Cirrhosis Injury Research Articles

Treatment With Albumin, Octreotide and Midodrine Is Effective as a Bridge to Liver Transplant in Both Hepatorenal Syndrome and Non HRS Acute Kidney Injury in Cirrhosis.

Treatment With Albumin, Octreotide and Midodrine Is Effective as a Bridge to Liver Transplant in Both Hepatorenal Syndrome and Non HRS Acute Kidney Injury in Cirrhosis.

Kidney damage biomarkers: Novel tools for the diagnostic assessment of acute kidney injury in cirrhosis

Kidney damage biomarkers: Novel tools for the diagnostic assessment of acute kidney injury in cirrhosis

Kidney injury in cirrhosis: pathophysiological and therapeutic aspects of hepatorenal syndromes

Acute kidney injury (AKI) is frequent in patients with cirrhosis. AKI and hyponatraemia are major determinants of the poor prognosis in advanced cirrhosis. The hepatorenal syndrome (HRS) denotes a functional and potential reversible impairment of renal function. Type 1 HRS, a special type of AKI, is a rapidly progressive AKI, whereas the renal function in type 2 HRS decreases more slowly. HRS is precipitated by factors such as sepsis that aggravate the effective hypovolaemia in decompensated cirrhosis, by lowering arterial pressure and cardiac output and enhanced sympathetic nervous activity. Therefore, attempts to prevent and treat HRS should seek to improve liver function and to ameliorate arterial hypotension, central hypovolaemia and cardiac output, and to reduce renal vasoconstriction. Ample treatment of HRS is important to prevent further progression and death, but as medical treatment only modestly improves long-term survival, these patients should always be considered for liver transplantation. Hyponatraemia, defined as serum sodium <130 mmol/L, is common in patients with decompensated cirrhosis. From a pathophysiological point of view, hyponatraemia is related to an impairment of renal solute-free water excretion most likely caused by an increased vasopressin secretion. Patients with cirrhosis mainly develop hypervolaemic hyponatraemia. Current evidence does not support routine use of vaptans in the management of hyponatraemia in cirrhosis.

Management of acute kidney injury in cirrhosis.

Acute kidney injury (AKI) is a relatively frequent problem, occurring in approximately 20% of hospitalized patients with cirrhosis. Although serum creatinine (S Cr) is the most commonly used method to determine AKI because of easy availability and low cost, practically it underestimates the extent of kidney injury in patients with chronic liver disease. AKI is defined as an abrupt rise in S Cr of 0.3mg/dl or more (>26.4mmol/l) or an increase of 150% or more (1.5-fold) from baseline. The cause of AKI in cirrhosis is multifactorial and is unique in terms of pathogenesis. The most common causes of AKI in cirrhosis can be subdivided into either functional or structural. The functional group includes volume-responsive (prerenal azotemia) and volume-unresponsive states (hepatorenal syndrome). Volume responsive is the most common type of AKI due to frequent use of diuretics, large volume abdominal paracentesis and gastrointestinal bleeding in patients with liver disease. The structural causes include acute tubular necrosis, tubulointerstitial and glomerular diseases. Patients with decompensated cirrhosis are in a vasodilatory state leading to a decrease in effective arterial blood volume, predisposing to AKI. Therefore, management of AKI depends on the underlying cause, and therapy should be directed toward removal of the cause. The outcome in cirrhosis when patients are on dialysis is very dismal. Every effort should be made to prevent AKI.

Clinical profile, precipitating factors & in-hospital mortality of acute kidney injury in cirrhosis of liver

Clinical profile, precipitating factors & in-hospital mortality of acute kidney injury in cirrhosis of liver

Acute Kidney Injury in Cirrhosis: A Changing Spectrum

Acute Kidney Injury in Cirrhosis: A Changing Spectrum

Urinary Neutrophil Gelatinase-Associated Lipocalin Predicts Mortality and Identifies Acute Kidney Injury in Cirrhosis

