Cirrhosis Mortality Research Articles

Acute Hepatitis C: Current Status and Future Perspectives

The hepatitis C virus (HCV) infection continues to represent a significant public health threat and is a leading cause of liver cirrhosis, liver cancer, and liver-related mortality. The World Health Organization (WHO) has set a goal for 2030: to eliminate HCV infection as a public health threat by reducing new HCV infections by 90% and mortality by 65%. The early phase of HCV infection represents a pivotal point in the evolution of hepatitis C. Despite a favourable course in the majority of patients, approximately 50–70% of individuals with recently acquired hepatitis C will develop a chronic infection, defined as the persistence of viremia for a period exceeding six months. The diagnosis and treatment of a recent HCV infection should facilitate engagement in multidisciplinary care, prevent the development and complications of chronic liver disease, and reduce ongoing transmission in key populations. Therefore, early treatment in the early phase of infection compared with deferring treatment until the chronic infection remains a valid approach in the era of direct antiviral agents (DAAs). This approach is supported by a cost-effectiveness analysis. The aim of this review is to synthesise the existing knowledge on the early phase of hepatitis C virus infection, with a particular focus on the current risk factors, natural history, therapeutic management, and future perspectives.

Outcomes of fenestration versus none in extracardiac total cavopulmonary connection.

Fenestrated total cavopulmonary connection has gained popularity due to its capacity to reduce systemic venous pressure and enhance cardiac output. However, there is ongoing debate about the immediate and long-term advantages of fenestration in this context. A retrospective cohort study was conducted involving 97 patients who underwent extracardiac total cavopulmonary connection at Chiang Mai University Hospital between January 1999 and December 2019. The patients were initially categorized into two groups: fenestrated (n = 71) and nonfenestrated (n = 26). After exclusion and reassignment, the long-term outcomes were analyzed for the fenestrated (n = 68) and nonfenestrated (n = 25) groups. To address potential confounding factors between the two groups, propensity scores were computed using logistic regression analysis. The study found no significant differences in preoperative and operative data. Immediate postoperative outcomes showed no significant variations in major complications, intensive care unit stay, oxygen saturation, and posttotal cavopulmonary connection pressure. In the long-term assessment, the fenestrated group demonstrated significantly lower rates of mortality, protein-losing enteropathy, liver mass, and cirrhosis. However, after employing a multilevel model stratified by propensity score analysis, only long-term mortality rate was significantly lower in the fenestrated group (hazard ratio = 0.12, 95% confidence interval = 0.02-0.97). Fenestration patency closed gradually through spontaneous closure and device intervention. The study found no major differences in immediate postoperative outcomes. In the fenestrated cohort, significantly lower incidences of protein-losing enteropathy, liver mass, cirrhosis, and long-term mortality were observed. However, multilevel model stratified by propensity score analysis indicated that only the lower long-term mortality demonstrated a major effect.

Spot Urine Sodium to Potassium Ratio as a Tool to Assess Severity and Mortality among Patients with Decompensated Cirrhosis having Ascites

Background: Decompensated cirrhosis of liver is considered as a systemic disease affecting the functions of several other organs. Renal function is an independent prognostic factor for patients with decompensated cirrhosis, but assessing renal function through glomerular filtration rate are not convenient, especially for routine use. Previous study found that spot urinary sodium to potassium ratio (UNa/K) was associated with renal dysfunction which influences the severity and outcome in decompensated cirrhosis of liver patients having ascites. Aims and objectives: The present study was aimed to determine the relation of the ratio of sodium to potassium in randomly collected urine samples with severity of disease and mortality in decompensated cirrhosis having ascites. Materials and Methods: This longitudinal study was conducted at the Department of Gastrointestinal, Hepatobiliary and Pancreatic Disorders, BIRDEM General Hospital, Shahbagh, Dhaka, Bangladesh, from July, 2019 to August, 202l. A total of 150 patients with a confirmed diagnosis of decompensated cirrhosis with ascites were enrolled in this study. A detailed history and thorough clinical examination were carried out in each patient, along with relevant investigations. Data collection was done through a structured questionnaire. Data were analyzed using the statistical software SPSS 23. Results: Age of the patients was 59.0±12.91 (mean±SD) years, male predominance was observed (52%). The UNa/K ratio was 4.24±3.25 (mean±SD) with a range of 0.42 to 18.46. Diagnostic accuracy of UNa/K ratio in the detection of severity and mortality was estimated by the receiver operating characteristic (ROC) curve. The AUC of UNa/K ratio was 0.608 and 0.640 for severity and mortality respectively. Sensitivity, specificity, PPV and NPV at cut-off 2.55 were 50.0, 66.0, 42.4 and 72.5; at 2.65 were 54.0, 66.0, 44.3, and 74.2; at 2.87 were 58.0, 62.0, 43.3, and 74.7; at 3.21 were 58.0, 58.0, 40.8, and 73.4 respectively for severity score (MELD). Patients with UNa+/K+ less than 2.87 or equal, had a significantly higher MELD score category (p= 0.02). At 3 months follow-up, 24.7% mortality was observed. Sensitivity, specificity, PPV and NPV at cut-off 1.62 were 51.4, 85.8, 54.3 and 84.3; at 1.79 were 54.1, 79.7, 46.5 and 84.1; at 1.83 were 59.5, 77.0, 45.8 and 85.3; at 2.87 were 58.0, 62.0, 43.3, and 74.7 respectively for mortality. The UNa/K ratio was statistically low among the patients who didn’t survive (p<.05). Conclusion: This study revealed that decreased ratio of spot urinary sodium to potassium was associated with the severity and mortality among decompensated cirrhosis of liver patients with ascites. Bangladesh Crit Care J September 2024; 12 (2): 118-124

