Serum HBsAg kinetics and usefulness of interferon-inducible protein 10 serum in HBeAg-negative chronic hepatitis B patients treated with tenofovir disoproxil fumarate.

The kinetics of serum HBsAg and interferon-inducible protein 10 (IP10) levels in patients with chronic hepatitis B infection treated with tenofovir are unclear. We evaluated the changes of HBsAg levels and the predictability of IP10 for HBsAg decline in 160 HBeAg-negative patients receiving tenofovir for ≥12 months. Serum samples taken before and at 6, 12, 24, 36 and 48 months after tenofovir were tested for HBsAg levels. In 104 patients, serum samples before tenofovir were tested for IP10 levels. Compared to before tenofovir, HBsAg levels decreased by a median of 0.08, 0.11, 0.24, 0.33 and 0.38 log10 IU/mL at 6, 12, 24, 36 and 48 months, respectively (P < 0.001). HBsAg kinetics did not differ between nucleos(t)ide analogue(s) naive and experienced patients. The 12-, 24-, 36- and 48-month cumulative rates of ≥0.5 log10 HBsAg decline were 8%, 16%, 24% and 41% and of HBsAg ≤100 IU/mL were 9%, 12%, 14% and 18%, respectively. The only factor associated with HBsAg ≤100 IU/mL was lower HBsAg levels before tenofovir (P < 0.001), while HBsAg decline ≥0.5 log10 was associated with higher IP10 levels (P = 0.002) and particularly with IP10 > 350 pg/mL (P < 0.001). In conclusion, tenofovir decreases serum HBsAg levels in both nucleos(t)ide analogue(s) naive and experienced patients with HBeAg-negative chronic hepatitis B infection. After 4 years of therapy, HBsAg ≤100 IU/mL can be achieved in approximately 20% of patients, particularly in those with low baseline HBsAg levels. HBsAg decline is slow (≥0.5 log10 in 40% of patients after 4 years) and is associated only with higher baseline serum IP10 levels.

Non-variceal gastrointestinal bleeding in patients with liver cirrhosis: a review.

BACKGROUND: Non-variceal gastrointestinal (NVGI) bleeding in cirrhosis may be associated with life-threatening complications similar to variceal bleeding. AIM: To review NVGI bleeding in cirrhosis. METHODS: MEDLINE, Scopus, and ISI Web of Knowledge were searched, using the textwords "portal hypertensive gastropathy," "gastric vascular ectasia," "peptic ulcer," "Dieulafoy's," "Mallory-Weiss syndrome," "portal hypertensive enteropathy," "portal hypertensive colopathy," "hemorrhoids," and "cirrhosis." RESULTS: Portal hypertensive gastropathy (PHG) and gastric vascular ectasia (GVE) are gastric lesions that most commonly present as chronic anemia; acute upper GI (UGI) bleeding is a rare manifestation. Management of PHG-related bleeding is mainly pharmacological, whereas endoscopic intervention is favored in GVE-related bleeding. Shunt therapies or more invasive techniques are restricted in refractory cases. Despite its high incidence in cirrhotic patients, peptic ulcer accounts for a relatively small proportion of UGI bleeding in this patient population. However, in contrary to general population, the pathogenetic role of Helicobacter pylori infection remains questionable. Finally, other causes of UGI bleeding include Dieulafoy's lesion, Mallory-Weiss syndrome, and portal hypertensive enteropathy. The most common non-variceal endoscopic findings reported in patients with lower gastrointestinal bleeding are portal hypertensive colopathy and hemorrhoids. However, the vast majority of studies are case reports and, therefore, the incidence, diagnosis, and risk of bleeding remain undefined. Endoscopic interventions, shunting procedures, and surgical techniques have been described in this setting. CONCLUSIONS: The data on NVGI bleeding in liver cirrhosis are surprisingly scanty. Large, multicenter epidemiological studies are needed to better assess prevalence and incidence and, most importantly, randomized studies should be performed to evaluate the success rates of therapeutic algorithms.

Meta-analysis: antiviral treatment for hepatitis D.

