Risk and Prognosis of Acute Liver Injury Among Hospitalized Patients with Hemodynamic Instability: A Nationwide Analysis

Introduction and aim. Critically ill patients in states of circulatory failure are at risk of acute liver injury, from mild elevations in aminotransferases to substantial rises consistent with hypoxic hepatitis or “shock liver”. The present study aims to quantify the national prevalence of acute liver injury in patients with hemodynamic instability, identify risk factors for its development, and determine predictors of mortality.Material and methods. The 2009-2010 Nationwide Inpatient Sample was interrogated using ICD-9-CM codes for hospital admissions involving states of hemodynamic lability. Multivariable logistic regression was used to evaluate the risks of acute liver injury and death in patients with baseline liver disease, congestive heart failure, malnutrition, and HIV.Results. Of the 2,865,446 patients identified in shock, 4.60% were found to have acute liver injury. A significantly greater proportion of patients with underlying liver disease experienced acute liver injury (22.03%) and death (28.47%) as compared to those without liver disease (3.18% and 18.82%, respectively). The odds of developing acute liver injury were increased in all baseline liver diseases studied, including all-cause cirrhosis, hepatitis B, hepatitis C, alcoholic liver disease, and non-alcoholic fatty liver disease, as well as in congestive heart failure and malnutrition. All-cause cirrhosis and alcoholic liver disease, however, conferred the greatest risk. Similar trends were seen with mortality. HIV was not a predictor for acute liver injury.Conclusion. Liver injury is a major concern among patients with protracted circulatory instability, especially those suffering from underlying liver disease, heart failure, or malnutrition.     

Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases

The centrilobular liver cell necrosis observed in hypoxic hepatitis is generally attributed to failure of hepatic blood perfusion. Accordingly, this injury of the liver is commonly recognized under the terms "shock liver" or "ischemic hepatitis." During a 10-year period, 142 episodes of hypoxic hepatitis were consecutively identified in the intensive care unit of a general hospital, and the clinical, biological, and hemodynamic parameters were prospectively collected on individual files. We conducted the current study to assess retrospectively the role of the hemodynamic mechanisms of tissue hypoxia: ischemia, passive venous congestion, and hypoxemia. Among the 142 episodes of hypoxic hepatitis, 138 were separated in 4 main groups based on clinical features: decompensated congestive heart failure (80 cases), acute cardiac failure (20 cases), exacerbated chronic respiratory failure (19 cases), and toxic/septic shock (19 cases). An elementary hemodynamic evaluation, including blood pressure, central venous pressure, and arterial blood gas analysis, was carried out in every episode and a more complete hemodynamic assessment through pulmonary artery catheterization was performed in 61 episodes.The hemodynamic mechanisms responsible for hypoxic hepatitis were different in the 4 groups. In congestive heart failure and acute heart failure, the hypoxia of the liver resulted from decreased hepatic blood flow (ischemia) due to left-sided heart failure and from venous congestion secondary to right-sided heart failure. In chronic respiratory failure, liver hypoxia was mainly due to profound hypoxemia. In toxic/septic shock, oxygen delivery to the liver was not decreased but oxygen needs were increased, while the liver was unable to use oxygen properly. In all conditions underlying hypoxic hepatitis, except toxic/septic shock, a shock state was observed in only about 50% of the cases. Therefore, the expressions "shock liver" or "ischemic hepatitis" are misleading and should be replaced by the more general term "hypoxic hepatitis."     

Liver transplantation for acute or chronic liver failure by hepatitis non-A, non-B and hepatitis C viral infections: a postoperative follow-up.

Orthotopic liver transplantation (OLT) was performed for liver failure related to hepatitis non-A, non-B (HNANB) or hepatitis C (HCV) infections in 12 patients. Of those, 8 patients had chronic and 4 acute hepatic failure. To determine the incidence of recurrent infection, the clinical course, histological findings and serological HCV markers (HCV-RNA and detection of anti HCV antibodies, respectively) were comparatively studied in these patients. Recurrent infection was apparent in 5 of 6 patients transplanted for liver cirrhosis attributable to chronic HCV infection and with HCV-RNA detectable in serum. The clinical course of infection after OLT varied considerably. Chronic active hepatitis, progressing to liver cirrhosis 13 months postoperatively and an acute hepatitis, resolving spontaneously were seen in one case each. Recurrent infection led to chronic persistent hepatitis in the remainder. None of the patients with acute liver failure experienced recurrent infection. HCV-RNA was detectable in all the patients after OLT, with HCV-RNA present pretransplant, however the presence of HCV-RNA in serum was not necessarily associated with clinical illness.     

Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder

Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure.     

The heart and the liver

Cardiac failure affects the liver and liver dysfunction affects the heart. Chronic and acute heart failure can lead to cardiac cirrhosis and cardiogenic ischemic hepatitis. These conditions may impair liver function and treatment should be directed towards the primary heart disease and seek to secure perfusion of vital organs. In patients with advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced cardiac performance with systolic and diastolic dysfunction and electrophysical abnormalities, termed cirrhotic cardiomyopathy. Pathophysiological mechanisms include reduced β-adrenergic receptor signal transduction and defective cardiac electromechanical coupling. However, the QT interval is prolonged in approximately half of patients with cirrhosis and it may be improved by β-blockers. No specific therapy can be recommended but it should be supportive and directed against the heart failure. Transjugular intrahepatic portosystemic shunt insertion and liver transplantation affect cardiac function in portal hypertensive patients and cause stress to the cirrhotic heart, with a risk of perioperative heart failure. The risk and prevalence of coronary artery disease are increasing in cirrhotic patients and since perioperative mortality is high, careful evaluation of such patients with dobutamine stress echocardiography, coronary angiography and myocardial perfusion imaging is required prior to liver transplantation. Future research should focus on beneficial effects of treatment on cardiac function and mortality.     

"Acute liver failure": the heart may be the matter

Hypoxic hepatitis secondary to heart failure is a known and treatable cause of liver failure. The diagnosis may be difficult, especially when symptoms of heart failure are absent. We present two patients who were transferred to our hospital with the diagnosis of acute liver failure to be screened for a liver transplantation. Both patients had increased serum levels ofaminotransferases, lactic acidosis, coagulation disorders, and non-specific clinical symptoms. Echocardiography revealed right ventricular dysfunction. Treatment with inotropes resulted in a fast normalization of liver enzymes, acidosis and coagulation, confirming the diagnosis hypoxic hepatitis. In conclusion, when the cause of acute liver dysfunction is unclear, hypoxic hepatitis due to heart failure should be considered and echocardiography should be performed, even when symptoms are non-specific for heart failure.     

Hepato-cardiac disorders

Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist's clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases     

Hepato-cardiac disorders简

Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases     

Effect of CCL4-induced cirrhosis on the pathophysiologic course of acute myocardial infarction in nonarteriosclerotic vs arteriosclerotic male rats.

Arteriosclerotic and nonarteriosclerotic rats were treated with carbon tetrachloride (CCL4) to induce cirrhosis of the liver. Massive myocardial infarction was then induced in intact and CCL4-treated animals. During acute necrosis (Days 1 thru 3), animals were killed at 4, 8, 12 and 24 h on Days 1 and 2, and during myocardial repair on Days 4, 5 and 8. During the induction of cirrhosis, animals developed polydypsia, polyuria, and hyperglycemia; during myocardial infarction, the arteriosclerotic + cirrhotic animals developed severe and persistent congestive heart failure, i.e., hydrothorax. Adrenal and thymus gland weights and corticosterone levels indicated that cirrhosis per se increased pituitary--adrenal activity, particularly in arteriosclerotic animals. Enzyme levels of SGOT and SGPT demonstrated severe hepatic damage due to cirrhosis and acute myocardial infarction. Blood triglycerides and cholesterol responded abnormally in cirrhotic animals during acute myocardial ischemia due to their entrapment within hepatic cells. The cirrhotic animals manifested poor myocardial repair with persistent foci of necrosis, calcification, and a high incidence of large, occlusive, atrial thrombi. It is suggested that cirrhosis interferes with lipid metabolism and adrenal steroid conjugation leading to abnormal levels of mineralocorticoids which favor congestive heart failure, poor myocardial repair, and atrial thrombosis.     

