Gastrointestinal symptoms and disorders related to COVID-19. Lessons learned from gastroenterologists

COVID-19 is mainly a respiratory illness caused by the SARS-CoV-2 but can also lead to GI symptoms. The primary host receptor which mediates the mechanism as SARS-CoV-2 enters the cell is the ACE2 receptor. Therefore, GI symptoms can be common in COVID-19, and in some cases, they are the first manifestation even before fever and respiratory symptoms. In addition, the liver function tests alteration often is related to a worse prognosis. The exact incidence of GI symptoms is a matter of debate. Moreover, wide variation concerning GI symptoms frequency exists, but the predominant ones seem to be diarrhea, anorexia, nausea, vomiting, and abdominal pain or discomfort.This review summarizes the most relevant findings of COVID-19 on the digestive system, including the liver, biliary tract, pancreas, the most common GI symptoms, and the atypical clinical GI manifestations.Copyright © 2022 Sociedad Medica del Hospital General de Mexico. Published by Permanyer.

Hepatitis C Virus Micro-Elimination Program in an Open Population

Introduction and Objectives: Among the WHO, goals for 2030 are to detect >90% of people with HCV and link >80% to treatment. Our institution serves an open population without social security. This study aimed to describe the detection strategy that was carried out in the open population, using two-step HCV detection tests at "Hospital General de Mexico" from January to December 2021. Material(s) and Method(s): The study was conducted in an open population that transits for our hospital for any reason and agreed to take the risk factor questionnaire and the rapid test for the detection of anti-HCV antibodies (RT);those who were reactive underwent viral load (PCR to detect HCV-RNA). Descriptive statistics and the statistical package STATA v.14 were used. Result(s): In 2021, 33,523 subjects were screened;71.5% were women, mean age of 47+/-10 years. Reported at least one risk factor for HCV 53.5%. The most frequent risk factors were: Multiple sexual partners (MSP)/sexually transmitted diseases (STDs) 36.2%, tattoos/piercings 26.7%, surgery before 1995 20.2%, transfusion before 1994 5.4%, health workers after accidental puncture 4.2%. Of the 33,523, 0.7% were reactive in the RT;of them, the PCR was positive in 57.9% (prevalence of viremia= 0.4%). Among the viremic, the risk factors identified were: blood transfusion before 1995 37%, MSP/STDs 35%, surgery before 1995 30%, tattoos/piercings 30%, and drugs 3.5%. Of all viremic, 134 (100%) were linked to attention at the Mexican health sector;114 (85.1%) without insurance treated at our hospital;89 (78%) received DAAs at our institution in 2021 and have completed the time to assess SVR12, per protocol the SVR12 rate was 97.7% (2 failures), by intention to treat SVR12 was 93.2% (2 failures, 1 missing, three deaths from COVID-19). The remaining 25 patients detected in 2021 (22%) and without eligibility continued the protocol for treatment with DAAs during the year 2022. Conclusion(s): The prevalence of HCV was similar to that previously reported. Traditional risk factors such as transfusion or surgery are still very prevalent. Timely diagnosis of HCV allows treatment to be linked to an optimal level of SVR12 in accordance with the WHO goals.Copyright © 2023

Low Serum Albumin at Admission Is Associated with Mortality among Inpatients with Cirrhosis: A Multi-National Experience

