A.F. Attili

Incidence and natural history of small esophageal varices in cirrhotic patients

BACKGROUND/AIMS The incidence and natural history of small esophageal varices (EV) in cirrhotics may influence the frequency of endoscopies and the decision to start a pharmacological treatment in these patients. METHODS We prospectively evaluated 206 cirrhotics, 113 without varices and 93 with small EV, during a mean follow-up of 37+/-22 months. Patients with previous gastrointestinal bleeding or receiving any treatment for portal hypertension were excluded. Endoscopy was performed every 12 months. RESULTS The rate of incidence of EV was 5% (95%CI: 0.8-8.2%) at 1 year and 28% (21.0-35.0%) at 3 years. The rate of EV progression was 12% (5.6-18.4%) at 1 year and 31% (21.2-40.8%) at 3 years. Post-alcoholic origin of cirrhosis, Child-Pughs class (B or C) and the finding of red wale marks at first examination were predictors for the variceal progression. The two-years risk of bleeding from EV was higher in patients with small varices upon enrollment than in those without varices: 12% (95% CI: 5.2-18.8%) vs. 2% (0.1-4.1%); (P<0.01). Predictor for bleeding was the presence of red wale marks at first endoscopy. CONCLUSIONS In patients with no or small EV, endoscopy surveillance should be planned taking into account cause and degree of liver dysfunction.

Cirrhotic Patients Are at Risk for Health Care–Associated Bacterial Infections

BACKGROUND & AIMS Bacterial infections are a frequent and serious burden among patients with cirrhosis because they can further deteriorate liver function. We assessed the epidemiology, risk factors, and clinical consequences of bacterial infections in hospitalized cirrhotic patients. METHODS In a cohort of hospitalized cirrhotic patients (n = 150) referred to a tertiary care setting, all episodes of bacterial infections were recorded prospectively. Infections were classified as community-acquired (CA), health care-associated (HCA), or hospital-acquired (HA). Site of infection, characteristics of bacteria, and prevalence of antibiotic resistance were reported; consequences for liver function and patient survival were evaluated. RESULTS Fifty-four infections were observed among 50 patients (12 CA, 22 HCA, and 20 HA). Bacterial resistance was more frequent among patients with HCA or HA infections (64% of isolates). Mortality was 37% from HA, 36% from HCA, and 0% from CA infections. Independent predictors of infection included a previous infection within the past 12 months (P = .0001; 95% confidence interval [CI], 2.2-10.6), model of end-stage liver disease score ≥ 5 (P = .01; 95% CI, 1.3-6.1), and protein malnutrition (P = .04; 95% CI, 1.5-10). Infectious episodes worsened liver function in 62% of patients. Patients with infection more frequently developed ascites, hepatic encephalopathy, hyponatremia, hepatorenal syndrome, or septic shock. Child class C (P = .006; 95% CI, 1.67-23.7), sepsis (P = .005; 95% CI, 1.7-21.4), and protein malnutrition (P = .001; 95% CI, 2.8-38.5) increased mortality among patients in the hospital. CONCLUSIONS In hospitalized cirrhotic patients, the most frequent infections are HCA and HA; these infections are frequently resistant to antibiotics. As infections worsen, liver function deteriorates and mortality increases. Cirrhotic patients should be monitored closely for infections.

A new highly effective short-term therapy schedule for Helicobacter pylori eradication

Although triple therapy regimens suggested in the Current European guidelines give fairly good results, several studies have reported an unsatisfactory Helicobacter pylori eradication rate (< 80%).