BACKGROUND: There is no satisfactory treatment for patients with hepatitis D (HDV). AIM: To evaluate treatment for HDV using meta-analysis. METHODS: Medline, Scopus, Cochrane Library and ISI Web of Knowledge searches using the textwords 'Hepatitis D', 'therapy', "interferon", "peginterferon", "pegylated interferon", "lamivudine", "pegifn", "ifn" and "Hepatitis D", and abstracts from major Gastroenterology/Liver meetings. ENDPOINTS: end of treatment biochemical (biochemical EOT) and virological response (virological EOT), end of follow-up virological response (EOFUP VR), histological improvement and intrahepatic HDAg clearance. RESULTS: We included randomised clinical trials (RCTs) comparing Group A: interferon-A (IFNa) vs. no treatment (three RCTs, n ;= ;137 patients), Group B: low dose vs. high dose IFNa (two RCTs, n ;= ;60), Group C: IFNa ;+ ;lamivudine vs. IFNa (two RCTs, n ;= ;48) and Group D: pegylated IFNa (PEG-IFNa) vs. other medications (two RCTs, n ;= ;157). Group A. IFNa was better for biochemical EOT [OR, 0.11 (95% CI, 0.04-0.2)] and virological EOT [OR, 0.08 (95% CI, 0.03-0.2)], but not for EOFUP VR. Group B. High dose IFNa was better for biochemical EOT [OR, 0.24 (95% CI,0.08-0.73)] and virological EOT [OR, 0.27 (95% CI, 0.1-0.74)]. Group C. There was a trend favouring histological improvement [OR, 2.9 (95% CI, 0.6-13.4)]. Group D. PEG-IFNa was better for virological EOT [OR, 0.419 (95% CI, 0.18-0.974)], EOFUP VR [OR, 0.404 (95% CI, 0.189-0.866)] and improvement in necroinflammatory activity [OR, 0.308 (95% CI, 0.129-0.732)]. CONCLUSIONS: Long-term suppression of HDV RNA by IFNa is not maintained despite an end of treatment response; adding lamivudine is not beneficial. PEG-IFNa is superior to other medications with respect to EOT and EOFUP. New RCTs should test combinations of PEG-IFNa and newest antivirals.

Meta-analysis: ursodeoxycholic acid for primary sclerosing cholangitis.

BACKGROUND: There is no satisfactory medical treatment for patients with primary sclerosing cholangitis. There are conflicting data regarding the clinical benefit of high doses of ursodeoxycholic acid (UDCA) in primary sclerosing cholangitis. AIM: To evaluate using meta-analysis, if UDCA (standard or high-dose) is useful in primary sclerosing cholangitis. METHODS: We searched MEDLINE using the textwords 'PSC', 'treatment', 'UDCA' and retrieved all abstracts from the major Gastroenterology and Liver meetings. We included randomised clinical trials comparing standard or high-dose of UDCA (>15 mg/kg body weight per day) vs. placebo or no intervention. End-points: mortality or liver transplantation, pruritus, fatigue, cholangiocarcinoma and histological progression. RESULTS: We identified eight randomised clinical trials comprising 567 patients. Five used standard doses and three high doses of UDCA. There was no significant difference in mortality [OR, 0.6 (95% CI, 0.4-1.4)], in pruritus [OR, 1.5 (95% CI, 0.3-7.2)], in fatigue [OR, 0.0 (95% CI, 0.1-7.7)], in cholangiocarcinoma [OR, 1.7 (95% CI, 0.6-5.1)] and in histology stage progression [OR, 0.9 (95% CI, 0.34-2.44)]. No differences were found in the subgroup analyses. CONCLUSION: Neither standard nor high-dose UDCA influence favourably the progression of primary sclerosing cholangitis.

Patients with gastroesophageal reflux disease and respiratory manifestations do not present lung function disorders during cardiopulmonary exercise test.

