Predictors of Outcomes of COVID-19 in Patients With Chronic Liver Disease: US Multi-center Study.

BACKGROUND & AIMS: 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. Clinicaltrials.gov number NCT04439084.

Hepatology Consultants Often Disagree on Etiology of Abnormal Liver Biochemistries in COVID-19 but Agree on Management.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with elevated liver biochemistries in approximately half of hospitalized patients, with many possible etiologies. AIM: To assess agreement on the etiology of abnormal liver biochemistries and diagnostic recommendations in COVID-19. METHODS: Twenty hepatology consultations were reviewed by three senior hepatologists who provided a differential diagnosis and diagnostic recommendations. Kappa agreement on the primary etiology was calculated. RESULTS: Kappa agreement between hepatologists on the primary etiology of elevated liver biochemistries was 0.10 (p = 0.03). Agreement was greater around drug-induced liver injury 0.51 (p < 0.0001) and SARS-CoV-2-related liver injury 0.17 (p = 0.03). Serial liver biochemistries were recommended in all consultations over other evaluations. CONCLUSION: In COVID-19, elevated liver biochemistries present a diagnostic challenge and can often be monitored conservatively.

Impact of chronic liver disease on outcomes of hospitalized patients with COVID-19: A multicentre United States experience.

Liver injury has been described with COVID-19, and early reports suggested 2%-11% of patients had chronic liver disease (CLD). In this multicentre retrospective study, we evaluated hospitalized adults with laboratory-confirmed COVID-19 and the impact of CLD on relevant clinical outcomes. Of 363 patients included, 19% had CLD, including 15.2% with NAFLD. Patients with CLD had longer length of stay. After controlling for age, gender, obesity, cardiac diseases, hypertension, hyperlipidaemia, diabetes and pulmonary disorders, CLD and NAFLD were independently associated with ICU admission ([aOR 1.77, 95% CI 1.03-3.04] and [aOR 2.30, 95% CI 1.27-4.17]) and mechanical ventilation ([aOR 2.08, 95% CI 1.20-3.60] and [aOR 2.15, 95% CI 1.18-3.91]). Presence of cirrhosis was an independent predictor of mortality (aOR 12.5, 95% CI 2.16-72.5). Overall, nearly one-fifth of hospitalized COVID-19 patients had CLD, which was associated with more critical illness. Future studies are needed to identify interventions to improve clinical outcomes.

Role of surface antibody in hepatitis B reactivation in patients with resolved infection and hematologic malignancy: A meta-analysis.

Patients with resolved hepatitis B virus (HBV) infection who are treated for hematological malignancies remain at risk for HBV reactivation. Because of conflicting studies about whether the antibody to hepatitis B surface antigen (anti-HBs) protects against reactivation in patients with resolved infection (hepatitis B surface antigen negative) receiving chemotherapy for hematological malignancies, we conducted a meta-analysis to determine if anti-HBs reduces HBV reactivation risk. We sought English-language studies through March 1, 2016, in Medline and other sources that examined reactivation in patients with resolved HBV infection receiving chemotherapy for hematologic malignancies. The absolute risks and odds ratio (OR) of reactivation with versus without anti-HBs were estimated in random-effects model meta-analyses. In 20 studies involving 1,672 patients not receiving antiviral prophylaxis, the reactivation risk was 14% (95% confidence interval [CI] 9.4%-19%) in 388 patients who had antibodies to hepatitis B core antigen only versus 5.0% (95% CI 3.0%-7.0%) in 1,284 patients who also had anti-HBs. Anti-HBs reduced reactivation risk with a pooled OR of 0.21 (95% CI 0.14-0.32) versus patients with antibody to hepatitis B core antigen only. Similar results were found when limiting the analysis to rituximab chemotherapy (OR = 0.19, 95% CI 0.11-0.32) and lymphoma (OR = 0.18, 95% CI 0.11-0.28). CONCLUSION: In patients with resolved HBV receiving chemotherapy for hematological malignancies without antiviral prophylaxis, anti-HBs positivity is associated with a decreased risk of reactivation; HBV screening in this patient population should include the routine use of anti-HBs, and those who are anti-HBs-negative should receive antiviral prophylaxis. Future studies should examine the effect of anti-HBs serum titers, the potential role for booster vaccinations, and antiviral prophylaxis prior to chemotherapy in this patient population. (Hepatology 2017;66:379-388).

Hepatitis B Virus Reactivation and Prophylaxis During Solid Tumor Chemotherapy: A Systematic Review and Meta-analysis.