Incidence, natural history, and risk factors of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt with polytetrafluoroethylene-covered stent grafts

BACKGROUND AND AIMS:The aim of this study was to assess the incidence, natural history, and risk factors of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) with the new polytetrafluoroethylene (PTFE)-covered stent grafts in cirrhotic patients.PATIENTS AND METHODS:Seventy-eight cirrhotic patients treated by TIPS with PTFE-covered stent grafts and followed by the same medical team—according to a prospective protocol for diagnostic workup and surveillance strategy—were reviewed. The follow-up was 19.9 ± 20.6 months.RESULTS: At least one episode of HE occurred in 35 of 78 (44.8%) patients. The probability of remaining free of HE was 53.8% (95% confidence interval [CI] 41.4–66.2] at 1 yr and 50.9% at 2 yr (95% CI 38.2–63.8%). The total number of HE episodes was 89. Fifty-five percent of the episodes were grades III–IV. The occurrence of HE tended to be constant during the follow-up, probably because of the very low incidence of shunt dysfunction (13.6% at 2 yr). Moreover, in six patients, a refractory HE required the reduction of the shunt diameter. One patient died due to variceal bleeding after this procedure. At a multivariate analysis, an older age, high creatinine levels, and low serum sodium and low albumin values were shown to be independent factors for the occurrence of HE. Serum creatinine level was the only variable related to the development of refractory HE at the logistic multivariate analysis.CONCLUSIONS: HE after TIPS with PTFE-covered stent grafts is frequent; its incidence is not confined to the first post-TIPS period, but it has the tendency to be frequent over time. Refractory HE occurred in 8% of patients and may be successfully managed by reducing the stent diameter. The selection of patients undergoing TIPS placement should be very accurate, especially for those subjects with abnormal creatinine level.

Regulation and deregulation of cholangiocyte proliferation.

HOLANGIOCYTES C are the epithelial cells which line the intrahepatic biliary tree, a network of interconnecting ducts of increasing diameter from the duct of Hering to the extrahepatic bile ducts (l-6). Cholangiocytes determine the final bile composition through a series of secretory and absorptive processes regulated by a number of hormones and neuropeptides (2-5). The intrahepatic bile ducts are the target of damage in a group of chronic cholestatic liver diseases recently classified as Vanishing Bile Duct Syndromes (4,7-9). These diseases are characterized by the progressive disappearance of intrahepatic bile ducts, which leads to a severe ductopenic condition in the terminal stages (79). The residual bile ducts tend to proliferate as a compensatory mechanism (8). Thus, the course of these diseases is characterized by a balance between damage (loss) of bile ducts and compensatory proliferation of the residual ducts. The terminal decompensated stages are characterized by the inefficacy of proliferation to balance for the loss of intrahepatic bile ducts. Therefore, a therapeutic strategy designed to support efficacious cholangiocyte proliferation could delay progression to ductopenia. This represents a challenge for the future. The aim of this review is to focus on current knowledge of the regulation and dysregulation of cholangiocyte proliferation.

High prevalence of spontaneous portal-systemic shunts in persistent hepatic encephalopathy: A case-control study†

Large spontaneous portal‐systemic shunts have been occasionally described in patients with cirrhosis. This study was undertaken to assess the prevalence of portal‐systemic shunts in patients with cirrhosis with recurrent or persistent hepatic encephalopathy (HE) as compared with patients with cirrhosis without HE. Fourteen patients with cirrhosis with recurrent or persistent HE (cases) and 14 patients with cirrhosis without previous or present signs of overt HE matching for age and degree of liver failure (controls) were studied. Each patient underwent neurological assessment and cerebral magnetic resonance (MR) imaging to exclude organic neurological pathological conditions. HE evaluation included psychometric performance (Trail‐Making Test A), electroencephalogram (EEG), mental status examination and grading, arterial, venous, and partial pressure of ammonia determination. The presence of portal‐systemic shunts was assessed by portal venous phase multidetector‐row spiral computed tomography (CT). Large spontaneous portal‐systemic shunts were detected in 10 patients with HE and in only 2 patients without HE (71% vs. 14%; chi square = 9.16; df = 1.0; P = .002). The patients with HE presented ascites (P = .002) and medium/large esophageal varices (P = .02) less frequently than the control group. In conclusion, our study suggests that large spontaneous shunts may often sustain the chronicity of HE; the presence of large shunts should be sought in patients with cirrhosis with recurrent or persistent HE. (HEPATOLOGY 2005;42:1158–1165.)