Gastroesophageal reflux disease (GERD) has been associated with a variety of pulmonary manifestations, but it is unclear if gastroesophageal reflux causes any abnormality in pulmonary function. Cardiopulmonary exercise test (CPET) is a specialized method that is used to evaluate respiratory function during exercise. The aim of this study was to reveal any abnormality of pulmonary function in patients with GERD and respiratory symptoms. We evaluated 34 patients with GERD (24 men and 10 women, aged 21-63) and extraesophageal respiratory symptoms (wheezing and/or cough) before therapy and after a 12-week treatment with double dose of omeprazole. No patient presented abnormal spirometry. CPET was performed in all the patients at baseline and after completion of the 12-week treatment. CPET parameters including VO(2) rest, VO(2) max, VCO(2) rest, VCO(2) max, O(2)-puls rest, O(2)-puls max, HR (heart rate) rest, HRmax, PETCO(2) rest, PETCO(2) max, and VE/VCO(2) slope were recorded pretreatment and posttreatment. Twenty-four patients (70.6%) had esophagitis (grade A-D), 16 patients had hiatal hernia (47.1%), and 13 patients (38.2%) tested positive for Helicobacter pylori. All of the patients completed the CPET. No one presented shortness of breath or respiratory symptoms. CPET parameters were within normal limits in all of the patients. Twenty-eight patients were reevaluated. No improvement in any CPET parameter posttreatment was observed despite remission of esophageal and extraesophageal respiratory symptoms in all patients. No statistically significant difference was observed pretreatment and posttreatment between the patients older and younger than 40 years, smokers and nonsmokers, Hp(+) and Hp(-) patients, and those with and without hiatal hernia and esophagitis. The patients with GERD and respiratory manifestations and normal spirometry present no pulmonary dysfunction during CPET. No alterations in CPET values posttreatment or differences in CPET values according to age, smoking, Hp status, presence of esophagitis, or hiatal hernia were observed.

Review article: the therapeutic and prognostic benefit of portal pressure reduction in cirrhosis.

BACKGROUND: Hepatic venous pressure gradient (HVPG) measurement is not a routinely used technique, despite its therapeutic and prognostic value. AIM: To review the role of HVPG from published literature. METHODS: Systematic literature review. RESULTS: In acute variceal bleeding, HVPG is prognostic identifying 'difficult to treat' group, which now has defined clinical correlations. In secondary prevention of portal hypertensive bleeding, a reduction to < or = 12 mmHg confers near complete protection against rebleeding. The target of > or = 20% HVPG reduction from baseline needs prospective assessment to test a change of therapy, if no reduction occurs. The acute HVPG response to beta-blockade needs further assessment. In primary prevention, the cost-effectiveness of HVPG measurement is not favourable given the efficacy of medical therapy. In chronic liver disease, wedge hepatic venous pressure (WHVP) is prognostic for survival. Pharmacological reduction in portal pressure decreases complications and improves survival, possibly independent of a concomitant improvement in liver function. This latter requires urgent confirmation as it is clinically very relevant. HVPG monitoring can be used to assess anti-viral therapy particularly in cirrhosis, ergonomically combined with transjugular biopsy. CONCLUSIONS: The prognostic and therapeutic value of HVPG is established beyond portal hypertensive bleeding for which there are some clinical surrogates. HVPG measurement should now be part of everyday clinical practice.

Endoscopic retrogade cholangiopancreatography is safe and effective method for diagnosis and treatment of biliary and pancreatic disorders in octogenarians.

BACKGROUND AND AIM: Diagnosis and treatment of pancreatic and biliary diseases represents a special problem in old patients who often suffer from one or more concomitant diseases. The aim of this study was to evaluate the safety and efficacy of ERCP in very old patients (octogenarians). PATIENTS AND METHODS: Patients 80 years or older who underwent ERCP from October 2001 to December 2005 were studied retrospectively. RESULTS: A total of 209 patients (121 women, 88 men), with a mean age 86 +/- 4.4 years old (80-102) underwent 251 ERCPs. All but three patients tolerated the procedure well. Three procedures were not completed due to patients' discomfort (1.4%). Two of these patients underwent percutaneous transhepatic cholangiography and the other one was treated conservatively. A cholangiogram was obtained in 193 cases (92.3%), although in 7 patients an additional attempt was required. The main endoscopic findings were common bile duct stones in 51.8% (100/193) and cancer in 28% (54/193) of patients. Based on the diagnostic findings, a therapeutic intervention was indicated in 189 patients (90.4%) and was achieved in 181 of them (95.8%). Complications were observed in 9.6% of ERCPs (24/251). Post - ERCP mild pancreatitis was the more frequent complication in 11 procedures (4.4%). No severe pancreatitis was observed. Six procedures were complicated by cholangitis (2.4%) and two by cholecystitis (0.8%). Early surgical intervention was required in 2 cases because of oesophageal perforation and retroperitoneal perforation respectively. Two patients died (0.8%); one patient with pancreatic cancer died due to septic shock after inadequate biliary drainage and the other one died after operation for retroperitoneal perforation. CONCLUSIONS: In conclusion, ERCP is safe and effective method for diagnosis and treatment of biliary and pancreatic disorders in octogenarians despite the high comorbidity in this group of patients.