GLP-1 Receptor Agonists and Risk for Cirrhosis and Related Complications in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing cause of cirrhosis. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective in improving liver inflammation in patients with MASLD. To determine whether use of GLP-1 RAs is associated with lower risk of developing cirrhosis and its complications, including decompensation and hepatocellular cancer (HCC), among patients with MASLD. This retrospective cohort study with an active comparator, new-user design used data from the national Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry. Patients with MASLD and diabetes who were seen at 130 Veterans Health Administration hospitals and associated ambulatory clinics and who initiated either a GLP-1 RA or dipeptidyl peptidase 4 inhibitor (DPP-4i) between January 1, 2006, and June 30, 2022, were included. Patients were followed up from baseline until one of the study outcomes or the end of the study period (December 31, 2022), whichever came first. Each GLP-1 RA new user was propensity score matched in 1:1 ratio to a patient who initiated a DPP-4i during the same month. Separate analyses were conducted among patients without and with cirrhosis at baseline. For patients without cirrhosis, the primary outcome was progression to cirrhosis defined by validated diagnoses codes or a noninvasive marker of liver fibrosis, and secondary outcomes were cirrhosis complications defined both as a composite and individual complications, including decompensation, HCC, or liver transplant, and all-cause mortality. For patients with cirrhosis, the primary outcome was a composite outcome of cirrhosis complications, and secondary outcomes were decompensation, HCC, and all-cause mortality. Of 16 058 patients who initiated GLP-1 RAs, 14 606 did not have cirrhosis (mean [SD] age, 60.56 [10.31] years; 13 015 [89.1%] male), and 1452 had cirrhosis (mean [SD] age, 66.99 [7.09] years; 1360 [93.7%] male) at baseline. These patients were matched to an equal number of patients who initiated a DPP-4i. In patients without cirrhosis, GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of cirrhosis (9.98 vs 11.10 events per 1000 person-years; hazard ratio [HR], 0.86; 95% CI, 0.75-0.98). Similar results were seen for the secondary outcomes. GLP-1 RA use, compared with DPP-4i use, was associated with a lower risk of the composite outcome of cirrhosis complications (1.89 vs 2.55 events per 1000 person-years; HR, 0.78; 95% CI, 0.59-1.04) and mortality (21.77 vs 24.43 events per 1000 person-years; HR, 0.89; 95% CI, 0.81-0.98). There were no associations between GLP-1 RA use and outcomes in patients with cirrhosis. In this cohort study, GLP-1 RA use was associated with a lower risk of progression to cirrhosis and mortality among patients with MASLD and diabetes. The protective association was not seen in patients with existing cirrhosis, underscoring the importance of treatment earlier in the disease course.

The association of dietary inflammatory indices and mortality in patients with cirrhosis: a cohort based study

Dietary intake has an undeniable role in the development and progression as well as the prevention and treatment of cirrhosis. This study was conducted with the aim of investigating the association between dietary inflammatory indices and total mortality in patients with cirrhosis. A total of 166 outpatients with cirrhosis who were diagnosed within the last 6 months were followed up for 48 months in this cohort study. A 168-question valid food frequency questionnaire was used to evaluate dietary intake. Accordingly, the dietary inflammatory index (DII), empirical dietary inflammatory pattern (EDIP) and dietary inflammatory score (DIS) were calculated. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated through cox proportional hazards regression models for an association of cirrhosis mortality and three dietary inflammatory indices. After full adjustment for confounders, the results showed that mortality risk increased significantly with increasing dietary inflammatory indices. Compared to the first tertile, the risk of mortality due to cirrhosis was associated with 4.8 times increase in the third tertile of DII (HR = 4.8, 95% CI = 1.1–19.8, p trend = 0.029), 3.3 times in the third tertile of EDIP (HR = 3.3, 95% CI = 1.3–8, p trend = 0.004), and 2.2 times increased in the third tertile of DIS (HR = 2.2, 95% CI = 1–4.7, p trend = 0.032). The results of the present study indicated a significant association between dietary inflammatory indices and total mortality among patients with cirrhosis. Additional research is necessary to confirm our findings.

