary logistic regression was employed to identify risk factors for risk model establishment. The predictive value of the risk model was assessed with a receiver operating characteristic (ROC) curve.ResultsCompared with the survival group, the patient age, incidence of hepatic encephalopathy and hepatorenal syndrome, infection and ascites rate, MELD score, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), INR, and serum creatinine levels were significantly elevated, whereas the total cholesterol level was significantly decreased in the death group (all P<0.05). Patient age [odds ratio (OR) =1.11, P=0.03], hepatic encephalopathy (OR =8.31, P=0.02), infection (OR =4.27, P=0.005), ascites (OR =4.54, P=0.006), MELD score (OR =1.39, P<0.001), INR (OR =5.89, P=0.001), and total cholesterol (OR =0.31, P=0.002) were identified as prognostic factors affecting patient mortality. Although both the MELD score and the risk model established in the present study could differentiate patient outcomes, the area under the curve (AUC) (0.94 vs. 0.82, P<0.001) and sensitivity (91.1% vs. 58.2%, P<0.001) of the established risk model were significantly higher than those of the MELD score.ConclusionsPatient age, hepatic encephalopathy, infection, ascites, MELD score, INR, and total cholesterol level were independent prognostic factors. The prognostic model established based on these risk factors may have favorable predictive value.

Metastatic Breast Cancer Simulating Cirrhosis with Portal Hypertension and Acute Liver Failure: A Case of “Pseudocirrhosis”

Pseudocirrhosis describes morphological changes in the liver that resemble cirrhosis, but the histopathological findings are not suggestive of cirrhosis. It occurs most often in patients with metastatic breast cancer, although it has also been reported in other malignancies. As in cirrhosis, portal hypertension is often seen in patients with pseudocirrhosis. Pseudocirrhosis is a rare but important complication of metastatic cancer. We will describe the case of a 45-year-old woman with a history of breast cancer, without any previously known liver disease presenting with subacute liver failure. Initial imaging studies indicated cirrhosis of the liver without signs of focal malignancy. Full diagnostic workup was negative for specific causes of liver disease and provided no evidence of tumor recurrence. Malignant pseudocirrhosis is an unusual type of metastatic tumor, with spread representing a rare but important differential diagnosis of progressive liver failure.

