Pre-existing Chronic Liver Disease Research Articles

Liver dysfunction during COVID-19 pandemic: Contributing role of associated factors in disease progression and severity.

In December 2019, a new strain of coronavirus was discovered in China, and the World Health Organization declared it a pandemic in March 2020. The majority of people with coronavirus disease 19 (COVID-19) exhibit no or only mild symptoms such as fever, cough, anosmia, and headache. Meanwhile, approximately 15% develop a severe lung infection over the course of 10 d, resulting in respiratory failure, which can lead to multi-organ failure, coagulopathy, and death. Since the beginning of the pandemic, it appears that there has been consideration that pre-existing chronic liver disease may predispose to deprived consequences in conjunction with COVID-19. Furthermore, extensive liver damage has been linked to immune dysfunction and coagulopathy, which leads to a more severe COVID-19 outcome. Besides that, people with COVID-19 frequently have abnormal liver function, with more significant elevations in alanine aminotransferase and aspartate aminotransferase in patients with severe COVID-19 compared to those with mild/moderate disease. This review focuses on the pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the liver, as well as the use of liver chemistry as a prognostic tool during COVID-19. We also evaluate the findings for viral infection of hepatocytes, and look into the potential mechanisms behind SARS-CoV-2-related liver damage.

The association between chronic liver diseases and preeclampsia

BackgroundPreeclampsia is a multisystem disorder characterized by an abnormal vascular response to placentation associated with increased systemic vascular resistance. As liver involvement is one of the main clinical features of preeclampsia, we sought to determine if there is an association between chronic liver diseases and preeclampsia.MethodsA retrospective matched case–control analysis was conducted in a tertiary medical center. Three hundred eleven (311) pregnant women with preexisting chronic liver disease (study group), including viral and autoimmune hepatitis, non-alcoholic fatty liver, Wilson disease, and cirrhosis, were match for age, parity, and number of fetuses to 933 healthy pregnant women (control group). The primary outcome measure was the incidence of preeclampsia in each group. Secondary outcome measures were obstetrical and neonatal complications. Confounders found to be significant on univariate analysis were evaluated using logistic regression models, and odds ratios (OR) and confidence intervals (CI) were calculated.ResultsPreeclampsia was diagnosed in 28 women (9.0%) in the study group and 33 women (3.54%) in the control group (p < 0.001).On multivariate analysis adjusted for maternal age, parity, previous preeclampsia, chronic hypertension, gestational diabetes mellitus, pregestational diabetes mellitus, antiphospholipid syndrome, and mode of conception, chronic liver disease was found to be an independent risk factor for preeclampsia (aOR 2.631, 95% CI 1.518–4.561). Although there was no difference in the gestational week at delivery between the groups (38.6 ± 2.13 vs. 38.8 ± 2.17 for study and control group, respectively, p = 0.410), the study group had a lower mean neonatal birthweight (3088 ± 551 vs. 3182 ± 566 g, p = 0.011). There were no between-group differences in the other parameters evaluated.ConclusionIn our study, preexisting chronic liver disease was associated with a 2.6-fold increased risk of preeclampsia.

Characteristics of Drug-induced Liver Injury in Chronic Liver Disease: Results from the Thai Association for the Study of the Liver (THASL) DILI Registry.

The impact of drug-induced liver injury (DILI) on patients with chronic liver disease (CLD) is unclear. There are few reports comparing DILI in CLD and non-CLD patients. In this study, we aimed to determine the incidence and outcomes of DILI in patients with and without CLD. We collected data on eligible individuals with suspected DILI between 2018 and 2020 who were evaluated systematically for other etiologies, causes, and the severity of DILI. We compared the causative agents, clinical features, and outcomes of DILI among subjects with and without CLD who were enrolled in the Thai Association for the Study of the Liver DILI registry. Subjects with definite, or highly likely DILI were included in the analysis. A total of 200 subjects diagnosed with DILI were found in the registry. Of those, 41 had CLD and 159 had no evidence of CLD in their background. Complementary and alternative medicine (CAM) products were identified as the most common class of DILI agents. Approximately 59% of DILI in the CLD and 40% in non-CLD group were associated with CAM use. Individuals with pre-existing CLD had similar severity including mortality. Twelve patients (6%) developed adverse outcomes related to DILI including seven (3.5%) deaths and five (2.5%) with liver failure. Mortality was 4.88% in CLD and 3.14% in non-CLD subjects over median periods of 58 (8-106) days and 22 (1-65) days, respectively. In this liver disease registry, the causes, clinical presentation, and outcomes of DILI in subjects with CLD and without CLD patients were not different. Further study is required to confirm our findings.

