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Background Male osteoporosis is under-diagnosed and poorly studied. With the ageing population, osteoporotic fracture in men is an emerging health problem. The aim of this study was to study the prevalence of osteoporosis and its association with serum testosterone and serum vitamin D in elderly men (>60 years old) attending the outpatient department (OPD). Methods An observational cross-sectional study was performed in elderly men (>60 years old) attending OPD of a tertiary care hospital of Western Maharashtra between April 2017 and June 2019. Patients with rheumatological disorders, history of vertebral/femoral fractures, chronic kidney disease, chronic liver disease, thyroid disorders and alcohol dependence were excluded. Data were analysed using the chi-square test and descriptive statistics. Results In total, 408 male patients were included. The mean age was 68.33 years. Osteoporosis was seen in 39.5% of patients (161/408) with a T score of ≤2.5. Osteopenia was noted in 48.3% of patients (197/408). T and Z scores had significant correlation (p = Conclusion Osteoporosis was noted in 39.5% of the elderly men. In addition, decreased testosterone, COPD and BPH were significantly associated with male osteoporosis. It is important to screen elderly men to diagnose osteoporosis early and prevent osteoporotic fractures.

Sarcopenia, defined as progressive and generalized loss of muscle mass and strength, is common in chronic liver disease. It significantly impacts the quality of life and increases the risk of liver-related complications and mortality in cirrhotic patients. Moreover, recent studies showed a negative impact of sarcopenia on patients awaiting liver transplantation (LT), on post-LT outcomes, and on response to hepatocellular carcinoma therapies. Data about the influence of sex on the incidence, prevalence, diagnosis and treatment of sarcopenia in chronic liver diseases are poor and conflicting. The aims of this review of the literature are to define sex differences in sarcopenic cirrhotic patients and to highlight the necessity of a sex stratified analysis in future studies. This analysis of the literature showed that most of the studies are retrospective, with a higher prevalence of sarcopenia in males, probably due to anatomical differences between the sexes. Moreover, diagnostic criteria for sarcopenia are different between studies, as there is not a defined cut-off and, as a consequence, no comparable results. In conclusion, sex seems to have an impact on sarcopenia, and future studies must accurately investigate its role in identifying and treating high-risk patients, reducing the negative impact of sarcopenia on the survival and quality of life of cirrhotic patients.

Patients with chronic liver disease (CLD), including cirrhosis, are at increased risk of intractable viral infections and are hyporesponsive to vaccination. Hallmarks of CLD and cirrhosis include microbial translocation and elevated levels of type I interferon (IFN-I). We aimed to investigate the relevance of microbiota-induced IFN-I in the impaired adaptive immune responses observed in CLD.We combined bile duct ligation (BDL) and carbon tetrachloride (CCl4) models of liver injury with vaccination or lymphocytic choriomeningitis virus infection in transgenic mice lacking IFN-I in myeloid cells (LysM-Cre IFNARflox/flox), IFNAR-induced IL-10 (MX1-Cre IL10flox/flox) or IL-10R in T cells (CD4-DN IL-10R). Key pathways were blocked in vivo with specific antibodies (anti-IFNAR and anti-IL10R). We assessed T-cell responses and antibody titers after HBV and SARS-CoV-2 vaccinations in patients with CLD and healthy individuals in a proof-of-concept clinical study.We demonstrate that BDL- and CCL4-induced prolonged liver injury leads to impaired T-cell responses to vaccination and viral infection in mice, subsequently leading to persistent infection. We observed a similarly defective T-cell response to vaccination in patients with cirrhosis. Innate sensing of translocated gut microbiota induced IFN-I signaling in hepatic myeloid cells that triggered excessive IL-10 production upon viral infection. IL-10R signaling in antigen-specific T cells rendered them dysfunctional. Antibiotic treatment and inhibition of IFNAR or IL-10Ra restored antiviral immunity without detectable immune pathology in mice. Notably, IL-10Ra blockade restored the functional phenotype of T cells from vaccinated patients with cirrhosis.Innate sensing of translocated microbiota induces IFN-/IL-10 expression, which drives the loss of systemic T-cell immunity during prolonged liver injury.Chronic liver injury and cirrhosis are associated with enhanced susceptibility to viral infections and vaccine hyporesponsiveness. Using different preclinical animal models and patient samples, we identified that impaired T-cell immunity in BDL- and CCL4-induced prolonged liver injury is driven by sequential events involving microbial translocation, IFN signaling leading to myeloid cell-induced IL-10 expression, and IL-10 signaling in antigen-specific T cells. Given the absence of immune pathology after interference with IL-10R, our study highlights a potential novel target to reconstitute T-cell immunity in patients with CLD that can be explored in future clinical studies.

BACKGROUND AND AIMS: Noninvasive tools (NITs) reliably categorise patients with compensated advanced chronic liver disease (cACLD) into high-risk and low-risk group for harbouring varices needing treatment. Here, we assess the ability of these NITs to predict the need for nonselective beta-blockers at baseline based on risk of variceal bleeding (VB) on follow-up. METHODS: This was a retrospective multicentre analysis of patients with cACLD categorised at baseline into different risk groups by NITs (Baveno-VI, expanded Baveno-VI, platelet-albumin, platelet-model for end-stage liver disease (MELD) and anticipate study platelet criteria) and by endoscopy (high risk vs low risk/no varices). VB event rates on follow-up were estimated in different risk strata. Decision curve analysis (DCA) was used to estimate the benefit of administering nonselective beta-blockers (NSBB) using NITs over endoscopic classification at different threshold probabilities of VB event rates and estimating the number needed to treat (NNT) to identify one additional bleeder over endoscopy. RESULTS: A total of 1284 patients (mean age: 44.7 ± 13.5 years, 72.4% males) of hepatitis B (29.2%), nonalcoholic fatty liver disease (24.9%), hepatitis C (20.1%), and alcohol (17.5%)-related cACLD were included with 323 (25.2%) having high-risk varices. Ninety-eight (7.6%) patients developed VB over a median follow-up of 20 (9–35) months. The 1-year and 3-year rate of VB with all NITs was 5.7–7.4% and 13.2–16.4% among high-risk and 0–2.3% and 0–5% among low-risk subgroups, respectively (P

Patients with chronic liver disease (CLD) with or without cirrhosis remain at risk of developing hepatic decompensation when infected with viral or bacterial pathogens. The Advisory Committee on Immunization Practices (ACIP) currently recommends vaccination in CLD against hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcus, herpes zoster, tetanus, diphtheria, pertussis, and SARS-CoV-2. Inactivated vaccines are preferred over live attenuated ones, especially in transplant recipients where live vaccines are contraindicated. As the severity of the liver disease progresses, vaccine efficacy declines, and therefore, vaccines should be ideally administered early in the disease course for optimal immune response. Despite the strong recommendations, overall vaccination coverage in CLD remains poor; however, it is encouraging to note that in recent years coverage against influenza and pneumococcus has shown some improvement. Inadequate access to healthcare, lack of information on vaccine safety, poor financial reimbursement for healthcare providers, and vaccine misinformation are often responsible for low immunization rates. This review summarizes the impact of vaccine-preventable illness in those with CLD, updated vaccine guidelines, seroconversion rates in the vaccinated, and barriers faced by healthcare professionals in immunizing those with liver disease.