The predictive value of liver failure-related etiology for clinical outcomes

To assess the predictors of outcomes for different subtypes of liver failure, and the effectiveness of artificial liver support systems in the treatment of liver failure. The clinical data of 112 patients with hepatitis B virus (HBV)- and non-HBV-related liver failure admitted to the intensive care unit (ICU) of the Fifth People's Hospital of Wuxi were collected from January to December 2020. The relevant etiologies of acute, subacute, acute-on-chronic, subacute-on-chronic, chronic subtype liver failure were analyzed. The efficacies of artificial liver support systems in the treatment of various subtypes of liver failure were also compared. The correlation of various indicators was analyzed by Spearman correlation analysis, the risk factors affecting the prognosis of patients with liver failure were analyzed by multivariate Logistic regression equation, and receiver operator characteristic curve (ROC curve) of subjects was plotted to evaluate the predictive value of each risk factor for the prognosis of patients with liver failure. Among the 112 liver failure patients, 63 were caused by hepatitis B and 49 were caused by non-hepatitis B. The liver failure caused by hepatitis B was 6 times higher than for men than for women, which was higher than that of non-HBV liver failure group (1.33 times). Antithrombin III (AT III) and total bilirubin (TBil) levels of subacute liver failure were higher than those of pre-liver failure in the HBV liver failure group [AT III: (59.33±14.57)% vs. (35.66±20.72)%, TBil (μmol/L): 399.21±112.94 vs. 206.08±126.96, both P < 0.05]. The levels of AT III in patients with pre-liver failure and chronic liver failure in the non-HBV liver failure group were significantly higher than those with acute liver failure [(58.33±15.28)%, (44.00±19.10)% vs. (31.33±7.57)%, both P < 0.05], patients with acute liver failure had significantly lower level of TBil than pre-liver failure (μmol/L: 107.83±49.73 vs. 286.20±128.92, P < 0.05), the TBil levels in patients with subacute and acute-on-chronic liver failure were also significantly higher than that in pre-liver failure group (μmol/L: 417.27±118.60, 373.00±187.00 vs. 286.20±128.92, both P < 0.05). Patients with subacute liver failure, subacute-on-chronic liver failure and chronic liver failure in the non-HBV failure group were significantly longer than those in acute liver failure (days: 36.00±8.31, 27.52±11.71, 27.72±22.71 vs. 11.00±1.41, all P < 0.05). There was no statistically significant difference in the case fatality rate of using the artificial liver support system between the HBV failure group and the non-HBV failure group (55.6% vs. 50.0%, P < 0.05), the levels of AT III in the two groups of surviving patients were significantly higher than that of the dead [HBV liver failure group: (36.20±6.26)% vs. (27.33±8.87)%, non-HBV liver failure group: (41.06±4.16)% vs. (28.71±12.35)%, both P < 0.01]. Correlation analysis showed that there was a clear positive correlation between AT III and TBil in the dead patients of HBV liver failure group and the survival and death patients of non-HBV liver failure group (r values were 0.069, 0.341, 0.064, and P values were 0.723, 1.196 and 0.761, respectively); there was a significant inverse correlation between AT III and TBil in the HBV liver failure group (r = -0.105, P = 0.745). Multivariate Logistic regression analysis showed that AT III was an independent risk factor affecting the prognosis of patients with non-HBV liver failure [odd ratio (OR) = 1.023, 95% confidence interval (95%CI) was -0.001 to 0.001, P = 0.007]. TBil was an independent risk factor affecting prognosis of patients with HBV liver failure (OR = 1.005, 95%CI was -0.002 to -7.543, P = 0.033). The analysis of ROC curve showed that AT III had a predictive value for the prognosis of patients with non-HBV liver failure, the area under the ROC curve (AUC) = 0.747, the 95%CI was 0.592-0.902, P = 0.009. When the optimal truncation value was 39.5%, its sensitivity and specificity were 83.33% and 56.25%, respectively. Artificial liver support system treatment of liver failure was difficult to effectively reduce the mortality of patients with end-stage liver failure. In addition to AT III, TBil also could be used as an indicator to assess liver compensatency and predict prognosis in liver failure patients.