Clinical liver disease in patients with rheumatoid arthritis taking methotrexate.

Between 1981 and 1989, 3 of 134 patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) developed clinically significant hepatic dysfunction and showed histologic evidence of severe liver disease (fibrosis and cirrhosis). Factors identified in these patients that may have been linked to liver toxicity included diabetes, congestive heart failure and Felty's syndrome. In the patient group that received a post-MTX liver biopsy, pulmonary fibrosis and obesity were significantly associated with hepatic fibrosis/cirrhosis. Severe liver disease may occur in patients with RA treated with low dose MTX (less than 3%). Early liver biopsy is recommended in selected cases.     

Congestive heart failure as cause of fulminant hepatic failure

In this patient with long-standing cardiomyopathy and congestive heart failure the syndrome of fulminant hepatic failure developed on two occasions; he recovered both times. There was no evidence of viral or toxic hepatitis as a cause of his liver failure. We conclude that in this case, aggravation of long-standing congestive heart failure may have led to severe hepatocellular necrosis with signs of encephalopathy not commonly observed.     

Pleural effusion and serum soluble fas-ligand levels are elevated in different clinical conditions

Fas ligand (FasL) plays an important role in the regulation of apoptosis. Soluble FasL (sFasL) is produced by a cleavage of FasL from the cell surface by metalloproteinase. Whether or not sFasL exists or is elevated in the pleural effusion of different etiologies is unknown. The present study is designed to determine pleural effusion and serum sFasL levels under different clinical conditions, and ascertain if there exists a significant difference in the levels found in different clinical conditions, and whether this difference can be used as a tool for differential diagnosis. Soluble FasL levels in the pleural effusion and serum of 103 patients, including 37 with malignant pleural effusion, 24 with uncomplicated parapneumonic effusion, 8 with bacterial empyema, 16 with tuberculous pleurisy, and 18 with transudate effusion (8 with congestive heart failure and 10 with viral liver cirrhosis), were analyzed with ELISA assays. Pleural effusion from patients with bacterial empyema (median 79.4 pg/ml) and TB pleurisy (median 31.9 pg/ml) contained significantly higher amounts of sFasL than the pleural effusion from all other conditions studied (p <0.001). Viral liver cirrhosis had a significantly higher serum sFasL level (median 53.6 pg/ml, p = 0.025, when compared with other patients). Patients with congestive heart failure had the lowest serum sFasL levels when compared with other patients (p = 0.014). There was no significant correlation between pleural effusion sFasL levels and other parameters, such as effusion LDH, cell count, neutrophil, and lymphocyte percentage. In conclusion, soluble FasL is a useful marker for the differentiation of bacterial empyema and TB pleurisy from other disease entities. In addition, the elevation of serum sFasL levels in viral liver cirrhosis can also be used to differentiate cirrhosis from congestive heart failure, in which both effusions are transudate.     

Analysis of hepatic hemodynamics by a new method of per-rectal portal scintigraphy using 99mTcO4- (direct intramural administration of radioisotope)

To depict of porto-systemic collaterals clearly, and to analyze of hemodynamics of liver, we developed new method of per-rectal portal scintigraphy (direct intramural administration of 99mTcO4- by 23G needle). And we used this method in patient with liver diseases (acute hepatitis: 5, chronic hepatitis: 7, liver cirrhosis: 25 cases). From time activity curve of the liver and the heart, liver/heart ratio; index of porto-systemic shunt via inferior mesenteric vein (IMV) and first flow ratio(k); index of portal blood flow from IMV pathway/index of hepatic total blood flow were calculated. In our method, the images of portal vein, liver, heart, especially porto-systemic collaterals were visualized more clearly than enema methods. The liver/heart ratio was significantly lower in patients with liver cirrhosis than that in non-cirrhotic patients (p less than 0.01), which indicated that patients with liver cirrhosis had more porto-systemic collaterals than non-cirrhotic diseases. The k was more lower in liver cirrhosis than in acute hepatitis (p less than 0.01). And the k was also more lower in chronic hepatitis than in acute hepatitis (p less than 0.1), which indicated that portal blood flow via IMV reduced in early stage of chronic liver diseases. In conclusion, new method of per-rectal portal scintigraphy has more advantage for analysis of hepatic hemodynamics than enema methods.     