Background Patients with cirrhosis and coronavirus disease-2019 (COVID-19) have high in-hospital mortality. The information on outcome of cirrhosis patients in post-hospitalization period are limited. Aims We aimed to study the outcome of cirrhosis patients with COVID-19 after hospital discharge. Methods The records of the cirrhosis patients discharged after COVID-19 were reviewed. Their data were compared with a similar number of cirrhosis patients without COVID-19 after propensity score matching for age, sex, etiology of cirrhosis, and model for end-stage liver disease (MELD) score. Results Cirrhosis patients with (n=92) or without (n=92) COVID-19 were included in 1:1 ratio. The mortality among COVID-19 (22; 23.9%) and non-COVID-19 (19; 20.7%) were comparable (HR 1.224; 95% CI 0.663-2.263, P=0.520), over a similar duration of follow-up [186 (86-271) vs 183 (103-274)]. Among COVID-19 patients, 45; 48.9% developed a new acute decompensation-increased ascites (40; 43.5%), hepatic encephalopathy (20; 21.7%), or variceal bleeding (8; 8.7%) whereas 25 (27.2%) patients needed re-hospitalization. A proportion of participants continued to have either fatigue/weakness (24/80; 30.0%), sleep disturbances (11/80; 13.7%), or joint pains (16/80; 20.0%). The most common causes of death in patients of both groups were end-stage liver disease: 16 (72.7%) vs 9 (47.4%), followed by multiorgan dysfunction: 4 (18.2%) vs 6 (31.6%), GI bleeding: 2 (9.1%) vs. 4 (21.0%), P=0.484. A lower albumin level, higher international normalized ratio, bilirubin, Child-Turcotte-Pugh, and MELD scores at discharge predicted mortality in the COVID-19 group. Conclusion Short-term outcomes of patients with cirrhosis who survive the initial insult of COVID-19 are not different from patients without COVID-19, and survival is determined by the severity of liver disease at discharge.

Background & aims There is no “gold standard” tool for the assessment of frailty in cirrhosis. This study compares Liver Frailty Index (LFI), Short Physical Performance Battery (SPPB), Fried Frailty Criteria (FFC), and Clinical Frailty Scale (CFS) for frailty assessment and ascertains its impact on predicting mortality and hospitalizations in a cohort of outpatients with cirrhosis. Methods 116 patients were enrolled in this prospective observational cohort study. Frailty assessment was done using LFI, SPPB, FFC, and CFS. All patients were followed up for 6 months. The primary outcome was the first of either all-cause unplanned hospitalization or all-cause mortality occurring within 6 months of the study period. Results 100 (86.2%) males and 16 (13.8%) females with a mean age of 50.2 (48.4–51.9, 95% CI) years were included. The most common cause of cirrhosis was alcoholic liver disease (47.4%) followed by hepatitis C (12.9%) and Nonalcoholic steatohepatitis (NASH) (10.3%). There was no significant difference in prevalence of frailty based on LFI (43.1%), FFC (36.2%), CFS (44%), and SPPB (47.4%) (P > 0.05). Frail patients had worse outcomes compared to the Not frail group. At 6 months, the mortality rate in Frail patients was 42% versus 1.5% for the Not frail; hospitalization in Frail patients occurred in 92% versus 6% in the Not frail. On multivariable analysis, independent predictors of mortality were Frailty [OR 14 (1.4–54.2)], alcohol-related cirrhosis [OR 4.2 (1.1–16.3)], Child-Turcotte-Pugh (CTP) [OR 2.1 (1.4–2.9)] and Chronic liver disease questionnaire (CLDQ) [OR 0.1 (0.1–0.4)] scores. Conclusions LFI, SPPB, FFC, and CFS are comparable in frailty assessment in patients with cirrhosis. Importantly, comparability of the commonly used scores for frailty assessment and prediction of hospitalization and mortality allows flexibility for clinical application.

Depression and chronic liver disease (CLD) are important causes of disability, morbidity and mortality worldwide and their prevalence continues to rise. The rate of depression in CLD is high compared to that of the general population and is comparable to the increased rates observed in other medical comorbidities and chronic inflammatory conditions. Notably, a comorbid diagnosis of depression has a detrimental effect on outcomes in cirrhosis. Systemic inflammation is pivotal in cirrhosis-associated immune dysfunction - a phenomenon present in advanced CLD (cirrhosis) and implicated in the development of complications, organ failure, disease progression, increased infection rates and poor outcome. The presence of systemic inflammation is also well-documented in a cohort of patients with depression; peripheral cytokine signals can result in neuroinflammation, behavioural change and depressive symptoms via neural mechanisms, cerebral endothelial cell and circumventricular organ signalling, and peripheral immune cell-to-brain signalling. Gut dysbiosis has been observed in both patients with cirrhosis and depression. It leads to intestinal barrier dysfunction resulting in increased bacterial translocation, in turn activating circulating immune cells, leading to cytokine production and systemic inflammation. A perturbed gut-liver-brain axis may therefore explain the high rates of depression in patients with cirrhosis. The underlying mechanisms explaining the critical relationship between depression and cirrhosis remain to be fully elucidated. Several other psychosocial and biological factors are likely to be involved, and therefore the cause is probably multifactorial. However, the role of the dysfunctional gut-liver-brain axis as a driver of gut-derived systemic inflammation requires further exploration and consideration as a target for the treatment of depression in patients with cirrhosis.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease worldwide. Despite the high prevalence, no screening recommendations yet exist. We designed a prospective observational study to estimate the prevalence of NAFLD in the family of patients with NAFLD and develop a predictive model for identifying it. METHODOLOGY: The prevalence of NAFLD in patients’ family members was estimated using ultrasonography, and univariate and multivariate odds were calculated for its predictors. A model was created using the significant parameters on multivariate odds, and its performance was tested using the area under the receiver operating characteristic (AUROC). RESULTS: Among 447 family members of 191 patients with NAFLD, the prevalence of NAFLD was 55.9%. Family members with NAFLD were younger and had lower serum levels of aspartate aminotransferase, alanine aminotransferase (ALT), triglycerides. The liver stiffness measurement and controlled attenuation parameter values were also lesser in family members compared to the index cases. Age, body mass index (BMI), and ALT were independent predictors of NAFLD in the family members. A model combining age and BMI had an AUROC of 0.838 [95% confidence interval (CI) 0.800–0.876, P < 0.001]. Age ≥30 years and BMI ≥25 kg/m(2) had an odds ratio of 33.5 (95% CI 17.0–66.0, P < 0.001) for prediction of NAFLD, in comparison to BMI

BACKGROUND/OBJECTIVES: Cirrhosis of liver is associated with loss of liver function, portal hypertension, and pancreatic β-cell dysfunction leading to hepatogenous diabetes (HD). Often HD is an underestimated and understudied problem, particularly in the Indian subcontinent, where the prevalence of both Chronic liver disease (CLD) and diabetes is high. Hence this study was planned to highlight the prevalence of HD and its association with the severity of cirrhosis. METHODS: A total of 121 cirrhotic patients without a history of diabetes were included in this prospective cross-sectional study. Seventy five g oral glucose tolerance test (OGTT) was done in all patients. Fasting serum insulin levels were done to calculate insulin resistance (IR) using homeostatic model assessment-insulin resistance (HOMA-IR). Upper gastrointestinal endoscopy was done to detect varices. Patients were divided into HD group and non-HD group for comparison of results. RESULTS: HD was seen in 52 (42.98%) patients; among them, 63.4% did not show evidence of HD by fasting plasma glucose (FPG) levels. Impaired glucose tolerance (IGT) was seen in 58 (47.93%) patients. Compared with the non-HD group, the HD group had significantly higher model for end-stage liver disease (MELD) score (P = 0.038), HOMA-IR (P 15), CTP score (>10), higher bilirubin levels, large varices, bleeding varices, and HCC. FPG levels and glycated hemoglobin (HbA1c) cannot be relied upon, and OGTT aids in the unmasking of HD in these patients.