Successful Liver Transplantation From a SARS-CoV-2 Positive Donor to a Positive Recipient: Potential Role of Monoclonal Antibodies.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic initially resulted in a decline in organ transplantation, including a 35.9% decrease in the United States.1 Although there are many factors contributing to this, potential donors who tested positive for SARS-CoV-2 have been largely excluded from donation. Simultaneously, there was uncertainty about safety of transplanting a recipient with coronavirus disease 2019 (COVID-19). Although there are emerging reports of liver transplantation from SARS-CoV-2-infected deceased donors,2 optimal risk mitigation strategies are unclear. Herein, we report a case of liver transplantation from a SARS-CoV-2 positive deceased donor to a SARS-CoV-2 positive recipient who was managed with anti spike monoclonal antibodies. This report did not require review board approval. Our patient was a 33 y-old female with adult-onset Still’s disease, treated previously with canakinumab, admitted for severe acute-on-chronic liver failure of unclear etiology. She had experienced several months of relapsing elevations in liver biochemistries attributed to lobular hepatitis of unclear etiology. She developed jaundice with progressive encephalopathy over 3 wk, culminating in a clinical scenario consistent with subacute liver failure, with a calculated Model for End-stage Liver Disease-Sodium score of 35. Concurrently, multiple household contacts developed mild upper respiratory symptoms and were diagnosed with COVID-19. She had not undergone SARS-CoV-2 vaccination. Upon admission, the patient was jaundiced, encephalopathic, and coagulopathic, although normoxic, and her chest radiograph did not show infiltrates. Urgent evaluation for liver transplantation was initiated. Nasopharyngeal SARS-CoV-2 polymerase chain reaction was positive (cycle threshold N 33.0, open reading frame 27.6; ARIES SARS-CoV-2 assay, Luminex Corp), and serum SARS-CoV-2 nucleocapsid antibody was negative. Because of high-risk comorbidities and likely impending transplantation, she received casirivimab and imdevimab on hospital day 1. She received an organ offer for liver transplantation on hospital day 4. The donor was incidentally found to have a positive SARS-CoV-2 polymerase chain reaction on routine donor screening without evidence of clinical disease. The donor had died from trauma, and the liver was normal. After shared decision-making, she proceeded with orthotopic liver transplantation and received a 5-d course of remdesivir after transplantation. She received induction immunosuppression with methylprednisolone and maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and prednisone. She did receive augmented prophylactic anticoagulation with enoxaparin 30 mg twice per day; however, this was complicated by perihepatic hematoma requiring reoperation for evacuation and hemostasis on posttransplant day 8. She experienced no thrombotic complications. She was dismissed from the hospital 11 d following transplantation and remained in isolation for 20 d posttransplantation. She did not develop respiratory symptoms or abnormal lung imaging in 30 d of follow-up. There is currently little experience transplanting a SARS-CoV-2 positive donor to a SARS-CoV-2 positive recipient.3 We utilized anti spike monoclonal antibodies to mitigate the risk of progression to severe infection while awaiting transplantation. This treatment has been associated with good outcomes in solid organ transplantation4 and has been utilized as postexposure prophylaxis.5 We propose anti spike monoclonal antibodies may have a role in mitigating the risks of SARS-CoV-2 donor-derived infection and progression to severe disease posttransplantation. Our case highlights that donor SARS-CoV-2 positivity does not necessarily preclude nonlung organ transplantation, and risks of transmission must be balanced with the risk of death while remaining on the transplant waitlist. SARS-CoV-2-directed monoclonal antibody therapy and/or preemptive remdesivir administration may have roles in this setting; however, additional studies on strategies to mitigate donor-derived COVID-19 are necessary.

A Study of the Relationship between Oxidative Stress and Risk of Developing Hepatocellular Carcinoma in People with Hepatitis B Infection; A Systematic Review Study

Introduction: Hepatitis B infection is a severe global public health issue. It is the 10th biggest cause of death worldwide. Objective: This review focuses on the relationship between oxidative stress and the risk of developing of acute and chronic hepatitis B complications. Methods: The data were collected by searching Science Direct, Google Scholar, PubMed, Scopus, Springer and National Center for Biotechnology Information (NCBI). The Keywords used as search terms were “Hepatitis B”, “Acute and Chronic hepatitis”, “HBV induced inflammatory reaction”, “hepatitis B and Oxidative stress” and “free radical induced hepatitis B complication”.Results: Chronic infections with chronic active hepatitis, acute or sub-acute hepatic necrosis, cirrhosis, liver failure, and hepatocellular cancer in people with hepatitis B infection are all complications of viral hepatitis. Extrahepatic complications are common in patients with chronic hepatitis infection, including cryoglobulinemia, non-Hodgkin lymphoma, focal lymphocytic sialadenitis, autoimmune thyroiditis, porphyria cutanea tarda, and lichen planus. Wide variations in hepatitis B incubation durations show that the redox state of cells can influence viral activity. Viral replication is more active with more severe oxidative stress, with dispersion from lysed or dead cells. Although the precise mechanisms of ROS participation in the pathogenesis of inflammatory disorders are still debated. Conclusion: Viral activity can be determined by the oxidative stress status of the cells which can be the main cause of the development of hepatocellular carcinoma related to the complications of acute and chronic hepatitis B.

