Bruce A. Runyon

The Serum-Ascites Albumin Gradient Is Superior to the Exudate-Transudate Concept in the Differential Diagnosis of Ascites

OBJECTIVEnTo compare the serum-ascites albumin gradient to the exudate-transudate concept in the classification of ascites.nnnDESIGNnProspective collection of ascitic fluid data from patients with well-characterized causes of ascites.nnnSETTINGnHepatology inpatient and outpatient ward and consult service of a large, urban hospital.nnnPATIENTSnA total of 901 paired serum and ascitic fluid samples were collected from consecutive patients with all forms of ascites.nnnINTERVENTIONSnNone.nnnMAIN OUTCOME MEASURESnThe utility of the serum-ascites albumin gradient and the old exudate-transudate concept (as defined by ascitic fluid total protein concentration [AFTP]) were compared for their ability in discriminating the cause for ascites formation.nnnRESULTSnThe albumin gradient correctly differentiated causes of ascites due to portal hypertension from those that were not due to portal hypertension 96.7% of the time. The AFTP, when used as defined in the old exudate-transudate concept, classified the causes of ascites correctly only 55.6% of the time. This resulted in part because the AFTP of most spontaneously infected samples (traditionally expected to be exudates) was low, and the AFTP of most cardiac ascites samples (traditionally expected to be transudates) was high.nnnCONCLUSIONSnThe exudate-transudate concept should be discarded in the classification of ascites. The serum-ascites albumin gradient is far more useful than the AFTP as a marker for portal hypertension, but the latter remains a useful adjunct in the differential diagnosis of ascites.

Care of patients with ascites

Ascites is the pathologic accumulation of fluid in the peritoneal cavity. The condition develops most frequently as part of the decompensation of previously asymptomatic chronic liver disease (Table 1). Ascites is the most common complication of such disease, occurring in 50 percent of patients within 10 years of a diagnosis of compensated cirrhosis; in comparison, variceal bleeding develops in only 25 percent2. The development of fluid retention in a person with chronic liver disease is a poor prognostic sign; only 50 percent of such people survive two years3. The prognosis of patients with noncirrhotic ascites is quite variable .xa0.xa0.

Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012

Ascites is the most common of the three major complications of cirrhosis, the other complications being hepatic encephalopathy and variceal hemorrhage. Cirrhosis is the most common cause of ascites in the United States. Development of ascites may be the first evidence of the presence of cirrhosis. Obesity makes the physical examination less helpful in detecting ascites. Imaging may provide the first evidence of the presence of ascites. Patients with ascites are frequently admitted to hospitals. Effective care of these patients can reduce the frequency of these readmissions. This version of the American Association for the Study of Liver Diseases Practice Guideline is the fourth iteration of this guideline and represents a thorough update of the 2009 version. Introduction

Optimization of ascitic fluid culture technique

The conventional method of ascitic fluid culture detects bacteria in only 42%-65% of patients who have neutrocytic ascites and suspected spontaneous bacterial peritonitis. In this study ascitic fluid was cultured by the conventional method as well as by a new method consisting of bedside inoculation of blood culture bottles with ascites. The conventional cultures grew bacteria in only 13 (43%) of 30 episodes of neutrocytic ascites, whereas the blood culture bottles grew bacteria in 28 (93%); this difference was significant (p less than 0.0001). The blood culture bottle method also resulted in more rapid detection of bacterial growth. The median concentration of bacteria in infected ascites was one organism per milliliter. Bedside inoculation of blood culture bottles with ascitic fluid is more sensitive than the conventional method in detecting bacterial peritonitis. The insensitivity of the conventional method is probably due to the low concentration of bacteria in infected ascites and the small volume of ascites cultured by this method.

Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis

Prevention and Management of Gastroesophageal Varices and Variceal Hemorrhage in Cirrhosis Guadalupe Garcia-Tsao, M.D.,1 Arun J. Sanyal, M.D.,2 Norman D. Grace, M.D., FACG,3 William D. Carey, M.D., MACG,4 the Practice Guidelines Committee of the American Association for the Study of Liver Diseases and the Practice Parameters Committee of the American College of Gastroenterology 1Section of Digestive Diseases, Yale University School of Medicine and VA-CT Healthcare System, New Haven, Connecticut; 2Division of Gastroenterology, Virginia Commonwealth University Medical Center, Richmond, Virginia; 3Division of Gastroenterology, Brigham and Women’s Hospital, Boston, Massachusetts; 4The Cleveland Clinic, Cleveland, Ohio

Utility of an algorithm in differentiating spontaneous from secondary bacterial peritonitis

To prospectively assess the value of an algorithm in differentiating spontaneous from secondary bacterial peritonitis, we performed serial paracenteses in 43 episodes of ascitic fluid infection (28 spontaneous and 15 secondary) in 40 patients. The algorithm involved identification of (a) secondary peritonitis associated with gut perforation, based on previously proposed criteria in patients with neutrocytic ascites (ascitic fluid total protein greater than 1 g/dl, glucose less than 50 mg/dl, and lactate dehydrogenase greater than the upper limit of normal for serum) and (b) separation of spontaneous from secondary peritonitis (unassociated with perforation) based on the response of the ascitic fluid cell count to antibiotic therapy. The perforation criteria had 100% sensitivity in detecting episodes of actual gut perforation; their specificity, however, was low (45%). After 48 h of treatment the concentration of ascitic fluid neutrophils was below the baseline pretreatment value in all episodes of spontaneous peritonitis but in only two thirds of the patients with secondary peritonitis. This algorithm is useful in (a) identifying patients who have infected ascites associated with perforation of an intraabdominal viscus, and (b) differentiating spontaneous from nonperforation secondary peritonitis on the basis of the response of the ascitic fluid cell count to appropriate antibiotic therapy. The optimal time for repeat paracentesis in patients with infected ascites appears to be 48 h after initiation of treatment.