BACKGROUND: Sickle cell disease (SCD) is a rare hemoglobinopathy which can result in chronic liver disease and cirrhosis. Patients with SCD have an increased risk of hematologic malignancy, but the prevalence of hepatocellular carcinoma (HCC) in this population is unknown. Herein, the association of SCD with HCC was examined using registry data. METHODS: The SEER-Medicare database was queried to identify patients diagnosed with HCC between 2000 and 2015, and further stratified by SCD status. Propensity matching was performed to examine cancer-related survival and treatment outcomes. RESULTS: Overall 56,934 patients with HCC were identified, including 81 patients with SCD. Patients with SCD more frequently had cirrhosis [48.1% (39/81) vs 23.5% (13,377/56,853), p

Obesity and its associated comorbidities are rapidly increasing in the US population. Therefore, metabolic associated fatty liver disease (MAFLD), previously known as nonalcoholic fatty liver disease (NAFLD), has become a leading indication for liver transplantation. Lifestyle modifications as a sole therapy have been insufficient to reduce the burden of chronic liver disease secondary to MAFLD. Endoscopic bariatric interventions (EBI) appear to be safe and effective therapies for obesity and chronic liver disease secondary to MAFLD. Gastric EBI include endoscopic sleeve gastroplasty (ESG) and intragastric balloons (IGB). Small bowel EBI are also evolving in the field of bariatric endoscopy.

Hepatocellular adenomas (HCA) are rare hepatocellular neoplasms which usually arise in non-cirrhotic liver, although rarely can arise in the background of chronic liver disease. While the majority of hepatocellular adenoma (HCA) are benign and may be managed conservatively, complications like hemorrhage and transformation to hepatocellular carcinoma (HCC) can occur. Risk stratification based on a combination of clinical, radiologic, histologic, and molecular features is necessary for appropriate management. This review focuses on diagnostic challenges in the diagnosis of HCA and its distinction from other hepatocellular proliferations such as focal nodular hyperplasia (FNH), hepatocellular carcinoma (HCC) and hepatocellular nodules in other clinical setting.

Management of coagulopathy in patients with advanced liver disease undergoing therapeutic endoscopic procedures is complex. Improvements in the understanding of hemostasis at a physiologic level have highlighted the inaccuracy of currently available clinical tests, like platelet count and prothrombin time, in estimating hemostasis in patients with cirrhosis. With identification of novel factors that contribute to bleeding risk in patients with cirrhosis, there is a dearth of clinical trial data that account for all potentially relevant factors and that examine interventions to reduce bleeding risk. Precise recommendations regarding transfusion strategies based on hemostatic test results in patients with cirrhosis are impractical.

Background : The purpose of the study was to assess the epidemiology, risk factors and outcomes of native vertebral osteomyelitis (NVO) in patients with Staphylococcus aureus bacteremia (SAB). Methods : A retrospective institutional review was conducted at Mayo Clinic, Minnesota. Patients aged ≥ 18 years with SAB who developed NVO from January 1, 2006 to December 31, 2020 were included and 3-month follow-up data were abstracted. Data pertaining to patient demographics, risk factors and outcomes were recorded using REDCap. A 1:2 nested case-control analysis was performed, and controls were matched according to age, sex and year of SAB diagnosis. Results : A total of 103 patients had NVO. A majority (60.2%) of patients was male, with a median age of 62.0 years. Thirty-one (30.1%) cases were caused by methicillin-resistant S. aureus (MRSA). The lumbar spine was most commonly (57.6%) and the most commonly reported comorbid conditions included diabetes mellitus (36.9%) and coronary artery disease (27.2%). Mortality at three-month follow-up was 18.6%. Nested case-control analysis revealed that injection drug use (IDU) and tobacco consumption were significant risk factors associated with NVO, while chronic hemodialysis and chronic liver disease (CLD) were associated with a decreased risk of NVO. Conclusions : Atherosclerotic vascular disease was prominent in our contemporary cohort with NVO in the setting of SAB. Diabetes mellitus, tobacco consumption, older age and male sex likely contributed to this profile. Because IDU was associated with NVO, an increased number of cases should be anticipated among patients with IDU given the ongoing opioid epidemic in the United States.

Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an 18F-labeled MAGL inhibitor ([18F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [18F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl4) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [18F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [18F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [18F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [18F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues., Graphical abstract This study comprehensively evaluated [18F]MAGL-4-11, a 18F-labeled monoacylglycerol lipase (MAGL) radioligand, in preclinical liver fibrosis models and human specimens, which would facilitate drug development in MAGL-related liver fibrosis disease.Image 1

Background Haematopoietic stem cell (HSC) infusion has demonstrated short-term improvement in liver functions in patients with chronic liver disease. The combination of HSC with mesenchymal stem cells (MSCs), which has an immunomodulatory effect, may augment the effects and enhance the duration of improvements on liver functions. The aim of the present study was to assess the safety of infusing the combination of autologous HSCs and MSCs in decompensated liver cirrhosis. Methods In phase I of the study, in vitro assessment was performed to observe the effect of coculturing MSCs with HSCs on their viability and cytokine profiles. Phase II of the study was to assess the safety of combination of stem cell infusions. Bone marrow (50 ml) was aspirated for MSC isolation and expansion using standard protocol. Patients received subcutaneous doses (n = 5) of granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization followed by leukapheresis for harvesting HSCs using CliniMacs. HSCs and MSCs were infused through the hepatic artery under fluoroscopic guidance and were monitored for any adverse effects. Results In vitro studies revealed 94% viable HSCs in coculture similar to monoculture. HSCs released only interleukin (IL)-8, whereas MSCs secreted IL-8 and IL-6 in monocultures, and both IL-8 and IL-6 were secreted in coculture. G-CSF administration– and bone marrow aspiration–related complications were not observed. Infusion of the cells through the hepatic artery was safe, and no postprocedural complications were noted. Conclusion The combination of autologous HSC and MSC infusion is a safe procedure in patients with decompensated liver cirrhosis, and the outcomes needed to be assessed in larger studies. Trial number NCT04243681 .