Pregnancy after liver transplantation following idiopathic subacute liver failure: A multidisciplinary Approach

Liver transplantation (LT) is the definitive treatment for end stage liver disease. Liver cancer, viral hepatitis and alcohol related liver diseases are the common causes for transplantation. The outlook for pregnancy in post-transplant patient is generally good although they are considered higher risk than the general population. &nbsp;As far back as 1978, the first successful pregnancy in a liver transplant patient was reported with as many as 12 pregnancies per year occurring in liver transplant recipients in the UK. We present a 27-year old primigravida who had liver transplant when she was 9 years old due to idiopathic subacute liver failure. She conceived spontaneously and had an unremarkable multidisciplinary antenatal care with induction of labour and vaginal delivery at 38 weeks gestation with good outcomes. This case highlights the importance of multidisciplinary team (MDT) management and follow-up in liver transplant patients.

Clinical features of elderly patients with drug-induced liver failure: An analysis of 65 cases

Objective To investigate the features and medication of elderly patients with drug-induced liver failure (DILF), and to provide a reference for clinical prevention and treatment of DILF in elderly patients. Methods A total of 65 elderly patients, aged ≥60 years, who were diagnosed with DILF in The Fifth Medical Center of Chinese PLA General Hospital from January 2015 to December 2019 were enrolled and divided into groups based on the criteria for clinical outcome evaluation. The patients who were cured or improved were enrolled as response group, and those who had no response or died were enrolled as non-response group. Related clinical data were collected and analyzed, including age, sex, underlying diseases, type of the drug used, clinical classification, complications, and prognosis. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results Among the 65 elderly patients with DILF, there were 17 male patients (26.2%) and 48 female patients (73.8%), with a male/female ratio of 1∶ 2.82. Subacute liver failure (SALF) was the main type of DILF in the elderly patients (81.5%), and cholestasis type was the most common clinical type (40%). There were 26 patients in the response group and 39 in the non-response group, accounting for 40% and 60%, respectively, of all patients. As for complications, compared with the non-response group, the response group had a significantly higher proportion of patients with pleuroperitoneal fluid (61.5% vs 28.2%, P Conclusion SALF is the most common type of DILF in the elderly, and cholestasis type is the main clinical type of DILF. Patients with hepatic encephalopathy and hepatorenal syndrome tend to have poor prognosis.

Candida Infective Endocarditis: A Retrospective Study of Patient Characteristics and Risk Factors for Death in 703 United States Cases, 2015-2019.

Background Candida endocarditis is a rare, sometimes fatal complication of candidemia. Past investigations of this condition are limited by small sample sizes. We used the Vizient clinical database to report on characteristics of patients with Candida endocarditis and to examine risk factors for in-hospital mortality.MethodsThis was a multicenter, retrospective cohort study of 703 inpatients admitted to 179 US hospitals between October 2015 and April 2019. We reviewed demographic, diagnostic, medication administration, and procedural data from each patient’s initial encounter. Univariate and multivariate logistic regression analyses were used to identify predictors of in-hospital mortality.ResultsOf 703 patients, 114 (16.2%) died during the index encounter. One hundred fifty-eight (22.5%) underwent an intervention on a cardiac valve. On multivariate analysis, acute and subacute liver failure was the strongest predictor of death (odds ratio [OR], 9.2; 95% confidence interval [CI], 4.8 –17.7). Female sex (OR, 1.9; 95% CI, 1.2–3.0), transfer from an outside medical facility (OR, 1.8; 95% CI, 1.1–2.8), aortic valve pathology (OR, 2.7; 95% CI, 1.5–4.9), hemodialysis (OR, 2.1; 95% CI, 1.1–4.0), cerebrovascular disease (OR, 2.2; 95% CI, 1.2–3.8), neutropenia (OR, 2.5; 95% CI, 1.3–4.8), and alcohol abuse (OR, 2.9; 95% CI, 1.3–6.7) were also associated with death on adjusted analysis, whereas opiate abuse was associated with a lower odds of death (OR, 0.5; 95% CI, 0.2–0.9).ConclusionsWe found that the inpatient mortality rate was 16.2% among patients with Candida endocarditis. Acute and subacute liver failure was associated with a high risk of death, whereas opiate abuse was associated with a lower risk of death.

