Salvatore Piano

The empirical antibiotic treatment of nosocomial spontaneous bacterial peritonitis: Results of a randomized, controlled clinical trial

Spontaneous bacterial peritonitis (SBP) is a common, life‐threatening complication of liver cirrhosis. Third‐generation cephalosporins have been considered the first‐line treatment of SBP. In 2014, a panel of experts suggested a broader spectrum antibiotic regimen for nosocomial SBP, according to the high rate of bacteria resistant to third‐generation cephalosporins found in these patients. However, a broader‐spectrum antibiotic regimen has never been compared to third‐generation cephalosporins in the treatment of nosocomial SBP. The aim of our study was to compare meropenem plus daptomycin versus ceftazidime in the treatment of nosocomial SBP. Patients with cirrhosis and nosocomial SBP were randomized to receive meropenem (1 g/8 hours) plus daptomycin (6 mg/kg/day) or ceftazidime (2 g/8 hours). A paracentesis was performed after 48 hours of treatment. A reduction in ascitic fluid neutrophil count <25% of pretreatment value was considered a treatment failure. The primary outcome was the efficacy of treatment defined by the resolution of SBP after 7 days of treatment. Thirty‐two patients were randomized and 31 were analyzed. The combination of meropenem plus daptomycin was significantly more effective than ceftazidime in the treatment of nosocomial SBP (86.7 vs. 25%; Pu2009<u20090.001). Ninety‐day transplant‐free survival (TFS) was not significantly different between the two groups. In the multivariate analysis, ineffective response to first‐line treatment (hazard ratio [HR]: 20.6; Pu2009=u20090.01), development of acute kidney injury during hospitalization (HR: 23.2; Pu2009=u20090.01), and baseline mean arterial pressure (HR: 0.92; Pu2009=u20090.01) were found to be independent predictors of 90‐day TFS. Conclusion: The combination of meropenem plus daptomycin is more effective than ceftazidime as empirical antibiotic treatment of nosocomial SBP. Efficacy of the empirical antibiotic treatment is a strong predictor of 90‐day survival in patients with nosocomial SBP. (Hepatology 2016;63:1299–1309)

Affective and Psychiatric Disorders in Celiac Disease

Several extraintestinal clinical manifestations have been reported in celiac disease (CD). Among them, growing evidence suggests the association between CD and affective and psychiatric disorders. In this review the most frequent affective and psychiatric disorders associated with CD and the possible mechanisms involved in these associations were analyzed. The available data suggest that screening for CD in patients with affective and/or psychiatric symptoms may be useful since these disorders could be the expression of an organic disease rather than primary psychiatric illnesses.

Predictors of Early Readmission in Patients With Cirrhosis After the Resolution of Bacterial Infections

Objectives:In patients with cirrhosis, infections represent a frequent trigger for complications, increasing frequency of hospitalizations and mortality rate. This study aimed to identify predictors of early readmission (30 days) and of mid-term mortality (6 months) in patients with liver cirrhosis discharged after a hospitalization for bacterial and/or fungal infection.Methods:A total of 199 patients with cirrhosis discharged after an admission for a bacterial and/or fungal infection were included in the study and followed up for a least 6 months.Results:During follow-up, 69 patients (35%) were readmitted within 30 days from discharge. C-reactive protein (CRP) value at discharge (odds ratio (OR)=1.91; P=0.022), diagnosis of acute-on-chronic liver failure during the hospital stay (OR=2.48; P=0.008), and the hospitalization in the last 30 days previous to the admission/inclusion in the study (OR=1.50; P=0.042) were found to be independent predictors of readmission. During the 6-month follow-up, 47 patients (23%) died. Age (hazard ratio (HR)=1.05; P=0.001), model of end-stage liver disease (MELD) score (HR=1.13; P<0.001), CRP (HR=1.85; P=0.001), refractory ascites (HR=2.22; P=0.007), and diabetes (HR=2.41; P=0.010) were found to be independent predictors of 6-month mortality. Patients with a CRP >10u2009mg/l at discharge had a significantly higher probability of being readmitted within 30 days (44% vs. 24%; P=0.007) and a significantly lower probability of 6-month survival (62% vs. 88%; P<0.001) than those with a CRP ≤10u2009mg/l.Conclusions:CRP showed to be a strong predictor of early hospital readmission and 6-month mortality in patients with cirrhosis after hospitalization for bacterial and/or fungal infection. CRP values could be used both in the stewardship of antibiotic treatment and to identify fragile patients who deserve a strict surveillance program.

The Treatment of Hepatorenal Syndrome.