To compare initial clinical/laboratory parameters and outcomes of mortality/rebleeding of endoscopy performed12 h(early UGIE) versus endoscopy performed after 12-24h(late UGIE) of ED admission in children with acute upper gastrointestinal bleeding(AUGIB) due to portal hypertension.This is a retrospective cohort study. From January 2010 to July 2017, medical records of all children admitted to a tertiary care hospital with AUGIB due to portal hypertension were reviewed until 60 days after ED admission.A total of 98 ED admissions occurred from 73 patients. Rebleeding was identified in 8/98(8%) episodes, and 9 deaths were observed. UGIE was performed in 92(94%) episodes, and 53(58%) of them occurred within 12 h of ED admission. Episodes with early UGIE and late UGIE were similar in terms of history/complaints/laboratory data at admission, chronic liver disease associated, AUGIB duration, and initial management. No statistically significant associations were found between early UGIE and the outcomes of death/rebleeding and prevalence of endoscopic hemostatic treatment (band ligation or sclerotherapy) compared to late UGIE. In the multivariable logistic regression model, the endoscopic hemostatic treatment showed a negative association with early UGIE(OR=0.33;95%CI=0.1-0.9;p = 0.04).This study suggests that in pediatric patients with AUGIB and portal hypertension, UGIE may be performed after 12-24 h without harm to the patient, facilitating better initial clinical stabilization/treatment and optimization of resources.

Background Single nucleotide polymorphisms (SNPs) in genes including PNPLA3, TM6SF2, HSD17B13 and SERPINA1 have been identified as risk modifiers of progression in chronic liver disease (CLD). However, it is unclear whether genotyping for these risk variants is useful in clinical routine. Methods Liver disease severity was assessed by liver stiffness measurement (LSM) and by presence of clinical manifestations of advanced-chronic liver disease (ACLD) in 779 consecutive CLD patients at the time of referral to a tertiary center. The associations of risk variants with CLD severity were calculated individually and in a combined model using a polygenic risk-score. Results Non-alcoholic fatty liver disease (NAFLD) was the most common etiology (n = 511, 65.6%), and ACLD was present in 217 (27.9%) patients. The PNPLA3-G-allele remained independently associated with higher LSM (adjusted-B: 2.508 [95%CI: 0.887–4.130], P = 0.002) or the presence of ACLD (aOR: 1.562 [95%CI: 1.097–2.226], P = 0.013). SERPINA1-Z-allele was also independently associated with LSM (adjusted-B: 4.558 [95%CI: 1.182–7.934], P = 0.008), while the other risk alleles did not attain statistical significance. Combining these risk alleles into a polygenic risk-score was significantly associated with LSM (adjusted-B: 0.948 [95%CI: 0.153–1.743], P = 0.020). Conclusion PNPLA3 risk-variants are linked to liver disease severity at the time of first referral to an outpatient hepatology clinic.

Viruses are a common cause of hepatitis in children. Hepatitis A and E cause acute infections while Hepatitis B, C and D can lead to chronic infection with increased morbidity and mortality due to chronic liver disease and hepatocellular carcinoma in later life. Acute infections may be fulminant causing acute liver failure necessitating a liver transplant. Our understanding of these viruses continues to evolve, and this review aims to summarize the current strategies in diagnosis, prevention and use of anti-viral drugs to treat these infections.

Obesity has led fatty liver disease to become the most common chronic liver disease in children worldwide. Pediatric professional organizations have agreed that screening for fatty liver disease in children is the need of the hour. Once identified, prevention is key through appropriate dietary and activity prescriptions. Research continues to identify key pathways and genetic risk factors that predispose certain children to the more severe manifestations of this silent epidemic. We hope these novel observations lead to breakthrough treatments for these children that are severely impacted, such that they may no longer need liver transplantation as young adults.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally and is estimated to affect approximately 25% of the world's population. Data about the prevalence and incidence of NAFLD in Africa are scarce, but the prevalence is estimated to be 13·5% for the general population. This is likely to be an underestimate considering the increasing burden of non-communicable diseases, particularly the rising prevalence of obesity and type 2 diabetes, driven by the overlapping challenges of food insecurity, nutritional transition, and associated increased consumption of calorie-dense foods. Establishing the true prevalence of NAFLD, raising public awareness around the risk factors behind the increase in NAFLD, and proactively addressing all components of metabolic syndrome will be important to combat this silent epidemic, which will have long-term health-care costs and economic consequences for the region.

Chronic liver disease (CLD) is currently a major health problem worldwide, which is accompanied by chronic liver injury and lack of clinically effective treatment; however, systematic characterization of chronic liver injury procedures at single-cell resolution is lacking. In the present study, we established chronic liver injury mouse models and conducted single-cell RNA sequencing (scRNA-seq), including choline-deficient, ethionine-supplemented (CDE) and 3,5-diethoxycarbonyl 1,4-dihydrocollidinen (DDC) mouse models. We captured in total 16,389 high-quality cells and identified 12 main cell types in scRNA-seq data. Macrophages and endothelial cells are the largest cell populations in our dataset. Transcriptional trajectory analysis revealed different expression patterns of cells between CDE and DDC models and identified potential liver injury markers, such as Ets1, Gda, Itgam, and Sparc. Differential analysis identified 25 and 152 differentially expressed genes in CDE and DDC macrophages, respectively. In addition, 413 genes were detected to exclusively express in specific pseudotime states of macrophages. These genes were found to participate in immune-related biological processes. Further cell-cell communication analysis found extensive receding of cell-cell interactions between different cell types in the liver injury process, especially in the DDC model. Our study characterized the single-cell transcriptional landscape in the process of chronic liver injury, promoting the understanding of the underlying molecular mechanisms and providing candidate clinical strategy for effective intervention of chronic liver diseases., Graphical abstract, We systematically characterized single-cell transcriptome in two different liver injury mouse models by single-cell RNA sequencing (scRNA-seq).

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease globally. miRNAs (miRs) regulate various cellular events that lead to NAFLD. In this study we tested the hypothesis that miR-155 is an important regulator of steatohepatitis and fibrosis pathways. Wild type (WT) or miR-155 deficient (KO) mice received a high fat-high cholesterol-high sugar-diet (HF-HC-HS) for 34 weeks and liver tissues were analyzed. In patients with nonalcoholic steatohepatitis and in the mouse model of HF-HC-HS diet we found increased miR-155 levels in the liver compared to normal livers. Upon HF-HC-HS diet feeding, miR-155 KO mice displayed less liver injury, decreased steatosis, and attenuation in fibrosis compared to WT mice. ALT, triglyceride levels, and genes involved in fatty acid metabolic pathway were increased in WT mice whereas miR-155 KO mice showed attenuation in these parameters. HF-HC-HS diet-induced significant increase in the expression of NLRP3 inflammasome components in the livers of WT mice compared to chow fed diet. Compared to WT mice, miR-155 KO showed attenuated induction in the NLRP3, ASC, and caspase1 inflammasome expression on HF-HC-HS diet. Fibrosis markers such as collagen content and deposition, αSMA, Zeb2, and vimentin were all increased in WT mice and miR-155 KO mice showed attenuated fibrosis marker expression. Overall, our findings highlight a role for miR-155 in HF-HC-HS diet-induced steatosis and liver fibrosis.

