Sound Touch Elastography for Noninvasive Assessment of Liver Stiffness in Patients With Chronic Heart Failure.

Heart failure (HF) can damage various organs, including the liver, a phenomenon known as "cardiohepatic syndrome." The latter is characterized by liver congestion and hepatic artery hypoperfusion, which can lead to liver damage. In this study, we aimed to assess liver damage quantitatively in chronic HF (CHF) with sound touch elastography (STE). A total of 150 subjects were enrolled, including HF with reduced ejection fraction (HFrEF) groups (left ventricular ejection fraction ≤40%, n = 45), HF with mildly reduced ejection fraction (HFmrEF) groups (left ventricular ejection fraction between 41% and 49%, n = 40), and right-sided HF (RHF) groups (n = 25); normal groups (n = 40). Liver stiffness measurement (LSM) was performed in all subjects by STE. The other hepatic parameters were also measured. The LSM was 5.4 ± 1.1 kPa in normal subjects and increased slightly to 5.9 ± 0.7 kPa in patients with HFmrEF. However, the HFrEF and RHF groups had significantly higher LSMs of 8.4 ± 2.0 kPa and 10.3 ± 2.7 kPa, respectively. The LSM of HFrEF was significantly higher than that of HFmrEF, whereas the increase in LSM in patients with RHF was significant relative to HFmrEF and HFrEF. In addition, the other parameters showed abnormal values in only RHF and HFrEF. In conclusion, STE is a useful clinical technique for the noninvasive evaluation of liver stiffness associated with CHF, which could help patients with CHF manage their treatment regimens.

Assessment of lower limb muscle strength can predict fall risk in patients with chronic liver disease.

Falls are caused by a combination of factors, including loss of lower limb muscle strength (LMS), and associated with declined performance status (PS). Age-related sarcopenia is generally associated with decreased muscle mass and strength of lower limb muscle but without a noticeable loss of those of upper limb or trunk muscle. However, no reports have focused on falls or LMS in chronic liver disease (CLD) patients. This study is the first to analyze the risk factors for falls in patients with CLD, focusing on LMS measurement using the Locomoscan. This study enrolled 315 CLD patients whose LMS was measured. The patients who experienced falls more than 1 year ago or during the observation period were classified as those who experienced falls. We found that risk factors for falls were PS1/2 and decreased LMS (< 0.32 N/kg). The group with sarcopenia had a higher frequency of decreased LMS (54 vs. 26%, p = 0.001) and falls (24 vs. 4.4%, p < 0.001) compared to the non-sarcopenia group. This study found that decreased LMS was an independent risk factor for falls. Assessment of LMS may be used as a better marker associated with the risk of falls in patients with CLD.

Mild Thrombocytopenia, a Predictor of Outcomes After Laparoscopic Cholecystectomy: Assessment of Surgical Risk in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND: A common cause of mild thrombocytopenia is chronic liver disease, the most common etiology being metabolic dysfunction-associated steatotic liver disease (MASLD). Mild thrombocytopenia is a well-defined, independent marker of hepatic fibrosis in patients with chronic liver disease. Currently, there is a paucity of information available to characterize perioperative risk in patients with MASLD; therefore, the characterization of perioperative morbidity is paramount. We used a platelet threshold of 150×10 9 as a surrogate for fibrosis in patients undergoing laparoscopic cholecystectomy to study its effect on perioperative complications and mortality. PATIENTS AND METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program database for laparoscopic cholecystectomies occurring from 2005 through 2018. Demographic differences between patients with and without thrombocytopenia were evaluated using the t test or the χ 2 test, whereas adjusted and unadjusted differences in outcome risk were evaluated using log-binomial regression models. RESULTS: We identified 437,630 laparoscopic cholecystectomies of which 6.9% included patients with thrombocytopenia. Patients with thrombocytopenia were more often males, older, and with chronic disease. Patients with thrombocytopenia and higher Aspartate Aminotransferase to Platelet Ratio Index scores had 30-day mortality rates risk ratio of 5.3 (95% CI: 4.8-5.9), with higher complication rates risk ratio of 2.4 (95% CI: 2.3-2.5). The most frequent complications included the need for transfusion, renal, respiratory, and cardiac. CONCLUSIONS: Perioperatively, patients with mild thrombocytopenia undergoing laparoscopic cholecystectomy had higher mortality rates and complications compared with patients with normal platelet counts. Thrombocytopenia may be a promising, cost-effective tool to identify patients with MASLD and estimate perioperative risk, especially if used in high-risk populations.