Hemorrhagic ascites due to congestive heart failure

Ascites due to congestive heart failure (CHF) is characteristically serous in gross appearance. Although hemorrhage into ascites commonly indicates a malignant or inflammatory cause, cirrhosis of the liver is a well known cause of bloody ascites. We report a case of hemorrhagic ascites due to biventricular congestive heart failure in which workup for other causes was negative and hemorrhage cleared after 4 months. In as much as the mechanism of ascites is similar in both cirrhosis and CHF, we propose that a similar mechanism could cause bleeding into ascites in CHF.     

肝病患者内毒素血症的临床意义

目的探讨四种肝病内毒素血症（ｅｎｄｏｔｏｘｅｍｉａ,ＥＴＭ）的发生率及其临床意义方法１９９７－０２／１９９８－０６山西医科大学第一医院传染病科住院的急、慢性肝炎、肝炎肝硬变及重症肝炎患者３２０例采用基质显色法鲨试验定量检测血浆内毒素（ｅｎｄｏｔｏｘｉｎ,ＥＴ）水平,应用放射免疫分析法测定血浆肿瘤坏死因子（ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒＴＮＦ）水平,采用琼脂单向免疫扩散法测定血浆纤维连接蛋白（ｆｉｂｒｏｎｅｃｔｉｎ,Ｆｎ）含量,采用速率法在全自动生化分析仪．上测定血浆丙氨酸转氨酶（ａｌａｎｉｎｅ　ａｍｉｎｏｔｒａｎｓｆｅｒａｓｅＡＬＴ）活性．结果肝病患者血浆ＥＴ,ＡＬＨ,ＴＮＦ含量明显高于健康对照组（Ｐ＜０．０１）,而在肝炎肝硬变、重症肝炎组Ｆｎ含量均明显低于对照组重症肝炎、肝炎肝硬变、慢性肝炎、急性肝炎患者肠源性内毒素血症（Ｉｎｔｅｓｔｉｎａｌｅｎｄｏｔｏｘｅｍｉａ,ＩＥＴＭ）发生率分别为９３．３％,８４．３％,７９．０％与７５．０％．结论肝病患者长期持续存在的ＩＥＴＭ可加剧肝细胞损伤,在急性肝炎重症化与慢性化中均具有其重要作用     

Immunological parameters in the differential diagnosis of ascites secondary to peritoneal carcinomatosis, hepatic cirrhosis, and congestive heart failure]

As a contribution to the study of ascites in patients with liver cirrhosis, congestive heart failure and peritoneal carcinomatosis evaluate in serum and ascites the concentrations of alphafetoprotein, carcinoembryonic antigen and fibronectin, they might suggest a diagnosis for the basic pathology. Forty-seven patients were studied, from whom 23 with cirrhosis, 17 peritoneal carcinomatosis and 7 with congestive heart failure. We conclude that: a) none of the tools usually employed in the analysis of ascitic fluid alone can make the base pathological process responsible for producing ascites; b) fibronectins were more useful for differential diagnosis between cirrhosis and carcinomatosis; c) alpha-fetoprotein and carcinoembryonic antigen were not useful for the definition for differential diagnosis.     

Overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis with unusual initial presentation as fulminant hepatic failure

Autoimmune hepatitis and primary biliary cirrhosis are generally easy to discriminate on the basis of clinical, laboratory, and histological findings. The presence of anti-mitocondrial antibodies seropositivity and cholestatic clinical, laboratory, and/or histological features in patients with autoimmune hepatitis indicates the overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis. Fulminant hepatic failure is an unusual initial form of presentation of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome. We report the case of a 50-year-old woman with autoimmune hepatitis and primary biliary cirrhosis overlap syndrome who presented with fulminant hepatic failure. Fulminant hepatic failure has a high mortality rate and may require liver transplant. Our patient revealed a good response to corticosteroid and ursodeoxycholic acid therapy. It is important to identify and distinguish autoimmune hepatitis and variant syndromes from other forms of liver disease because of response to corticosteroid therapy.     