Background &Aims Liver transplant (LT) recipients or other immunocompromised patients were not included in the registration trials of vaccine studies against SARS-CoV-2. Although clinical efficacy of COVID vaccines in immunocompromised patients was unknown, many societies had recommended vaccination of this highly vulnerable patient population. Methods In this prospective study, we determined antibody (Ab) response to spike protein, 4 weeks after the 2nd dose of mRNA vaccines or after the single dose of Johnson & Johnson vaccine, in LT recipients and those with chronic liver diseases (CLD) with and without cirrhosis. Results Of the 233 patients enrolled so far, 62 had LT, 79 had cirrhosis (10 decompensated) and 92 had CLD without cirrhosis. Ab titers were defined as undetectable (250 U/mL). Of the 62 patients who had LT, Ab levels were undetectable in 11 patients and suboptimal (median titer 17.6, range 0.47 - 212 U/mL) in 27 patients. Among 79 patients with cirrhosis, 3 had undetectable Ab and 15 had suboptimal (median titer 41.3, range 0.49 - 221 U/L) response. Of the 92 patients without cirrhosis, four had undetectable Ab and 19 had suboptimal (median titer 95.5, range 4.9 - 234 U/L) Ab response. Liver transplantation, use of 2 or more immunosuppression medications and vaccination with a single dose of Johnson & Johnson vaccine were associated with poor immune response on multivariable analysis. No patient had any serious adverse events. Conclusions Poor antibody response after SARS-CoV-2 vaccination was seen in 61% of LT recipients and 24% of those with CLD. Lay summary The clinical efficacy of COVID vaccines in immunocompromised patients is unknown. We did a prospective study to evaluate immune responses to COVID vaccines (Moderna, Pfizer or Johnson & Johnson) in 62 liver transplant recipients, 79 subjects with cirrhosis and 92 subjects with chronic liver diseases without cirrhosis. We found that 17.8% of liver transplant recipients, 3.8% of those with cirrhosis and 4.3% of those with chronic liver diseases without cirrhosis had undetectable antibody levels. In total, 61.3% of liver transplant recipients and 24% of those with chronic liver diseases (with or without cirrhosis) had poor antibody response (undetectable or suboptimal). Liver transplantation, use of immunosuppressive medications and vaccination with a single dose of Johnson & Johnson vaccine were associated with poor antibody response when adjusted for other factors., Graphical abstract

Acute liver failure (ALF) in the paediatric patient is a multisystem complex disorder, which occurs in the absence of chronic liver disease. Globally, viruses remain a common cause but drugs, metabolic and autoimmune conditions are important triggers. In up to half of cases no specific cause is identified. The definition entails a coagulopathy with a Prothrombin time (PT) ≥ 15seconds or International Normalized Ratio (INR) ≥ 1.5 not corrected by vitamin K in the presence of hepatic encephalopathy (HE) or a PT ≥ 20 or INR ≥2 or above regardless of HE. HE can be difficult to recognize in children and is defined differently than HE in adults. Timely recognition of ALF improves outcomes and allows time to undertake investigations, provide supportive therapy and arrange transfer to a specialist paediatric liver centre with transplant capacity. The purpose of this article is to review the aetiologies of ALF in children and outline an approach to investigation, management and treatment.

INTRODUCTION Chronic liver disease (CLD) is characterized by changes in haemostasis, embracing both hypo- and hypercoagulability. Global hemostatic tests such as thrombin generation assays evaluate the hemostatic balance, to better assess bleeding and thrombotic risks. In addition, procoagulant state in patients with CLD has been demonstrated using modified thrombin generation assays with thrombomodulin, a cofactor for protein C activation. In this study, we prospectively determined thrombin generation and thrombomodulin resistance in patients with CLD staged with liver stiffness measurement (LSM), using both the fully automated analyzer ST Genesia® Thrombin Generation System (STG) and the calibrated automated thrombogram assay (CAT). MATERIALS AND METHODS Demographic, clinical and laboratory characteristics, and blood samples were collected from 65 patients with CLD. Liver stiffness was measured by transient elastography, and thrombin generation and thrombomodulin resistance, by STG and CAT. RESULTS Patients were separated based on LSM of

BACKGROUND & AIMS Early determination of the prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important to guide clinical management and decrease mortality. The aim of this study was to develop a new simplified prognostic score to accurately predict outcomes in patients with HBV-ACLF. METHODS Prospective clinical data from 2,409 hospitalized patients with acute deterioration of HBV-related chronic liver disease were used to develop a new prognostic score that was validated in an external group. RESULTS A total of 954 enrolled patients with HBV-ACLF were diagnosed based on the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) criteria. Six predictive factors were significantly related to 28-day mortality and constituted a new prognostic score (=1.649×ln(international normalized ratio)+0.457×hepatic encephalopathy score+0.425×ln(neutrophil)+0.396×ln(total bilirubin)+0.576×ln(serum urea)+0.033×age). The C-indices of the new score for 28-/90-day mortality (0.826/0.809) were significantly higher than those of 4 other scores (COSSH-ACLF, 0.793/0.784; CLIF-C ACLF, 0.792/0.770; MELD, 0.731/0.727; MELD-Na, 0.730/0.726; all p

Coronavirus disease 2019 (COVID-19) is associated with a significant morbidity and mortality in patients with cirrhosis. There is a significantly higher morbidity and mortality due to COVID-19 in patients with decompensated cirrhosis as compared to compensated cirrhosis, and in patients with cirrhosis as compared to non-cirrhotic chronic liver disease. The fear of COVID-19 before or after liver transplantation has lead to a significant reduction in liver transplantation numbers, and patients with decompensated cirrhosis remain at risk of wait list mortality. The studies in liver transplantation recipients show that risk of mortality due to COVID-19 is generally driven by higher age and comorbidities. The current review discusses available literature regarding outcomes of COVID-19 in patients with cirrhosis and outcomes in liver transplant recipients.

Chronic liver disease (CLD) may be associated with pleural effusions (PEs). This article prospectively evaluates whether detection of PEs on thoracic ultrasound (TUS) at the bedside independently predicts mortality and length of stay (LOS) in hospitalized patients with a decompensated CLD. A total of 116 consecutive inpatients with decompensated cirrhosis underwent antero-posterior chest radiographs (CXR) and TUS to detect PEs. Their median age was 54 y (interquartile range, 47-62), 90 (70.6%) were male, and 61 (52.6%) fell into the Child-Pugh class C categorization. TUS identified PEs in 58 (50%) patients, half of which were small enough to preclude thoracentesis. CXR failed to recognize approximately 40% of PEs seen on TUS. The identification of PEs by TUS was associated with a longer LOS (10 vs. 5.5 d, p0.001) and double mortality (39.7% vs. 20.7%, p = 0.021). In multivariate analysis, PEs were independently related to poor survival (hazard ratio 2.08, 95% confidence interval [CI] 1.02-4.25; p = 0.044). Patients with both Child-Pugh C stage and PEs had the lowest survival rate (70 vs. 317 d, p = 0.001). In conclusion, PEs identified by TUS in hospitalized patients with decompensated CLD independently predict a poor outcome and portend a longer LOS.

Currently, one of the most serious public health issues is the increasing number of cases of chronic liver disease and cirrhosis both of which can lead to liver failure. The only effective method of treatment for this life-threatening condition remains liver transplantation. Unfortunately, the chronic shortage of transplantable organs seriously limits its accessibility to patients. Thus, tremendous research has been done to develop methods capable of replacing liver transplantation by artificial means or to create techniques to partially or fully replace liver function in patients with impaired livers, until liver regeneration or transplantation. This review article is focused on research results that utilize living cells in order to establish bridging therapies in cases of liver failure. This includes both experimental and clinically tested techniques, such as hepatocyte transplantation and usage of the hybrid bioartificial liver devices. The article also discusses research which presents the long-term culture of hepatocytes in conditions that preserve their differentiated state, which is important for such applications as drug development and toxicity testing. Last but not least, the article describes the groundbreaking efforts toward building sophisticated scaffolds for hepatocyte culture that mimic their natural environment, which are based on decellularized tissues and on three-dimensional bioprinting.

