One-week losartan administration increases sodium excretion in cirrhotic patients with and without ascites

Background. Losartan, a highly selective angiotensin II type 1 receptor antagonist, has been reported to have a significant portal hypotensive effect in cirrhotic patients. A recent study also showed that losartan exerted a dramatic natriuretic effect in preascitic cirrhosis. The influence of losartan on renal hemodynamics and sodium homeostasis in cirrhotic patients with ascites is unclear. This study was undertaken to evaluate the renal effects of 1-week losartan treatment in cirrhotic patients with and without ascites. Methods. All 12 patients in the study received a daily oral dose of 25 mg losartan for 7 consecutive days. Effective renal plasma flow, urine volume, creatinine clearance, 24h urine sodium excretion and fractional excretion of sodium, blood urea nitrogen, and serum creatinine were measured before and after treatment. Results. In cirrhotic patients without ascites, creatinine clearance, 24-h urinary sodium excretion, and fractional excretion of sodium were significantly increased after losartan administration. Effective renal plasma flow and serum creatinine showed almost no change after treatment. In cirrhotic patients with ascites, creatinine clearance, 24-h urinary sodium excretion, fractional excretion of sodium, and effective renal plasma flow were significantly increased after losartan administration. In addition, the magnitudes of the increases in the fractional excretion of sodium and in the 24-h urinary sodium excretion were greater in cirrhotic patients with ascites than in those without ascites. Conclusions. One-week treatment with losartan increases sodium excretion in association with an improvement of renal function in cirrhotic patients with and without ascites. The natriuretic effect was more profound in cirrhotic patients with ascites than in those without ascites. Received: May 1, 2001 / Accepted: August 24, 2001     

Non-selective beta-blocker treatment does not impact on kidney function in cirrhotic patients with varices

Goals and background: Non-selective beta-blockers (NSBBs) are used for bleeding prophylaxis in cirrhotic patients with gastroesophageal varices (GEVs). Recent data suggested that NSBB treatment might increase the risk of renal dysfunction in patients with refractory ascites due to an impaired response to acute haemodynamic stress.

Study: Retrospective longitudinal assessment of kidney function in a cohort of cirrhotic patients with GEVs with vs. without NSBB therapy. Serum creatinine (SCre), estimated glomerular filtration rate (eGFR), incidence of acute kidney injury (AKI), new onset of large volume ascites and TIPS-/transplant-free survival were compared.

Results: Among 176 patients, 93 patients received NSBBs, while 83 did not. Most patients were male (77.8%), had alcoholic aetiology (52.3%) and compensated cirrhosis (51.1% Child-A, MELD: 12.1?±?3.8). Over a 3-year follow-up, renal function was comparable between patients with and without NSBB treatment. Incidence of AKI was similar in NSBB vs. no-NSBB patients (p?=?.323). Even in potential risk groups (ascites, MAP <90?mmHg, baseline creatinine?>?ULN, hyponatraemia, MELD score ≥15 points, Child–Pugh B/C), there was no difference in SCre or eGFR with vs. without NSBBs (p?=?n.s. at 74/78 and 76/78 of analysed time points). However, multivariate analysis revealed that the presence of ascites (HR: 3.901, 95%CI: 1.352–11.251; p?=?.012) and pre-existing renal impairment (HR: 4.315, 95%CI: 1.054–17.672; p?=?.042) were independent risk factors for AKI. Importantly, NSBB use (HR: 0.319, 95%CI: 0.120–0.848; p?=?.022) was independently associated with improved TIPS-/transplant-free survival.

Conclusions: In our cohort of unselected, mostly compensated cirrhotic patients with GEVs, NSBB treatment was neither associated with worsening of kidney function nor with increased incidence of AKI. On the contrary, NSBB treatment improved TIPS-/transplant-free survival.     