Frailty in end-stage liver disease: Understanding pathophysiology, tools for assessment, and strategies for management.

Frailty and sarcopenia are frequently observed in patients with end-stage liver disease. Frailty is a complex condition that arises from deteriorations across various physiological systems, including the musculoskeletal, cardiovascular, and immune systems, resulting in a reduced ability of the body to withstand stressors. This condition is associated with declined resilience and increased vulnerability to negative outcomes, including disability, hospitalization, and mortality. In cirrhotic patients, frailty is influenced by multiple factors, such as hyperammonemia, hormonal imbalance, malnutrition, ascites, hepatic encephalopathy, and alcohol intake. Assessing frailty is crucial in predicting morbidity and mortality in cirrhotic patients. It can aid in making critical decisions regarding patients' eligibility for critical care and transplantation. This, in turn, can guide the development of an individualized treatment plan for each patient with cirrhosis, with a focus on prioritizing exercise, proper nutrition, and appropriate treatment of hepatic complications as the primary lines of treatment. In this review, we aim to explore the topic of frailty in liver diseases, with a particular emphasis on pathophysiology, clinical assessment, and discuss strategies for preventing frailty through effective treatment of hepatic complications. Furthermore, we explore novel assessment and management strategies that have emerged in recent years, including the use of wearable technology and telemedicine.

Autoimmune Hepatitis and Obstetrical Outcomes: A Nationwide Assessment.

INTRODUCTION: Previous research identified AIH as linked to unfavorable obstetrical outcomes in a US nationwide retrospective study from 2012-2016. Our aim is to update the literature and strengthen the AIH-pregnancy outcomes relationship. METHODS: Using the National Inpatient Sample database in the US, from 2016 to 2020, we compared pregnant females with a diagnosis of AIH to those with and without other chronic liver diseases (CLD), using ICD-10-CM codes. Baseline characteristics were analyzed using T-test and Chi-Square, and multivariate regression was used to estimate the differences in maternal outcomes adjusted for age, race, insurance status, geographical location, hospital characteristics, and comorbid conditions. RESULTS: Out of 19,392,328 hospitalizations for pregnant females ≥ 18 years old from 2016 to 2020, 1095 had AIH, 179,655 had CLD, and 19,206,696 had no CLD. No mortality was observed among individuals with AIH. When compared to individuals without CLD, AIH was associated with an 82% increase in the odds of preterm delivery (AIH: 8% vs. Without CLD: 5%, adjusted Odds Ratio = 1.82, 95% CI 1.06-3.14), with no significant differences in gestational diabetes mellitus, hypertensive complications, and postpartum hemorrhage, and a 0.6 day longer hospital stay. Furthermore, there were no significant differences in outcomes between AIH and CLD. CONCLUSIONS: Our study reinforces the association of AIH with adverse obstetrical outcomes (e.g., preterm delivery), however, we found that there is no difference in GDM and hypertensive complications, as suggested in prior studies. Therefore, further investigations are needed to clarify the association between AIH and these obstetrical complications.

Needs evaluation questionnaire for liver disease: a novel assessment of unmet needs in patients with chronic liver disease.