Non-alcoholic fatty liver disease (NAFLD) has become a major cause of chronic liver disease (CLD) worldwide. Our aim was to assess the burden of liver complications (LC, cirrhosis and liver cancer) related to NAFLD (LC-NAFLD) between 2009-2019 in Asia and the Middle East and North Africa (MENA) region.We used Global Burden of Disease data to assess incidence, mortality, and disability-adjusted life years (DALYs) for LC-NAFLD from Asia and the MENA region. Annual % change (APC) in rates were computed using a joinpoint regression model. Associations of LC-NAFLD with low physical activity, diet and metabolic risks were determined by partial Spearman correlation coefficients (ρ).Globally in 2019, there were 170,000 incident cases of LC-NAFLD, accounting for 6.6% of LC incident cases from all CLDs. There were 168,969 deaths related to LC-NAFLD, accounting for 8.6% of LC deaths from all CLDs. Asia accounted for 48.3% of the global incidence of LC-NAFLD and for 46.2% of deaths attributable to LC-NAFLD, while MENA accounted for 8.9% and 8.6%, respectively. There were 2.08 million DALYs in Asia and 340,000 DALYs in MENA. From 2009 to 2019, regions in Asia and MENA experienced a rise in DALYs attributable to LC-NAFLD (compared to LC from other CLDs), ranging from South Asia (APC = +2.12% vs. -0.94%) to high-income Asia Pacific (APC = -0.07%, p = 0.646 vs. -0.97%). In Asia, NAFLD-related DALYs were significantly correlated with dietary risks (95% CI 0.280-0.763, p = 0.004), metabolic risks (0.341-0.790, p0.001) and tobacco use (0.134-0.691, p = 0.007). In MENA, low physical activity (0.557-0.918, p0.001), metabolic risks (0.432-0.888, p = 0.001), and dietary risks (0.315-0.855, p = 0.001) correlated with DALYs.NAFLD is posing a substantial burden in Asia and MENA. About half of the global burden of LC-NAFLD is accounted for by these regions.Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the most common causes of chronic liver disease worldwide. We used Global Burden of Disease data to assess the incidence, mortality, and disability-adjusted life years attributable to NAFLD-related liver complications in Asia, the Middle East and North Africa. NAFLD is poised to contribute to a substantial liver disease burden in these regions. Regional and global policies are needed to address the increasing burden of complications of NAFLD.

Summary Background and aims Prospective cohort studies linking dietary patterns and non-alcoholic fatty liver disease (NAFLD) are limited, especially in Asian populations. This study aimed to prospectively investigate the association between dietary patterns and risk of NAFLD in a general Chinese adult population. Methods This study included a total of 17,360 participants free from NAFLD at baseline. Dietary patterns at baseline were identified with factor analysis based on responses to a validated 100-item food frequency questionnaire. NAFLD was diagnosed by abdominal ultrasound after excluding other causes related to chronic liver disease. Cox proportional regression models were used to assess the association between dietary patterns and risk of NAFLD. Results During a median follow-up of 4.2 years, 4034 NAFLD cases were documented. Three main dietary patterns were extracted: sugar rich dietary pattern, vegetable rich dietary pattern, and animal food dietary pattern. After adjusting for age, sex, body mass index, smoking, alcohol, education, occupation, income, physical activity, total energy intake, personal and family history of disease, depressive symptoms, dietary supplement use, inflammation markers, and each other dietary pattern score, comparing the highest with the lowest quartiles of dietary pattern scores, the multivariable hazard ratios (95% confidence interval) of NAFLD were 1.11 (1.01, 1.23) for sugar rich dietary pattern, 0.96 (0.86, 1.07) for vegetable rich dietary pattern, and 1.22 (1.10, 1.36) for animal food dietary pattern. Further adjustment for waist circumference instead of body mass index provided similar results. Conclusion Dietary patterns rich in animal foods or sugar were associated with a higher risk of NAFLD among Chinese adults, whereas a vegetable rich dietary pattern was not associated.

Background: in Italy, Hepatitis-B-vaccine is advised and provided free-of-charge for subjects with chronic liver disease (CLD), including liver cirrhosis. Aims: to evaluate HB-vaccine-coverage and variables associated with lack of vaccination in cirrhotic patients with particular attention to cirrhosis' etiology. Methods: cirrhotic patients of any etiology (excluding HBsAg+) referring to 8 tertiary-centers were prospectively enrolled for a-six-months-period in 2019. Subjects were asked if they received HB-vaccine previously. Multiple-logistic-regression-analysis was performed to identify independent predictors of lack of vaccination. Results: 731 cases were recruited. Overall-vaccine-coverage was 16.3% (23.7% in those younger than 65y, 10.0% in those older than 64y; p64 y (OR: 4.27; CI 95%: 2.52-7.24), educational level

Direct oral anticoagulants (DOACs) emerged as effective and safe alternatives to traditional anticoagulants for the prevention and treatment of venous thromboembolic disease and the prevention of stroke in non-valvular atrial fibrillation. Patients with advanced chronic liver disease (ACLD) have a higher risk of thromboembolism and bleeding than patients with normal liver function. Therefore, anticoagulation and, in particular, direct oral anticoagulants play a central role. Portal vein thrombosis is a relatively frequent complication in patients with ACLD, but its treatment remains challenging. DOACs have been introduced in clinical practice and demonstrated similar efficacy and safety profiles compared with vitamin K antagonist and heparins. However, further data about the use of DOACs in patients suffering from ACLD are needed. This review summarizes current knowledge in terms of anticoagulation in patients with ACLD and focuses on the available data about the use of DOACs in this population.

Background & Aims The impact of chronic liver disease on outcomes in patients with COVID-19 is uncertain. Hence, we aimed to explore this association. Methods We explored the outcomes of all adult inpatients with COVID-19 in France, in 2020. We computed adjusted odds ratios to measure the associations between chronic liver disease, alcohol use disorders, mechanical ventilation and day-30, in-hospital, mortality. Results The sample comprised 259,110 patients (median [IQR] age 70 (54–83) years; 52% men), including 15,476 (6.0%) and 10,006 (3.9%) patients with chronic liver disease and alcohol use disorders, respectively. Death occurred in 38,203 (15%) patients, including 7,475 (28%) after mechanical ventilation, and 2,941 (19%) with chronic liver disease. The adjusted odds ratios for mechanical ventilation and day-30 mortality were 1.54 (95% CI 1.44–1.64, p, Graphical abstract

As liver is one of the primary organs involved in glucose homeostasis, it is not surprising that patients with liver dysfunction in chronic liver disease usually develop impaired glucose tolerance and subsequently overt diabetes later in their natural course. Diabetes that develops after the onset of cirrhosis of liver is usually referred to as hepatogenous diabetes (HD). It is an underrecognized and a hallmark endocrinological event in chronic liver disease. HD is associated with a higher risk of developing hepatic decompensations, such as ascites, variceal bleeding, hepatic encephalopathy, renal dysfunction, refractory ascites, and hepatocellular carcinoma along with reduced survival rates than normoglycemic patients with cirrhosis of liver. It is quite different from type 2 diabetes mellitus with the absence of classical risk factors, dissimilar laboratory profiles, and decreased incidence of microvascular complications. Furthermore, the management of patients with HD is challenging because of altered pharmacokinetics of most antidiabetic drugs and increased risk of hypoglycemia and other adverse effects. Hence, a clear understanding of the epidemiology, pathophysiology, clinical implications, laboratory diagnosis, and management of HD is essential for both hepatologists as well as endocrinologists, which is narrated briefly in this review.