Terlipressin and Albumin in Patients with Cirrhosis and Type I Hepatorenal Syndrome

Purpose: Hepatorenal syndrome (HRS) is a pre-renal-like dysfunction that generally onsets in cirrhotic patients presenting ascites. We investigated the improvement of renal function in subjects with hepatorenal syndrome after terlipressin administration and the survival times after this treatment. Fifty-two patients affected by cirrhosis, with diagnosis of hepatorenal syndrome were treated with intravenous terlipressin plus albumin (group A) or with albumin alone (group B). Liver and renal function, plasma renin activity, and aldosterone plasma levels were monitored. Results: Patients from group A showed a significant improvement (p < 0.001) of renal function valued by creatinine rate compared with the results obtained in group B. The probability of survival was higher in the group A (p < 0.0001). Conclusions: Our results seem to confirm that the administration of terlipressin plus albumin improves renal function in patients with cirrhosis and type I HRS and that a reversal of hepatorenal syndrome is strongly associated with improved survival.     

The renal effects of the addition of low-dose aspirin to COX-2 selective and nonselective antiinflammatory drugs

Objective: We aimed to evaluate the effect on renal functions and blood pressure of the addition of low dose aspirin (LDA) to cyclooxygenase-2 (COX-2) inhibitors or nonselective NSAIDs. Methods: Two groups each containing 14 patients with one group using celecoxib and the other indomethacin regularly for at least 1 week were included into the study. Both groups were initially administered 100 mg/day (week 1), and later 300 mg/day (week 2) aspirin. Baseline and weekly serum creatinine, uric acid, electrolytes, creatinine clearance (CrCl) and blood pressure were obtained. Results: Contrary to the celecoxib group, in the indomethacin group, both after the first and the second weeks the mean serum creatinine increased and CrCl decreased when compared to baseline values (p values<0.05). In the indomethacin group, when compared to baseline values systolic blood pressure was significantly higher after week 1 and uric acid level after week 2 (p values=0.01). The frequency of patients with a 20% decrease in CrCl at the end of week 2 was higher in the indomethacin group than in the celecoxib group (42.9% vs. 0%, p=0.016). The difference between the mean creatinine (p=0.017) and CrCl values (p=0.007) from baseline until after week 2 was more significant in the indomethacin group than in the celecoxib group. Conclusions: The addition of LDA to patients using indomethacin led to significant renal dysfunction. Subjects using celecoxib seem to have been protected from the renal side effects of LDA.A conflict of interest statement: There are no conflicts of interest.     

Renal function and cognitive impairment in patients with liver cirrhosis

Objective. Cognitive impairment is a common problem in patients with liver cirrhosis. Its pathogenesis is multifactorial and ammonia is considered to play a central role. Renal function has been shown to be important for ammonia metabolism in cirrhosis. Although renal dysfunction is common in cirrhotic patients, its effect on cognitive function is largely unexplored. Material and methods. A total of 128 consecutive cirrhotic patients were prospectively evaluated for the presence of cognitive dysfunction according to the West-Haven criteria and by means of two psychometric tests. Serum creatinine, sodium and potassium as well as plasma ammonia concentrations were assessed. Glomerular filtration rate was also measured by ⁵¹Cr- EDTA clearance in a subgroup of patients. Results. Forty-one patients (32%) were found to have cognitive dysfunction (clinical evaluation and/or psychometric tests). Sixteen patients (13%) found with serum creatinine levels above reference values had cognitive dysfunction more frequently than patients with creatinine within the normal range (69% versus 31%; p=0.001), but did not differ in aetiology or severity of cirrhosis (p>0.1). Patients with loop diuretics versus without did not differ in creatinine values (p>0.1). Multivariate analysis showed that cognitive dysfunction was related to hospital admission at inclusion in the study, international normalized ratio and serum creatinine (p<0.05 for all), but not to potassium or sodium levels. Plasma ammonia concentration was related to serum creatinine (r=0.26, p=0.004) and the glomerular filtration rate (r=?0.44, p=0.023). Conclusions. Renal dysfunction seems to be related to cognitive impairment in patients with liver cirrhosis and might be implicated in the pathogenesis of hepatic encephalopathy.     