Improved survival of patients presenting with acute variceal bleeding. Prognostic indicators of short- and long-term mortality.

BACKGROUND AND AIM: Variceal bleeding is a severe complication of portal hypertension with a mortality rate between 30% and 60% in previous studies. During the last two decades the treatment of these patients has been improved. The aim of this study was to investigate the clinical outcome of patients after an episode of acute variceal bleeding and to identify risk factors for early and late mortality in these patients. MATERIALS AND METHODS: All patients with acute variceal bleeding hospitalised at two large hospitals between January 1, 1999 and June 30, 2004, were retrospectively enrolled in this study. After discharge, patients were followed until death or study closure date, on June 30, 2005. Bleeding related mortality, 6-week, 1-year and overall mortality were evaluated as well as factors related to early and late mortality. RESULTS: One hundred and forty one patients were included (114 men, 27 women) with a mean age of 60.5+/-13.5 years. In hospital, 6-week, 1-year and overall mortality were 12.1%, 18.4%, 32.6% and 48.2%, respectively. The mean length of hospitalisation was 11.4+/-9 days (1-55) and the mean packed red blood cell requirement was 3.9+/-3.7 (0-25). The rate of recurrent bleeding was 10.7% during initial hospitalisation. Being Child-Pugh C (p=0.003) and shock on admission (p=0.037) were independent predictors of 6-week mortality, while being Child-Pugh C (p=0.028), presence of hepatocellular carcinoma or other neoplasia (p=0.04) and partial thromboplastin time (p=0.021) during the initial admission were independent predictors for 1-year mortality. Mortality was not affected by the presence of active bleeding and/or white nipple at emergency endoscopy. Also presence of infection was not an adverse factor of clinical outcome in our patients. CONCLUSIONS: In conclusion, the clinical outcome of patients with acute variceal bleeding is better in comparison with previous studies. The severity of liver failure as well as the presence of neoplasia mainly affects the survival.

Risk factors, sequential organ failure assessment and model for end-stage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit.

BACKGROUND: Prognostic scores in an intensive care unit (ICU) evaluate outcomes, but derive from cohorts containing few cirrhotic patients. AIMS: To evaluate 6-week mortality in cirrhotic patients admitted to an ICU, and to compare general and liver-specific prognostic scores. METHODS: A total of 312 consecutive cirrhotic patients (65% alcoholic; mean age 49.6 years). Multivariable logistic regression to evaluate admission factors associated with survival. Child-Pugh, Model for End-stage Liver Disease (MELD), Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were compared by receiver operating characteristic curves. RESULTS: Major indication for admission was respiratory failure (35.6%). Median (range) Child-Pugh, APACHE II, MELD and SOFA scores were 11 (5-15), 18 (0-44), 24 (6-40) and 11 (0-21), respectively; 65% (n = 203) died. Survival improved over time (P = 0.005). Multivariate model factors: more organs failing (FOS) (<3 = 49.5%, > or =3 = 90%), higher FiO(2), lactate, urea and bilirubin; resulting in good discrimination [area under receiver operating characteristic curve (AUC) = 0.83], similar to SOFA and MELD (AUC = 0.83 and 0.81, respectively) and superior to APACHE II and Child-Pugh (AUC = 0.78 and 0.72, respectively). CONCLUSIONS: Cirrhotics admitted to ICU with > or =3 failing organ systems have 90% mortality. The Royal Free model discriminated well and contained key variables of organ function. SOFA and MELD were better predictors than APACHE II or Child-Pugh scores.