Hepatitis E virus superinfection impairs long-term outcome in hospitalized patients with hepatitis B virus-related decompensated liver cirrhosis

Introduction and objectivesHepatitis E virus (HEV) superinfection is a common excerbating event in patients with chronic hepatitis B, but the impact on the long-term prognosis is not clear. This study investigates the specific role of HEV superinfection in the long-term outcome of hepatitis B virus (HBV) patients with liver cirrhosis.Patients and methodsA retrospective, observational cohort study was conducted using clinical, laboratory, and survival data collected from patients suffering from hepatitis B cirrhosis with or without HEV superinfection. Disease progression and mortality rates were analyzed.ResultsAfter a two-year follow-up, HEV superinfection was identified in 27 of 811 patients. The transplantation-free mortality was significantly increased (51.9% vs. 14.3%, p< 0.001) in HEV superinfection compared to that in hepatitis B cirrhosis patients without HEV superinfection. Logistic regression analysis demonstrated that elderly people were independent host risk factors for hepatitis B cirrhosis patients with HEV superinfection before and after propensity score matching (PSM). Moreover, HEV superinfection was a risk factor for patients with hepatitis B cirrhosis with new acute decompensation (AD) and acute-on-chronic liver failure (ACLF) during hospitalization. A multivariate Cox proportional hazards regression model demonstrated that acute HEV co-infection is associated with two-year mortality (hazard ratio [HR]: 2.49; 95% CI: 1.40–4.43; p= 0.002; and HR: 5.79; 95% CI: 1.87–17.87; p= 0.002) in patients with hepatitis B cirrhosis before and after PSM.ConclusionsElder patients with hepatitis B cirrhosis are susceptible to HEV superinfection, accelerating disease progression and increasing long-term mortality in hospitalized patients with HBV-related decompensated liver cirrhosis.     

The brain in congestive heart failure

In the present paper we discuss two issues about relationships between congestive heart failure and the brain. First, major acute cerebrovascular events are very frequent among elderly people, but stroke does not appear to be frequently associated with congestive heart failure. Second, some cardiovascular conditions may determine progressive damage of cerebral tissue, with consequent impairment of cognitive functions. The association of cognitive impairment and cardiovascular diseases may dramatically increase morbility and mortality risks in the elderly. Recent studies seem to show that hypotension and congestive heart failure are risk factors for dementia in elderly people. In view of this data, an Italian multicentric study on congestive heart failure in hospitalized elderly patients (CHF Italian Study I) included a brief screening of cognitive abilities (MMSE). The presence of congestive heart failure induced a significant decrease of MMSE scores: mean MMSE score after statistical adjustment for the other variables was about one point lower in patients with congestive heart failure respect to elderly patients affected by heart disease but without congestive heart failure. A novel multicentric study (CHF Italian Study II) has been performed to identify cognitive functions more specifically impaired during congestive heart failure in the elderly. Preliminary data relative to 385 patients, confirmed that congestive heart failure may induce a generalized impairment of cognitive functions. These data have relevant clinical implications because they demonstrate that a multidisciplinary approach is necessary in these patients, both for prevention and rehabilitation therapy.     

Esophageal varices without portosystemic venous pressure gradient in a patient with post-pericardiotomy constrictive pericarditis: a case report

A 51-year-old woman was admitted with intractable congestive heart failure and progressive anemia. She had undergone mitral valve replacement for mitral regurgitation at age 23 years. Subsequently, her mitral prosthesis was replaced twice due to thrombotic stack and valve insufficiency. Signs of congestive heart failure became evident at age 46 years. Gastrointestinal endoscopy revealed esophageal varices, which were treated by endoscopic variceal ligation. Cardiac catheterization disclosed elevated pulmonary capillary wedge pressure (mean 16 mmHg), right atrial pressure (mean 15 mmHg), and hepatic vein wedge pressure (mean 15 mmHg). She died at age 53 years. Autopsy showed severe congestive liver but not liver cirrhosis. Esophageal varices may progress in spite of the absence of porto-systemic pressure gradient in patients with severely high venous pressure.