BACKGROUND: Solid tumor chemotherapy regimens pose a risk for hepatitis B virus (HBV) reactivation, but screening and antiviral prophylaxis remains controversial because of insufficient evidence. PURPOSE: To determine the risk for HBV reactivation with and without antiviral prophylaxis and the effectiveness of prophylaxis in adults with solid tumors and chronic or resolved HBV infection. DATA SOURCES: MEDLINE through 1 July 2015 and Web of Science, Cochrane Central Register of Controlled Trials, TOXNET, and Scopus through 1 March 2015. STUDY SELECTION: 26 English-language observational studies and randomized, controlled trials in patients with chronic or resolved HBV receiving chemotherapy for solid tumors. DATA EXTRACTION: Study characteristics, quality, and risk of bias were assessed by 1 researcher and verified by another independent researcher. DATA SYNTHESIS: Random-effects model meta-analyses were used to estimate the risk and odds ratio (OR) of reactivation with versus without antiviral prophylaxis. Reactivation in chronic HBV without prophylaxis ranged from 4% to 68% (median, 25%) with substantial heterogeneity. Prophylaxis reduced the risk for HBV reactivation (OR, 0.12 [95% CI, 0.06 to 0.22]), HBV-related hepatitis (OR, 0.18 [CI, 0.10 to 0.32]), and chemotherapy interruption (OR, 0.10 [CI, 0.04 to 0.27]). In 3 studies of patients with resolved HBV infection, none received HBV prophylaxis and reactivation risk ranged from 0.3% to 9.0%. LIMITATIONS: Significant heterogeneity in underlying study populations and treatment regimens, incomplete baseline data, possibility of publication bias, and limited study quality. Most studies were observational and from Asia. CONCLUSION: In patients with chronic HBV receiving solid tumor chemotherapy, the risk for HBV reactivation is similar to the risk with other types of immunosuppressive therapy. Results support HBV screening and antiviral prophylaxis before initiation of chemotherapy for solid tumors. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences and National Institutes of Health.

Gastroenterologists Have Suboptimal Hepatitis B Virus Screening Rates in Patients Receiving Immunosuppressive Therapy.

BACKGROUND AND AIMS: Hepatitis B reactivation in patients undergoing immunosuppressive therapy can lead to liver failure and death. Prior studies have shown suboptimal hepatitis B screening rates, but few have compared screening rates across specialties or factors associated with screening. METHODS: A retrospective study was performed using a hospital-based chemotherapy database and outpatient pharmacy records from January 1999 to December 2013. HBV screening rates prior to initiation of immunosuppression were determined. Multivariate analysis was used to determine predictors of HBV screening. RESULTS: Of the 4008 study patients, 47 % were screened prior to receiving immunosuppressive therapy; only 48 % on rituximab and 45 % of those on anti-TNF therapy were screened. Transplant specialists screened most frequently (85 %) while gastroenterologists screened the least (34 %). Factors significantly associated with HBV screening were younger age, Asian race, use of anti-rejection therapy, and treatment by a transplant specialist (p < 0.001). CONCLUSION: HBV screening prior to immunosuppressive therapy is suboptimal, especially among gastroenterologists. Efforts to improve screening rates in at risk populations are needed.

The Role of Life Style Modifications in Comprehensive Non-Alcoholic Fatty Liver Disease Treatment.

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Risk of non-melanoma skin cancer in autoimmune hepatitis.

BACKGROUND: Most patients with autoimmune hepatitis (AIH) require long-term immunosuppressive therapy (IS). While it is well established that solid organ transplant recipients have a high risk of developing non-melanoma skin cancer (NMSC) as a result of immunosuppression, little is known about the risk of NMSC associated with IS in patients with AIH. OBJECTIVES: The aim of this study is to determine the incidence and risk factors for NMSC in patients on IS for AIH. METHODS: We reviewed the medical records of all patients with AIH seen at a tertiary care medical center between 1998 and 2008. We compared the incidence of NMSC to an age- and sex-matched control population and analyzed risk factors for NMSC. RESULTS: A total of forty-five patients with AIH were identified. Twenty NMSC lesions were found in eight patients. Compared to the age and sex-matched general population, the risk of SCC and BCC were increased as quantified by elevated standardized incidence ratios (28.5 and 5.0, respectively). Patients who developed NMSC were on average 24 years older (78.4 vs. 54.2 years old, p < 0.0001) and had AIH diagnosed at a more advanced age (66.0 vs. 45.4 years old, p = 0.0003). CONCLUSION: The risk of NMSC is significantly increased in patients with AIH on immunosuppression. Independent risk factors include current age and age at diagnosis of AIH.

Neopterin as a marker of response to antiviral therapy in hepatitis C virus patients.

Predicting the efficacy of antiviral treatment of hepatitis C virus (HCV) is of importance for both patient well-being and health care expense. The expression of interferon-stimulated genes (IFN-SGs) in the liver was suggested as a marker of response to anti-viral therapy. IFN-SGs encode the guanosine triphosphate cyclohydrolase 1 (GTPCH), a rate-limiting enzyme of pteridines biosynthesis. Neopterin, a stable byproduct of GTPCH-catalyzed reaction, is used as a marker of interferon-induced GTPCH activation. We hypothesized that assessment of neopterin concentrations might predict the response to antiviral therapy. Neopterin concentrations were evaluated in 260 HCV patients treated by pegylated interferon combined with ribavirin. Mean and median pretreatment neopterin concentrations were lower in patients with sustained virological response than in nonresponders. The rate of response was twofold higher among patients with pretreatment neopterin levels <16 nmol/L than in patients with neopterin levels ≥16 nmol/L, even after controlling for HCV genotype status. Our study suggests that the pretreatment level of neopterin might be used in routine clinical practice as rapid and cost-effective marker to predict the response to antiviral therapy in HCV patients.