Prevention of paracentesis-induced circulatory dysfunction in cirrhosis: Standard vs half albumin doses. A prospective, randomized, unblinded pilot study

Background

Paracentesis-induced circulatory dysfunction is a well-known complication of large volume paracentesis. Albumin infusion (8 g of albumin/L of ascites removed) is effective in preventing it, but high costs and scant availability limit its use.

Aim

To compare standard vs half albumin doses.

Methods

Seventy cirrhotic patients treated with large volume paracentesis were randomized to receive intravenous albumin as prevention of paracentesis-induced circulatory dysfunction: group 1 (35 patients) received 4 g/L of ascites removed, group 2 (35 patients) received 8 g/L of ascites removed.

Results

The incidence of paracentesis-induced circulatory dysfunction (14% vs 20% in group 1 and group 2, respectively; p = ns), hyponatremia (9% vs 6%, p = ns) and renal impairment (0% in both groups) on the 6th day from paracentesis was similar between the two groups. After 6 months of follow-up, rates of survival and of recurrence of ascites requiring large volume paracentesis were not different between the two groups.

Conclusions

This unblinded, randomized, pilot study suggests that treatment with half doses of albumin is effective in the prevention of paracentesis-induced circulatory dysfunction and its related clinical complications in cirrhotic patients with tense ascites treated by large volume paracentesis. If confirmed, these results could support a significant costs reduction in the management of ascites in cirrhotic patients.     

Noninvasive assessment of spontaneous baroreflex sensitivity in patients with liver cirrhosis

Abstract: Aims/Background: An impairment of baroreceptor sensitivity has been found in liver cirrhosis. Noninvasive and spontaneous estimates of baroreflex sensitivity are obtained from beat-to-beat blood pressure and heart rate recordings by means of cross-spectrum analysis and calculation of alpha-index (as a measure of baroreflex gain). The aim of the present study was to investigate the function of the spontaneous baroreflex sensitivity related to clinical Child score in liver cirrhosis. Methods: The alpha-index was evaluated in 40 cirrhotic patients (18 with and 22 without ascites) and 17 healthy subjects by analysing finger arterial pressure recorded noninvasively with the Portapres device. Results: Baroreflex sensitivity was significantly lower in cirrhotic patients with and without ascites compared with healthy subjects (p<0.01). Furthermore, in patients with ascites the baroreflex gain was significantly related to plasma sodium (p<0.01). A significant inverse relationship was present between baroreflex gain and grade of Child score and the severity of ascites (p<0.01). There were no significant relationships between hormonal parameters (catecholamines, renin, aldosterone, arginine-vasopressin, atrial natriuretic peptide and nitric oxide) and baroreflex gain. No significant differences were found between healthy subjects and cirrhotic patients with respect to systolic and diastolic blood pressure total variability in a supine position, whilst it was lower in cirrhotic patients with ascites in a tilted position (p<0.05). Conclusion: Our findings showed that baroreflex sensitivity was significantly impaired in cirrhotic patients when compared with healthy subjects. In addition, there was a significant trend toward lower baroreflex sensitivity values with the grade score of Child class (p<0.01). Spectral analysis of the alpha-index provides viable alternatives to the pharmacological approach for estimation of baroreflex sensitivity and may represent a prognostic tool to identify cirrhotic patients at increased risk of adverse events.     

Transjugular intrahepatic portosystemic shunt versus paracentesis plus albumin in patients with refractory ascites who have good hepatic and renal function: a prospective randomized trial

Background

Transjugular intrahepatic portosystemic shunt (TIPS) has recently been reported to be effective in the treatment of cirrhotic patients with refractory ascites. However, the clinical utility of TIPS in the subset of refractory ascitic patients with good hepatic and renal function is uncertain. The aim of this study was to compare the efficacy of TIPS to that of large-volume paracentesis in cirrhotic patients with refractory ascites who have good hepatic and renal function.