Development of Ectopic Livers by Hepatocyte Transplantation Into Swine Lymph Nodes.

Orthotopic liver transplantation continues to be the only effective therapy for patients with end‐stage liver disease. Unfortunately, many of these patients are not considered transplant candidates, lacking effective therapeutic options that would address both the irreversible progression of their hepatic failure and the control of their portal hypertension. In this prospective study, a swine model was exploited to induce subacute liver failure. Autologous hepatocytes, isolated from the left hepatic lobe, were transplanted into the mesenteric lymph nodes (LNs) by direct cell injection. At 30‐60 days after transplantation, hepatocyte engraftment in LNs was successfully identified in all transplanted animals with the degree of ectopic liver mass detected being proportional to the induced native liver injury. These ectopic livers developed within the LNs showed remarkable histologic features of swine hepatic lobules, including the formation of sinusoids and bile ducts. On the basis of our previous tyrosinemic mouse model and the present pig models of induced subacute liver failure, the generation of auxiliary liver tissue using the LNs as hepatocyte engraftment sites represents a potential therapeutic approach to supplement declining hepatic function in the treatment of liver disease.

Effect and mechanism of silent information regulator 6 on gluconeogenesis in chronic-on-acute liver failure

Objective To investigate the effect and mechanism of silent information regulator 6 (SIRT6) and gluconeogenesis-dependent rate-limiting enzymes in hepatocytes in oxidative stress injury rats and chronic-on-acute (sub-acute) liver failure (ACLF) patients. Methods From August 2016 to May 2018, 10 patients with ACLF from Beijing Youan Hospital Affiliated to Capital Medical University were included in the ACLF group, and 10 normal donors were included in the normal control group. Level of fasting blood glucose, total bilirubin, albumin, and alanine aminotransferase (ALT) were studied. Sprague Dawley rat hepatocytes were isolated and divided into control group (without any intervention), model group (H2O2 intervention for 6 h), mammalian rapamycin target protein (mTOR) activation group (mTOR activation was added to the model group), mTOR inhibition group (mTOR inhibitor was added on the basis of the model group). Protein electrophoresis and polymerase chain reaction was used to detect the relative expression of glucose-6-phosphatase (G6P), phosphoenolpyruvate (PEPCK), SIRT6, and mTOR. Results The ALT and total bilirubin level in ACLF group were significantly higher than those in the normal control group, and the differences were statistically significant (all P<0.05). In ACLF group, level of SIRT6 (0.15±0.07) μg/L and fasting blood glucose (3.19±0.59) mmol/L were significantly lower than those in the normal control group (0.46±0.15) μg/L and (7.07±2.07) mmol/L, the difference was statistically significant (all P<0.05). The relative expression of PEPCK and G6P protein in liver tissue of ACLF group was significantly lower than that of normal control group. The relative expression of SIRT6, PEPCK, and G6P in the model group were lower than those in the control group, and the differences were statistically significant (all P<0.05). When mTOR is activated, the relative expression of PEPCK, G6P, and SIRT6 was higher than those in the model group, and after mTOR inhibition, the relative expression of PEPCK, G6P, and SIRT6 was lower than in the model group. Conclusion ACLF, SIRT6 may inhibit gluconeogenesis, and increased the occurrence of hypoglycemia through activating mTOR signaling pathway. Blocking of SIRT6 levels may slow down the progress of ACLF. Key words: Acute-on-chronic liver failure; Glucose-6-phosphatase; Phosphoenolpyruvate carboxykinase; Silent information regulator 6; Mammalian rapamycin target protein