Acute-on-chronic liver failure: A 20-year retrospective review of a tertiary paediatric liver centre.

Acute-on-chronic liver failure (ACLF) is an acute deterioration of pre-existing chronic liver disease related to a precipitating event. We characterised paediatric ACLF at Birmingham Children's Hospital (BCH) utilising European Association of Liver Disease CLIF criteria, including prevalence, triggers and outcomes. All BCH patients from 2000 to 2020 with CLD who underwent initial liver transplant or died on the transplant waiting list or whilst too unwell to be listed were reviewed. From 2000 to 2020, 24 (4%) children with ACLF were identified. Death occurred in 18 (75%). Transplant occurred in 9 (36%), 3 of which died. ACLF triggers were sepsis organism negative 11 (46%), sepsis organism positive 8 (33%) and GI bleed 5 (17%). Bilirubin at the time of transplant/death in those with ACLF who lived compared with those who died was 529umol/L (381) versus 665 (210) (p=0.38), creatinine 138 umol/L (147) versus 67 (46) (p=0.41), PT 33sec (14) versus (32 (15) (p=0.72), Grade 3, 4hepatic encephalopathy 1 (17%) versus 10 (56%) (p=0.17), vasopressor use 1 (17%) versus 17 (94%) (p=0.001) and ventilation 3 (50%) versus 17 (94%) (p=0.035). Acute-on-chronic liver failure whilst infrequent has high rates of mortality. The use of vasopressors and ventilation is more frequent in those who die from ACLF.

Clinical features and risk predictor markers in COVID-19 patients in correlation with disease severity and comorbidities- A data-based retrospective study

Background: COVID-19 infection displays a highly heterogeneous spectrum of severities. Laboratory findings are pivotal cues to assess disease severity and aid in retarding/ reversing disease progression. This study aims to identify the haematological, biochemical, and immunological specifics of COVID-19 patients with varying severity and associated comorbidities. Methods: This retrospective study recruited a total of 192 RT PCR confirmed COVID-19 patients. Data on laboratory findings, clinical characteristics, treatment, and hospital stay were obtained and analysed. Results: The patients were grouped into mild, moderate, and severe categories based on disease severity. 96 patients had mild disease, 31 were classified as having moderate COVID-19, and 67 patients had severe COVID-19. 39.58% of the patients were females. The overall death rate among admitted COVID-19 patients is observed to be 19.02%, sepsis and multi-organ failure as the most common cause. The variation in laboratory variables and comorbidities as CAD, CKD, HTN, DM strongly correlate with the severity and increases with the age factor. Pre-existing chronic liver disease emerged to be a comorbidity of significance for acquiring severe COVID-19. Conclusion: Presence of comorbidities, advanced age and male sex emerged as important risk factors while derangements in thrombo-inflammatory markers and haematological indices might be crucial predictors of disease progression. Thromboembolism or superinfection induced sepsis, and multi-organ failure emerged as leading contributors to mortality. High-risk patterns in thrombo inflammatory and immunohematological markers allow for early detection of the disease progression and aid in the institution of personalized intensive therapeutic interventions and monitoring to avoid further deaths.

Characteristics and outcomes of patients with COVID-19 and liver injury: a retrospective analysis and a multicenter experience.

