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Background: The etiology of acute liver failure (ALF) remains one of the most important factors in determining prognosis and predicting outcomes. In a significant proportion of ALF cases, however, the etiology remains unknown and is categorized as indeterminate ALF (IND‐ALF). In this study, we summarize findings from patients with IND‐ALF from 32 transplant centers across the United States, and we compare laboratory, prognostic, and outcome data for patients with IND‐ALF. Methods: Between 1998 and 2019, 3364 adult patients with ALF or acute liver injury (ALI) from 32 liver transplant centers were enrolled in the ALFSG registry. The primary clinical outcome of interest was 21‐day transplant‐free survival (TFS). Results: Of the 3364 patients enrolled in the ALFSG registry, 3.4 % (n = 114) were adjudicated as true indeterminate. On multivariate analysis, patients with a lower bilirubin, lower INR, lack of use of mechanical ventilation and no clinical features of coma at baseline had a higher odds ratio of transplant free survival. The number of deaths were similar between patients with true‐IND ALF versus patients with indeterminable ALF (29.8% vs. 27.2%), with almost half of the patients requiring liver transplant (42.1% vs. 45.7%). Conclusion: We illustrate the poor prognoses that true‐IND‐ALF and indeterminable ALF carry and the need for emergency liver transplantation in most cases. [ABSTRACT FROM AUTHOR]

Background & Aims Accumulating evidence indicates that micro RNAs play a role in a number of disease processes including the pathogenesis of liver fibrosis in hepatitis C infection. Our goal is to add to the accruing information regarding micro RNA deregulation in liver fibrosis to increase our understanding of the underlying mechanisms of pathology and progression. Methods We used next generation sequencing to profile all detectable micro RNAs in liver tissue and serum from patients with hepatitis C, stages F1-F4 of fibrosis. Results We found altered expression of several micro RNAs, in particular, miR-182, miR199a-5p, miR-200a-5p and miR-183 were found to be significantly upregulated in tissue from liver biopsies of hepatitis C patients with advanced fibrosis, stage F3 and F4, when compared with liver biopsies from patients with early fibrosis, stages F1 and F2. We also found miR-148-5p, miR-1260b, miR-122-3p and miR-378i among the micro RNAs most significantly down-regulated from early to advanced fibrosis of the liver. We also sequenced the serum micro RNAs; however, we were not able to detect significant changes in circulating micro RNAs associated with fibrosis stage after adjusting for multiple tests. Conclusions Adding measurements of tissue micro RNAs acquired during routine biopsies will continue to increase our knowledge of underlying mechanisms of fibrosis. Our goal is that these data, in combination with studies from other researchers and future long-term studies, could be used to enhance the staging accuracy of liver biopsies and expand the surveillance of patients at increased risk for cancer and progression to advanced fibrosis. [ABSTRACT FROM AUTHOR]

Sarcopenia, or loss of skeletal muscle mass, is associated with increased mortality and morbidity in liver transplant ( LT) candidates. Six-minute walk distance (6 MWD) and health-related quality of life ( HRQOL) as assessed by short form 36 scores ( SF-36) also impact clinical outcomes in these patients. This study explored the relationship between the sarcopenia, 6 MWD, and HRQOL in LT candidates. Sarcopenia was evaluated based on skeletal muscle mass index ( SMI) quantified from abdominal computed tomography. Patients were followed until death, removal from the wait list or the end of the study period. Two hundred and thirteen patients listed for LT were included. The mean SMI, 6 MWD and mean gait speed were 54.3 ± 9.7, 370.5 m and 1 m/s, respectively. Sarcopenia was noted in 22.2% of LT candidates. There was no correlation between sarcopenia, 6 MWD, and SF-36 scores. The 6 MWD, but not sarcopenia, was an independent predictor of mortality (hazard ratio = 2.1 [0.9-4.7]). In summary, sarcopenia did not emerge as a significant predictor of waitlist mortality and also failed to correlate with either functional capacity or HRQOL in LT candidates. In patients with ESLD awaiting LT, 6 MWD appears to be a more useful prognostic indicator than the presence of sarcopenia. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is common among patients with end-stage liver disease ( ESLD). The primary aim of our study was to assess the prevalence of vitamin D deficiency, secondary hyperparathyroidism, and bone disease in patients with ESLD awaiting LT. Methods We retrospectively studied 190 patients at our center. Serum total 25-hydroxyvitamin D (25- OH D), parathyroid hormone ( PTH), calcium, and bone mineral analysis ( BMA) were recorded. Standard World Health Organization ( WHO) criteria were used to diagnose osteopenia/osteoporosis. Only patients with normal serum creatinine were analyzed. Results Thirty-two of 190 patients were excluded from the final analysis (missing serum total 25-OH D levels in three patients and elevated serum creatinine, 29 patients). 105 of 158 (66.4%) evaluable patients had 25-OH D levels <25 ng/mL. Patients included in the analysis (n = 158) were divided according to serum total 25-OH D levels: 0-10 ng/mL (n = 23), 11-20 ng/mL (n = 64), and >20 ng/mL (n = 71). There were no significant differences in mean serum PTH and corrected calcium levels among the three subgroups. Only three patients had elevated serum PTH. Patients with total 25-OH D ≤ 10 ng/mL had higher model for end-stage liver disease (MELD) scores vs. those with 25-OH D > 20 ng/mL (13.3 ± 3, range 8-21, vs. 11.9 ± 3.4, range 6-29, p = 0.004). Irrespective of vitamin D status, bone disease was present in 64.6% of patients. Conclusion Low vitamin D levels and bone disease are common among patients with ESLD awaiting LT. Despite a high prevalence of low serum total 25- OH D, our cohort maintained normal corrected calcium levels and did not develop secondary hyperparathyroidism. We propose that free serum 25- OH D and vitamin D-binding protein may be necessary to accurately establish the diagnosis of vitamin D deficiency in the setting of ESLD. Additional studies are needed to further define mechanisms of bone disease in patients with ESLD. [ABSTRACT FROM AUTHOR]