Patients with chronic liver disease face debilitating complications in their daily living and constantly report several types of unmet needs, but there is a paucity of validated questionnaires to assess these needs. In this study, we present the development of the Needs Evaluation Questionnaire for Liver Diseases (NEQ-LD) for the assessment of unmet needs in patients with chronic liver disease. Two hundred eighty-six outpatients with chronic liver diseases from a single tertiary referral center completed the NEQ-LD and related validity measures. Item response theory analyses were performed and demonstrated the strong psychometric properties of the questionnaire. Differential item functioning analyses showed that the scale functions equally across groups differing for age, sex, and presence of cirrhosis, suggesting the large applicability of the NEQ-LD for the assessment of unmet needs and between-group comparisons. Criterion validity measures provided evidence that unmet needs were positively associated with measures of depression and anxiety and negatively associated with measures of subjective well-being and physical and mental health. Unmet needs were expressed by a high percentage of patients, especially in the areas of information and dialogue with clinicians. One third of the sample reported material needs. Most of the items describing unmet needs were reported more frequently by patients with cirrhosis. Conclusion: We developed a reliable, valid, and largely employable instrument that can promote patient-centered care and facilitate support services in Hepatology.

Fat Soluble Vitamin Assessment and Supplementation in Cholestasis.

Malnutrition in children with chronic cholestasis is a prevalent issue and a major risk factor for adverse outcomes. Fat soluble vitamin (FSV) deficiency is an integral feature of cholestatic disease in children, often occurring within the first months of life in those with neonatal cholestasis and malnutrition. This review focuses on FSVs in cholestasis, with particular emphasis on a practical approach to surveillance and supplementation that includes approaches that account for differing local resources. The overarching strategy suggested is to incorporate recognition of FSV deficiencies in cholestatic children in order to develop practical plans for close monitoring and aggressive FSV repletion. Routine attention to FSV assessment and supplementation in cholestatic infants will reduce long periods of inadequate levels and subsequent adverse clinical sequalae.

Review article: epidemiology, pathogenesis and management of liver disease in adults with cystic fibrosis.

BACKGROUND: Cystic fibrosis-related liver disease (CFLD) is the leading cause of death in cystic fibrosis (CF), after pulmonary disease. To improve identification and management of this condition requires an understanding of the underlying disease mechanism. AIMS: This review summarises the current understanding of CFLD epidemiology, pathology, diagnosis and management. METHODS: Relevant reports on cystic fibrosis liver disease were identified using a literature search and summarised. RESULTS: CFLD is a heterogeneous condition with several different co-existent pathologies, including environmental and genetic factors. Incidence of clinically significant CFLD continues at a linear rate into early adulthood and has been described in up to 25% of CF patients. Diagnosis strategies lack precision and patient risk stratification needs to look beyond Childs-Pugh scoring. Efficacious therapies are lacking and, at present, newer modulator therapies lack data in CFLD and carry an increased risk of hepatotoxicity. Outcomes of liver transplant are comparable to non-CF transplant indications. CONCLUSIONS: The incidence of CFLD increases with age and hence is increasingly important to adult patients with CF. Effective therapies are lacking. For progress to be made a better understanding of pathogenesis and disease detection are required.

Subjective global nutritional assessment as a nutritional tool in childhood chronic liver disease.

Objective of the study was to assess subjective global nutritional assessment (SGNA) in children with chronic liver diseases (CLD). Children aged 3 months to 18 years with CLD were prospectively enrolled (January 2016 to October 2018). SGNA was performed as per validated pro forma for children. Nutritional categories were categorised into three groups: A (well-nourished), B (moderately malnourished) and C (severely malnourished). Agreement between SGNA and anthropometric measures, prediction of morbidity and death or liver transplantation (LT) at 1-year post-enrolment by SGNA and inter-observer reliability of SGNA were assessed. Ninety-two subjects were enrolled, median age 23·5 (3-216) months. SGNA classified 47 patients (51·1 %) in group A, 26 (28·3 %) in group B and 19 (20·6 %) in group C. Kendall coefficients disclosed significant association of SGNA with all anthropometric measurements, greatest with weight for age (r = -0·637), height for age (r = -0·581) and mid-arm fat area (r = -0·449). At 12 months follow-up, twenty children died and four received LT. A significantly higher number of children with malnutrition (groups B and C) had poor outcome (OR 6·74 (95 % CI 2·21, 20·55), P = 0·001), increased risk of hospital readmission (OR 12·2 (95 % CI 4·60, 35·88), P = 0·001), higher rate of infectious complications (OR 22·68 (95 % CI 7·29, 70·53), P < 0·0001) and lower median survival with native liver (Log Rank < 0·001) as compared with group A. Inter-observer agreement in assessment of SGNA was good (90·2 %). SGNA, in contrast to anthropometric measures, is a better nutritional assessment tool. It is reliable, comprehensive and predicts poor outcome in childhood CLD.