Background: MELD and Child-Pugh scores have traditionally been used as prognostic indicators in patients with cirrhosis. Albumin infusions in outpatients have been associated with improved outcomes, but not in transplant waitlisted patients or inpatients. This aim of this study was to assess whether low serum albumin (sAlb) on admission alone is a poor prognostic indicator among cirrhotic inpatients from a new multi-national cohort. Method(s): The CLEARED study is a global study that enrolled consecutive non-electively admitted inpatients without organ transplant or COVID-19 from 6 continents. Admission demographics, medical history, laboratory data, inpatient course, death/hospice transfer and mortality at 30 days post-discharge were recorded. Patients were divided into 3 groups: sAlb <28gm/L(A), sAlb >=28 but <35gm/L (B), and sAlb>=35gm/L (C) were compared. Multi-variable logistic regression was performed using inpatient mortality and overall 30-day mortality as outcomes. Result(s): 2429 patients were enrolled from 21 countries worldwide. The distribution was A:49%, B:39%, C:12%. Gp A patients were significantly younger (54yrs vs. 57yrs vs 58yrs p<0.0001) but with similar gender distribution, and higher MELD-Na score of 25 vs. 20 vs. 17 (p<0.0001). Gp A patients were more likely to have alcohol as etiology of cirrhosis (49% vs. 45% vs 38%, p=0.004), and were more likely to have either infection (27% vs. 18% vs. 13%, p<0.0001), HE (39% vs. 33% vs. 23%, p=0.005) or fluid related issues as a reason for admission (p<0.0001). More patients in Gp A received albumin infusion during their hospital stay (120gm vs. 100gm vs. 100gm p=0.0004), mostly for the indications of AKI (47% vs. 49% vs. 47%, p=0.79) and performance of large volume paracentesis (44% vs. 42% vs. 41%, p=0.80), followed by bacterial peritonitis indication (22% vs. 17% vs. 11%, p=0.01). Group A patients had longer hospital stays (9 days vs. 8 days vs. 7 days (p<0.001), but similar ICU transfer (23% vs. 22% vs. 20%, p=0.55). group A patients were more likely to die while inpatients (19% vs. 11% vs. 5%, p<0.0001), or by 30 days post-discharge (29% vs. 20% vs. 9%, p<0.0001). Table shows the admission variables associated with a poor outcome. Conclusion(s): Hypoalbuminemia is extremely common among admitted cirrhotic patients, with sAlb of <28gm/L occurring in almost half. Together with MELD-Na score and infection at admission, a low sAlb is associated with a poor outcome in these patients. Future studies will need to validate these findings and to assess whether albumin infusions will improve the outcome of these patients. (Figure Presented).

Differences in Mortality Rates in Inpatients with Cirrhosis Depends on the Low, Middle or High Income Country Location: Multi-National Cleared Consortium Experience

Background: Although cirrhosis is a major cause of mortality worldwide, there could be disparities in outcomes. This needs a global consortium to study disparities in inpatient cirrhosis care Aim: Define the impact of location in prediction of outcomes in inpts with cirrhosis. Method(s): CLEARED prospectively enrolled non-electively admitted cirrhosis pts without COVID from all continents. To ensure equity, we allowed only 50 pts/site. Admission details, cirrhosis history, inpatient & 30-day course were recorded. World bank classification of low/low middle income (LMI), upper middle (UMI) & High income (HI) were used. Cirrhosis details, inpatient & 30-day outcomes were compared between groups. Multi-variable regression was performed using inpatient & 30-day mortality as outcomes. Result(s): 2758 pts from 21 countries from all continents, including Africa & Australia, were included.727 were L/LMI, 1050 UMI & 981 pts were from HICs. More men & younger pts were in LMI. Cirrhosis details: More pts in HI gp had 6M hospitalizations & infections, HE & ascites while prior variceal bleeding was higher in LMI . Prior HCC & transplant listings were lower in LMI but similar in UMI/HI. Alcohol & NASH was highest in HI. Viral hepatitis & cryptogenic were highest in UMI.Admissions: Admission MELD was highest in LMI. LMI pts were admitted more for GI Bleed, HE, & DILI, while anasarca & HBV flares were higher in UMI. Higher SBP (36% vs 24% vs 21% p<0.0001) & lowest skin/soft-tissue infections were in LMI (5% vs 5% vs 10% p=0.008);rest were similar. Nosocomial infections, driven by UTI were highest in LMI & HI pts (15% vs 14% vs 11% UMI, p=0.03). Admission diuretics, PPIs, Lactulose & statins were highest & antivirals lower in HI. SBP prophylaxis & rifaximin were highest in LMI pts. Outcome(s): More LMI pts needed ICU & had more organ failures (Fig B). Discharge MELD was highest in LMI. In-hospital mortality was highest & transplant lowest in LMI. This extended to 30-day mortality & transplant in LMI patients vs HI pts.Regression: In-hospital mortality was linked with age, infections, MELD & being in a LMI/UMI vs HIC while being on a transplant list, diabetes, & SBP prophylaxis were protective (Fig C). 30-day mortality predicted by age, ascites, HCC, discharge MELD, organ failures, LMI/UMI vs HIC but rifaximin was protective(Fig D). In-hospital transplant was higher with high MELD, admission rifaximin & listed pts &lower in LMI (OR 0.26) & UMI (OR 0.22) & age. 30-day transplant was higher in those with hyponatremia, ascites & HRS, on the list & on rifaximin and lower in LMI (OR 0.24) & UMI (OR 0.59) vs HI. Conclusion(s): In a global study of inpatients with cirrhosis, there were major differences in outcomes. Not being in a high-income country significantly increased the risk of inpatient and 30-day mortality independent of demographics, medications, in-hospital course, and cirrhosis severity likely due to disparities in access to transplant, which should be accounted for in global models. (Figure Presented).

