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Terlipressin and Albumin vs Albumin in Patients With Cirrhosis and Hepatorenal Syndrome : A Randomized Study

BACKGROUND & AIMS Hepatorenal syndrome is common in patients with advanced cirrhosis and constitutes a major problem in liver transplantation. There is no effective medical treatment for hepatorenal syndrome. METHODS Forty-six patients with cirrhosis and hepatorenal syndrome, hospitalized in a tertiary care center, were randomly assigned to receive either terlipressin (1-2 mg/4 hour, intravenously), a vasopressin analogue, and albumin (1 g/kg followed by 20-40 g/day) (n = 23) or albumin alone (n = 23) for a maximum of 15 days. Primary outcomes were improvement of renal function and survival at 3 months. RESULTS Improvement of renal function occurred in 10 patients (43.5%) treated with terlipressin and albumin compared with 2 patients (8.7%) treated with albumin alone (P = .017). Independent predictive factors of improvement of renal function were baseline urine volume, serum creatinine and leukocyte count, and treatment with terlipressin and albumin. Survival at 3 months was not significantly different between the 2 groups (terlipressin and albumin: 27% vs albumin 19%, P = .7). Independent predictive factors of 3-month survival were baseline model for end-stage liver disease score and improvement of renal function. Cardiovascular complications occurred in 4 patients treated with albumin alone and in 10 patients treated with terlipressin and albumin, yet permanent terlipressin withdrawal was required in only 3 cases. CONCLUSIONS As compared with albumin, treatment with terlipressin and albumin is effective in improving renal function in patients with cirrhosis and hepatorenal syndrome. Further studies with large sample sizes should be performed to test whether the improvement of renal function translates into a survival benefit.

Prognostic importance of the cause of renal failure in patients with cirrhosis.

BACKGROUND & AIMS The prognostic value of the different causes of renal failure in cirrhosis is not well established. This study investigated the predictive value of the cause of renal failure in cirrhosis. METHODS Five hundred sixty-two consecutive patients with cirrhosis and renal failure (as defined by serum creatinine > 1.5 mg/dL on 2 successive determinations within 48 hours) hospitalized over a 6-year period in a single institution were included in a prospective study. The cause of renal failure was classified into 4 groups: renal failure associated with bacterial infections, renal failure associated with volume depletion, hepatorenal syndrome (HRS), and parenchymal nephropathy. The primary end point was survival at 3 months. RESULTS Four hundred sixty-three patients (82.4%) had renal failure that could be classified in 1 of 4 groups. The most frequent was renal failure associated with infections (213 cases; 46%), followed by hypovolemia-associated renal failure (149; 32%), HRS (60; 13%), and parenchymal nephropathy (41; 9%). The remaining patients had a combination of causes or miscellaneous conditions. Prognosis was markedly different according to cause of renal failure, 3-month probability of survival being 73% for parenchymal nephropathy, 46% for hypovolemia-associated renal failure, 31% for renal failure associated with infections, and 15% for HRS (P < .0005). In a multivariate analysis adjusted for potentially confounding variables, cause of renal failure was independently associated with prognosis, together with MELD score, serum sodium, and hepatic encephalopathy at time of diagnosis of renal failure. CONCLUSIONS A simple classification of patients with cirrhosis according to cause of renal failure is useful in assessment of prognosis and may help in decision making in liver transplantation.

Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: A prospective study with time-dependent analysis

OBJECTIVES:The aim of this study was to investigate whether hyponatremia is a risk factor of overt hepatic encephalopathy (HE) in cirrhosis.METHODS:A total of 61 patients with cirrhosis were evaluated prospectively for 1 year and all episodes of overt HE were recorded. Predictive factors of HE were analyzed using a conditional model (Prentice, Williams, and Peterson) for recurrent events to assess the relationship between HE and time-dependent covariates. The effects of hyponatremia on the brain concentration of organic osmolytes were analyzed in 25 patients using 1H-magnetic resonance spectroscopy.RESULTS:Twenty-eight of the 61 patients developed 57 episodes of overt HE during follow-up. Among a number of clinical and laboratory variables analyzed, the only independent predictive factors of overt HE were hyponatremia (serum sodium <130 mEq/l), history of overt HE, serum bilirubin, and serum creatinine. Hyponatremia was associated with low brain concentration of organic osmolytes, particularly myo-inositol (MI). Furthermore, patients with low brain MI levels had a higher probability of development of overt HE compared with that of patients with high brain MI levels.CONCLUSIONS:In patients with cirrhosis, the existence of hyponatremia is a major risk factor of the development of overt HE. Treatment of hyponatremia may be a novel therapeutic approach to preventing HE in cirrhosis.