Dietary total antioxidant capacity in relation to disease severity and risk of mortality in cirrhosis; results from a cohort study

Liver Cirrhosis, defined as the final stage of chronic liver disease, may become more prevalent in the lower level of body defense against oxidation and inflammation. Therefore, we assessed the association of dietary total antioxidant capacity (DTAC) with the severity and mortality of cirrhosis in a cohort study. 120 newly diagnosed cirrhosis patients from Tehran, Iran, participated in this study. The patients’ habitual diet was assessed using a 168-item validated food frequency questionnaire. Both ferric-reducing antioxidant potential (FRAP) and oxygen radical scavenging capacity (ORAC) methods were computed to achieve DTAC scores. The association between DTAC with disease severity and mortality was estimated by multivariate linear regression and cox proportional hazards regression models. Dietary total antioxidant capacity-ORAC had a significant inverse association with disease severity in both crude and adjusted models (P for trend: <0.001 and 0.016 respectively). The risk of mortality in the first and second tertiles of ORAC was 5.56 (95 % CI: 2.25–13.75; P = 0.002) and 3.20 (95 % CI: 1.25–8.19; P = 0.015) higher than those in the third category, respectively. In conclusion, a higher antioxidant capacity of diet is associated with less disease severity and mortality risk in cirrhosis.

Frailty and risk of metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases

Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by physical frailty and the frailty index, categorizing participants as non-frail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: hazard ratio [HR] 1.66, 95% CI 1.40-1.97; frailty index: HR 2.01, 95% CI 1.67-2.42) and frailty (physical frailty: HR 3.32, 95% CI 2.54-4.34; frailty index: HR 4.54, 95% CI 3.65-5.66) than in those with non-frailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as MRI-derived liver proton density fat fraction >5%, than the non-frail group (physical frailty: odds ratio 1.64, 95% CI 1.32-2.04; frailty index: odds ratio 1.48, 95% CI 1.30-1.68). Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. While frailty is common and associated with a poor prognosis in people with MASLD (metabolic dysfunction-associated steatotic liver disease) and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.

Sarcopenia is associated with short- and long-term mortality in patients with acute-on-chronic liver failure.

While sarcopenia is recognized as a predictor of mortality in cirrhosis, its influence on acute-on-chronic liver failure (ACLF) remains uncertain. Despite multiple studies examining the impact of sarcopenia on short-term mortality in patients with ACLF, the sample size of these studies was limited, and their outcomes were inconsistent. Therefore, this study aimed to explore the impact of sarcopenia on both short- and long-term mortality in patients with ACLF. This retrospective cohort study included 414 patients with ACLF that were treated between January 2016 and September 2022. Sarcopenia was diagnosed based on the measurement of the skeletal muscle index at the third lumbar vertebra (L3-SMI). Subsequently, the patients were divided into sarcopenia and non-sarcopenia groups. We analysed the basic clinical data of the two groups. Multivariate Cox proportional analysis was used to analyse short-term (28days) and long-term (1year and overall) mortality rates. A total of 414 patients were included, with a mean age of 52.88±13.41years. Among them, 318 (76.8%) were male, and 239 (57.7%) had sarcopenia. A total of 280 (67.6%) patients died during the study period. Among them, 153 patients died within 28days (37%) and 209 patients died within 1year (50.5%). We found that the 28-day, 1-year and overall mortality rates in the sarcopenia group were significantly higher than those in the non-sarcopenia group (37% vs. 22.3%, P<0.01; 50.5% vs. 34.9%, P<0.01; and 67.6% vs. 53.1%, P<0.01, respectively). Multivariate Cox regression analysis revealed that sarcopenia was significantly associated with increased mortality. The hazard ratios for sarcopenia were 2.05 (95% confidence interval [CI] 1.41-3.00, P<0.01) for 28-day mortality, 1.81 (95% CI 1.29-2.54, P<0.01) for 1-year mortality and 1.82 (95% CI 1.30-2.55, P<0.01) for overall mortality. In addition, muscle density and international normalized ratio were associated with short- and long-term mortality. Sarcopenia is associated with both short- and long-term mortality in patients with ACLF. Therefore, regular monitoring for sarcopenia is important for these patients.