Background and aims. Patients with COVID-19 frequently present abnormal elevated liver function tests of unknown clinical significance. We aimed to investigate the characteristics and factors influencing outcome in patients with confirmed SARS-CoV-2 infection and liver injury on admission.Methods. This is a retrospective observational study of patients hospitalized in two COVID units in Romania. Relevant data on clinical and laboratory parameters and medication administered during the admission were analyzed to identify predictors of a negative outcome. Patients with confirmed COVID-19 and liver function tests (LFTs) above the upper limit of normal were included in the analysis.Results. From 1,207 patients, we identified 134 patients (11%) with abnormal LFTs during hospitalization. The majority of patients had mildly elevated levels and a predominantly cholestatic pattern of liver injury. Patients who received lopinavir/ritonavir were more likely to have increased ALAT levels (p<0.0001). Sixteen patients had pre-existing chronic liver disease, and they were more likely to suffer from severe COVID-19 (p=0.009) and have a negative outcome (p<0.001), but on multivariate analysis, only the severity of COVID-19 was predictive of death (OR 69.9; 95% CI 6.4-761.4).Conclusions. Mild liver injury is relatively common in COVID-19 and possibly influenced by medication. Patients with chronic liver disease are at high risk for negative outcome, but the severity of the infection is the only predictor of death.

The frequency of feto-maternal complications in patients with intrahepatic cholestasis of pregnancy.

Objective: To determine the frequency of complications in patients with intrahepatic cholestasis of pregnancy. Study Design: Descriptive Case Series. Setting: Department of Obstetrics &amp; Gynecology, Shahida Islam Medical College, Lodhran. Period: July 2019 to December 2020. Material &amp; Methods: A total of 141 patients with intrahepatic cholestasis of pregnancy of age 18 to 40 years were included. Patients with multiple pregnancies, history of alcohol intake, CR and preexisting chronic liver disease were excluded. All women were followed till delivery (gestational age ≤ 41 weeks) and feto-maternal outcome i.e. postpartum hemorrhage, cesarean section, APGAR score &lt;7 at 5 minutes, low birth weight, prematurity, meconium stained liquor and intrauterine fetal death (yes/no) was noted. Results: Feto-maternal outcome was as follows; postpartum hemorrhage in 18 (12.77%), cesarean section in 47 (33.33%), preterm birth in 34 (24.11%), APGAR score &lt;7 at five minutes in 13 (9.22%), meconium stained liquor in 45 (31.91%) patients, low birth weight in 14 (9.93%) and Intra-uterine fetal death in 11 (7.80%) patients. Conclusion: Our study concluded that we should develop some serious recommendations for these high risk patients in our routine practice. It will reduce the morbidity and mortality related to this high risk condition.

Liver Injury in Patients Hospitalized for COVID-19: Possible Role of Therapy.

Patients with COVID-19 show a high prevalence of liver injury. The pattern of this liver damage is still not fully understood. Different etiopathogenetic factors may concur; from a direct cytopathic effect, once the virus binds to the ACE-2 receptors, to the immune-mediated collateral damage, due to cytokine storm. The presence of pre-existing chronic liver disease is a contributing factor for acute organ damage during SARS-CoV2 infection. Last but not least, treatments probably play a role, also, in determining hepatotoxicity: many of the drugs we have used or are still using to treat COVID-19, combined with non-invasive ventilation, are known to sometimes determine acute liver injury. Although liver damage associated with COVID-19 is often transient and can resolve without any special treatment, it is important to understand the underlying mechanisms, particularly to better treat its more severe forms.

Acute hepatitis E virus superinfection increases mortality in patients with cirrhosis

BackgroundAlthough acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases the mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD).MethodsThis study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed.ResultsAmong the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately eightfold increase in the 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate.ConclusionsOur findings suggest that the acute hepatitis E mortality rate was low in healthy individuals but higher in patients with cirrhosis, and especially high in those with ACLF.

Health-related Disruptions Due to COVID-19 Pandemic in Patients Chronically Infected with Hepatitis B Virus (HBV)

Background and Aim: Ongoing COVID-19 pandemic have impacted the health care of patients with pre-existing chronic liver disease. The aim of the present study was to assessthe health-related disruptions due to COVID-19 pandemic in patients with chronic HBV infection.

Multiple organ involvement and ICU considerations for the care of acute liver failure (ALF) and acute on chronic liver failure (ACLF) in children.