Relationships between bile salts hydrophilicity and phospholipid composition in bile of various animal species

Bile salts and phospholipids from bile of chicken, dog, sheep, rat, ox, pig, guinea-pig and man were analyzed by high-performance liquid chromatography. Bile salts showed marked differences in their hydrophilic properties, owing to hydroxyl structure and type of conjugation. Phospholipids were generally similar, containing 90-95% of phosphatidylcholine which was made of molecular species containing palmitic acid in the sn-1 position. The comparative analysis of bile salts and phosphatidylcholines profile demonstrated that bile salts hydrophilicity influences the quantity of phosphatidylcholine in bile but not the quality.

Natural history of gallstone disease: Expectant management or active treatment? Results from a population-based cohort study

Background and Aims:  The knowledge of natural history is essential for disease management. We evaluated the natural history (e.g. frequency and characteristics of symptoms and clinical outcome) of gallstones (GS) in a population‐based cohort study.

Role of determination of partial pressure of ammonia in cirrhotic patients with and without hepatic encephalopathy

BACKGROUND/AIMS To compare venous, arterial and partial pressure of ammonia (pNH(3)) in 27 consecutive cirrhotics with hepatic encephalopathy, 15 cirrhotics without hepatic encephalopathy and nine controls; to reevaluate all parameters after the improvement of encephalopathy. METHODS Patients were studied by clinical examination and psychometric testing. pNH(3) was calculated from arterial ammonia and pH. RESULTS In patients with encephalopathy, each form of ammonia was higher than in both controls and patients without encephalopathy. The correlation with the severity of hepatic encephalopathy was similar for venous (r=0.72), arterial ammonia (r=0.76) and pNH(3) (r=0.75). The sensitivity and specificity of each variable in correctly classifying the patients as having or not having hepatic encephalopathy was also similar. Each form of ammonia decreased after the resolution or amelioration of symptoms. However, even in the 17 patients with complete resolution of hepatic encephalopathy, all three ammonia determinations resulted unchanged or increased in some patients. CONCLUSIONS Despite the significant correlation between pNH(3) and hepatic encephalopathy, our study suggests that neither pNH(3) nor arterial ammonia are, from a clinical point of view, more useful than venous ammonia: all three determinations being limited both for the diagnosis of hepatic encephalopathy and for the clinical management of the patients.

The Natural History of Portal Hypertensive Gastropathy in Patients with Liver Cirrhosis and Mild Portal Hypertension

BACKGROUND:Portal hypertensive gastropathy is a potential cause of bleeding in patients with liver cirrhosis. Studies on its natural history have often included patients submitted to endoscopic or pharmacological treatment for portal hypertension.PATIENTS AND METHODS:A total of 222 cirrhotic patients with mild degree of portal hypertension (i.e., with no or small varices at entry, without previous gastrointestinal bleeding and medical, endoscopic, or angiographic treatment) were followed up with upper endoscopy every 12 months for 47 ± 28 months.RESULTS:Upon enrollment 48 patients presented portal hypertensive gastropathy (43 mild and 5 severe) and the presence of esophageal varices was the only independent predictor of the presence of this gastric lesion at multivariate analysis. The incidence of portal hypertensive gastropathy was 3.0% (1.1–4.9%) at 1 yr and 24% (18.1–29.9%) at 3 yr, while the progression was 3% (1–6.9%) at 1 yr and 14% (4.2–23.8%) at 3 yr. The presence of esophageal varices and the Child-Pugh class B or C at enrollment were predictive of the incidence of portal hypertensive gastropathy, while only Child-Pugh class B or C was correlated with the progression from mild to severe, at multivariate analysis. During follow-up 16 patients bled from portal hypertensive gastropathy (9 acutely and 7 chronically) and one patient died of exsanguination from this lesion.CONCLUSIONS:The natural history of portal hypertensive gastropathy is significantly influenced by the severity of liver disease and severity of portal hypertension. Acute bleeding from portal hypertensive gastropathy is infrequent but may be severe.