The impact of the COVID-19 epidemic on hospital admissions for alcohol-related liver disease and pancreatitis in Japan.

During the coronavirus disease 2019 (COVID-19) pandemic, there have been health concerns related to alcohol use and misuse. We aimed to examine the population-level change in cases of alcohol-related liver disease and pancreatitis that required admission during the COVID-19 epidemic by interrupted time series (ITS) analysis using claims data. We defined the period from April 2020, when the Japanese government declared a state of emergency, as the beginning of the COVID-19 epidemic. This ITS analysis included 3,026,389 overall admissions and 10,242 admissions for alcohol-related liver disease or pancreatitis from 257 hospitals between July 2018 and June 2020. The rate of admissions per 1000 admissions during the COVID-19 epidemic period (April 2020-June 2020) was 1.2 times (rate ratio: 1.22, 95% confidence interval: 1.12-1.33) compared to the pre-epidemic period. Analyses stratified by sex revealed that the increases in admission rates of alcohol-related liver disease or pancreatitis for females were higher than for males during the COVID-19 epidemic period. The COVID-19 epidemic in Japan might associates an increase in hospital admissions for alcohol-related liver disease and pancreatitis. Our study could support the concern of alcohol consumption and health problems during the COVID-19 pandemic.

Sleep and liver disease: a bidirectional relationship.

Sleep is a complex, highly regulated process essential for human health and wellbeing. Increasingly, sleep-wake disturbance has been implicated in the pathogenesis of chronic liver disease, particularly the development and progression of non-alcoholic fatty liver disease and alcohol-related liver disease. Patients with cirrhosis also have a high burden of sleep abnormalities with substantial implications for their quality of life and physical health. This Review summarises the epidemiology and pathophysiology of sleep-wake disturbance in liver disease and discusses the multiple converging pathways leading to abnormal sleeping patterns in patients with cirrhosis. This includes contributions from altered melatonin metabolism, neuromuscular complications, and aberrant thermoregulation. In turn, a vicious cycle is established whereby disrupted sleep can further contribute to liver disease progression. We also begin to unravel the complex, interlinking relationship between sleep-wake disturbance and hepatic encephalopathy, discussing both overlapping and distinct mechanisms and clinical features. Finally, we summarise the current and future therapeutic approaches aiming to improve sleep quality in patients with cirrhosis.

Polyclonal hypergammaglobulinaemia: assessment, clinical interpretation, and management.

This Review outlines a practical approach to assessing and managing polyclonal hypergammaglobulinaemia in adults. Polyclonal hypergammaglobulinaemia is most commonly caused by liver disease, immune dysregulation, or inflammation, but can also provide an important diagnostic clue of rare diseases such as histiocyte disorders, autoimmune lymphoproliferative syndrome, Castleman disease, and IgG4-related disease. Causes of polyclonal hypergammaglobulinaemia can be divided into eight categories: liver disease, autoimmune disease and vasculitis, infection and inflammation, non-haematological malignancy, haematological disorders, IgG4-related disease, immunodeficiency syndromes, and iatrogenic (from immunoglobulin therapy). Measuring serum concentrations of C-reactive protein and IgG subclasses are helpful in diagnosis. IL-6-mediated inflammation, associated with persistently elevated C-reactive protein concentrations (≥30 mg/L), is an important driver of polyclonal hypergammaglobulinaemia in some cases. Although the presence of markedly elevated serum IgG4 concentrations (>5 g/L) is around 90% specific for diagnosing IgG4-related disease, mildly elevated serum IgG4 concentrations are seen in many conditions. In most cases, managing polyclonal hypergammaglobulinaemia simply involves treating the underlying condition. Rarely, however, polyclonal hypergammaglobulinaemia can lead to hyperviscosity, requiring plasmapheresis.