Kidney failure predicts mortality in patients with cirrhosis. Identification of kidney failure etiology and recognition of those at the highest mortality risk remains a challenge. We hypothesized that urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts mortality and identifies hepatorenal syndrome (HRS) in patients with cirrhosis. Prospectively enrolled patients with cirrhosis were investigated by uNGAL immunoblot upon hospital admission. Kidney failure type was determined blinded to NGAL measurements. One hundred eighteen patients were enrolled. Fifty-two (44 %) patients had normal kidney function, 14 (12 %) stable chronic kidney disease, 17 (14 %) prerenal azotemia, 20 (17 %) HRS, and 15 (13 %) intrinsic acute kidney injury (iAKI). Patients with HRS had uNGAL levels intermediate between prerenal azotemia [median (IQR) 105 (27.5-387.5) vs. 20 (15-45) ng/mL, p = 0.004] and iAKI [325 (100-700), p < 0.001]. Fifteen (13 %) patients died. In unadjusted analysis, uNGAL predicted inpatient mortality (OR 2.00, 95 % CI 1.36-2.94) and mortality or liver transplantation (OR 2.01, 95 % CI 1.42-2.85). In multiple regression models, uNGAL > 110 ng/mL (OR 6.05, 95 % CI 1.35-27.2) and HRS (OR 6.71, 95 % CI 1.76-25.5) independently predicted mortality, adjusting for age and serum creatinine >1.5 mg/dL. uNGAL strongly predicts short-term inpatient mortality in both unadjusted and adjusted models. Patients with HRS may have uNGAL levels intermediate between those with prerenal azotemia and iAKI. Further studies are needed to determine if uNGAL can improve discrimination of HRS from other types of acute kidney injury and predict short- and long-term cirrhosis outcomes.

Melatonin prevents increased asymmetric dimethylarginine in young rats with bile duct ligation

Identifying and treating kidney injury in cirrhosis is important. Bile duct ligation (BDL) is a commonly used cholestatic liver disease model. We hypothesized that asymmetric dimethylarginine (ADMA) is involved in BDL-induced oxidative stress and kidney injury, which can be prevented by melatonin. We also intended to elucidate whether increased ADMA is due to increased protein arginine methyltransferase-1 (PRMT1, ADMA-synthesizing enzyme) and/or decreased dimethylarginine dimethylaminohydrolase (DDAH, ADMA-metabolizing enzyme). Three groups of young rats were studied, sham (N = 7), untreated BDL rats (N = 9), and melatonin-treated BDL rats (N = 6, BDL + M). Melatonin-treated BDL rats received daily melatonin 1 mg/kg/day via intraperitoneal injection. One-third of the young BDL rats died compared with none in the BDL + M group. All surviving rats were killed 14 days after surgery. BDL rats had higher plasma aspartate aminotransferase, alanine aminotransferase, direct and total bilirubin, and ammonia levels than shams. They also had kidney injury characterized by increased tubulointerstitial injury scores and plasma creatinine and symmetric dimethylarginine levels, which melatonin prevented. Plasma ADMA levels were elevated in BDL rats, combined with increased hepatic PRMT1 and decreased renal DDAH activity. In addition, melatonin increased hepatic DDAH2 expression, increased DDAH activity and concomitantly decreased ADMA contents in both the liver and kidney. In conclusion, melatonin therapy decreased mortality and prevented kidney injury induced by BDL via reduction of ADMA (by increasing DDAH activity) and oxidative stress.

Immunologic Characterization of Posthepatitis Cirrhosis Caused by HBV and HCV Infection

No specific treatment can reverse the liver injury in cirrhosis. This study aims to characterize immune status and correlations between cirrhosis induced by HBV and HCV. Phenotypes of peripheral blood lymphocyte subsets (T, NK, regulatory T cells) and Th cytokine secretion were analyzed using flow cytometry in 42 HBV-cirrhotic and 40 HCV-cirrhotic patients. Cirrhotic patients had a lower proportion of CD3+CD8+T cells and NK cells, while the proportion of CD3+CD4+T cells and Treg cells were higher than those of healthy controls. The levels of Th2 cytokine (IL-6) in cirrhotic patients were increased, while only the Th1 cytokine (IFN-γ) increased in HBV-cirrhotic patients. These findings show that there is no difference between the cirrhotic groups except in the IFN-γ level. In cirrhosis, defects in innate, adaptive immune cells are likely regardless of which virus is involved. A cytokine imbalance may play a role in the development of posthepatitic cirrhosis.