Methods

Sixty cirrhotic patients with refractory ascites who presented with a Child?CPugh score of <11, serum bilirubin of <3?mg/dl and creatinine of <1.9?mg/dl were assigned randomly to TIPS (n?=?30) or large-volume paracentesis plus albumin (n?=?30). The primary endpoint was survival. The secondary endpoints were response to treatment and development of hepatic encephalopathy.

Results

The baseline characteristics were similar in the two groups. Seventeen patients treated with TIPS and 21 treated with paracentesis died during the study period. The cumulative probabilities of survival at 1 and 2?years were 80 and 64% in the TIPS group and 49 and 35% in the paracentesis group (p?<?0.005). TIPS was significantly superior to paracentesis in the control of ascites (p?<?0.005). Treatment failure was more frequent in the paracentesis group, whereas the frequency of hepatic encephalopathy was greater in the TIPS group.

Conclusions

In cirrhotic patients with refractory ascites who have good hepatic and renal function, TIPS improves survival and provides better control of ascites than large-volume paracentesis.     

Effects of "body compression" on parameters related to ascites formation: therapeutic trial in cirrhotic patients

Decreased effective circulating blood volume is an important factor in ascites formation in liver cirrhosis. We designed a "body compression" apparatus as a means to restore effective blood volume and investigated its effectiveness in reducing ascites formation in cirrhotics in terms of its effect on parameters of ascites formation noted below. The subjects, eight cirrhotics with ascites and eight cirrhotics without ascites were given spironolactone (50–75 mg/day) and furosemide (40–80 mg/day) while they received a diet containing 85 mEq of sodium per day. All four limbs and the lower abdomen were compressed with constant pressure [height (cm) divided by 13.6 mmHg] once, for 3 h, using stroke rehabilitation splints, while patients lay supine. In cirrhotics both with and without ascites, urine volume, urinary sodium excretion, and creatinine clearance during the body compression were greater than values during control (non-compression) periods (urine volume, means 285 vs 169 ml/3 h; P < 0.001, urinary sodium excretion 15.8 vs 9.5mEq/3h; p < 0.001, creatinine clearance 74 vs 59 ml/min, P < 0.001, respectively). The increased basal plasma renin activity, angiotensin II, aldosterone, and norepinephrine levels in all cirrhotics were significantly decreased by the body compression. In another group of six cirrhotics who received no diuretics or albumin, repeat body compression alleviated ascites in three with well preserved renal function, but was ineffective in three with markedly impaired renal function. These results suggest that the improvement in renal function brought about by the body compression is attributable to an increase in effective circulating blood volume. This maneuver may be a useful complementary therapy in patients with cirrhotic ascites with well preserved renal function. (Received Jan. 12, 1998; accepted June 26, 1998)     

The Dose-Dependent Effect of Misoprostol on Indomethacin-Induced Renal Dysfunction in Well Compensated Cirrhosis

Misoprostol (200 μg) has been shown to acutely counteract the indomethacin-induced renal dysfunction in well compensated cirrhotic patients. The aim of this study was to determine if the prophylactic value of misoprostol was dose-dependent. Parameters of renal he-mody namics and tubular sodium and water handling were assessed by clearance techniques in 26 well compensated cirrhotic patients before and after an oral combination of 50 mg of indomethacin and various doses of misoprostol. The 200-μg dose was able to totally abolish the deleterious renal effects of indomethacin, whereas the 800-μg dose resulted in significant worsening of renal hemodynamics and sodium retention. These changes were maximal in the hour immediately after medications and slowly returned toward base-line levels thereafter. These results suggest that the renal protective effects of misoprostol is dose-dependent. However, until this apparent ability of 200 μg of misoprostol to prevent the adverse effects of indomethacin on renal function is confirmed with chronic frequent dosing, it would be prudent to avoid nonsteroidal anti-inflammatory therapy in patients with cirrhosis.     

Renal vein dilation predicts poor outcome in patients with refractory cirrhotic ascites

Aim

Renal venous hypertension is known to be associated with worsening of renal function in patients with decompensated heart failure. Intra‐abdominal hypertension including cirrhotic ascites also leads to renal venous hypertension. We aimed to clarify the effect of renal venous hypertension on cirrhotic ascites.