The burden of cirrhosis mortality by county, race, and ethnicity in the USA, 2000–19: a systematic analysis of health disparities

Cirrhosis is responsible for substantial health and economic burden in the USA. Reducing this burden requires better understanding of how rates of cirrhosis mortality vary by race and ethnicity and by geographical location. This study describes rates and trends in cirrhosis mortality for five racial and ethnic populations in 3110 US counties from 2000 to 2019. We estimated cirrhosis mortality rates by county, race and ethnicity, and year (2000-19) using previously validated small-area estimation methods, death registration data from the US National Vital Statistics System, and population data from the US National Center for Health Statistics. Five racial and ethnic populations were considered: American Indian or Alaska Native (AIAN), Asian or Pacific Islander (Asian), Black, Latino or Hispanic (Latino), and White. Cirrhosis mortality rate estimates were age-standardised using the age distribution from the 2010 US census as the standard. For each racial and ethnic population, estimates are presented for all counties with a mean annual population greater than 1000. From 2000 to 2019, national-level age-standardised cirrhosis mortality rates decreased in the Asian (23·8% [95% uncertainty interval 19·6-27·8], from 9·4 deaths per 100 000 population [8·9-9·9] to 7·1 per 100 000 [6·8-7·5]), Black (22·8% [20·6-24·8], from 19·8 per 100 000 [19·4-20·3] to 15·3 per 100 000 [15·0-15·6]), and Latino (15·3% [13·3-17·3], from 26·3 per 100 000 [25·6-27·0] to 22·3 per 100 000 [21·8-22·8]) populations and increased in the AIAN (39·3% [32·3-46·4], from 45·6 per 100 000 [40·6-50·6] to 63·5 per 100 000 [57·2-70·2] in 2000 and 2019, respectively) and White (25·8% [24·2-27·3], from 14·7 deaths per 100 000 [14·6-14·9] to 18·5 per 100 000 [18·4-18·7]) populations. In all years, cirrhosis mortality rates were lowest among the Asian population, highest among the AIAN population, and higher in males than females for each racial and ethnic population. The degree of heterogeneity in county-level cirrhosis mortality rates varied by racial and ethnic population, with the narrowest IQR in the Asian population (median 8·0 deaths per 100 000, IQR 6·4-10·4) and the widest in the AIAN population (55·1, 30·3-78·8). Cirrhosis mortality increased over the study period in almost all counties for the White (2957 [96·9%] of 3051 counties) and AIAN (421 [88·8%] of 474) populations, but in a smaller proportion of counties for the Asian, Black, and Latino populations. For all racial and ethnic populations, cirrhosis mortality rates increased in more counties between 2000 and 2015 than between 2015 and 2019. Cirrhosis mortality increased nationally and in many counties from 2000 to 2019. Although the magnitude of racial and ethnic disparities decreased in some places, disparities nonetheless persisted, and mortality remained high in many locations and communities. Our findings underscore the need to implement targeted and locally tailored programmes and policies to reduce the burden of cirrhosis at both the national and local level. US National Institutes of Health (Intramural Research Program, National Institute on Minority Health and Health Disparities; National Heart, Lung, and Blood Institute; Intramural Research Program, National Cancer Institute; National Institute on Aging; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Office of Disease Prevention; and Office of Behavioral and Social Sciences Research).

FRI-104 The respiratory assessment of cirrhotic patients: six-minute walk test is an independent predictor of mortality in cirrhosis

FRI-104 The respiratory assessment of cirrhotic patients: six-minute walk test is an independent predictor of mortality in cirrhosis

Circulating bacterial peptides and linked metabolomic signatures are indicative of early mortality in pediatric cirrhosis.