Autoimmune hepatitis (HAI) is likely induced by Epstein Barr Virus (EBV) infection

Introduction and Objectives HAI is an immune-mediated chronic inflammatory liver condition of uncertain etiology. There are genetic factors and triggering agents such as toxicity, infections, and medications, among others. Case summary An 18-year-old woman with nausea, vomiting, abdominal pain and jaundice, positivity for Hepatitis A IgM (IGM-HAV). PCR SARS COV 2 negative, creatinine 0.56, FA 297, GGT 463, DHL 756, INR 1.4 BT 5.32, BI 2.87, BD 2.45, ALB 3.57, AST 136, ALT 135, Hb 8.9, Neutrophils 500. Hematology concludes with hemophagocytic syndrome (SH). HCV AND HBV negative, IGG 1560, ANTI DNA 108, ANA 1:80, IGM-HAV reactive, EBV 29.9125 copies/ml. Cyclosporine is administered by SH. 10 months after she is assessed in the liver clinic for the persistence of transaminasemia. By ultrasound hepatosplenomegaly, without dilation of the bile duct. Liver biopsy reported inflammatory infiltrate of periportal predominance with interface activity, macrovesicular steatosis, without fibrosis, without hemophagocytosis, with biochemical and histological data compatible with HAI with a simplified score of 7 points. (Fig. 1). Discussion HAI is associated with positive autoantibodies, hypergammaglobulinemia and necro inflammatory features in histology. HAV and EBV can induce HAI, as it induces autologous antibodies against triose phosphate isomerase. The patient has complicated EBV infection with SH and persistence of IGM-HAV for 11 months. Liver biopsy with autoimmune hepatitis data, probably as a result of EBV infection and false positive for IgM-HAV for EBV coinfection. Conclusion A woman with EBV, probable false-positive HAV and EBV-induced HAI is reported. Funding The resources used in this study were from the hospital without any additional financing Declaration of interest The authors declare no potential conflicts of interest.

CLEARED Global consortium results highlight regional variation and need for equity in inpatient outcomes in hospitalized patients with Chronic Liver Disease