In the background of chronic liver disease, hepatocellular carcinoma develops via a complex, multistep process called hepatocarcinogenesis. This article reviews the causes contributing to the process. Emphasis is made on the imaging manifestations of the pathologic changes seen at many stages of hepatocarcinogenesis, from regenerative nodules to dysplastic nodules and then to hepatocellular carcinoma.

Contrast-enhanced MR imaging plays an important role in the evaluation of patients with chronic liver disease, particularly for detection and characterization of liver lesions. The two most commonly used contrast agents for liver MR imaging are extracellular agents (ECAs) and hepatobiliary agents (HBAs). In patients with liver disease, the main advantage of ECA-enhanced MR imaging is its high specificity for the diagnosis of progressed HCCs. Conversely, HBAs have an additional contrast mechanism, which results in high liver-to-lesion contrast and highest sensitivity for lesion detection in the hepatobiliary phase. Emerging data suggest that features depicted on contrast-enhanced MR imaging scans are related to tumor biology and are predictive of patients' prognosis, likely to further expand the role of contrast-enhanced MR imaging in the clinical care of patients with chronic liver disease.

Effective communication between radiologists and physicians involved in the management of patients with chronic liver disease is paramount to ensuring appropriate and advantageous incorporation of liver imaging findings into patient care. This review discusses the clinical benefits of innovations in radiology reporting, what information the various stakeholders wish to know from the radiologist, and how radiology can help to ensure the effective communication of findings.

MRI is an important problem-solving tool for accurate characterization of liver lesions. Chronic liver disease alters the typical imaging characteristics and complicates liver imaging. Awareness of imaging pitfalls and technical artifacts and ways to mitigate them allows for more accurate and timely diagnosis.

Here we review artificial intelligence (AI) models which aim to assess various aspects of chronic liver disease. Despite the clinical importance of hepatocellular carcinoma in the setting of chronic liver disease, we focus this review on AI models which are not lesion-specific and instead review models developed for liver parenchyma segmentation, evaluation of portal circulation, assessment of hepatic fibrosis, and identification of hepatic steatosis. Optimization of these models offers the opportunity to potentially reduce the need for invasive procedures such as catheterization to measure hepatic venous pressure gradient or biopsy to assess fibrosis and steatosis. We compare the performance of these AI models amongst themselves as well as to radiomics approaches and alternate modality assessments. We conclude that these models show promising performance and merit larger-scale evaluation. We review artificial intelligence models that aim to assess various aspects of chronic liver disease aside from hepatocellular carcinoma. We focus this review on models for liver parenchyma segmentation, evaluation of portal circulation, assessment of hepatic fibrosis, and identification of hepatic steatosis. We conclude that these models show promising performance and merit a larger scale evaluation.

Background The rapid spread of the coronavirus disease 2019 (COVID-19) with high mortality rate necessitates disease characterization and accurate prognostication for prompt clinical decision-making. The aim of this study is to study clinical characteristics and predictors of mortality in hospitalized patients with COVID-19 in India. Methods Retrospective cohort study was conducted in a tertiary care hospital in northern India. All consecutive confirmed hospitalized COVID-19 cases aged 15 years and older from 13 Apr till 31 Aug 2020 are included. Primary end point was 30-day mortality. Results Of 1622 patients ,1536 cases were valid. Median age was 36 years, 88.3% were men and 58.1% were symptomatic. Fever (37.6%) was commonest presenting symptom. Dyspnea was reported by 15.4%. Primary hypertension (8.5%) was commonest comorbidity, followed by diabetes mellitus (6.7%). Mild, moderate, and severe hypoxemia were seen in 3.4%, 4.3%, and 0.8% respectively. Logistic regression showed greater odds of moderate/severe disease in patients with dyspnea, hypertension, Chronic Kidney Disease (CKD), and malignancy. Seventy six patients died (4.9%). In adjusted Cox proportional hazards model for mortality, patients with dyspnea (hazard ratio [HR]: 14.449 [5.043-41.402]), altered sensorium (HR: 2.762 [1.142-6.683]), Diabetes Mellitus (HR: 1.734 [1.001-3.009]), malignancy (HR:10.443 [4.396-24.805]) and Chronic Liver Disease (CLD) (HR: 14.432 [2.321-89.715]) had higher risk. Rising respiratory rate (HR: 1.098 [1.048-1.150]), falling oxygen saturation (HR: 1.057 per unit change 95% CI: 1.028-1.085) were significant predictors. Conclusion Analysis suggests that age, dyspnea, and malignancy were associated with both severe disease and mortality. Diabetes Mellitus and Chronic Liver Disease were associated with increased the risk of fatal outcome. Simple clinical parameters such as respiratory rate and oxygen saturation are strong predictors and with other risk factors at admission can be effectively used to triage patients.

Lusutrombopag is an oral platelet production promoter for thrombocytopenia in patients with chronic liver disease (CLD) that is usually administered before an invasive procedure. However, not all patients showed adequate platelet elevation. To the best of our knowledge, there is only one case report published so far on patients treated with lusutrombopag before tooth extraction. Here, we reported three cases of CLD complicated by thrombocytopenia treated with lusutrombopag before tooth extraction, whose platelet count (PLC) increased appropriately in two cases but did not rise in the third case, necessitating platelet transfusion. Case 1 was that of a 72-year-old male with cirrhosis, hepatocellular carcinoma, hypertension, chronic renal failure, and low PLC (4.7 × 104/μL). Case 2 was that of a 67-year-old female with cirrhosis, diabetes, and chronic renal failure, low PLC (3.6 × 104/μL). Both the PLCs of cases 1 and 2 increased appropriately after the administration of lusutrombopag, and we were able to perform extraction without platelet transfusion. Case 3 was that of a 56-year-old female with idiopathic portal hypertension, giant spleen, portal vein embolism, and systemic lupus erythematosus, whose PLC was reduced at 2.9 × 104/μL. Abdominal ultrasonography revealed an abnormal enlargement of the spleen. The PLC did not increase after lusutrombopag administration, and platelet transfusion was required during surgery in this case. Furthermore, PLC did not increase on the day after platelet transfusion. Therefore, this suggested that PLC did not increase by lusutrombopag or platelet transfusion because of splenomegaly caused by idiopathic portal hypertension.

Background Microvesicles (MVs) play a role in inflammation, coagulation, and vascular homeostasis in liver disease. Aim To characterize circulating plasma MVs profile in patients with decompensated cirrhosis and acute kidney injury (AKI). Methods We measured the levels of total, endothelial, platelet, tissue factor (TF)+, leukocyte and hepatocyte MVs by new generation flow-cytometry in a prospective cohort of patients with decompensated cirrhosis with and without AKI. Results Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Patients with cirrhosis with AKI had significantly higher calcein+ (total), endothelial, and platelet-MVs. Conversely, TF+, leukocyte, and hepatocyte-MVs were comparable between groups. Resolution of AKI was associated with significantly decreased total and endothelial-MVs that became comparable with those in patients without AKI. Platelet MVs significantly decreased but remained higher compared to patients without AKI. TF+MVs significantly decreased and became lower than patients without AKI. Leukocyte and hepatocyte-MVs remained unchanged. Creatinine (OR 4.3 [95%CI 1.8–10.7]), MELD (OR 1.13 [95%CI 1.02–1.27]), any bleeding (OR 9.07 [95%CI 2.02–40.6]), and hepatocyte-MVs (OR 1.04 [95%CI 1.02–1.07]) were independently associated with 30-day mortality. Conclusion AKI worsened vascular and cellular homeostasis in patients with cirrhosis, particularly by inducing endothelial dysfunction and platelet activation. AKI did not worsen systemic inflammation and hepatocytes activation.