Patients with pediatric cirrhosis-sepsis (PC-S) attain early mortality. Plasma bacterial composition, the cognate metabolites, and their contribution to the deterioration of patients with PC-S to early mortality are unknown. We aimed to delineate the plasma metaproteome-metabolome landscape and identify molecular indicators capable of segregating patients with PC-S predisposed to early mortality in plasma, and we further validated the selected metabolite panel in paired 1-drop blood samples using untargeted metaproteomics-metabolomics by UHPLC-HRMS followed by validation using machine-learning algorithms. We enrolled 160 patients with liver diseases (cirrhosis-sepsis/nonsepsis [n=110] and noncirrhosis [n=50]) and performed untargeted metaproteomics-metabolomics on a training cohort of 110 patients (Cirrhosis-Sepsis/Nonsepsis, n=70 and noncirrhosis, n=40). The candidate predictors were validated on 2 test cohorts-T1 (plasma test cohort) and T2 (1-drop blood test cohort). Both T1 and T2 had 120 patients each, of which 70 were from the training cohort. Increased levels of tryptophan metabolites and Salmonella enterica and Escherichia coli-associated peptides segregated patients with cirrhosis. Increased levels of deoxyribose-1-phosphate, N5-citryl-d-ornithine, and Herbinix hemicellulolytic and Leifsonia xyli segregated patients with PC-S. MMCN-based integration analysis of WMCNA-WMpCNA identified key microbial-metabolic modules linked to PC-S nonsurvivors. Increased Indican, Staphylobillin, glucose-6-phosphate, 2-octenoylcarnitine, palmitic acid, and guanidoacetic acid along with L. xyli, Mycoplasma genitalium, and Hungateiclostridium thermocellum segregated PC-S nonsurvivors and superseded the liver disease severity indices with high accuracy, sensitivity, and specificity for mortality prediction using random forest machine-learning algorithm. Our study reveals a novel metabolite signature panel capable of segregating patients with PC-S predisposed to early mortality using as low as 1-drop blood.

Association of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) With an Increased Risk of Congestive Heart Failure in Hospitalized Patients With Cirrhosis: A Propensity Score-Matched Analysis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to increased cardiovascular (CV) risks, notably congestive heart failure (CHF). We evaluated the influence of MASLD on CHF and mortality among hospitalized cirrhotic patients. We analyzed the National Inpatient Sample from 2016 to 2020, identifying adult cirrhosis patients. We focused on CHF and in-hospital mortality, plus hospital stay length, costs, and discharge status. Propensity score matching created balanced cohorts for comparison. Poisson and logistic regression provided adjusted CHF risks and mortality odds ratios (ORs) for MASLD patients. Before matching, 4.1% of 672,625 cirrhotic patients had MASLD. Post-matching, each group had 23,161 patients. Patients with MASLD showed higher CHF risk (OR 1.14, 95% CI 1.10-1.21, p<0.001) but lower in-hospital mortality (OR 0.57, 95% CI 0.52-0.63, p<0.01) and decreased costs (median $24,447 vs. $28,630, OR 0.86, 95% CI 0.85-0.87, p<0.001). In this nationwide study of patients with cirrhosis, MASLD was associated with a higher prevalence of CHF and lower in-patient mortality. These findings mirror the "adiposity paradox" phenomenon, where obese/overweight individuals with cardiometabolic dysfunction may experience less severe or beneficial health outcomes than those with a normal weight. Further investigation is warranted to decode the intricate interplay between MASLD, cirrhosis, CHF, and in-hospital mortality and its clinical practice implications.

Global burden of liver cirrhosis 1990–2019 and 20 years forecast: results from the global burden of disease study 2019

Background Cirrhosis is a disease that imposes a heavy burden worldwide, but its incidence varies widely by region. Therefore, we analysed data on the incidence and mortality of cirrhosis in 204 countries and territories from 1990–2019 and projected the disease development from 2019–2039. Methods Data on the incidence and mortality of liver cirrhosis from 1990 to 2019 were acquired from the public Global Burden of Disease (GBD) study. In addition, the average annual percentage change (AAPC) and estimated annual percentage change (EAPC) of the age-standardized rate (ASR) of cirrhosis in different regions were calculated. The estimates of risk factor exposure were summarized, and the proportion of causes and risk factors of liver cirrhosis and their relationship with the human development index (HDI) and socio–demographic index (SDI) were analysed. Trends in the incidence of cirrhosis in 2019–2039 were predicted using Nordpred and BAPC models. Results Globally, the ASR of cirrhosis incidence decreased by 0.05% per year from 25.7/100,000 in 1990 to 25.3/100,000 in 2019. The mortality risk associated with cirrhosis is notably lower in females than in males (13 per 100,000 vs 25 per 100,000). The leading cause of cirrhosis shifted from hepatitis B to C. Globally, alcohol use increased by 14%. In line, alcohol use contributed to 49.3% of disability-adjusted life years (DALYs) and 48.4% of global deaths from liver cirrhosis. Countries with a low ASR in 1990 experienced a faster increase in cirrhosis, whereas in 2019, the opposite was observed. In countries with high SDI, the ASR of cirrhosis is generally lower. Finally, projections indicate that the number and incidence of cirrhosis will persistently rise from 2019–2039. Conclusions Cirrhosis poses an increasing health burden. Given the changing etiology, there is an imperative to strengthen the prevention of hepatitis C and alcohol consumption, to achieve early reduce the incidence of cirrhosis.