Background and aims: A global study with equitable participation for cirrhosis and chronic liver disease (CLD) outcomes is needed. We initiated the Chronic Liver disease Evolution And Registry for Events and Decompensation (CLEARED) study to provide this global perspective. Aim to evaluate determinants of inpatient mortality and organ dysfunction in a multi-center worldwide study. Method: We prospectively enrolled pts with CLD/Cirrhosis >18 years without organ transplant or COVID-19 who were admitted non-electively. To maintain equity in outcome analysis, a maximum of 50 pts/site were allowed. Data for admission variables, hospital course, and inpatient outcomes (ICU, death, organ dysfunction [ODF]) were recorded. This was analyzed for death and ODs using significant variables on admission and including World Bank classification of low/middle-income countries (LMIC). A model for in-hospital mortality for all variables during the hospital course, including ODs) was analyzed. Results: 1383 pts (55 ± 13 yrs, 64% men, 39% White, 30% Asian, 10% Hispanic, 9% Black, 12% other) were enrolled from 49 centers (Fig A). 39% were from high-income while the rest were from LMICs. Admission MELDNa 23 (6–40) with history in past 6 months of hospitalizations 51%, infections 25%, HE 32%, AKI 23%, prior LVP 15%, hydrothorax 8% and HCC 4%. Leading etiologies were Alcohol 46% then NASH 23%, HCV 11% and HBV 13%. Most were on lactulose 52%, diuretics 53%, PPI 49% and statins 11%, SBP prophylaxis 16%, beta-blockers 35% and rifaximin 31%. 90% were admitted for liver-related reasons;GI bleed 30%, HE 34%, AKI 33%, electrolyte issues 30%, anasarca 24% and 25% admission infections. In-hospital course: Median LOS was 7 (1–140) days with 25% needing ICU. 15% died in hospital, 3% were transplanted, 46% developed AKI,15% grade 3–4 HE, 14% shock, 13% nosocomial infections and 13% needed ventilation. Logistic Regression: Fig B shows that liver-related/unrelated factors on admission which predicted in-hospital mortality and development of organ dysfunction with MELDNa and Infections being common among all models. Nosocomial infections and organ dysfunctions predicted mortality when all variables were considered. High-income countries had better mortality outcomes likely due to transplant and ICU availability. AUCs were >0.75 (Figure Presented) Conclusion: In this worldwide equitable experience, admission cirrhosis severity and infections are associated with inpatient outcomes, which are greater in low-income settings. Liver-related and unrelated factors and regional variations are important in defining critical care goals and outcome models in inpatients with cirrhosis.

ASPARTATE AMINOTRANSFERASE, AGE AND D-DIMER IN COVID-19 PATIENTS: A USEFUL PROGNOSTIC MODEL

Introduction: Some patients with SARSCov-2 infection develop severe disease (SARS);however, the factors associated with severity are not yet fully understood. Some reports indicate that liver injury may be a poor prognostic factor. Aim: To identify the biochemical factors related to the development of SARS with mechanical ventilation (MV) requirement in patients with SARSCov-2 and COVID-19. Methods Type of study: Observational. Cohort study. Procedure: Data from COVID-19 patients were collected at admission time to a tertiary care center. Differential factors were identified between seriously ill SARS+MV patients versus stable patients without MV. Transformation to the natural logarithm of significant variables was performed and multiple linear regression was applied, then a predictive model of severity called AAD (Age-AST-D dimer) was constructed. Results: 166 patients were included, 114(68.7%) men, mean age 50.6±13.3 years-old, 27(16.3%) developed SARS+MV. In the comparative analysis between those with SARS+MV versus stable patients without MV we found significant raises of ALT (225.4±341.2 vs. 41.3±41.1;P=0.003), AST 325.3±382.4 vs. 52.8±47.1;P=0.001), LDH (764.6±401.9 vs. 461.0±185.6;P=0.001), D dimer (7765±9109 vs. 1871±4146;P=0.003), age (58.6±12.7 vs. 49.1±12.8;P=0-001). The results of the regression are shown in the Table, where model 3 was the one that best explained the development of SARS+MV;with these variables was constructed the model called AAD, where: [AAD= 3.896 + ln(age)x-0.218 + ln(AST)x-0.185 + ln(DD)x0.070], where a value ≤ 2.75 had sensitivity=0.797 and 1-specificity= 0.391, AUROC=0.74 (95%CI: 0.62-0.86;P<0.0001), to predict the risk of developing SARS+MV (OR=5.8, 95%CI: 2.2-15.4;P=0.001). Conclusions: Elevation of AST (probable marker of liver damage) is an important predictor of progression to SARS, together with elevation of D-dimer and age early (at admission) and efficiently predict which patients will potentially require MV.