New onset diabetes after transplantation (NODAT) occurs less frequently in living donor liver transplant (LDLT) recipients than in deceased donor liver transplant (DDLT) recipients. The aim of this study was to compare the incidence and predictive factors for NODAT in LDLT versus DDLT recipients. The Organ Procurement and Transplant Network/United Network for Organ Sharing database was reviewed from 2004 to 2010, and 902 LDLT and 19,582 DDLT nondiabetic recipients were included. The overall incidence of NODAT was 12.2% at 1 year after liver transplantation. At 1, 3, and 5 years after transplant, the incidence of NODAT in LDLT recipients was 7.4, 2.1, and 2.6%, respectively, compared to 12.5, 3.4, and 1.9%, respectively, in DDLT recipients. LDLT recipients have a lower risk of NODAT compared to DDLT recipients (hazard ratio = 0.63 (0.52-0.75), P < 0.001). Predictors for NODAT in LDLT recipients were hepatitis C (HCV) and treated acute cellular rejection (ACR). Risk factors in DDLT recipients were recipient male gender, recipient age, body mass index, donor age, donor diabetes, HCV, and treated ACR. LDLT recipients have a lower incidence and fewer risk factors for NODAT compared to DDLT recipients. Early identification of risk factors will assist timely clinical interventions to prevent NODAT complications. [ABSTRACT FROM AUTHOR]

New-onset diabetes after transplantation (NODAT) is common after liver transplant and associated with poorer outcomes. The aim of this study was to identify risk factors for NODAT in liver transplant recipients off corticosteroids. In 225 adult nondiabetic liver transplant recipients, the mean age was 51.7 years, the majority were men (71%), and half had HCV (49%). The mean calculated MELD score at transplantation was 18.7, and 19% underwent living-donor transplant (LDLT). One year after transplantation, 17% developed NODAT, and an additional 16% had impaired fasting glucose. The incidence of NODAT in patients with HCV was 26%. In multivariate analysis, HCV, pretransplant FPG, and LDLT were significant. Each 10 mg/dL increase in pretransplant FPG was associated with a twofold increase in future development of NODAT. The incidence of NODAT after liver transplant in patients off corticosteroids is 17%. Risk factors for developing NODAT include HCV and pretransplant FPG; LDLT is protective. [ABSTRACT FROM AUTHOR]

Gene therapy has reached the forefront of studies and research over the last 30 years because of its potential for curing, treating, and preventing diseases associated with DNA mutations. Type 1 and type 2 diabetes are two examples of very common polygenic and multifactorial diseases. The huge amount of scientific literature on this topic reflects a growing general interest in the possibilities of altering our genetic heritage and thus controlling the onset of diseases associated with mutations and relative risk factors. We have focussed on the new treatment opportunities and possibility of enhancing an individual's health, physical well-being, and even an individual's behaviour through technologies specially designed for therapeutic purposes, which have been presented in literature. This historical perspective shows how this type of research, however, was immediately subjected to an ethical evaluation, especially regarding the decoding of the human genome and the questions raised by the alteration of our genetic heritage through new biotechnologies. Moreover, understanding the limitations of gene therapy protocol experiments and the multifactorial nature of many diseases, which have a genetic base, also contributes to these considerations. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives. To determine the importance of acute cardiac events as a cause of mortality compared to non-cardiac events in the four month period following liver transplantation (LT) using current preoperative cardiac screening strategies. Patients and Methods.We retrospectively reviewed timing, type, and outcome of adverse cardiac events, and all cause mortality in the 4 month postoperative period in 393 consecutive LT patients from October 1999 to February 2008. Results. Of 30 total deaths (7.6% overall mortality rate), 27 (90%) were due to surgical or medical complications and 3 (10%) were primary cardiac deaths (0.8% cardiac mortality rate). Acute cardiac events occurred in 26 patients (6.6%), including 13 arrhythmias (50%), 7 new onset heart failures (27%), and 6 myocardial infarctions (23%). Twelve of 13 intraoperative events were arrhythmias (92%) including two of three cardiac deaths. Conclusions. Using current preoperative screening recommendations, deaths from primary cardiac events within four months of LT are very uncommon (0.8%), especially compared with deaths related to medical and surgical complications (6.9%). [ABSTRACT FROM AUTHOR]