Overweight and obesity, hepatic steatosis, and progression of chronic hepatitis C: a retrospective study on a large cohort of patients in the United States

BACKGROUNDnHepatic steatosis has been associated with chronic hepatitis C (CHC), but its prevalence, risk factors, and clinical significance remain to be determined.nnnAIMSnThe present study determined the frequency of, and risk factors for hepatic steatosis and its association with activity and progression of CHC in a large cohort of U.S. patients.nnnMETHODSnThis is a retrospective study that utilized systematic chart review and statistical analyzes to investigate 324 U.S. patients with CHC from a university medical center and a regional VA medical center.nnnRESULTSnThe frequency of hepatic steatosis was 66.0%. We demonstrated that not only being obese, but also overweight (i.e. body mass index > or =25 kg/m(2)) was independently associated with hepatic steatosis. In our cohort of patients with CHC, hepatic steatosis, especially grade II/III steatosis, was significantly associated with elevated aspartate aminotransferase at entry, persistently elevated alanine aminotransferase, and stage III/IV fibrosis. Grade II/III steatosis, was significantly associated with a higher histology activity index as well. Multivariate analysis indicated that steatosis, especially grade II/III steatosis, was independently associated with stage III/IV fibrosis.nnnCONCLUSIONSnBeing overweight/obese serves as an independent risk factor for hepatic steatosis in U.S. patients with CHC. Steatosis accelerates activity and progression of CHC, and is independently associated with stage III/IV hepatic fibrosis in these patients.

Octreotide/Midodrine Therapy Significantly Improves Renal Function and 30-Day Survival in Patients with Type 1 Hepatorenal Syndrome

Type 1 hepatorenal syndrome (HRS) can be a rapidly fatal consequence of liver failure. Recent studies have utilized vasoconstrictor therapies to combat splanchnic vasodilatation. We aimed to evaluate the efficacy of a promising treatment for type 1 HRS. We compared the survival of HRS patients who received octreotide and midodrine treatment at Rancho Los Amigos Medical Center with a concurrent untreated control group of HRS patients who did not receive this treatment. Of the 81 patients, 60 were treated with octreotide/midodrine and 21 were controls. Mortality was significantly lower in the treatment group (43%) than in the controls (71%; P < 0.05). Furthermore, 24 study patients (40%) had a sustained reduction of serum creatinine compared with only 2 controls (10%; P < 0.05). This large retrospective study suggests that octreotide/midodrine treatment appears to improve 30-day survival. A randomized, controlled trial is the next important step toward evaluating this treatment modality.

A Rodent Model of Cirrhosis, Ascites, and Bacterial Peritonitis

We sought to develop a rodent model of spontaneous bacterial peritonitis and report here the preliminary results of carbon tetrachloride-induced cirrhosis in which ascites and bacterial peritonitis predictably develop. Of 41 rats that survived the initial carbon tetrachloride toxicity, 38 (92.7%) developed cirrhosis with ascites. Of these 38, 21 (55.3%) developed 24 episodes of ascitic fluid infection without iatrogenic colonization. No surgically treatable source of infection was identified at autopsy in any rat; therefore, the infections were presumed to be spontaneous. Eight (50%) of the 16 rats with culture-positive ascitic fluid at postmortem examination also had spontaneous pleural fluid infection with the same organism. Escherichia coli and Proteus sp. were the organisms most commonly isolated. This rodent model of cirrhosis with ascites appears to be the first high-yield animal model of spontaneous bacterial peritonitis. Ascitic fluid infection in these rats resembles ascitic fluid infection in humans. This model will allow further investigation of the mechanisms of pathogenesis of ascitic fluid infection and provide insight into the prevention and treatment of spontaneous bacterial peritonitis and pleural fluid infection in patients with cirrhosis.

Spontaneous Bacterial Peritonitis

Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascitic fluid in patients with decompensated cirrhosis. The modifier ‘spontaneous’ distinguishes this from surgical peritonitis. The infecting organisms are usually enteric gram-negatives which have translocated from the bowel. Symptoms of infection occur in most patients with SBP, including fever, abdominal pain, mental status changes, and ileus. A high index of suspicion should exist for SBP in patients with cirrhosis and ascites. Diagnostic abdominal paracentesis can be undertaken with minimal risk and should be performed in all patients admitted to the hospital, during times of worsening clinical appearance, or when gastrointestinal bleeding occurs. The ascitic fluid polymorphonuclear cell count is the most sensitive test in evaluating for infection. Cultures of the ascitic fluid are helpful in identifying the organism and are best performed by bedside injection of blood culture bottles. Ascites total protein, lactate dehydrogenase, and glucose levels can assist in distinguishing SBP from secondary peritonitis. Empirical therapy is recommended after paracentesis if suspicion for infection exists. Cefotaxime is the best-studied antibiotic for this purpose and has excellent penetration into ascites with no nephrotoxicity. Prophylaxis should be limited to high-risk settings. Mortality rates in SBP have declined dramatically, largely due to earlier detection and improved therapy.