Epidemiology, pathogenesis, diagnosis, surveillance, and management of hepatocellular carcinoma associated with vascular liver disease.

Vascular liver disease (VLD) presents special challenges in the diagnosis, surveillance, and treatment of hepatocellular carcinoma (HCC). HCC arising in the setting of vascular liver disease is often thought to be due to elevated hepatic arterial blood flow, rather than progressive fibrosis from chronic inflammation as with other chronic liver conditions such as viral hepatitis, autoimmune, and metabolic liver diseases. Vascular alteration inherent in VLD often impedes HCC non-invasive diagnosis and loco-regional treatment that depend on vascular properties found in typical liver environment. Benign and pre-malignant liver nodules such as focal nodular hyperplasia and hepatocellular adenoma are also more common in certain VLDs, further adding to surveillance and diagnostic challenges. In this synopsis, we aimed to review available literature on the epidemiology, surveillance, diagnosis, and management of HCC in patients with VLD and specifically Budd-Chiari syndrome, congenital porto-systemic shunts, Fontan-associated liver disease, hereditary hemorrhagic telangiectasia.

Quantitative liver surface nodularity score based on imaging for assessment of early cirrhosis in patients with chronic liver disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Early stage of cirrhosis is of great value in the diagnosis and management in patients with chronic liver disease (CLD). Recent studies have shown that quantitative liver surface nodularity (LSN) score based on imaging techniques can be used to predict the early cirrhosis stage noninvasively, with varied diagnostic accuracy and limited sample size. Hence, this study will evaluate the diagnostic accuracy of LSN in the prediction of early cirrhosis. METHODS: We will conduct a comprehensive search in PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases to identify eligible studies. The literature screening, data extraction, data analysis, and quality assessment will then be carried out. The summary receiver-operating-characteristic (ROC) and pooled sensitivity, specificity will be calculated to summarize the diagnostic performance of LSN using a random-effect model. A meta-regression analysis will be performed to investigate the underlying cause of the heterogeneity. RESULTS: This study will evaluate the diagnostic accuracy of LSN score in the identification of early cirrhosis, which may further determine whether this method can be used as an alternative in the assessment of CLD patients. CONCLUSIONS: This study will help to determine the diagnostic accuracy and summarize the recent evidence on this issue. STUDY REGISTRATION: INPLASY2020100096.

Viscoelastic Tests as Point-of-Care Tests in the Assessment and Management of Bleeding and Thrombosis in Liver Disease.

Viscoelastic point-of-care (VET POC) tests provide a global assessment of hemostasis and have an increasing role in the management of bleeding and blood component delivery across several clinical settings. VET POC tests have a rapid turnaround time, provide a better overall picture of hemostasis, predict bleeding more accurately than conventional coagulation tests, and reduce blood component usage and health care costs. Despite commonly having abnormal conventional coagulation tests, most patients with chronic liver disease have a "rebalanced" hemostasis. However, this hemostatic balance is delicate and these patients are predisposed to both bleeding and thromboembolic events. Over recent years, VET POC tests have been increasingly studied for their potential as better functional tests of hemostasis in liver disease patients. This review provides a background on the most common VET POC tests (thromboelastography and rotational thromboelastometry) and discusses the current evidence for these tests in the prediction and management of bleeding and thrombosis in patients with chronic liver disease, and in liver resection and transplant. With the recent publication of several randomized controlled trials, there is growing evidence that VET POC tests may be used to improve bleeding risk assessment and reduce blood product use in liver disease patients outside of the transplant setting. However, consensus is still lacking regarding the VET POC tests' thresholds that should be used to trigger blood product transfusion. VET POC tests also show promise in predicting thrombosis in patients with liver disease, but further research is needed before they can be used to guide anticoagulant therapy.

Cystic Fibrosis-related Liver Disease is Associated With Increased Disease Burden and Endocrine Comorbidities.