Abstract PO3-18-01: Cirrhosis is associated with worse post-operative survival among patients with breast cancer: a population-based study

Abstract Background: The relationship between cirrhosis and breast cancer treatment and outcomes has not been specifically explored. We evaluated the association between cirrhosis and surgical outcomes in female patients with breast cancer. Methods: We performed a retrospective cohort study of female patients undergoing surgery for breast cancer between 2007-2018 using health administrative data from Ontario, Canada. Breast cancer surgeries were captured using Canadian Classification of Health Intervention codes. Patients with cirrhosis were identified using validated coding definitions. Overall and cancer-specific survival from time of surgery to December 2021 was compared between patients with and without cirrhosis using Kaplan-Meier survival analysis. Modified Poisson regression, chi-square and ANOVA were used to assess the association between cirrhosis and 90-day post-operative mortality, post-operative complications, length of hospital stay, intensive care unit (ICU) admission, and post-operative hepatic decompensation within 6 months. Results: A total of 83,880 females with breast cancer undergoing surgery were identified with 910 (1%) having cirrhosis. The median age at diagnosis was 65 (IQR 57-72) in patients with cirrhosis and 61 (IQR 51-71) in those without (p&amp;lt; 0.001). The most common etiology of cirrhosis was non-alcoholic fatty liver disease (n = 602, 66%) followed by alcohol-related (n =144, 16%) with n=27 (3%) having a history of decompensation within two years prior to surgery. Model for end stage liver disease score (MELD-Na) was available in 24% (n = 218), with a median score of 8 (IQR 6 – 11). Patients with cirrhosis had similar breast cancer stage at diagnosis as patients without cirrhosis (47% stage I, 38% stage 2, 11% stage 3, and 0.5% stage 4) with the most common type of surgical procedure being lumpectomy (71%) in both groups. Use of pre-operative chemotherapy was less common in patients with cirrhosis (5.9% vs 7.9%, p=0.026). Post-operative radiation and chemotherapy within 6-months after surgery was lower in patients with cirrhosis (56.8% vs 63.7%, p&amp;lt; 0.001 and 48.4% vs 52.2%, p=0.019, respectively). Patients with cirrhosis had higher 90-day post-operative mortality compared to those without (1.4% vs 0.3%, p &amp;lt; 0.001). After adjusting for age, income quintile, and breast cancer surgery, cirrhosis was independently associated with 90-day post-operative mortality (RR, 4.1; 95% CI 2.4-6.8). Patients with cirrhosis had a higher prevalence of incision complications (6.4% vs 4.6%, p= 0.007) and blood transfusions (2.9% vs 1.1%, p &amp;lt; 0.001), but similar rates of surgical site infections (6.4% vs 5.3%, p=0.138) and venous thromboembolism (0.3% vs 0.5%, p=0.5). Re-operation was slightly higher in patients without cirrhosis (3.2% vs 4.6%, p=0.05). Length of hospital stay was 2 days in patients with cirrhosis and 1.3 days for patients without (p &amp;lt; 0.001); ICU admission was more likely in patients with cirrhosis (1.8% vs 0.9%, p=0.008); and 18 (2%) patients with cirrhosis developed post-operative hepatic decompensation within 6 months. Survival in patients with cirrhosis was lower than those without (5-year OS 77% vs 87%, p&amp;lt; 0.0001); stage 0/I (83% vs 94%, p&amp;lt; 0.05), stage II (75% vs 87%, p&amp;lt; 0.05), stage III (62% vs 73%, p&amp;lt; 0.05), stage IV (40% vs 40%). Cancer-specific survival was also lower in patients with cirrhosis (5-year CSS 88% vs 91%, p=0.017). Conclusion: This large population-based study demonstrates that, compared to patients without cirrhosis, patients with cirrhosis are older with similar stage at diagnosis, but are somewhat less likely to receive adjuvant therapies. While they have slightly higher risks of certain post-operative complications and lower overall and cancer-specific survival, their outcomes remain favourable and should be considered for curative-intent therapies. Citation Format: Manisha Jogendran, Jennifer Flemming, Maya Djerboua, Shaila Merchant, Sean Bennett. Cirrhosis is associated with worse post-operative survival among patients with breast cancer: a population-based study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-18-01.

New Scanographic Index for the Detection of Frailty in Patients with Cirrhosis with a Prognostic Impact.