Methods

Two hepatologists measured the left renal vein diameter in 142 consecutive patients with refractory cirrhotic ascites using non‐contrast computed tomography. The renal vein diameter was measured at the renal vein main trunk and upstream of the confluence of collateral veins.

Results

The inter‐observer agreements were high for the measurements of the left renal vein (r = 0.918, P < 0.001). The median overall survival for patients with renal vein diameter ≥11 mm was less than that for patients with renal vein diameter <11 mm (P < 0.001; 2.5 vs. 32.0 months). One‐year survival rates were 15.3% versus 66.4%. Multivariate analysis revealed renal vein diameter ≥11 mm (hazard ratio, 2.94; P < 0.001; 95% confidence interval, 1.67–5.20) and a high Model for End‐stage Liver Disease score combined with serum sodium level (MELD‐Na) (hazard ratio, 3.39; P < 0.001; 95% confidence interval, 2.00–5.74) were significant independent predictors of mortality.

Conclusions

Renal vein dilation is a risk factor of mortality in patients with refractory cirrhotic ascites, independent of the MELD‐Na score.     

Effects of Nitric Oxide Inhibition by Methylene Blue in Cirrhotic Patients with Ascites

Increased endogenous nitric oxide production has been proposed as an important mediator of the peripheral arterial vasodilation and the hyperdynamic circulation in cirrhosis, whereas a decreased intrahepatic production of nitric oxide has been implicated in the pathogenesis of portal hypertension. The present study investigated the possible beneficial effects of methylene blue, which is a potent inhibitor of guanylate cyclase and nitric oxide synthase, on hyperdynamic circulation and renal function in cirrhotic patients with ascites together with the effects on portal hemodynamics. Twenty patients were evaluated at baseline and during 2 consecutive 4-hr periods after the administration of methylene blue at a dose of 3 mg/kg (10 patients) or placebo (10 patients). Mean arterial pressure, heart rate, cardiac output, systemic vascular resistance, plasma active renin, plasma aldosterone, plasma antidiuretic hormone, serum urea, serum creatinine, serum sodium, urinary flow rate, glomerular filtration rate, effective renal plasma flow, portal flow volume, and portal vein velocity were not modified by methylene blue or placebo. Urinary sodium excretion, fractional sodium excretion and serum nitric oxide levels were significantly decreased 4 hr after methylene blue administration (P < 0.05), to return toward basal levels over a further 4-hr period. It is concluded that methylene blue, at the dose used in the present study, has no effect on systemic and portal hemodynamics in cirrhotic patients with ascites. The reduction in renal sodium excretion, in the absence of changes in renal function and hemodynamics, suggests, at least partly, a direct antinatriuretic effect of methylene blue.     

Prognosis of patients with ascites after PleurX insertion: an observational study

Objective: To evaluate the safety of PleurX in cirrhotic patients with refractory ascites.

Methods: We prospectively registered patients who received a PleurX catheter cirrhosis-associated refractory ascites at our department from July 2015 to November 2016. Our control group consisted of matched cirrhotic patients with refractory ascites treated with large volume paracentesis (LVP) and patients with malignant ascites treated with PleurX during the same period.

Results: We included 25 patients with cirrhosis-related ascites (7 in PleurX group) and 17 with malignant ascites (14 in PleurX group). Of these, six patients had hepatocellular carcinoma and cirrhosis (5 in PleurX group). None were eligible for insertion of a TIPS or liver transplantation. The maximum duration of follow-up was (480 days) in the PleurX group and 366 days in the LVP group (median 84 and 173 days, respectively). There was no difference in mortality when comparing PleurX with LVP treatment (hazard ratios: 3.0 and 1.0, p?=?.23 and .96, respectively). Mortality was higher in patients with malignant ascites (p=?.01). We found no significant differences in adverse events (incl. spontaneous bacterial peritonitis) or in P-albumin, P-creatinine and P-sodium between the groups.

