Andreas Drolz

Hypoxic hepatitis - epidemiology, pathophysiology and clinical management

ZusammenfassungHypoxische Hepatitis (HH) – auch unter den Bezeichnungen ichämische Hepatitis oder Schockleber bekannt – ist durch eine zentrilobuläre Leberzellnekrose und einen fulminanten Anstieg der Serumaminotransferasen als Folge von kardialem, zirkulatorischem oder respiratorischem Versagen charakterisiert. Dies ist die häufigste Ursache der akuten Leberschädigung mit einer Prävalenz von bis zu 10 Prozent an Intensivstationen. Kritisch kranke Patienten mit HH und der Notwendigkeit einer Vasopressorentherapie haben ein signifikant erhöhtes Mortalitätsrisiko. Die häufigsten HH auslösenden Ursachen sind erniedrigtes Herzauswurfvolumen und septischer Schock, wobei in der großen Mehrheit der Fälle eine multifaktorielle Ätiologie der HH zugrunde liegt. HH kann verschiedene Komplikationen wie spontane Hypoglykämie, respiratorische Insuffizienz als Folge des hepatopulmonalen Syndroms und Hyperammoniämie verursachen. HH bildet sich nach erfolgreicher Behandlung der zugrunde liegenden Ursachen zurück. Derzeit sind keine Therapieansätze etabliert, die spezifisch die Leberfunktion verbessern. Ein frühestmögliches Erkennen der HH, ihrer zugrunde liegenden Ursachen sowie die unverzügliche Einleitung entsprechender Therapiemaßnahmen sind von zentraler prognostischer Bedeutung. Diese Übersichtsarbeit vermittelt den heutigen Wissensstand hinsichtlich Epidemiologie, Pathophysiologie, sowie diagnostischen und therapeutischen Möglichkeiten der HH.SummaryHypoxic hepatitis (HH), also known as ischemic hepatitis or shock liver, is characterized by centrilobular liver cell necrosis and sharply increasing serum aminotransferase levels in a clinical setting of cardiac, circulatory or respiratory failure. Nowadays it is recognized as the most frequent cause of acute liver injury with a reported prevalence of up to 10% in the intensive care unit. Patients with HH and vasopressor therapy have a significantly increased mortality risk in the medical intensive care unit population. The main underlying conditions contributing to HH are low cardiac output and septic shock, although a multifactorial etiology is found in the majority of patients. HH causes several complications such as spontaneous hypoglycemia, respiratory insufficiency due to the hepatopulmonary syndrome, and hyperammonemia. HH reverses after successful treatment of the basic HH-causing disease. No specific therapies improving the hepatic function in patients with HH are currently established. Early recognition of HH and its underlying diseases and subsequent initiation of therapy is of central prognostic importance. The purpose of this review is to provide an update on the epidemiology, pathophysiology, and diagnostic and therapeutic options of HH.

Coagulation parameters and major bleeding in critically ill patients with cirrhosis

Disturbances of coagulation and hemostasis are common in patients with liver cirrhosis. The typical laboratory pattern mimics disseminated intravascular coagulation (DIC). The aim of this study was to assess the impact of routine coagulation parameters in critically ill cirrhosis patients with regard to new onset of major bleeding and outcome. A total of 1,493 critically ill patients were studied prospectively. Routine coagulation parameters were assessed, and the DIC score was calculated based on platelets, fibrinogen, d‐dimer, and prothrombin index. New onset of major bleeding during the stay at the intensive care unit and mortality were assessed. Patients were followed for 1 year. Two hundred eleven patients of the cohort had liver cirrhosis. Platelets, fibrinogen, prothrombin index, activated partial thromboplastin time, and d‐dimer as well as the DIC score differed significantly between patients with and without cirrhosis (P < 0.001 for all). Moreover, fibrinogen, platelets, and activated partial thromboplastin time (but not prothrombin index) differed significantly between cirrhosis patients with and without major bleeding (P < 0.01 for all). Bleeding on admission, platelet count <30 < 109/L, fibrinogen level <60 mg/dL, and activated partial thromboplastin time values >100 seconds were the strongest independent predictors for new onset of major bleeding in multivariate regression analysis. One‐year mortality in cirrhosis patients with and without major bleeding was 89% and 68%, respectively (P < 0.05 between groups). Conclusion: Abnormal coagulation parameters and high DIC scores (primarily due to fibrinogen and platelets) correspond to increased bleeding risk in patients with liver cirrhosis in the intensive care unit, and fibrinogen and platelet count were identified as the best routine coagulation parameters for prediction of new onset of major bleeding; however, further studies are required to evaluate the potential therapeutic implications of these findings. (Hepatology 2016;64:556‐568)