Liver health is a key determinant of cardiovascular risk (CVR). Hepatic fibrosis is the shared common result of chronic hepatitis, irrespective of aetiology. Fibrosis profoundly distorts liver tissue architecture and perturbs hepatic physiology, dictates the course of chronic liver disease and is increasingly recognized as a CVR factor. The relative weights of pre-diabetes and hepatic fibrosis as risk factors for major adverse cardiac events (MACE) in patients with HCV remain an open issue. Sasso and Colleagues answered this research question by treating approximately half of 770 HCV positive pre-diabetic patients with direct antiviral agents (DAAs), while the rest served as historical controls. Data have shown that achieving HCV clearance with DAAs was associated with a 60% reduced risk of MACE, thereby implying that this antiviral strategy is recommended in HCV positive pre-diabetic patients, regardless of the severity of liver disease and concurrent CVR factors. This study paves the way for additional studies addressing the molecular patho-mechanisms and changes in the clinical spectrum involved in cardio-metabolic protection following HCV eradication in patients with pre-diabetes.

Background Despite national guidelines emphasizing the importance of vaccination or documenting immunity to hepatitis A virus and hepatitis B virus for patients with chronic liver disease, the success of adhering to these recommendations is suboptimal. We aim to evaluate the prevalence of vaccination or documented reactivity to hepatitis A antibody and hepatitis B surface antibody among US adults with chronic liver disease. Methods Using 2011-2018 National Health and Nutritional Examination Survey data, adults with nonalcoholic fatty liver disease, alcoholic liver disease, hepatitis B, and hepatitis C were evaluated to determine prevalence of vaccination (self-reported completion) and hepatitis A antibody reactivity or hepatitis B surface antibody reactivity. Results Overall prevalence of vaccination or hepatitis A antibody reactivity was lowest among individuals with nonalcoholic fatty liver disease (60.8%; 95% confidence interval [CI], 57.9-63.6) and alcoholic liver disease (61.8%; 95% CI, 59.0-64.6), and highest among individuals with hepatitis B (82.9%; 95% CI, 76.8-89.0). Prevalence of vaccination or hepatitis B surface antibody reactivity was much lower: 38.6% (95% CI, 35.7-41.4) in nonalcoholic fatty liver disease, 40.7% (95% CI, 34.4-47.0) in chronic hepatitis C virus, and 47.1% (95% CI, 44.3-49.9) in alcoholic liver disease. Conclusion Among US adults with chronic liver disease, prevalence of vaccination or documented reactivity to hepatitis A antibody and hepatitis B surface antibody was alarmingly low. These observations are particularly concerning given that underlying chronic liver disease increases risks of severe liver injury and decompensation from acute hepatitis A or hepatitis B infections.

BACKGROUND: Acute pulmonary oedema is a life-threatening syndrome diagnosed based on radiological and clinical findings. However, to our knowledge, no studies have investigated this syndrome in critically ill patients. OJECTIVE: To describe the prevalence of radiologically and clinically diagnosed pulmonary oedema (RCDPO) in critically ill patients, characteristics of diagnosed patients, and treatments and outcomes in this patient population. METHODS: We conducted a retrospective study using natural language processing to identify all radiological reports of pulmonary oedema among patients who had been admitted to single tertiary intensive care unit (ICU) over a 1-year period (January 2015 to January 2016). We reviewed clinical data, discharge diagnosis, treatment and outcomes for such patients, and used multivariable logistic regression analysis to identify the association of RCDPO with various outcomes. RESULTS: Out of 2001 ICU patients, we identified 238 patients (11.9%) with RCDPO. Patients with RCDPO were more acutely ill, had more chronic liver disease and had more chronic renal failure than critically ill patients who did not have RCDPO. They were typically admitted with acute cardiovascular disease; were more likely to receive invasive mechanical ventilation and continuous renal replacement therapy; had longer duration of ICU and hospital stay; were more likely to die in hospital; and, if discharged alive, were more likely to be admitted to a chronic care facility. In total, 46 RCDPO patients (19.3%) died in hospital. On multivariable analysis, only age and continuous renal replacement therapy were independently associated with mortality. In contrast, invasive mechanical ventilation was associated with a 2.5 times greater odds of radiological resolution. CONCLUSION: RCDPO affected about one in eight ICU patients. Such patients were sicker and had more comorbidities. The presence of RCDPO was independently associated with higher risk of death. Invasive mechanical ventilation was the only intervention independently associated with greater odds of radiological resolution.

Background & Aims Chronic liver disease and liver transplantation (LT) can delay both timing and ability of women to conceive. With increased awareness and availability of in vitro fertilisation (IVF), the need for accurate counselling is paramount. To date, minimal data exist on outcomes of IVF in patients with chronic liver disease, cirrhosis, or post-LT. We report the largest experience of IVF in women with liver-related subfertility (LRSF). Methods A retrospective analysis was performed on 42 women with LRSF who had undergone 57 IVF cycles between 1990 and 2019. Results Forty-two women with LRSF received IVF; 9 cycles in 6 women with cirrhosis, 14 cycles in 11 women post-LT, and 34 cycles in 25 women without cirrhosis. The main aetiologies of liver disease included HBV, HCV, and autoimmune hepatitis (AIH). Of 57 IVF cycles evaluated, 43 (75%) resulted in successful implantation. Eight (2 post-LT, 3 with cirrhosis, 4 without cirrhosis) resulted in miscarriage. The live birth rate (LBR) was 74% (32/43). Two of 9 (22%) patients with cirrhosis, 4/14 (29%) patients who were post-LT, and 6/34 (18%) patients without cirrhosis had unsuccessful IVF attempts. Nine of 57 (16%) IVF cycles resulted in new liver enzyme derangement during therapy, which improved after treatment completion. Six pregnancies (2 in patients who were post-LT, 4 without cirrhosis) were complicated by obstetric cholestasis (OC). Ovarian hyperstimulation syndrome (OHSS) was rare (n = 3, 7%). One patient with AIH-related cirrhosis decompensated after initiating IVF, warranting discontinuation of therapy. There were no maternal deaths. Three women developed a hypertensive disorder of pregnancy. Half the pregnancies resulted in premature deliveries (range 27–36 weeks). Conclusions In selected cases, IVF in women with LRSF can be successful. However, patients should be counselled on the potential increased risks of OHSS, OC, and prematurity. Lay summary Women with liver disease or those who have had a liver transplant can experience difficulties getting pregnant. In this study, we look at whether alternative approaches to achieve pregnancy are harmful in these women. Overall, there were no significant issues with the use of in vitro fertilisation in women with liver disease, but they need to be aware of potential risks, such as early delivery of the baby.