Conclusion: PleurX insertion for the treatment of refractory ascites in cirrhotic patients appears to be safe. Prospective randomized trials are necessary in order to confirm these findings.     

Indomethacin down-regulating HMGB1 and TNF-α to prevent pancreatitis after endoscopic retrograde cholangiopancreatography

Abstract

Background and aims: Several articles demonstrated that non-steroidal anti-inflammation drugs (NSAIDs) were effective in reducing the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (PEP). However, studies revealed inconsistent results. The mechanism of NSAIDs in preventing PEP is still little known. Therefore, the aim of our study was to evaluate the efficacy of NSAIDs for PEP prophylaxis and further to explore the mechanism of NSAIDs for prevention of PEP.

Methods: Patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) were randomly assigned to receive 100?mg rectal indomethacin or glycerin suppository 15–20?min before ERCP. The primary outcome was the rate of PEP. And the levels of serum HMGB1 and TNF-α were also measured before ERCP and 3 and 24?h after ERCP. Univariate analysis and multivariate analysis were carried out to estimate the independent risk factors for PEP.

Results: Totally, 100 patients were enrolled, 50 received indomethacin and 50 with placebo (glycerin suppository). PEP developed in six patients in indomethacin group and 16 in the control group, the difference was significant (p?=?.016). The levels of HMGB1 and TNF-α were significantly decreased in indomethacin group at 3 (p?p?p?=?.008) and usage of NSAIDs (OR, 0.278; 95% CI, 0.090–0.861; p?=?.026) were independent predictors of PEP.

Conclusions: Rectal indomethacin could significantly reduce the risk of PEP by down-regulating the levels of HMGB1 and TNF-α.     

Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure

BACKGROUND/AIMS: C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is considered to be involved in the regulation of vascular tone. Furthermore, the recent demonstration of CNP in human kidney and urine may indicate a role for CNP in fluid and electrolyte homeostasis. Therefore, the aim of the present study was to investigate the possible role of CNP in renal function disturbances in patients with cirrhosis of the liver. METHODS: Peripheral venous and urinary concentrations of CNP were determined in samples from 11 healthy controls, 20 cirrhotic patients with normal renal function (creatinine clearance 117 (8) ml/min), and 20 cirrhotic patients with impaired renal function (creatinine clearance 35 (4) ml/min). In a second protocol, arterial and renal venous plasma concentrations of CNP were determined in 37 patients with cirrhosis of the liver to estimate renal extraction ratios of CNP. A sensitive and specific radioimmunoassay was applied after solid phase extraction of samples. RESULTS: Plasma CNP was lower in cirrhotic patients with normal and impaired renal function than in controls (3.0 (0.4) and 2.7 (0.2) v. 4.2 (0.4) pg/ml, respectively; p<0.05; mean (SEM)). In contrast, urinary CNP was higher in patients with impaired renal function compared with those with normal renal function and healthy controls (47.2 (7.4) v. 20.8 (1.9) and 17.0 (3.0) ng CNP/g creatinine, respectively; p<0.05). Urinary CNP was found to be inversely related to urinary sodium excretion in cirrhotic patients (r=-0.56; p<0.01). No differences were observed between arterial and renal venous concentrations of CNP in cirrhosis (2.4 (0.2) v. 2.4 (0.2) pg/ml). In cirrhotic patients with hepatorenal syndrome or refractory ascites (n=5), urinary CNP decreased from 132 (59) to 38 (7) ng/g creatinine (p<0.05) one week after either ornipressin infusion or insertion of a transjugular intrahepatic portosystemic shunt together with an increase in urinary sodium excretion from 27 (17) to 90 (34) mmol/24 hours. CONCLUSIONS: Increased urinary CNP in cirrhotic patients in the absence of renal arteriovenous concentration gradients suggests enhanced renal CNP production in cirrhosis. Furthermore, an inverse relation between urinary CNP and urinary sodium excretion suggests a role for this peptide in renal sodium handling in patients with cirrhosis.     

