Background Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19). Methods We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD. Results Of the 978 patients in our cohort, 867 patients (mean age 56.9±14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29-4.55), decompensated cirrhosis (HR 2.91 [1.70-5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53-7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47-3.70]) and decompensated cirrhosis (OR 2.50 [1.20-5.21]) were independently associated with risk for severe COVID-19. Conclusions The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19.
World Health Organization and US Fulbright Program.
Tests to detect the presence and activity of hepatitis B virus (HBV) are the cornerstones of diagnosis and management. Assays that detect or measure serum levels of HB surface antigen, HB surface antibody, and HB core antibody are used to identify patients with exposure to HBV, whereas other tests provide information on the level of virus replication, the presence of specific variants, and presence of virus reservoirs. Newer diagnostic tests, used only in research settings so far, aim to quantify levels of intrahepatic HBV replication. Other tests have been developed to detect HBV infection in resource-limited settings. We review point of care tests (essential in global screening efforts), standard diagnostic tests used in routine clinical management, and newer tests that might be used in clinical trials of agents designed to cure HBV infection.
Background-Spontaneous loss of hepatitis B surface antigen (HBsAg), or functional cure, in patients with chronic hepatitis B (CHB) significantly reduces liver-related complications. Differential rates have been suggested by individual studies performed in non-endemic and endemic regions, potentially related to likelihood of spontaneous clearance if CHB was acquired as an adult versus child. We systematically determined a pooled annual rate of HBsAg loss in untreated CHB-infected adults and examined impact of regional endemicity. Methods-Pubmed/EMBASE were searched for observational cohort studies and non-treatment arms of randomized controlled trials (RCTs) reporting proportion of patients with CHB achieving spontaneous HBsAg loss. RCTs were excluded from meta-analyses due to substantial cohort differences. Results were stratified on whether the underlying cohort primarily arose from an endemic, defined as CHB prevalence >2%, or non-endemic region. We explored sources of heterogeneity through univariate meta-regression. Results-Of 4771 screened, 66 studies (11 RCTs, 38 prospective and 17 retrospective cohort studies) met inclusion criteria and 55 were included in meta-analyses with exclusion of RCTs. Spontaneous HBsAg loss occurred in 3489 (7.6%) of 45,975 patients with 341,862 person-years of follow-up. The pooled annual incidence rate of HBsAg loss was 1.13% (0.92-1.36%, I 2 =96%). Rates did not differ by endemicity: 1.13% (0.85-1.45%) in endemic vs 1.29% (0.99-1.62%) in non-endemic cohorts. Meta-regression showed proportion of cohort HBeAg-negative and cohort age were primary contributors to substantial heterogeneity. Conclusion-Globally, spontaneous HBsAg loss occurs infrequently (~1% per year) in treatment-naïve adults with CHB infection. The low and homogeneous rate of HBsAg loss
Special populations infected with chronic HBV include those with decompensated cirrhosis, coinfections (HIV, HCV, HDV), hemodialysis and renal failure, immunosuppressed including transplant patients, children and women in pregnancy. These populations differ in their natural history and risk for liver-related complications, the indications for anti-HBV therapy as well as the recommendations regarding the HBV drugs used, duration of therapy and anticipated endpoints. Reflecting the special populations with substantive changes in management in recent years, this review focuses on HBV-HIV coinfected patients, immunosuppressed patients at risk for reactivation, liver transplant recipients and pregnant women. Management of women in the context of pregnancy and post-partum requires consideration of risks to mother and fetus/infant, including the risk of mother-to-child transmission. HBV-HIV coinfected patients require initiation of treatment concurrent with their HIV therapy and the HBV drugs used must by selected to minimize HIV and HBV resistance long-term. Increasing recognition of the risk for HBV reactivation with immunosuppressive therapy has led to recommendations to use prophylactic HBV therapy in patients with moderate to high risk of reactivation. Liver transplant recipients with HBV require life-long therapy to prevent or treat HBV infection but with current therapies, graft and patient survival are excellent.
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