Frailty is linked to an increased incidence of hepatic decompensation and mortality in cirrhosis. The aim of our study was to identify a novel scanographic score that predicts frailty and its impact in cirrhosis. This study included 51 patients with cirrhosis. We used the frailty scale risk assessment score to identify frail patients. The density and area of different muscles at L3 level were analyzed on computed tomography (CT) sections. The L3 skeletal muscle area adjusted to height and density ratio (L3-SMDHR) was defined as L3 muscle wall*height/density. The L3-SMHDR is significantly higher in frail patients and in patients with Child B/C scores. Frailty was correlated with L3-SMHDR. Frailty and L3- SMHDR were correlated with liver-related events (LRE). We set the most appropriate cut-offs of L3-SMHDR for both sensitivity and specificity by using the ROC: 5.4 for males and 4.7 for females. The AUROC score was 0.784 for male and 0.975 for female patients. The Kappa score between frailty and L3-SMHDR was 0.752, with a percentage of agreement of 87.5%, showing a substantial agreement. This ratio with the divided categories has a sensitivity of 100%, a specificity of 76%, a positive predictive value of 79.3% and a negative predictive value of 100%. Patients with high L3-SMHDR have significantly lower survival time and a higher incidence of LRE. The L3-SMHDR is a new index for identifying frailty in cirrhosis by using measurable and reproducible variables. It can be used as a prognostic factor for frailty in patients with cirrhosis.

High prevalence of diabetes among young First Nations Peoples with metabolic dysfunction-associated steatotic liver disease: a population-based study in Australia

BackgroundLiver disease is an important contributor to the mortality gap between First Nations Peoples and non-Indigenous Australian adults. Despite a high burden of metabolic comorbidities among First Nations Peoples, data about the epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD) in this population is scarce.MethodsA retrospective analysis of all adults hospitalized with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) with/without cirrhosis during 2007–2019 in the state of Queensland was performed. Patients were followed from the first admission with MASLD/MASH (identified based on validated algorithms) to decompensated cirrhosis and overall mortality. We explored differences according to Indigenous status using Multivariable Cox regression.Findings439 First Nations Peoples and 7,547 non-Indigenous Australians were followed for a median of 4.6 years (interquartile range 2.7–7.2). Overall, women were overrepresented, but more so in the First Nations cohort (72.7% vs. 57.0%, p < 0.001). First Nations patients were younger, a higher proportion lived in remote and socioeconomic disadvantaged areas, and had higher comorbidity compared to non-Indigenous Australians (all p < 0.001). Diabetes, the most common comorbidity affecting both groups, was overrepresented in First Nations Peoples versus non-Indigenous Australians (43.5% vs. 30.8%, p < 0.001, respectively). Nineteen (4.3%) First Nations Peoples and 332 (4.4%) of non-Indigenous patients progressed to cirrhosis decompensation (9.0% [95%CI 4.5–17.7] vs. 7.7% [95%CI 6.6–8.9; p = 0.956] respectively within 10 years). In multivariable analysis, there was no association between Indigenous status and progression to decompensated cirrhosis (p = 0.759) and survival (p = 0.437).ConclusionsThis study provides the first population-based epidemiological data on MASLD in First Nations Australians. The high prevalence of diabetes (that is associated with advanced fibrosis and liver disease mortality) among young First Nations Peoples with MASLD raises concern about future risk of progressive liver disease in this patient population. These data highlight the importance of early identification of MASLD, and providing culturally appropriate intervention to reduce disease progression in parallel with the management of cardiometabolic comorbidities.

Epidemiology of NAFLD – Focus on diabetes

There is increasing appreciation of the complex interaction between nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D) and insulin resistance. Not only is the prevalence of NAFLD disease high among patients with T2D, the liver disease is also more progressive. Currently, the global prevalence of NAFLD in the general population (2016–2019) is 38 %. The prevalence of T2D among those with NAFLD is approximately 23 % while the prevalence of NAFLD among those with T2D can be as high as 70 %. The prevalence of nonalcoholic steatohepatitis (NASH) is approximately 7 % in the general population and 37 % among patients with T2D. Globally, the MENA and Latin America regions of the world appear to have the highest burden of both NAFLD and T2D. Compared to those with NAFLD but without T2D, those with NAFLD and T2D are at a much higher risk for disease progression to cirrhosis and for decompensated cirrhosis, hepatocellular carcinoma, and all-cause mortality. Given that highly effective new treatments are available for T2D, high risk NAFLD with T2D should be considered for these regimens. This requires implementation of risk stratification algorithms in the primary care and endocrinology practices to identify those patients at highest risk for adverse outcomes.