Liver disease results in approximately 15,000 pediatric hospitalizations per year in the United States and is a significant burden to child health. Major etiologies of liver failure and indications for transplantation in children include: biliary atresia, metabolic/genetic conditions, toxins, infections, tumors, and immune-mediated liver/biliary injury. Children requiring transplantation are placed on the United Network of Organ Sharing waitlist including those with acute liver failure (ALF) and acute on chronic liver failure (ACLF). ALF is a clinical syndrome in which a previously healthy child develops rapid-onset hepatic dysfunction, and becomes critically ill with multiple organ dysfunction within days. ACLF, by contrast, is generally described as an acute decompensation of pre-existing chronic liver disease (CLD) brought on by a precipitating event, with higher risk of mortality. Children with ALF and ACLF receive multidisciplinary care in pediatric intensive care units (ICUs) due to multiple organ system involvement and high risk of decompensation in these patients. The care of these patients requires a holistic approach that addresses the complex interplay between hepatic and extra-hepatic organ systems. This review will define and describe ALF and ACLF in the pediatric population, and outline the effects of ALF and ACLF on individual organ systems with diagnostic and management considerations in the ICU while awaiting liver transplantation.

High Prevalence of Pre-Existing Liver Abnormalities Identified Via Autopsies in COVID-19: Identification of a New Silent Risk Factor?

A high prevalence of hepatic pathology (in 17 of 19 cases) was reported in post-mortem (PM) examinations of COVID-19 patients, undertaken between March 2020 and February 2021 by a single autopsy pathologist in two English Coronial jurisdictions. The patients in our cohort demonstrated high levels of recognised COVID-19 risk factors, including hypertension (8/16, 50%), type 2 diabetes mellitus (8/16, 50%) and evidence of arteriopathy 6/16 (38%). Hepatic abnormalities included steatosis (12/19; 63%), moderate to severe venous congestion (5/19; 26%) and cirrhosis (4/19; 21%). A subsequent literature review indicated a significantly increased prevalence of steatosis (49%), venous congestion (34%) and cirrhosis (9.3%) in COVID-19 PM cases, compared with a pre-pandemic PM cohort (33%, 16%, and 2.6%, respectively), likely reflecting an increased mortality risk in SARS-CoV-2 infection for patients with pre-existing liver disease. To corroborate this observation, we retrospectively analysed the admission liver function test (LFT) results of 276 consecutive, anonymised COVID-19 hospital patients in our centre, for whom outcome data were available. Of these patients, 236 (85.5%) had significantly reduced albumin levels at the time of admission to hospital, which was likely indicative of pre-existing chronic liver or renal disease. There was a strong correlation between patient outcome (length of hospital admission or death) and abnormal albumin at the time of hospital admission (p = 0.000012). We discuss potential mechanisms by which our observations of hepatic dysfunction are linked to a risk of COVID-19 mortality, speculating on the importance of recently identified anti-interferon antibodies.

Efficacy and Safety of Deferasirox in Chelation Naïve HbEβ Thalassemia Patients: Initial Experience from a Tertiary Centre of Eastern India