Effects of dilutional hyponatremia on brain organic osmolytes and water content in patients with cirrhosis.

In advanced cirrhosis there is a reduction in the brain concentration of many organic osmolytes, particularly myo‐inositol (MI). Hyponatremia could theoretically aggravate these changes as a result of hypo‐osmolality of the extracellular fluid. The aim of this study was to determine the effects of hyponatremia on brain organic osmolytes and brain water content in cirrhosis. Brain organic osmolytes, measured by 1H–magnetic resonance spectroscopy, and brain water content, as estimated by magnetization transfer ratio (MTR) and measurement of brain volume were determined in 14 patients with dilutional hyponatremia, 10 patients without hyponatremia, and eight healthy subjects. Patients with hyponatremia had remarkable lower levels of MI compared with values in nonhyponatremic patients and healthy subjects. Brain MI levels correlated directly with serum sodium and osmolality. Serum sodium was the only independent predictor of low brain MI levels. Serum sodium also correlated directly with other brain organic osmolytes, such as choline‐containing compounds, creatine/phosphocreatine, and N‐acetyl‐aspartate. By contrast, brain glutamine/glutamate levels were higher in patients with cirrhosis compared with values in healthy subjects and correlated with plasma ammonia levels but not with serum sodium or osmolality. No significant differences were found in MTR values and cerebral volumes between patients with and without hyponatremia. In conclusion, dilutional hyponatremia in cirrhosis is associated with remarkable reductions in brain organic osmolytes that probably reflect compensatory osmoregulatory mechanisms against cell swelling triggered by a combination of high intracellular glutamine and low extracellular osmolality. These findings may be relevant to the pathogenesis of encephalopathy in hyponatremic patients. (HEPATOLOGY 2004;39:1613‐1622.)

Effects of contrast media on renal function in patients with cirrhosis: A prospective study

Patients with cirrhosis are frequently submitted to radiological procedures that require the administration of contrast media. Contrast media is a well‐known cause of renal failure, particularly in the presence of some predisposing conditions. However, it is not known whether cirrhosis constitutes a risk factor for contrast media–induced renal failure. The aim of this study was to assess the possible nephrotoxicity of contrast media in patients with cirrhosis. In a first protocol, renal function was evaluated with sensitive methods (glomerular filtration rate using iothalamate I 125 clearance and renal plasma flow using iodohippurate I 131 clearance) before and 48 hours after the administration of contrast media in 31 patients with cirrhosis (20 with ascites, 5 with renal failure). Solute‐free water clearance, urine sodium, prostaglandins, and markers of tubular damage were also measured. The administration of contrast media was not associated with significant changes in renal function tests, neither in the whole group of patients nor in patients with ascites or renal failure. Urinary prostaglandin E2 and N‐acetyl‐β‐D‐glucosaminidase increased significantly, but sodium and solute‐free water excretion remained unchanged. In a second protocol, a different series of 60 patients with cirrhosis and renal failure were examined prospectively. No patient had renal failure due to contrast media. Only in 1 patient with septic shock was contrast media a possible contributing factor. In conclusion, the administration of contrast media is not associated with adverse effects on renal function in patients with cirrhosis. Cirrhosis does not appear to be a risk factor for the development of contrast media–induced nephrotoxicity. (HEPATOLOGY 2004;40:646–651.)

