Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America.

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

Global disparities in mortality and liver transplantation in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium.

BACKGROUND: Cirrhosis, the end result of liver injury, has high mortality globally. The effect of country-level income on mortality from cirrhosis is unclear. We aimed to assess predictors of death in inpatients with cirrhosis using a global consortium focusing on cirrhosis-related and access-related variables. METHODS: In this prospective observational cohort study, the CLEARED Consortium followed up inpatients with cirrhosis at 90 tertiary care hospitals in 25 countries across six continents. Consecutive patients older than 18 years who were admitted non-electively, without COVID-19 or advanced hepatocellular carcinoma, were enrolled. We ensured equitable participation by limiting enrolment to a maximum of 50 patients per site. Data were collected from patients and their medical records, and included demographic characteristics; country; disease severity (MELD-Na score); cirrhosis cause; medications used; reasons for admission; transplantation listing; cirrhosis-related history in the past 6 months; and clinical course and management while hospitalised and for 30 days post discharge. Primary outcomes were death and receipt of liver transplant during index hospitalisation or within 30 days post discharge. Sites were surveyed regarding availability of and access to diagnostic and treatment services. Outcomes were compared by country income level of participating sites, defined according to World Bank income classifications (high-income countries [HICs], upper-middle-income countries [UMICs], and low-income or lower-middle-income countries [LICs or LMICs]). Multivariable models controlling for demographic variables, disease cause, and disease severity were used to analyse the odds of each outcome associated with variables of interest. FINDINGS: Patients were recruited between Nov 5, 2021, and Aug 31, 2022. Complete inpatient data were obtained for 3884 patients (mean age 55·9 years [SD 13·3]; 2493 (64·2%) men and 1391 (35·8%) women; 1413 [36·4%] from HICs, 1757 [45·2%] from UMICs, and 714 [18·4%] from LICs or LMICs), with 410 lost to follow-up within 30 days after hospital discharge. The number of patients who died while hospitalised was 110 (7·8%) of 1413 in HICs, 182 (10·4%) of 1757 in UMICs, and 158 (22·1%) of 714 in LICs and LMICs (p<0·0001), and within 30 days post discharge these values were 179 (14·4%) of 1244 in HICs, 267 (17·2%) of 1556 in UMICs, and 204 (30·3%) of 674 in LICs and LMICs (p<0·0001). Compared with patients from HICs, increased risk of death during hospitalisation was found for patients from UMICs (adjusted odds ratio [aOR] 2·14 [95% CI 1·61-2·84]) and from LICs or LMICs (2·54 [1·82-3·54]), in addition to increased risk of death within 30 days post discharge (1·95 [1·44-2·65] in UMICs and 1·84 [1·24-2·72] in LICs or LMICs). Receipt of a liver transplant was recorded in 59 (4·2%) of 1413 patients from HICs, 28 (1·6%) of 1757 from UMICs (aOR 0·41 [95% CI 0·24-0·69] vs HICs), and 14 (2·0%) of 714 from LICs and LMICs (0·21 [0·10-0·41] vs HICs) during index hospitalisation (p<0·0001), and in 105 (9·2%) of 1137 patients from HICs, 55 (4·0%) of 1372 from UMICs (0·58 [0·39-0·85] vs HICs), and 16 (3·1%) of 509 from LICs or LMICs (0·21 [0·11-0·40] vs HICs) by 30 days post discharge (p<0·0001). Site survey results showed that access to important medications (rifaximin, albumin, and terlipressin) and interventions (emergency endoscopy, liver transplantation, intensive care, and palliative care) varied geographically. INTERPRETATION: Inpatients with cirrhosis in LICs, LMICs, or UMICs have significantly higher mortality than inpatients in HICs independent of medical risk factors, and this might be due to disparities in access to essential diagnostic and treatment services. These results should encourage researchers and policy makers to consider access to services and medications when evaluating cirrhosis-related outcomes. FUNDING: National Institutes of Health and US Department of Veterans Affairs.

Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study.

BACKGROUND & AIMS: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. METHODS: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered. RESULTS: Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84-11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24-12.74], 11.76% [95% CI 4.73-22.30], 20.69% [95% CI 11.35-31.96] and 34.52% [95% CI 17.03-52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49-4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29-7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection. CONCLUSIONS: This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period.

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

BACKGROUND: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). PATIENTS AND METHODS: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. RESULTS: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. CONCLUSION: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.

WGO Guidance for the Care of Patients With COVID-19 and Liver Disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the least deadly but most infectious coronavirus strain transmitted from wild animals. It may affect many organ systems. Aim of the current guideline is to delineate the effects of SARS-CoV-2 on the liver. Asymptomatic aminotransferase elevations are common in coronavirus disease 2019 (COVID-19) disease. Its pathogenesis may be multifactorial. It may involve primary liver injury and indirect effects such as "bystander hepatitis," myositis, toxic liver injury, hypoxia, and preexisting liver disease. Higher aminotransferase elevations, lower albumin, and platelets have been reported in severe compared with mild COVID-19. Despite the dominance of respiratory disease, acute on chronic liver disease/acute hepatic decompensation have been reported in patients with COVID-19 and preexisting liver disease, in particular cirrhosis. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a higher risk of respiratory disease progression than those without MAFLD. Alcohol-associated liver disease may be severely affected by COVID-19-such patients frequently have comorbidities including metabolic syndrome and smoking-induced chronic lung disease. World Gastroenterology Organization (WGO) recommends that interventional procedures such as endoscopy and endoscopic retrograde cholangiopancreatography should be performed in emergency cases or when they are considered strictly necessary such as high risk varices or cholangitis. Hepatocellular cancer surveillance may be postponed by 2 to 3 months. A short delay in treatment initiation and non-surgical approaches should be considered. Liver transplantation should be restricted to patients with high MELD scores, acute liver failure and hepatocellular cancer within Milan criteria. Donors and recipients should be tested for SARS-CoV-2 and if found positive donors should be excluded and liver transplantation postponed until recovery from infection.