Aspartate aminotransferase as predictor of severity in SARSCoV-2 infection: linear regression model

Background and aim: Some patients with SARSCov-2 infection develop severe disease (SARS);however, the factors associated with severity are not yet fully understood. Some reports indicate that liver injury may be a poor prognostic factor. AIM: To identify the biochemical factors related to the development of SARS with mechanical ventilation (MV) requirement in patients with SARSCov-2 and COVID-19. Methods. Type of Study: Observational. Cohort study. Procedure: Data from COVID-19 patients were collected at admission time to a tertiary care center. Differential factors were identified between seriously ill SARS + MV patients versus stable patients without MV. Transformation to the natural logarithm of significant variables was performed and multiple linear regression was applied, then a predictive model of severity called AAD (Age-AST-D dimer) was constructed. Result(s): 166 patients were included, 114(68.7%) men, mean age 50.6 +/- 13.3 years-old, 27(16.3%) developed SARS + MV. In the comparative analysis between those with SARS + MV versus stable patients without MV we found significant raises of ALT (225.4 +/- 341.2 vs. 41.3 +/- 41.1;P = 0.003), AST 325.3 +/- 382.4 vs. 52.8 +/- 47.1;P = 0.001), LDH (764.6 +/- 401.9 vs. 461.0 +/- 185.6;P = 0.001), D dimer (7765 +/- 9109 vs. 1871 +/- 4146;P = 0.003), age (58.6 +/- 12.7 vs. 49.1 +/- 12.8;P = 0-001). The results of the regression are shown in the Table, where model 3 was the one that best explained the development of SARS + MV;with these variables was constructed the model called AAD, where: [AAD = 3.896 + ln(age)x-0.218 + ln(AST)x-0.185 + ln(DD)x0.070], where a value = 2.75 had sensitivity = 0.797 and 1-specificity = 0.391, AUROC = 0.74 (95%CI: 0.62-0.86;P 0.0001), to predict the risk of developing SARS + MV (OR = 5.8, 95%CI: 2.2-15.4;P = 0.001). Conclusion(s): Elevation of AST (probable marker of liver damage) is an important predictor of progression to SARS, together with elevation of D-dimer and age early (at admission) and efficiently predict which patients will potentially require MV. Conflicts of interest: The authors have no conflicts of interest to declare. [Formula presented] [Formula presented] Copyright © 2020

Impact of liver enzymes on SARSCoV-2 infection and on the severity of clinical disease

Background and aim: SARSCov-2 infection, currently responsible virus for the pandemic, can have a multi-organic impact, recent studies show that liver injury could be a manifestation of the disease, and liver disease could also be related to a worst prognosis. AIM: To compare the characteristics of patients with severe COVID-19 due to SARSCov-2 disease requiring intubation versus stable patients. Methods. Type of Study: Observational, a case-control, nested in a cohort study. Procedure: Complete medical records of patients admitted for COVID-19 at a third level center were reviewed. Clinical and biochemical data were collected and then characteristics between seriously ill patients who required intubation were compared versus stable patients without mechanical ventilation. Result(s): We included 166 patients with COVID-19 due to SARSCov-2 infection, 114(68.7%) were men, mean age was 50.6 +/- 13.3 years old, 27(16.3%) were assessed as seriously ill patients requiring intubation for SARS. The comparative analysis between those who required intubation versus those who remained without requiring intubation showed significant elevation of ALT, AST, LDH and D-dimer, also older age, see Table. Conclusion(s): This is the first study in a Mexican cohort, which demonstrate that seriously ill patients have significant raises of liver enzymes (AST, ALT) with prognostic implications in the SARSCov-2 disease course. Conflicts of interest: The authors have no conflicts of interest to declare.Copyright © 2020