Post liver transplant recurrence of infection with hepatitis C virus (HCV) occurs in approximately 50% of patients transplanted because of HCV-related liver disease. The aim of this study was to assess long-term quality of life, psychologic distress, and coping in patients with recurrent HCV after liver transplantation in comparison to patients transplanted for other etiologies of underlying liver disease. All liver transplant recipients transplanted at a University affiliated Veterans Affairs Medical Center who had greater than 6 months follow-up were sent a questionnaire investigating quality of life (assessed by Medical Outcomes study health survey SF-36), depression (assessed by Beck Depression Inventory), total mood disturbance (assessed by Profile of Mood States scale), coping (assessed by Billing and Moos Inventory of coping with illnesses), and employment status. Lower Beck Depression Inventory score (p=0.001), lower mood disturbance score (p=0.0001), overall satisfaction with present work (p=0.0001), and lesser use of avoidant coping (p=0.06) were predictors of better quality of life in long-term survivors of liver transplantation. At a mean follow-up of 4 yr after liver transplantation, patients with histopathologically diagnosed recurrent viral HCV hepatitis had significantly lower global quality of life score (mean score of 76.4 versus 86.2, p=0.011) and physical functioning score (mean score 20 versus 25, p=0.015), as compared to all other patients. In summary, quality of life and physical functioning were significantly impaired in liver transplant recipients with histopathologically diagnosed recurrent HCV hepatitis, as compared to those whose HCV hepatitis had not recurred or those transplanted for other reasons. [ABSTRACT FROM AUTHOR]

ABSTRACT- Of 20 patients with alcoholic liver cirrhosis and a superimposed episode of acute viral hepatitis, 12 developed hepatic encephalopathy or ascites or both. Four died of hepatic failure. Seventeen patients had received blood transfusions within 6 months before the acute hepatitic episode. Two patients were HBsAg-positive; the other 18 were presumptively diagnosed as having non-A, non-B hepatitis. However, hepatitis A virus infection was excluded in only three of the 18 patients. Histologic examination performed in 13 cases disclosed necrotizing inflammatory activity, which is commonly observed in acute viral hepatitis. The distinctive histologic feature was a meager regenerating activity. We conclude that patients with alcoholic cirrhosis complicated by acute viral hepatitis frequently develop hepatic failure and have a high fatality rate (20% in our series). [ABSTRACT FROM AUTHOR]

Background and Aims: Acute liver failure (ALF) is a serious condition, typically in individuals without prior liver disease. Drug-induced ALF (DIALF) constitutes a major portion of ALF cases. Our research aimed to identify potential genetic predispositions to DIALF., Methods: We analysed the potential genetic variants associated with DIALF using the whole exome sequencing data from 75 cases, including 40 non-Finnish European cases in the pilot study. Chi-square tests were performed for case-control analysis against the 1000 genomes project as the control. A replication study of 44 DIALF cases that included 24 non-Finnish Europeans was conducted to validate candidate variants. The association between clinical phenotype and genotypes was analysed using one-way analysis of variance., Results: Eight variants (rs561037, rs561042, rs608339, rs655260, rs1142886, rs1142888, rs1142889 and rs1142890) in the guanylate binding protein 4 (GBP4) were significantly associated with DIALF in non-Finnish Europeans in the pilot study and confirmed in the replication study. Rs561037 and rs561042 were highly significant with the lowest allele frequencies in both pilot and replication studies. An association was also found between these variants and milder clinical outcomes, indicated by lower peak levels of ALT, AST and higher Karnofsky performance scores., Conclusion: Our study identified eight GBP4 missense variants linked to a lower risk of DIALF in the non-Finnish European population. The GBP4 protein, activated by interferon-gamma, plays a critical role in innate immunity. These findings suggest that GBP4 variants might influence immune and inflammatory responses in DIALF, though further studies are needed to elucidate the underlying mechanisms., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)