Introduction: In India, more than 10,000 new cases of thalassemia are born every year. In Eastern India, Hb E Beta thalassemia accounts for more than 50 % of the disease burden (Olivieri NF et al, Indian J Med Res 2011;134:522-31). Initially patients were used to get chelation with deferoxamine or deferiprone mostly, but with wide availability of Deferasirox (DFX) it has become the most commonly used chelating agent in Eastern India, however. Limited data are available on chelation from this part of the country. Objective: To assess the response to DFX in chelation-naïve patients with HbE beta thalassemia in terms of changes of serum ferritin level and to document its adverse effects in these patients. Materials and Methods: The study was undertaken from January 2014 to September 2015 at the thalassemia clinic of Institute of Haematology and Transfusion Medicine, Medical College, Kolkata, India. Sixty five patients of HbE beta thalassemia with serum ferritin level >1000 ng/ml and no history of any sort of chelation therapy were enrolled. Evaluation was done to rule out any pre-existing chronic liver disease, renal disease, gastro-intestinal bleed or anaphylaxis. Deferasirox was given at the dose of 40 mg/kg daily to thalassemia major patients and at the dose of 10 mg/kg daily to non-transfusion dependent thalassemia (NTDT) patients. The adverse effects of Deferasirox on HbE beta thalassemia patients were closely monitored. Serial changes in serum ferritin, bilirubin, ALT and creatinine clearance were noted every 3 months. Results: 23% of total patients were NTDT. Mean baseline hemoglobin was 6.72±0.62 gm/dl and mean baseline serum ferritin was 2122±622 ng/ml. Nausea, vomiting, pain abdomen were the most common adverse effects seen (Figure 1). There was no incidence of drug discontinuation or dose reduction. 34% patients had no adverse effects. In rest of the patients, gastrointestinal symptoms were the most commonly associated complaints with DFX therapy. Proteinuria was also found in 21.4 % patients. There was significant reduction of serum ferritin level on repeated measurements. Alterations of bilirubin or ALT were found, but it was statistically not significant. Decrease in creatinine clearance was seen in significant number of patients on DFX. There was no significant association of absence or presence of adverse effects with concomitant hydroxyurea therapy in NTDT patients (Table 2). Discussions: DFX was well tolerated by the patients. Gastrointestinal symptoms, most commonly nausea followed by vomiting and pain abdomen, were the most common adverse effects as seen in other studies like EPIC trial (Ann Hematol 2013 92:211-219). No serious adverse effects like hypoaccusis, GI bleed, anaphylaxis, anasarca as mentioned in other studies (Ali Taher et al. Br J Haematol. 2009;147:752-759) leading to stoppage or dose reduction of DFX were observed. Mixed regression analysis for repeated measures revealed significant decrease in serum ferritin level in comparison to previous ferritin level with DFX therapy (Table No 1), as shown in similar study by Capellini et al (Blood. 2006;107:3455-3462). There was no statistical correlation with absence of any adverse effects when compared with concomitant hydroxyurea therapy, when applicable. Conclusion: Deferasirox was found to be effective in reducing serum ferritin level in Indian HbE beta thalassemia patients without any major adverse drug effects, although more studies with longer duration are needed to achieve robust evidence. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Derivation and Validation of a Nomogram for Predicting 90-Day Survival in Patients With HBV-Related Acute-on-Chronic Liver Failure.

Background: Conventional prognostic models do not fully reflect the severity of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). This study aimed to establish an effective and convenient nomogram for patients with HBV-related ACLF.Methods: A nomogram was developed based on a retrospective cohort of 1,353 patients treated at the Third Affiliated Hospital of Sun Yat-sen University from January 2010 to June 2016. The predictive accuracy and discriminatory ability of the nomogram were determined by a concordance index (C-index) and calibration curve, and were compared with current scoring systems. The results were validated using an independent retrospective cohort of 669 patients consecutively treated at the same institution from July 2016 to March 2018. This study is registered at ClinicalTrials.gov (NCT03992898).Results: Multivariable analysis of the derivation cohort found that independent predictors of 90-day survival were age, white blood cell (WBC) count, hemoglobin (Hb), aspartate aminotransferase (AST), total bilirubin (TBil), international normalized ratio, serum creatinine (Cr), alpha fetoprotein (AFP), serum sodium (Na), hepatic encephalopathy (HE), pre-existing chronic liver disease(PreLD), and HBV DNA load. All factors were included in the nomogram. The nomogram calibration curve for the probability of 90-day survival indicated that nomogram-based predictions were in good agreement with actual observations. The C-index of the nomogram was 0.790, which was statistically significantly greater than those for the current scoring systems in the derivation cohort (P < 0.001). The results were confirmed in the validation cohort.Conclusions: The proposed nomogram is more accurate in predicting the 90-day survival of patients with HBV-related ACLF than current commonly used methods.

COVID-19 and pediatric fatty liver disease: Is there interplay?

The rapid global spread of coronavirus disease 2019 (COVID-19) infection has become a major health issue with higher morbidity and mortality rates. Besides respiratory symptoms, a growing body of evidence indicates a variety of gastrointestinal manifestations including liver involvement. In this regard, several data supported an association between COVID-19 infection and liver injury in adults, while in children there is compelling but currently limited evidence. In particular, patients with COVID-19 have shown a higher risk of liver injury (mainly expressed as increased transaminase levels or hepatic steatosis). Conversely, a greater risk of more severe forms of COVID-19 infection has been observed in subjects with pre-existing chronic liver diseases. The dramatic interplay between COVID-19 and liver damage has been related to the inflammatory pathways chronically active in patients with nonalcoholic fatty liver disease and acutely in those affected by COVID-19, but other different pathogenic mechanisms have also been supposed. Of note, patients with previous metabolic comorbidities also had a higher risk of severe COVID-19 infection. This emphasizes the pathogenic interrelation of the inflammatory pathways with a dysregulated metabolic milieu in COVID-19 patients. Taking into account the prognostic role of fatty liver in COVID-19 patients and its intrinsic relationship with metabolic abnormalities even in childhood, a strict monitoring of this condition is recommended. We aimed to summarize the most recent evidence regarding the potential interplay between pediatric fatty liver and COVID-19.