Study of prevalence, risk factors for acute kidney injury, and mortality in liver cirrhosis patients

IntroductionAcute kidney injury (AKI) occurs frequently in patients with end-stage liver disease and cirrhosis and is associated with increased short-term mortality. This study aims to study the prevalence and risk factors associated with AKI development and mortality in cirrhosis of liver patients.MethodologyIn the current prospective study, hospitalized patients with liver cirrhosis from October 2021 to March 2023 were recruited. Demographic, clinical, and laboratory data were collected, which included, the etiology of cirrhosis, comorbidities, severity of liver disease, and relevant biochemical parameters. The patient was followed up for 90 days to record the clinical outcome. The statistical software SPSS was utilized to conduct the analysis.ResultsOf 364 liver cirrhosis patients, 25.2% (n, 92) had AKI and belonged to an average age of 51.54 ± 11.82 years. The majority of individuals in the study were males (90.4%), and alcohol (63.4%) was the most common etiology of liver cirrhosis. The present study showed that higher level of direct bilirubin (p = 0.011) and MELD score (p = 0.0001) were identified as significant risk factors for AKI development in patients with liver cirrhosis. Regarding mortality, the significant risk factors were the presence of AKI (p = 0.045) and MELD score (p = 0.025). Among AKI patients, 90-day mortality rates were higher in patients with acute tubular necrosis (p value = 0.010) and stage 3 AKI (p value = 0.001).ConclusionAKI is common in cirrhosis of liver patients. Elevated levels of direct bilirubin and MELD score emerged as significant factors associated with AKI development. Furthermore, AKI and MELD scores were identified as independent risk factors for mortality at both 30 and 90 days. Survival rates were influenced by both the type and stage of AKI; AKI stage 3 and ATN patients had significantly higher mortality rate. Early AKI detection and management are crucial for reducing mortality risk in liver cirrhosis patients.

Changing global epidemiology of chronic hepatitis C virus-related outcomes from 2010 to 2019: cirrhosis is the growing burden of hepatitis C virus-related disease.

Chronic infection with hepatitis C virus (HCV) has a long-term impact on hepatic consequences. A comprehensive evaluation of the global burden of HCV-related health outcomes can help to develop a global HCV prevention and treatment program. We used the 2019 Global Burden of Disease (GBD) Study to comprehensively investigate burden and temporal trends in incidence, mortality and disability-adjusted life-years (DALYs) of HCV-related diseases, including liver cancer and cirrhosis and other liver diseases across 264 countries and territories from 2010 to 2019. Globally, there were 152 225 incident cases, 141 811 deaths and approximately 2.9 million DALYs because of HCV-related liver cancer, and 551 668 incident cases, 395 022 deaths and about 12.2 million DALYs because of HCV-related cirrhosis in 2019. Worldwide, during the 2010-2019 period, liver cancer incidence declined, however, there was a 62% increase in cirrhosis incidence. In 2019, the Eastern Mediterranean was the region with the highest rates of incidence and mortality of both liver cancer and cirrhosis. Africa was the region with the fastest-growing trend of incidence of cirrhosis in the 2010-2019 period [annual percentage change (APC) = 2.09, 95% confidence interval (CI): 1.93-2.25], followed by the Western Pacific region (APC = 1.17, 95% CI: 1.09-1.22). Americas were the only region observing increased trends in liver cancer and cirrhosis mortality (APC = 0.70 and 0.12, respectively). We identified three patterns of temporal trends of mortality rates of liver cancer and cirrhosis in countries that reported HCV treatment rates. Urgent measures are required for diagnosis, treatment and research on HCV-related cirrhosis at global, regional and country levels, particularly in Africa, the Western Pacific and the Eastern Mediterranean.

Surgical risk stratification in patients with cirrhosis.

Individuals with cirrhosis experience higher morbidity and mortality rates than the general population, irrespective of the type or scope of surgery. This increased risk is attributed to adverse effects of liver disease, encompassing coagulation dysfunction, altered metabolism of anesthesia and sedatives, immunologic dysfunction, hemorrhage related to varices, malnutrition and frailty, impaired wound healing, as well as diminished portal blood flow, overall hepatic circulation, and hepatic oxygen supply during surgical procedures. Therefore, a frequent clinical dilemma is whether surgical interventions should be pursued in patients with cirrhosis. Several risk scores are widely used to aid in the decision-making process, each with specific advantages and limitations. This review aims to discuss the preoperative risk factors in patients with cirrhosis, describe and compare surgical risk assessment models used in everyday practice, provide insights into the surgical risk according to the type of surgery and present recommendations for optimizing those with cirrhosis for surgical procedures. As the primary focus is on currently available risk models, the review describes the predictive value of each model, highlighting its specific advantages and limitations. Furthermore, for models that do not account for the type of surgical procedure to be performed, the review suggests incorporating both patient-related and surgery-related risks into the decision-making process. Finally, we provide an algorithm for the preoperative assessment of patients with cirrhosis before elective surgery as well as guidance perioperative management.