Hepatorenal syndrome (HRS) is a severe complication that often occurs in patients with cirrhosis and ascites. HRS is a functional renal failure that develops mainly as a consequence of a severe cardiovascular dysfunction which is characterized by an extreme splanchnic arterial vasodilation and a reduction of cardiac output. HRS may develop in two clinical types: as an acute and rapidly progressive renal failure (AKI-HRS) or as chronic and not progressive renal failure (CKD-HRS). Several small studies and some randomized control studies have been published on the use of terlipressin plus albumin in the treatment of HRS, mainly on AKI-HRS. Terlipressin plus albumin was shown to improve renal function in almost 35-45% of patients with AKI-HRS, as well as to improve short-term survival in these patients. Terlipressin was most commonly used by intravenous boluses moving from an initial dose of 0.5-1 mg every 4 h to 3 mg every 4 h in the case of a nonresponse. In other studies, terlipressin was also given by continuous intravenous infusion. Thus, the best way to administer terlipressin in the treatment of HRS has not yet been defined. α-Adrenergic drugs, such as intravenous norepinephrine or oral midodrine plus subcutaneous octreotide, administered with albumin have also been used in the treatment of AKI-HRS, with promising results. However, we need further studies in order to define whether they can represent a real therapeutic alternative. In conclusion, available data are sufficient to state that the use of terlipressin plus albumin has really changed the management of HRS. Nevertheless, some crucial unsolved issues still exist, in particular: (a) how to predict nonresponse to treatment, (b) how to manage nonresponse to treatment and (c) how to consider the response in those patients who are candidates for liver transplant in the priority allocation process.

Infections complicating cirrhosis

Patients with cirrhosis have a high risk of bacterial infections. Bacterial infections induce systemic inflammation that may lead to organ failure and acute‐on‐chronic liver failure (ACLF) resulting in a high risk of short term mortality. The early diagnosis and treatment of bacterial infections is essential to improve the patients prognosis. However, in recent years, the spread of multidrug resistant (MDR) bacterial infections has reduced the efficacy of commonly used antibiotics such as third generation cephalosporins. In patients at high risk of MDR bacteria, such as those with nosocomial infections, the early administration of broad spectrum antibiotics has been shown to improve the prognosis. However, early de‐escalation of antibiotics is recommended to reduce a further increase in antibiotic resistance. Strategies to prevent acute kidney injury and other organ failures should be implemented. Although prophylaxis of bacterial infections with antibiotics improves the prognosis in selected patients, their use should be limited to patients at high risk of developing infections. In this article, we review the pathogenesis and management of bacterial infections in patients with cirrhosis.

Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome

Abstract This chapter will: • Discuss the pathophysiology, diagnosis and treatment of spontaneous bacterial peritonitis • Discuss prevention of acute kidney injury and hepatorenal syndrome in patients with spontaneous bacterial peritonitis • Discuss the management of hepatorenal syndrome in the setting of spontaneous bacterial peritonitis

Pathophysiology and Management of the Hepatorenal Syndrome

Abstract Acute kidney injury (AKI), is a common complication of cirrhosis, occurring in more than 20% of patients hospitalized for an acute decompensation of cirrhosis. Hepatorenal syndrome (HRS) accounts for 20% of AKI episodes in these patients. Two different clinical types of HRS are classically identified: Type-1 HRS, which is characterized by a rapidly progressive reduction of renal function and Type-2 HRS, which is a moderate renal failure with slowly progressive course, which usually is associated with refractory ascites. Type-1 HRS often develops after a precipitating event, such as spontaneous bacterial peritonitis or other bacterial infections and is the most life-threatening type of AKI in patients with cirrhosis. A reduction of circulating effective volume due to a severe splanchnic arterial vasodilation has been considered the main cause of HRS, however, new evidences suggests that systemic inflammation may be the main driver of the syndrome. Effective treatments for HRS are currently available. Liver transplantation is the best treatment of HRS, but only selected patients may be transplanted and the time to get a graft is unpredictable. The combination of vasoconstrictors plus albumin is the optimal medical treatment of HRS. In this chapter, the pathophysiology, diagnostic criteria and available treatment of HRS have been reviewed.

Long-term administration of human albumin improves survival in patients with cirrhosis and refractory ascites.

In patients with cirrhosis, the clinical benefit of the treatment with human albumin for ascites is debated, and no data are available regarding refractory ascites. In this study, in patients with cirrhosis and refractory ascites, we assessed the effect of long‐term albumin administration on emergent hospitalization and mortality.

Ascites and acute kidney injury

Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years.