COVID-19 impact on the liver

The coronavirus disease 2019 (COVID-19) pandemic imposed arestructuring of global health systems by rethinking spaces used for the care of these patients and the additions of intensive care, infectious diseases and pneumology departments. This paper provides evidence on the presence of severe acute respiratory syndrome coronavirus 2 in hepatocytes and its direct cytopathic activity, as well as the degree of liver damage due to drug toxicity, inflammation and hypoxia in COVID-19. A review of clinical trials has quantified liver damage through both pathology and biochemistry studies. Additionally, we briefly present the results of a study conducted in our clinic on 849 patients admitted for COVID-19 treatment, of which 31 patients had pre-existing chronic liver disease and 388 patients had values above the normal limit for alanine aminotransferase, aspartate aminotransferase, and total bilirubin. It was observed that patients with abnormal liver tests were significantly statistically older, had more comorbidities and had a higher percentage of unfavourable evolution (death or transfer to intensive care). The conclusion of this paper is that the main causes of liver damage are direct viral aggression, coagulation dysfunction and endothelial damage, and patients with impaired liver function develop more severe forms of COVID-19 which requires special care by a multidisciplinary team that includes a hepatologist.

Liver stiffness is associated with disease severity and worse clinical scenarios in coronavirus disease 2019: A prospective transient elastography study.

BackgroundPre‐existing chronic liver disease is currently considered a poor prognostic factor for coronavirus disease 2019 (COVID‐19). The present study aimed to investigate the association of liver stiffness measurement (LSM) with disease severity and clinical course of COVID‐19.MethodsWe prospectively recruited consecutive hospitalised adult patients with COVID‐19 in a 3‐month period. Demographic, laboratory, clinical and vibration‐controlled transient elastography (VCTE) features were recorded at entry, and all patients were prospectively followed‐up. Severe liver fibrosis was defined as an LSM value higher than 9.6 kPA. Multivariate logistic regression analysis was performed to reveal factors associated with disease severity and outcomes.ResultsOut of 98 eligible patients with COVID‐19, 12 (12.2%) had severe liver fibrosis. Patients with severe liver fibrosis had higher baseline disease severity (P = .022), more commonly required oxygen treatment at entry (P = .010), and had intensive‐care unit (ICU) requirements during the 6 (1‐39)‐day median follow‐up time (P = .017). The presence of severe liver fibrosis was independently associated with disease severity (odds ratio (OR): 7.685, 95% confidence interval (CI): 1.435‐41.162, P = .017) and ICU requirement (OR: 46.656, 95% CI: 2.144‐1015.090, P = .014). LSM was correlated with alanine aminotransferase levels (P = .005, r: 0.283), but not with other markers of acute hepatic injury or inflammation.ConclusionInitial VCTE application might help physicians identify patients who are more likely to have severe illness or worse clinical outcomes, in addition to other well‐established clinical and laboratory factors. Further multicentre prospective studies are warranted to validate our results.

Risk factors on admission associated with hospital length of stay in patients with COVID-19: a retrospective cohort study