A mouse model of subacute liver failure with ascites induced by step-wise increased doses of (-)-epigallocatechin-3-gallate

Acute liver failure is divided into hyperacute, acute and subacute liver failure. Ascites is a common complication of subacute liver failure. Although animal models of acute liver failure have been established, the study of the pathogenesis of subacute liver failure with ascites complication is hampered by the lack of experimental animal model. The present study aimed at providing a mouse model of subacute liver failure with ascites complication. Kunming mice were intraperitoneally injected with (-)-epigallocatechin-3-gallate (EGCG), a redox-active polyphenol from green tea, for 32 consecutive days with step-wise increased dosage. The EGCG treatment resulted in liver failure as evidenced by extensive hepatocyte necrosis observed histologically along with significant elevation of serum alanine aminotransferase, aspartate aminotransferase, total bilirubin and direct bilirubin levels as well as significant reduction of serum albumin. Liver fibrosis was not observed by Masson staining and fibrosis-associated proteins were not increased. The mortality was less than 12% and the survival mice developed noticeable ascites. Hepatic thioredoxin and glutathione systems were activated by the EGCG. These adaptive responses might render most mice tolerable to the EGCG treatment. The EGCG treatment significantly up-regulated renal urea transporter A1 and promoted its trafficking to apical membrane. These alterations, known to increase water reabsorption, may be responsible, at least in part, for the formation of the ascites. Overall, the mice treated with gradually elevated doses of EGCG exhibits some of the features observed in patients with subacute liver failure, especially ascites. This mouse model is a useful tool for investigating the pathogenesis of subacute liver failure with ascites complication.

2433 Sub-Acute Liver Failure as the Initial Manifestation of Metastatic Small Cell Lung Cancer

INTRODUCTION: The liver is a common site of metastasis in small cell lung carcinoma (SCLC), with 20% of cases metastasizing to the liver. However, most liver metastases are discovered at time of autopsy and not at initial diagnosis. Given the scarcity of literature regarding sub-acute liver failure as the presenting sign of metastatic SCLC, this case explores a patient who presented with sub-acute liver failure secondary to diffuse, infiltrative metastatic SCLC. CASE DESCRIPTION/METHODS: A 54 year old Caucasian male with no significant past medical history presented with jaundice and ascites. He denied any history of alcohol consumption, any personal or family history of liver disease, and consumption of any supplements or over the counter medications. Physical examination was notable for marked abdominal distension with shifting dullness, grade I hepatic encephalopathy, and mild asterixis. He did not have findings of chronic liver disease. Labs were significant for a creatinine of 1.1, sodium of 128, total bilirubin of 8.9, ALT 85, AST 227, alkaline phosphatase 153, and an INR of 3.03, with a MELD-Na score of 32. Laboratory workup was negative for causes of liver failure, including infectious and autoimmune etiologies. A triple phase contrast enhanced CT abdomen showed multiple hypodense lesions too small to characterize, without any large enhancing liver mass seen. Given the patient's high MELD-Na score and an initial concern for liver failure, the patient was transferred to our institution for liver transplant. To determine the etiology of his suspected cirrhosis after negative serologic workup, a transjugular liver biopsy was obtained. Pathology results were not consistent with cirrhosis, and instead revealed diffuse, infiltrative metastatic small cell carcinoma from a suspected primary lung cancer in the setting of a 1.8 cm lung lesion later seen on CT chest. He was subsequently removed from liver transplant consideration. The patient unfortunately expired due to liver failure. DISCUSSION: This is a case of a patient who presented with sub-acute liver failure due to metastatic small cell carcinoma. Liver failure is a rare presentation of metastatic disease but has been reported in malignancies such as metastatic breast cancer. While SCLC metastasis to the liver is common, it has only rarely been described to cause sub-acute liver failure.