Acute kidney injury in cirrhosis

Acute renal failure (ARF), recently renamed acute kidney injury (AKI), is a relatively frequent problem, occurring in approximately 20% of hospitalized patients with cirrhosis. Although serum creatinine may underestimate the degree of renal dysfunction in cirrhosis, measures to diagnose and treat AKI should be made in patients in whom serum creatinine rises abruptly by 0.3 mg/dL or more (>/=26.4 micromol/L) or increases by 150% or more (1.5-fold) from baseline. The most common causes of ARF (the term is used interchangeably with AKI) in cirrhosis are prerenal azotemia (volume-responsive prerenal AKI), acute tubular necrosis, and hepatorenal syndrome (HRS), a functional type of prerenal AKI exclusive of cirrhosis that does not respond to volume repletion. Because of the progressive vasodilatory state of cirrhosis that leads to relative hypovolemia and decreased renal blood flow, patients with decompensated cirrhosis are very susceptible to developing AKI with events associated with a decrease in effective arterial blood volume. HRS can occur spontaneously but is more frequently precipitated by events that worsen vasodilatation, such as spontaneous bacterial peritonitis. Specific therapies of AKI depend on the most likely cause and mechanism. Vasoconstrictors are useful bridging therapies in HRS. Ultimately, liver transplantation is indicated in otherwise reasonable candidates in whom AKI does not resolve with specific therapy.

Plasma Endothelin‐1 Levels of Children with Cirrhosis

Summary:We measured plasma concentration of endothelin‐1 in three children with Byler's disease, five with biliary atresia after portoenterostomy, and nine controls. No patients had ascites or hepatorenal syndrome. Plasma endothelin‐1 levels were significantly higher in patients with Byler's disease than in the controls (5.19 ± 0.90 versus 1.81 ± 0.19 pg/ml, respectively; p &lt; 0.01), but were normal in operated biliary atresia. Urinary concentrations of N‐acetyl‐β‐L‐glucosaminidase (NAG) were significantly higher in the patients with Byler's disease than in controls. Plasma endothelin‐1 level correlated significantly with serum concentration of bile acid (r = 0.91; p &lt; 0.01) and urinary concentration of NAG (r = 0.92; p &lt; 0.01). We conclude that plasma endothelin‐1 levels are high in patients with severe biliary cirrhosis and that endothelin‐1 may partially contribute to development of renal injury in cirrhosis.

DNA synthesis in hepatotoxic liver injury

An autoradiographic technique employing tritiated thymidine was used to study hepatic DNA synthesis in rats intoxicated with single or repeated doses of CCl 4. Results indicate the regenerative response which follows hepatotoxic injury can be correlated with histological activity of the liver lesion and is influenced by a circulating humoral factor. DNA synthesis was related to the degree of necrosis and inflammation, persisting with activity in acute lesions and returning to normal in inactive cirrhosis. In cirrhosis the regenerative response was noted in both parenchymal and connective tissue cells. It was of the same magnitude after reinjury as in normal animals receiving their first insult with CCl 4. Subsidence of histological activity and restoration of a normal DNA synthesis pattern was delayed after additional injury in cirrhosis. A thermostable substance carried in the albumin fraction of plasma and present during initiation of the regenerative response after administration of CCl 4 evoked a four-fold increase in DNA synthesis in the normal adult rat. It induced an increase in labeling during the early phase of the regenerative response but had no apparent influence on DNA synthesis during its maximum response following CCl 4 injury. Pretreatment with physiological doses of growth hormone and testosterone had no significant effect on either hepatic DNA synthesis, mitoses, necrosis, or inflammation following receipt of CCl 4. In contrast, cortisone decreased both the inflammatory reaction and DNA synthesis following administration of this hepatotoxin.