Treating patients with COVID-19 is expensive, thus it is essential to identify factors on admission associated with hospital length of stay (LOS) and provide a risk assessment for clinical treatment. To address this, we conduct a retrospective study, which involved patients with laboratory-confirmed COVID-19 infection in Hefei, China and being discharged between January 20 2020 and March 16 2020. Demographic information, clinical treatment, and laboratory data for the participants were extracted from medical records. A prolonged LOS was defined as equal to or greater than the median length of hospitable stay. The median LOS for the 75 patients was 17 days (IQR 13–22). We used univariable and multivariable logistic regressions to explore the risk factors associated with a prolonged hospital LOS. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated. The median age of the 75 patients was 47 years. Approximately 75% of the patients had mild or general disease. The univariate logistic regression model showed that female sex and having a fever on admission were significantly associated with longer duration of hospitalization. The multivariate logistic regression model enhances these associations. Odds of a prolonged LOS were associated with male sex (aOR 0.19, 95% CI 0.05–0.63, p = 0.01), having fever on admission (aOR 8.27, 95% CI 1.47–72.16, p = 0.028) and pre-existing chronic kidney or liver disease (aOR 13.73 95% CI 1.95–145.4, p = 0.015) as well as each 1-unit increase in creatinine level (aOR 0.94, 95% CI 0.9–0.98, p = 0.007). We also found that a prolonged LOS was associated with increased creatinine levels in patients with chronic kidney or liver disease (p < 0.001). In conclusion, female sex, fever, chronic kidney or liver disease before admission and increasing creatinine levels were associated with prolonged LOS in patients with COVID-19.

Hepatitis E in solid organ transplant recipients: A systematic review and meta-analysis.

BACKGROUNDHepatitis E virus (HEV) infection is underdiagnosed due to the use of serological assays with low sensitivity. Although most patients with HEV recover completely, HEV infection among patients with pre-existing chronic liver disease and organ-transplant recipients on immunosuppressive therapy can result in decompensated liver disease and death.AIMTo demonstrate the prevalence of HEV infection in solid organ transplant (SOT) recipients. METHODSWe searched Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible articles through October 2020. The inclusion criteria consisted of adult patients with history of SOT. HEV infection is confirmed by either HEV-immunoglobulin G, HEV-immunoglobulin M, or HEV RNA assay.RESULTSOf 563 citations, a total of 22 studies (n = 4557) were included in this meta-analysis. The pooled estimated prevalence of HEV infection in SOT patients was 20.2% [95% confidence interval (CI): 14.9-26.8]. The pooled estimated prevalence of HEV infection for each organ transplant was as follows: liver (27.2%; 95%CI: 20.0-35.8), kidney (12.8%; 95%CI: 9.3-17.3), heart (12.8%; 95%CI: 9.3-17.3), and lung (5.6%; 95%CI: 1.6-17.9). Comparison across organ transplants demonstrated statistical significance (Q = 16.721, P = 0.002). The subgroup analyses showed that the prevalence of HEV infection among SOT recipients was significantly higher in middle-income countries compared to high-income countries. The pooled estimated prevalence of de novo HEV infection was 5.1% (95%CI: 2.6-9.6) and the pooled estimated prevalence of acute HEV infection was 4.3% (95%CI: 1.9-9.4).CONCLUSIONHEV infection is common in SOT recipients, particularly in middle-income countries. The prevalence of HEV infection in lung transplant recipients is considerably less common than other organ transplants. More studies examining the clinical impacts of HEV infection in SOT recipients, such as graft failure, rejection, and mortality are warranted.

COVID-19 and liver disease: mechanistic and clinical perspectives.

Our understanding of the hepatic consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resultant coronavirus disease 2019 (COVID-19) has evolved rapidly since the onset of the pandemic. In this Review, we discuss the hepatotropism of SARS-CoV-2, including the differential expression of viral receptors on liver cell types, and we describe the liver histology features present in patients with COVID-19. We also provide an overview of the pattern and relevance of abnormal liver biochemistry during COVID-19 and present the possible underlying direct and indirect mechanisms for liver injury. Furthermore, large international cohorts have been able to characterize the disease course of COVID-19 in patients with pre-existing chronic liver disease. Patients with cirrhosis have particularly high rates of hepatic decompensation and death following SARS-CoV-2 infection and we outline hypotheses to explain these findings, including the possible role of cirrhosis-associated immune dysfunction. This finding contrasts with outcome data in pharmacologically immunosuppressed patients after liver transplantation who seem to have comparatively better outcomes from COVID-19 than those with advanced liver disease. Finally, we discuss the approach to SARS-CoV-2 vaccination in patients with cirrhosis and after liver transplantation and predict how changes in social behaviours and clinical care pathways during the pandemic might lead to increased liver disease incidence and severity.