Clinical and pathologic factors associated with survival in young adult patients with fibrolamellar hepatocarcinoma

BackgroundFibrolamellar Carcinoma (FLC), a subtype of hepatocellular carcinoma (HCC), is a rare primary hepatic malignancy. Several aspects of the clinic features and epidemiology of FLC remain unclear because most of the literature on FLC consists of case reports and small cases series with limited information on factors that affect survival.MethodsWe did a retrospective analysis of the clinical and histological characteristics of FLC. We also determined the rate of cellular proliferation in biopsies of these tumors. We assessed whether these variables were associated with survival.ResultsWe found 15 patients with FLC out of 174 patients with HCC (8.6%). Between patients with these neoplasms, we found statistically significant survival, age at onset, level of alpha fetoprotein, and an earlier stage of the disease. The 1, 3 and 5 year survival in patients with FLC was of 66, 40 and 26% respectively. The factors associated with a higher survival in patients with FLC were age more than 23 years, feasibility of surgical resection, free surgical borders, absence of thrombosis or invasion to hepatic vessels and the absence of alterations in liver enzymes. The size of the tumor, gender, cellular proliferation and atypia did not affect the prognosis.ConclusionWe concluded that FLC patients diagnosed before 23 years of age have worse prognosis than those diagnosed after age 23. Other factors associated with worse prognosis in this study are: lack of surgical treatment, presence of positive surgical margins, vascular invasion, and altered hepatic enzymes.

Anabolic–androgenic steroids and liver injury

Athletes and nonathletes have been using anabolic–androgenic steroids (AAS) for a long time, in an inadequate and unsurveilled manner, with the aim of improving sports performance or for cosmetic purposes. AAS consumption is becoming more widespread and involving younger people, and there is a trend for self‐administration of higher doses and for combining AAS with other potentially harmful drugs. Almost any subject abusing AAS will experience adverse effects. Therefore, adverse effects from these exposures, including liver toxicity, are expected to increase in the years to come. The present manuscript describes a representative case of intrahepatic cholestasis with the intention to discuss AAS‐related liver toxicity (including the potential therapeutic role of ursodeoxycholic acid) and to comment on several aspects of the clinical scenario the gastroenterologist should be aware of.

Nutritional assessment and treatment of patients with liver cirrhosis

Prevalence of chronic liver diseases, including liver cirrhosis, is increasing worldwide. The nutritional state assessment in these patients is complicated, and besides anthropometry is based on several other tools in order to be more accurate. Specific dietary recommendations are needed in patients with chronic liver diseases in order to help prevent and treat liver decompensation because malnutrition is an independent predictor of mortality. This review focuses on essential aspects in the nutritional assessment of cirrhotic patients and some general recommendations for their treatment.

Malnutrition assessed through phase angle and its relation to prognosis in patients with compensated liver cirrhosis: A prospective cohort study

BACKGROUND Malnutrition is a frequent complication of cirrhosis and it has been associated to more severe disease and development of complications. Phase angle is a bedside reliable tool for nutritional assessment based on conductivity properties of body tissues. AIM To evaluate the association between malnutrition assessed through phase angle and mortality in patients with liver cirrhosis. METHODS We performed a prospective cohort study in a tertiary care centre; 249 patients were enrolled with 48 months of follow-up. Clinical, nutritional (malnutrition = phase angle ≤ 4.9°) and biochemical evaluations were performed. Students t-test and χ(2) method were used as appropriate. Kaplan-Meier curves and multivariate Cox regression were used to evaluate mortality. RESULTS Mean follow-up was 33.5 months. Survival analysis showed higher mortality in the malnourished group compared to the well-nourished group (p = 0.076), Kaplan-Meier curves were further stratified according to compensated and decompensated status showing higher mortality in compensated patients according to Child-Pugh (p = 0.002) and Model for End-Stage Liver Disease score (p = 0.008) when malnutrition was present. Multivariate analysis showed that malnutrition was independently associated with mortality (HR = 2.15, 1.18-3.92). CONCLUSIONS In our cohort, malnutrition was independently associated with mortality. This is the first study showing higher mortality in malnourished compensated cirrhotic patients.

Acute-on-chronic liver failure: a review.

There is no universally accepted definition of acute-on-chronic liver failure; however, it is recognized as an entity characterized by decompensation from an underlying chronic liver disease associated with organ failure that conveys high short-term mortality, with alcoholism and infection being the most frequent precipitating events. The pathophysiology involves inflammatory processes associated with a trigger factor in susceptible individuals (related to altered immunity in the cirrhotic population). This review addresses the different definitions developed by leading research groups, epidemiological and pathophysiological aspects, and the latest treatments for this entity.