BACKGROUND: Cystic fibrosis-related liver disease (CFLD) is the leading nonpulmonary cause of mortality in cystic fibrosis (CF). We evaluated and compared the burden of disease and nonrespiratory comorbidities of those with severe CFLD and those without (noCFLD). METHODS: A retrospective nationwide (Australia) longitudinal review (from 1998 to 2016) of severe CFLD patients compared with noCFLD controls (matched 1 : 1 for age, genotype, pancreatic insufficiency, and center). RESULTS: One hundred sixty-six patients with severe CFLD and 166 with noCFLD were identified. Forced expiratory volume in 1 second percentage of predicted (FEV1%) was significantly lower in CFLD than noCFLD across all ages (estimate [SE] -6.05% [2.12]; P = 0.004). Median (IQR) hospitalizations per patient per year were higher in CFLD than noCFLD for: respiratory indications (0.6 [0.2-1.3] vs 0.4 [0.1-0.9]; P = 0.002); gastrointestinal indications (0.09 [0-0.2] vs 0 [0-0.05]; P < 0.001); and other indications (0.05 [0-0.2] vs 0 [0-0.1]; P = 0.03). In the CFLD cohort, there was increased use of nasogastric (12.6% vs 5.4%; OR 2.51 [95% CI 1.06-6.46]; P = 0.03) and gastrostomy nutritional supplementation (22.9% vs 13.2%; OR 1.93 [95% CI 1.05-3.63]; P = 0.03). Additionally, the CFLD cohort had a higher frequency of bone diseases, osteopenia (26.5% vs 16.8%; OR 1.77 [95%CI 1.01-3.15]; P = 0.04) and osteoporosis (16.2% vs 8.4%; OR 2.1 [95% CI 1.01-4.52]; P = 0.04), as well as CF-related diabetes (38.5% vs 19.2%; OR 2.61 [95% CI 1.55-4.47]; P = 0.001). CONCLUSIONS: Patients with severe CFLD have greater disease burden, with higher number of hospitalizations (both respiratory and nonrespiratory indications), nutritional interventions, and are at higher risk of CF-related bone disease and diabetes.

Liver function tests and fibrosis scores in a rural population in Africa: a cross-sectional study to estimate the burden of disease and associated risk factors.

OBJECTIVES: Liver disease is a major cause of morbidity and mortality in sub-Saharan Africa, but its prevalence, distribution and aetiology have not been well characterised. We therefore set out to examine liver function tests (LFTs) and liver fibrosis scores in a rural African population. DESIGN: We undertook a cross-sectional survey of LFTs. We classified abnormal LFTs based on reference ranges set in America and in Africa. We derived fibrosis scores (aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), fibrosis-4, gamma-glutamyl transferase (GGT) to platelet ratio (GPR), red cell distribution width to platelet ratio and S-index). We collected information about alcohol intake, and infection with HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). SETTING: We studied a population cohort in South-Western Uganda. PARTICIPANTS: Data were available for 8099 adults (median age 30 years; 56% female). RESULTS: The prevalence of HBV, HCV and HIV infection was 3%, 0.2% and 8%, respectively. The prevalence of abnormal LFTs was higher based on the American reference range compared with the African reference range (eg, for AST 13% vs 3%, respectively). Elevated AST/ALT ratio was significantly associated with self-reported alcohol consumption (p<0.001), and the overall prevalence of AST/ALT ratio >2 was 11% (suggesting alcoholic hepatitis). The highest prevalence of fibrosis was predicted by the GPR score, with 24% of the population falling above the threshold for fibrosis. There was an association between the presence of HIV or HBV and raised GPR (p=0.005) and S-index (p<0.001). By multivariate analysis, elevated LFTs and fibrosis scores were most consistently associated with older age, male sex, being under-weight, HIV or HBV infection and alcohol consumption. CONCLUSIONS: Further work is required to determine normal reference ranges for LFTs in this setting, to evaluate the specificity and sensitivity of fibrosis scores and to determine the aetiology of liver disease.