Plasma endothelin levels in patients with cirrhosis and their relationships to the severity of cirrhosis and renal function

Background/Aims: Increased plasma endothelin levels have been reported in patients with cirrhosis. However, the relationship between plasma endothelin concentrations and hyperdynamic circulation or renal functions has not been documented.Methods: We measured the plasma endothelin-1 and endothelin-3 concentrations using radioimmunoassay in 96 patients with cirrhosis (Pugh's A in 26, Pugh's B in 45 and Pugh's C in 25) and compared these values to 56 age- and sex-matched healthy subjects. Systemic and portal hemodynamic measurements, effective renal plasma flow, creatinine clearance, plasma aldosterone concentration and plasma renin activity were recorded for each patient.Results: Plasma endothelin-1 and endothelin-3 levels were significantly increased in patients with cirrhosis compared to healthy subjects. Additionally, plasma endothelin-1 and endothelin-3 values were higher in patients with cirrhosis and ascites than in those without ascites. Moreover, plasma endothelin-1 levels increased in relation to the severity of cirrhosis. On the other hand, modest negative correlations were found betwen endothelin-1 and creatinine clearance or effective renal plasma flow.Conclusions: Plasma endothelin-1 and endothelin-3 levels are increased in patients with cirrhosis compared to healthy subjects. The increase in plasma endothelin-1 levels is related at least in part to the severity of cirrhosis. Increased endothelin-1 levels may possibly contribute to renal dysfunction in patients with cirrhosis.     

Comparison of clinical characteristics and outcomes of spontaneous bacterial peritonitis and culture negative neutrocytic ascites

Objective: Ascitic fluid infections (AFI) in cirrhotic patients can be classified into two groups: spontaneous bacterial peritonitis (SBP) and culture-negative neutrocytic ascites (CNNA). The aim of this study was to compare the clinical characteristics and outcomes of the two groups of patients with AFI.

Methods: We retrospectively reviewed the medical records of cirrhotic patients with AFI. We evaluated demographic data, clinical presentations of AFI, laboratory findings, liver function, and mortality rates.

Results: Between January 2005 and December 2014, 533 patients with AFI were evaluated; 259 (48.6%) had SBP and 274 (51.4%) CNNA. Ascites neutrophil count (4410/mm³ versus 1046/mm³, p?<?.001) and the blood culture positive rate (38.1% versus 20.1%, p?<?.001) were higher in the SBP group, which also had a higher MELD score (24.29 versus 22.05, p?=?.004). Seven-day mortality was higher in the SBP group (9.4% versus 4.5%, p?=?.027) but there was no significant difference in 30-day (22.1% versus 17.5%) or 90-day mortality rate (36.1% versus 36.4%).

Conclusions: Patients in the SBP group had a higher MELD score, ascites neutrophil count, and positive blood culture rate. Although seven-day mortality rate was higher in the SBP group, the 30-day and 90-day mortality rates were similar in the two groups.     

Portosystemic myelopathy: Spastic paraparesis after portosystemic shunting

Objective. In patients with cirrhosis and spontaneous bacterial peritonitis (SBP), the use of intravenous albumin has been shown to prevent deterioration of renal function and to decrease the mortality rate, but the mechanisms remain unclear. The purpose of this study was to characterize the mechanisms of action of albumin with the focus on endotoxin and cytokines. Material and methods. Thirty patients with SBP were divided into two groups. Group 1 received antibiotics and albumin infusion (20% 50 cc every day for 3 days) and Group 2 received antibiotic treatment only. Twenty-four cirrhotic patients with sterile ascites were enrolled in Group 3 and received albumin infusion (20% 50 cc every day for 3 days). Plasma and ascitic fluid concentrations of endotoxin, nitric oxide products (NOx), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were analyzed before and after treatments, respectively. Results. Combination therapy of albumin and antibiotics can significantly (p<0.01) reduce plasma levels of TNF-α and IL-6, and ascitic fluid levels of endotoxin, TNF-α and IL-6 in cirrhotic patients with SBP. Without the addition of albumin to an antibiotic regimen, the plasma and ascitic fluid levels of NOx increased significantly in patients with SBP (p=0.005 and p=0.004, respectively). Conclusions. The results confirm that the beneficial effects of albumin are related to the reduction of the levels of TNF-α and NOx in both plasma and ascitic fluid. The infusion of albumin continuously for 3 days in addition to antibiotic treatment at the time of SBP detection is recommended as an effective therapy for patients with cirrhosis and SBP.     

