Hypoxic hepatitis with marked elevation of serum ferritin probably due to activation of intrahepatic macrophages: another form of hypoxic hepatitis hitherto not reported?

Background and study aims: Hypoxic hepatitis (HH) is an acute liver injury that develops in patients with underlying diseases, such as heart failure, respiratory failure, septic/toxic shock. However, some patients do not have underlying diseases or episodes which are known to result in HH. Here, we analyzed the clinical characteristics of this particular patient group (called ‘unknown HH’ hereafter) to understand its pathogenesis. Patients and methods: Between October 2010 and January 2016, 157 consecutive patients with acute liver injury were admitted to our hospital. Among these patients, 15 patients were categorized as unknown HH. Medical histories and blood test results of unknown HH were analyzed. Results: Among 15 patients of unknown HH, 11 were habitual drinkers and all experienced one of digestive symptoms which might result in mild hypovolemia such as vomiting, diarrhea, appetite loss, and epigastralgia. All patients of unknown HH presented marked elevation of serum ferritin concentration paralleled with aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) concentrations. The serum levels of ferritin, ALT, LDH, and prothrombin time-international normalized ratio (PT-INR) were rapidly decreased during hospitalization and all 15 patients of unknown HH recovered without any complication. Conclusions: We found the particular group of HH with marked elevation of serum ferritin probably due to intrahepatic macrophage activation. Anti-inflammatory treatments might be effective for this group of hypoxic hepatitis.

Prevalence and Characteristics of Hypoxic Hepatitis in COVID-19 Patients in the Intensive Care Unit: A First Retrospective Study

Purpose: Coronavirus disease 2019 (COVID-19) has been associated with acute liver injury in reports worldwide. But no studies to date have described hypoxic hepatitis (HH) in patients with COVID-19. We aim to identify the prevalence of and possible mechanisms of HH in COVID-19 patients in the Intensive Care Unit (ICU).Methods: This retrospective study was conducted on 51 patients with confirmed SARS-CoV-2 infection in the ICU at Zhongnan Hospital of Wuhan University from December 21, 2019, to March 11, 2020. Information on clinical features of enrolled patients was collected for analysis.Results: HH was observed in 5.88% of the ICU patients with SARS-CoV-2 infection. All HH patients were progressing to respiratory failure and peak alanine aminotransferase (ALT) values were 1665, 1414, and 1140 U/L during hospitalization, respectively. All patients with HH died as a result of the deterioration of multiple organ failure (MOF). The dynamic changes of ALT, aspartate transaminase (AST), and total bilirubin (TBIL) levels were more dramatic in HH groups. Levels of TBIL, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6(IL-6) showed statistically significant elevation in HH cases compared with that in non-HH cases (P < 0.001). Besides, the median survival time of the HH group was significantly shorter than the non-HH group (P < 0.05).Conclusions: In ICU, HH was not a rare condition in patients with severe COVID-19 and has a high mortality. The main causes of HH are respiratory and cardiac failure and may be associated with the immune-mediated inflammatory response. Clinicians should search for any underlying hemodynamic or respiratory instability even in patients with normal ALT levels on admission.

The Impact of Hypoxic Hepatitis on Clinical Outcomes after Extracorporeal Cardiopulmonary Resuscitation

Although there have been several reports regarding the association between hypoxic hepatic injury and clinical outcomes in patients who underwent conventional cardiopulmonary resuscitation (CPR), limited data are available in the setting of extracorporeal CPR (ECPR). Patients who received ECPR due to either in- or out-of-hospital cardiac arrest from May 2004 through December 2018 were eligible. Hypoxic hepatitis (HH) was defined as an increased aspartate aminotransferase or alanine aminotransferase level to more than 20 times the upper normal range. The primary outcome was in-hospital mortality. In addition, we assessed poor neurological outcome defined as a Cerebral Performance Categories score of 3 to 5 at discharge and the predictors of HH occurrence. Among 365 ECPR patients, 90 (24.7%) were identified as having HH. The in-hospital mortality and poor neurologic outcomes in the HH group were significantly higher than those of the non-HH group (72.2% vs. 54.9%, p = 0.004 and 77.8% vs. 63.6%, p = 0.013, respectively). As indicators of hepatic dysfunction, patients with hypoalbuminemia (albumin < 3 g/dL) or coagulopathy (international normalized ratio > 1.5) had significantly higher mortalities than those of their counterparts (p = 0.005 and p < 0.001, respectively). In multivariable logistic regression, age and acute kidney injury requiring continuous renal replacement therapy were predictors for development of HH (p = 0.046 and p < 0.001 respectively). Furthermore age, arrest due to ischemic heart disease, initial shockable rhythm, out-of-hospital cardiac arrest, lowflow time, continuous renal replacement therapy, and HH were significant predictors for in-hospital mortality. HH was a frequent complication and associated with poor clinical outcomes in ECPR patients.