Evidence for intestinal oxidative stress in patients with obstructive jaundice.

BACKGROUND: Obstructive jaundice results in failure of the intestinal barrier with consequent systemic endotoxemia associated with septic complications. We have recently shown that gut barrier failure in experimental obstructive jaundice is associated with high intestinal oxidative stress. This study was undertaken to investigate whether oxidative alterations occur in the intestinal mucosa of patients with obstructive jaundice. PATIENTS AND METHODS: Fifteen patients with malignant biliary obstruction and no signs of cholangitis and 15 control patients were subjected to duodenal biopsy to assess intestinal oxidative stress, estimated by lipid peroxidation (malondialdehyde - MDA) and glutathione redox state [reduced glutathione (GSH), glutathione disulphide (GSSG) and GSH/GSSG ratio]. In addition, mucosal biopsies were examined histologically and intestinal mucosal protein content was determined biochemically as an index of intestinal trophic state. RESULTS: Patients with obstructive jaundice presented high levels of intestinal oxidative stress, with significantly increased lipid peroxidation (P < 0.001). Glutathione redox state was also suggestive of high intestinal oxidative stress in jaundiced patients, indicated by significantly decreased GSH (P = 0.001) and GSH/GSSG ratio (P = 0.006) and increased GSSG (P = 0.026). Histological examination showed a mild infiltration of the lamina propria by chronic inflammatory cells in obstructive jaundice, whereas duodenal architecture remained intact and epithelial continuity was retained. Duodenal mucosa was atrophic in jaundiced patients as indicated by a significant reduction of mucosal protein content compared with controls (P = 0.001). Among oxidative stress parameters, intestinal GSH exhibited a significant positive correlation with mucosal protein content (r = 0.588, P = 0.021). CONCLUSIONS: Obstructive jaundice in humans induces intestinal oxidative stress, which may be a key factor contributing to intestinal barrier failure and the development of septic complications in this patient population.

Predisposing factors and clinical symptoms in HIV-negative patients with Candida oesophagitis: are they always present?

Candida oesophagitis (CO) is scarce among immunocompetent patients. This study aimed at evaluating predisposing factors, clinical symptoms and endoscopic findings in this group. We retrospectively reviewed 55 patients diagnosed as CO endoscopically (whitish plaques) and cytologically (fungal mycelia on brush cytology). Carcinoma, diabetes, acid suppression, steroids, gastric surgery and oesophageal motility disorders were considered as predisposing factors. Twenty of 55 patients lacked any predisposing factor for CO. These patients were more frequently asymptomatic (8/20) when compared with those with known predisposing factors (5/35) (p = 0.031). Moreover, dysphagia was more prevalent in the latter group (24/35 vs. 8/20; p = 0.039). Endoscopic findings correlated with the presence of neither predisposing factors nor symptoms (Wilcoxon p > 0.05). Thus, CO can be discovered in patients without apparent predisposing risk factors and clinical symptoms. Further studies are needed to elucidate the mechanisms of transition from colonisation to infection.

Gastric ulcers and risk for cancer. Is follow-up necessary for all gastric ulcers?

The aim of this study was to determine the accuracy of initial endoscopy combined with histology and to define whether there is a point in following-up all gastric ulcers until complete healing. We have studied all patients with gastric ulcers documented at endoscopy during a 6-year period. Ulcers were macroscopically characterised as benign or suspicious for malignancy, and biopsies were taken. A follow-up endoscopy and histology was performed 4-6 weeks and 3 months after an anti-ulcer treatment. Resistant ulcers were treated surgically. All patients were followed-up clinically and endoscopically for a year after complete ulcer healing. 802 patients with gastric ulcers were enrolled. At initial endoscopy, 732 ulcers (91.3%) were macroscopically characterised as benign and 70 ulcers (8.7%) as suspicious for malignancy. In the group of endoscopically benign ulcers, only one (0.1%) had malignancy detected by biopsy in the first examination. None of these ulcers turned out to be malignant on subsequent examinations. From the suspicious for malignancy ulcers, 20 (28.6%) were proven to be malignant. Endoscopy may recognise with great accuracy benign ulcers, but it overestimates the malignant ones. The cost-benefit of serial follow-up endoscopies should be re-evaluated in ulcers that appear benign, and biopsies are negative at the initial examination.