Jaundice increases the rate of complications and one‐year mortality in patients with hypoxic hepatitis

Hypoxic hepatitis (HH) is the most frequent cause of acute liver injury in critically ill patients. No clinical data exist about new onset of jaundice in patients with HH. This study aimed to evaluate the incidence and clinical effect of jaundice in critically ill patients with HH. Two hundred and six consecutive patients with HH were screened for the development of jaundice during the course of HH. Individuals with preexisting jaundice or liver cirrhosis at the time of admission (n = 31) were excluded from analysis. Jaundice was diagnosed in patients with plasma total bilirubin levels >3 mg/dL. One‐year‐survival, infections, and cardiopulmonary, gastrointestinal (GI), renal, and hepatic complications were prospectively documented. New onset of jaundice occurred in 63 of 175 patients with HH (36%). In patients who survived the acute event of HH, median duration of jaundice was 6 days (interquartile range, 3‐8). Patients who developed jaundice (group 1) needed vasopressor treatment (P < 0.05), renal replacement therapy (P < 0.05), and mechanical ventilation (P < 0.05) more often and had a higher maximal administered dose of norepinephrine (P < 0.05), compared to patients without jaundice (group 2). One‐year survival rate was significantly lower in group 1, compared to group 2 (8% versus 25%, respectively; P < 0.05). Occurrence of jaundice was associated with an increased frequency of complications during follow‐up (54% in group 1 versus 35% in group 2; P < 0.05). In particular, infections as well as renal and GI complications occurred more frequently in group 1 during follow‐up. Conclusion: Jaundice is a common finding during the course of HH. It leads to an increased rate of complications and worse outcome in patients with HH. (HEPATOLOGY 2012)

Statin therapy is associated with reduced incidence of hypoxic hepatitis in critically ill patients

BACKGROUND & AIMS Hypoxic hepatitis (HH) is a frequent and life-threatening complication associated with states of oxygen depletion in critically ill patients. Ischemia and reperfusion contribute to liver injury in HH. Experimental data suggest beneficial effects of statins in hepatic ischemia/reperfusion injury. This study was conducted to investigate whether statin treatment prior to intensive care unit (ICU) admission affects incidence rates and severity of HH. METHODS Eight hundred fifty-one patients admitted consecutively to three medical ICUs between December 2008 and December 2009 were prospectively screened for new occurrence of HH within 48 h following ICU admission. Statin treatment prior to ICU admission was assessed. 28-day-, 90-day-, and 1-year-survival as well as new-onset of complications in HH patients were prospectively documented. RESULTS Eighty-seven patients (10%) developed HH. Statin treatment prior to ICU admission was significantly associated with decreased incidence of HH within 48 h after ICU admission in the multivariate analysis (adjusted OR=0.42 (95% CI 0.19-0.95); p<0.05). Cardiogenic shock (p<0.001), septic shock (p<0.001) and active alcohol consumption (p<0.01) were identified as independent risk factors for development of HH. 28-day-, 90-day-, and 1-year-mortality rates in HH were 58%, 67%, and 74%, respectively. Statins were associated with improved 28-day-survival in the total study cohort (p<0.05), but did not affect 90-day- and 1-year-mortality, respectively. CONCLUSIONS Cardiogenic shock, septic shock, and active alcohol consumption were independent factors predisposing patients to new onset of HH. Statin treatment prior to ICU admission was the only protective factor regarding the new occurrence of HH in critically ill patients.