Mesenteric arteries responsiveness to acute variations of wall shear stress is impaired in rats with liver cirrhosis

Abstract

Objective. In liver cirrhosis, excessive splanchnic vasodilation is due to abnormal synthesis of endogenous vasodilators and to decreased sensitivity to vasoconstrictors. The role of mechanical stimuli such as wall shear stress (WSS) on splanchnic circulation remains unclear. The aim of this study was to assess the vasodilation induced by wall shear stress (WSS) and acute changes in blood flow in the mesenteric arteries in an experimental model of liver cirrhosis. Materials and Methods. The effect of acute changes in intraluminal flow (0, 10, and 20 μl/min) and WSS on the diameter of the mesenteric arteries (diameters <500 μm) of control and cirrhotic rats was assessed, at baseline and after the inhibition of nitric oxide synthase, cyclooxygenase and hemeoxygenase. Concentration–response curves to phenylephrine were also obtained. Results. In controls, the increase in intraluminal flow led to a significant increase in arterial diameter (p < 0.05), while WSS remained stable; the effect was maintained in vessels pre-constricted with phenylephrine, blocked by the exposure to indomethacin and L-NAME and restored by the subsequent addition of chromium mesoporphyrin (p < 0.05). In cirrhotic arteries, arterial diameters did not change in response to acute increase in flow, neither at baseline nor after exposure to indomethacin and L-NAME, while WSS increased (p < 0.01). Responsiveness to flow was partially restored (p < 0.05) after exposure of the arteries to chromium mesoporphyrin in addition to indomethacin and L-NAME. Conclusions. Arteries from cirrhotic rats showed an abolished responsiveness to acute variations in flow, which exposes the mesenteric endothelium to sudden variations in WSS.     

Prevalence of and factors associated with renal dysfunction in rheumatoid arthritis patients: a cross-sectional study in community hospitals

This study was designed to determine the prevalence of renal dysfunction in rheumatoid arthritis (RA) patients and to identify factors associated with this complication. Between October 2014 and May 2015, we consecutively recruited RA patients at rheumatology sections of community hospitals in Japan. Each patient’s absolute and body surface area (BSA)-indexed estimated glomerular filtration rate (eGFR) values were measured twice over a 3-month interval. Renal dysfunction was defined as absolute eGFR or BSA-indexed eGFR < 60. Albuminuria and hematuria were also recorded. Associations between renal dysfunction and possible risk factors were examined by multivariate logistic regression analyses. A total of 1908 outpatients with RA were included in this study. The prevalence of renal dysfunction based on absolute eGFR and BSA-indexed eGFR was 33.8 and 18.6%, respectively. Albuminuria was observed in 8.1% of this patient cohort, and the prevalence of hematuria was 7.5%. Advanced age (odds ratio [OR] 7.24, p < 0.001), female sex (OR 3.12, p < 0.001), hypertension (OR 2.22, p < 0.001), and obesity (OR 0.59, p < 0.001) were independently associated with the risk of absolute eGFR-based renal dysfunction. Advanced age (OR 5.19, p < 0.001) and hypertension (OR 3.05, p < 0.001) also had associations with BSA-indexed eGFR-based renal dysfunction. RA duration, stages, severity, and cumulative steroid dose were considered significant risk factors in univariate analyses, but their associations were less potent after adjustment for other covariates. Renal dysfunction is relatively common in RA patients and is mainly associated with advanced age and hypertension but not with RA-related factors.