Predictors of hemostatic failure after adrenaline injection in patients with peptic ulcers with non-bleeding visible vessel.

BACKGROUND: Non-bleeding visible vessel (NBVV) in patients with bleeding peptic ulcer is associated with a high risk of rebleeding. The aim of this study was to define factors associated with failure of endoscopic hemostasis and rebleeding in patients with NBVV. METHODS: Clinical and endoscopic parameters related to failure of endoscopic hemostasis with adrenaline in 191 bleeding peptic ulcer patients with NBVV were evaluated. RESULTS: Endoscopic hemostasis was permanently successful in 154 patients (80.6%). Emergency surgical hemostasis for rebleeding was required in 37 patients (19.4%). Univariate analysis showed that therapeutic failure was significantly related to the presence of shock on admission (P=0.003), posterior duodenal ulcers (P=0.001), peptic ulcer history (P=0.001), previous peptic ulcer bleeding (P=0.002), or lack of history of non-steroidal anti-inflammatory drugs consumption, when compared to use of such drugs (P=0.04). Patients where therapy failed had lower hemoglobin levels at admission (7.8+/-1.9 g/dL versus 10+/-2.4 g/dL, P=0.005). In a multivariate analysis low hemoglobin (P<0.001) as well as history of previous peptic ulcer bleeding (P=0.002) and posterior duodenal ulcers (P=0.001) were negative predictors. Using the mean value of hemoglobin as the cut-off point, it is noteworthy that only 2 out of 81 patients (2.5%) who had none of these predictive factors required emergency surgical hemostasis, whereas 34 out of 110 patients (30.9%) with at least one predictive factor required emergency surgery. CONCLUSION: It is possible, by employing specific characteristics, to define a subgroup of high-risk patients for rebleeding in patients with NBVV despite therapeutic endoscopy and thus candidates for a complementary endoscopic method of hemostasis or emergency surgical intervention.

Evidence for intestinal oxidative stress in obstructive jaundice-induced gut barrier dysfunction in rats.

AIM: An important factor that promotes bacterial and endotoxin translocation in obstructive jaundice is intestinal injury that causes increased permeability. However, little is known of the submicroscopic biochemical events leading to defects of the intestinal barrier. This study was undertaken to investigate the effect of experimental obstructive jaundice on intestinal lipid peroxidation, protein oxidation and thiol redox state. METHODS: Rats were randomly divided into controls, sham operated and bile duct ligated (BDL). After 10 days, intestinal barrier function was assessed by measuring endotoxin in portal and aortic blood. Tissue samples from the terminal ileum were examined histologically and morphometrically, while other samples were homogenized for the determination of lipid peroxidation, protein oxidation and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulphides (NPSSR), protein thiols (PSH) and protein disulphides (PSSP)]. RESULTS: Obstructive jaundice compromised intestinal barrier function leading to significant portal and systemic endotoxaemia. The intestinal mucosa in jaundiced rats was atrophic with significantly decreased villous density and total mucosal thickness. Determination of biochemical parameters of oxidative stress in the intestine showed increased lipid peroxidation and protein oxidation in BDL-rats. Thiol redox state revealed the presence of intestinal oxidative stress in jaundiced rats, indicated by a decrease in GSH and increased GSSG, NPSSR and PSSP. CONCLUSIONS: This study shows that experimental obstructive jaundice induces intestinal oxidative stress, which may be a key factor contributing to intestinal injury and leading to endotoxin translocation.

Non-invasive predictors of the presence of large oesophageal varices in patients with cirrhosis.