Renal replacement therapy in critically ill liver cirrhotic patients – Outcome and Clinical Implications

Current guidelines discourage renal replacement therapy (RRT) in critically ill cirrhotics in the lack of liver transplant (LT) options. This study aimed to identify patients who benefit from RRT in the short and long‐term.

Extracorporeal artificial liver support systems in the management of intractable cholestatic pruritus

Pruritus can occur as a severe complication of cholestasis. Several hypotheses suggest an important role for the accumulation of bile acids, endogenous opioids and – mire recently – lysophosphatidic acid. Bile acid sequestrants are the first‐line therapeutic agents. In refractory cases, a stepwise approach using rifampicin, oral opiate antagonists and the selective serotonine reuptake inhibitor sertraline should be tested. Recent case series reported effective relief of pruritus using extracorporal liver support systems and plasmapheresis.

Serum bile acids as marker for acute decompensation and acute-on-chronic liver failure in patients with non-cholestatic cirrhosis.

Retention of bile acids (BAs) plays a central role in hepatic damage and disturbed BA signalling in liver disease. However, there is lack of data regarding the association of BAs with clinical complications, acute decompensation (AD) and acute‐on‐chronic liver failure (ACLF). Thus, we aimed to evaluate the impact of circulating serum BAs for complications in patients with cirrhosis.

Schockleber und Cholestase beim kritisch Kranken

Liver dysfunction is frequently observed in critically ill patients. Its occurrence is associated with high morbidity and mortality. The most frequent entities of hepatic dysfunction in the intensive care unit are shock liver and cholestatic liver dysfunction with incidence rates up to 10 and 30 %, respectively.Both conditions are frequently triggered by hypoxic and/or ischemic events, most commonly cardiogenic shock and sepsis/septic shock. However, several other potential contributors have been identified especially for cholestatic liver dysfunction. Apart from chronic liver diseases and malignancies, iatrogenic factors such as total parenteral nutrition, high pressure ventilation, surgical procedures, drugs and blood transfusions promote its occurrence.In shock liver and in cholestatic liver disease, early detection and therapy of the underlying disease is the only established treatment.

Extracorporeal artificial liver support in hypoxic liver injury

The incidence of hypoxic liver injury, most commonly referred to as hypoxic hepatitis (HH), is up to 10% in critically ill patients. In the majority of cases, HH occurs as a consequence of haemodynamic impairment following cardiogenic or septic shock. A marked, dramatic increase in the aminotransferase levels in a setting of cardiocirculatory failure is the key characteristic of HH. HH may contribute to several complications such as hepatopulmonary syndrome and hypoglycaemia. The overall mortality after the onset of HH is approximately 50–60% within 1 month. We report a case of severe HH that was successfully bridged using the Molecular Adsorbent Recirculating System. In addition to the possible effects of extracorporeal liver support devices, the recognition of HH and therapy of the underlying disease that led to the occurrence of HH is of central importance.

Shock liver and cholestatic liver in critically ill patients

Liver dysfunction is frequently observed in critically ill patients. Its occurrence is associated with high morbidity and mortality. The most frequent entities of hepatic dysfunction in the intensive care unit are shock liver and cholestatic liver dysfunction with incidence rates up to 10 and 30 %, respectively.Both conditions are frequently triggered by hypoxic and/or ischemic events, most commonly cardiogenic shock and sepsis/septic shock. However, several other potential contributors have been identified especially for cholestatic liver dysfunction. Apart from chronic liver diseases and malignancies, iatrogenic factors such as total parenteral nutrition, high pressure ventilation, surgical procedures, drugs and blood transfusions promote its occurrence.In shock liver and in cholestatic liver disease, early detection and therapy of the underlying disease is the only established treatment.