BACKGROUND/AIMS: The usual clinical practice is to screen all patients with established cirrhosis at the time of diagnosis by upper endoscopy for the presence of varices. Patients with large varices should be treated with non-selective beta blockers to reduce the incidence of first variceal bleeding. However, fewer than 50% of cirrhotic patients have varices at screening endoscopy and most have small sized varices, with a low risk of bleeding. The aim of the present study was to determine whether clinical or laboratory non-endoscopic parameters could predict the presence of large oesophageal varices. PATIENTS/METHODS: Seventeen variables considered relevant to the prevalence of oesophageal varices were tested in 184 patients with cirrhosis, who underwent screening endoscopy. Small varices were regarded as those which flatten with insufflation or slightly protrude into the lumen, while large varices are those which protrude into the lumen or touch each other. None of the patients was on beta blockers or other vasoactive drugs or had a history of variceal bleeding. RESULTS: Oesophageal varices were present in 92 patients (50%), and large varices in 33 patients (17.9%). Variables associated with the presence of large oesophageal varices on univariate analysis were the presence of ascites and splenomegaly either by clinical examination or by ultrasound (p < 0.01), the presence of spiders (p = 0.02), platelet count (p < 0.0001), and bilirubin (p = 0.01). Factors independently associated with the presence of large oesophageal varices on multivariate analysis were platelet count, size of spleen and presence of ascites by ultrasound. Using mean values as cut-off points, it is noteworthy that only five out of 39 patients (12.8%) with platelets > or = 18(x 10(9)/l), spleen length < or = 135 mm and no ascites had varices. Moreover, all these patients had small sized varices. On the other hand, 15 out of 18 patients (83.3%) with a platelet count < 118 x 10(9)/l, spleen length > 135 mm and ascites had varices. Moreover, five out of those 18 patients had large varices (28.3%). CONCLUSION: Thrombocytopenia, splenomegaly and ascites are independent predictors of large oesophageal varices in cirrhotic patients. We suggest that endoscopy could be avoided safely in cirrhotic patients with none of these predictive factors, as large varices are absent in this group of patients.

Factors associated with failure of endoscopic injection haemostasis in bleeding peptic ulcers.

BACKGROUND: The effectiveness of a submucosal injection of adrenaline solution in endoscopic haemostasis is well documented in patients suffering from peptic ulcer bleeding. After treatment, however, a significant number of patients continue to bleed or rebleed, and require emergency surgical intervention. The aim of this study was to define factors associated with the failure of endoscopic injection haemostatic therapy in peptic ulcer bleeding. METHODS: In the period 1992 to 1998, we prospectively studied all patients suffering from peptic ulcer bleeding and identified endoscopically as being either bleeding actively or carrying a visible vessel. A total of 427 patients (343 men and 84 women; mean age 58.6 +/- 16.6 years) were all subjected to endoscopic injection with adrenaline solution on an emergency basis. Patients who eventually required surgical intervention for permanent haemostasis were considered as endoscopic haemostasis failures, whereas those who did not were considered as endoscopic treatment successes. We evaluated all clinical and endoscopic parameters that might have been related to failure of endoscopic injection therapy. RESULTS: Endoscopic injection haemostasis was successful in 341 patients (79.9%) and a failure in 86 (20.1%) who finally underwent emergency surgical haemostasis. On analysing the examined parameters, failure was significantly related to shock on admission (OR 2.31, 95% CI 1.33, 6.97), spurt bleeding at endoscopy (OR 2.45, 95% CI 1.51, 3.98), posteriorly located duodenal ulcer (OR 2.48, 95% CI 1.37, 7.01) and anastomotic ulcer (OR 3.39, 95% CI 1.37, 7.29). Endoscopic injection haemostasis therapy was less effective in patients with chronic ulcers compared to those who had acute NSAID-related ulcers. A history of peptic ulcer (OR 1.57, 95% CI 1.14, 3.05), previous peptic ulcer bleeding (OR 2.45, 95% CI 1.51, 3.98) or non-use of NSAIDs (OR 2.81, 95% CI 1.33, 4.62) were negative predictors for the outcome of endoscopic haemostasis. CONCLUSION: With the use of specific clinical and endoscopic characteristics it is possible to define a subgroup of high-risk patients for continued bleeding or rebleeding despite endoscopic injection therapy. These patients may be candidates for intensive monitoring, early surgical intervention or possibly complementary endoscopic haemostatic methods.

Autoimmune cholangitis in a patient with celiac disease: a case report and review of the literature.

Autoimmune cholangitis is a rare chronic cholestatic liver disease. We describe the case of a 65-year-old woman with celiac disease who presented to us with fever, jaundice and weight loss. Serum biochemical study showed marked increase in alkaline phosphatase and gammaGT levels. Antinuclear antibodies were positive, while antimitochondrial and anti-smooth-muscle antibodies were negative. Liver biopsy was compatible with primary autoimmune cholangitis. The patient was successfully treated with azathioprine and methylprednisolone. We describe here the uncommon association of autoimmune cholangitis with celiac disease and review the prevalence of liver diseases in patients with celiac disease.

Prevalence of intrapulmonary vascular dilatations in normoxaemic patients with early liver cirrhosis.

BACKGROUND: The aim of this study was to determine the prevalence of intrapulmonary vascular dilatations (IPVD) in normoxaemic patients with early liver cirrhosis and to compare their occurrence in progressive alcoholic versus postviral hepatic insufficiency. METHODS: Pulmonary function tests and arterial blood gas measurements were performed in 75 consecutive patients with cirrhosis of alcoholic and postviral aetiology. Contrast-enhanced echocardiography was used to identify IPVD. RESULTS: All patients were grade A or B in accordance with the Child-Pugh modified classification. Arterial blood gas analyses showed normoxaemia in all patients. Eight of 75 patients (10.7%) had a positive contrast echocardiogram, all with a decreased diffusion capacity (D1CO < 75% of the expected value). The abnormality was more prominent with advancing stage of liver failure (4.5% in grade A versus 19.4% in grade B; P < 0.05) and more common in patients with alcoholic cirrhosis (17.5% in alcoholic versus 2.9% in postviral cirrhosis; P < 0.05). CONCLUSION: In normoxaemic patients with early liver cirrhosis subclinical pulmonary vasodilatation, as assessed with contrast echocardiography, can occur. The finding is more prominent in alcoholic cirrhosis and possibly reflects an advancing degree of liver insufficiency.

Factors related to early mortality after transjugular intrahepatic portosystemic shunt for failed endoscopic therapy in acute variceal bleeding.

BACKGROUND: Uncontrolled variceal haemorrhage is the main indication for transjugular intrahepatic portosystemic shunt. However, mortality is 50% for this high-risk group. We have evaluated clinical and laboratory variables prior to transjugular intrahepatic portosystemic shunt in order to establish predictors of mortality, validated prospectively. METHOD: Over a 4-year period, 367 patients were admitted with variceal bleeding. In 54 patients endoscopic therapy for acute variceal bleeding failed and they had emergency transjugular intrahepatic portosystemic shunt. Failure of therapy was defined as continued bleeding after 2 endoscopy sessions (n=39) or vasoconstrictor-resistant bleeding from gastric/ectopic varices (n=15). Thirty-three variables were analysed from data available immediately prior to transjugular intrahepatic portosystemic shunt. RESULTS: Twenty-six patients died within 6 weeks. In a multivariate analysis, 6 factors had independent prognostic value: moderate/severe ascites, requirement for ventilation, white cell blood count (WBC), platelet count (PLT), partial thromboplastin time with kaolin (PTTK) and creatinine. A prognostic index (PI) score was derived, in which presence of moderate/severe ascites, or need for ventilation, scored 1: PI=1.54 (Ascites)+1.27 (Ventilation)+1.38 Ln (WBC)+2.48 ln (PTTK)+1.55 Ln (Creat)-1.05 Ln (PLT). Using this equation, 42% (n=10) of deaths occurred in the fifth quintile (PI > or = 18.52), where the mortality was 100%. The score was prospectively validated in a further 31 patients, giving 100% positive predictive value. Eleven further patients died, including all seven with a PI >18.5. No survivors had a PI >18.3. CONCLUSION: Despite immediate control of bleeding by transjugular intrahepatic portosystemic shunt, patients with uncontrolled variceal haemorrhage have a high mortality, particularly when associated with markers of advanced liver disease, sepsis and multi-organ failure. The use of transjugular intrahepatic portosystemic shunt is probably not justified in this subgroup. Our prognostic index can help identify such patients, and, if validated elsewhere, will help in deciding when to use transjugular intrahepatic portosystemic shunt.