Pasquale Conoscitore

Pharmacologic treatment can prevent pancreatic injury after ERCP: a meta-analysis

BACKGROUND The identification of therapeutic agents that can prevent the pancreatic injury after endoscopic retrograde cholangiopancreatography (ERCP) is of considerable importance. METHODS We performed a meta-analysis including 28 clinical trials on the use of somatostatin (12 studies), octreotide (10 studies), and gabexate mesilate (6 studies) after ERCP. Outcome measures evaluated were the incidence of acute pancreatitis, hyperamylasemia, and pancreatic pain. Three analyses were run separately: for all available studies, for randomized trials only, and for only those studies published as complete reports. RESULTS When all available studies were analyzed, somatostatin and gabexate mesilate were significantly associated with improvements in all three outcomes. Odds ratios (OR) for gabexate mesilate were 0.27 (95% CI [0.13, 0. 57], p = 0.001) for acute pancreatitis, 0.66 (95% CI [0.48, -0.89], p = 0.007) for hyperamylasemia, and 0.33 (95% CI [0.18, 0.58], p = 0. 0005) for post-procedural pain. Somatostatin reduced acute pancreatitis (OR 0.38: 95% CI [0.22, 0.65], p < 0.001), pain (OR 0. 24: 95% CI [0.14, 0.42], p < 0.001), and hyperamylasemia (OR 0.65: 95% CI [0.48, 0.90], p = 0.008). Octreotide was associated only with a reduced risk of post-ERCP hyperamylasemia (OR 0.51: 95% CI [0.31, 0.83], p = 0.007) but had no effect on acute pancreatitis and pain. The statistical significance of data did not change after analyzing randomized trials only or studies published as complete reports. For each considered outcome, the publication bias assessment and the number of patients that need to be treated to prevent one adverse effect were, respectively, higher and lower for somatostatin than for gabexate mesilate. CONCLUSIONS The pancreatic injury after ERCP can be prevented with the administration of either somatostatin or gabexate mesilate, but the former agent is more cost-effective. Additional studies comparing the efficacy of short-term infusion of somatostatin versus gabexate mesilate in patients at high risk for post-ERCP complications seem warranted.

Changing pattern of chronic hepatitis D in southern Europe

BACKGROUND & AIMS The aim of this study was to assess changes in the clinical pattern of hepatitis D virus (HDV) infection in Italy, brought about by improved control of hepatitis B and D viruses, and to establish the natural history of chronic hepatitis D. METHODS Histological diagnosis and clinical features of 122 patients with HDV recruited from 1987 to 1996 in three Italian tertiary referral centers (Torino, northern Italy; San Giovanni Rotondo and Castellana Grotte, southern Italy) were compared with those of 162 patients collected in the same centers in the previous decade. Patients from both groups with at least 6 months of follow-up were included in a new subgroup to assess the natural history of the disease. RESULTS Among 162 patients referred from 1977 to 1986, 9 (6%) had mild hepatitis at histology vs. 9 (8%) of 122 patients referred in the second decade; 105 (65%) vs. 21 (17%) had severe hepatitis; 46 (28%) vs. 38 (31%) had histological asymptomatic cirrhosis; and 2 (1%) vs. 54 (44%) had clinically overt cirrhosis. For 159 patients (121 men and 38 women; mean age, 34 +/- 11), a follow-up of more than 6 months was documented, and they were included in the natural history subgroup. After 78 +/- 59 months of follow-up, 112 (70%) survived free of liver transplantation: 9 underwent transplantation, 32 died of liver failure, and 6 of acquired immunodeficiency syndrome. Estimated 5- and 10-year probability of survival free of orthotopic liver transplantation was 100% and 100% for patients with mild hepatitis, 90% and 90% for severe hepatitis, 81% and 58% for histological asymptomatic cirrhosis, and 49% and 40% for clinical cirrhosis (P < 0.01), respectively. CONCLUSIONS Occurrence of fresh and severe forms of hepatitis D has diminished greatly in Italy. Contemporary patients represent cohorts infected years ago who survived the immediate medical impact of hepatitis D. The disease has been asymptomatic and nonprogressive in a minority; in the majority, it rapidly advanced to cirrhosis but thereafter subsided with stable clinical conditions for more than a decade.

Pancreatic Duct Stents in the Prophylaxis of Pancreatic Damage after Endoscopic Retrograde Cholangiopancreatography: A Systematic Analysis of Benefits and Associated Risks

Methods: The efficacy of pancreatic stenting in the prevention of pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) was evaluated by a meta-analysis of 6 controlled studies; 12 additional uncontrolled studies were analyzed for rates of associated risk. Results: Post-ERCP pancreatitis (PEP) developed in 16.5% of controls, and in 5.1 or 9.6% of the stent group at the per-protocol (PP) or intention-to-treat (ITT) analyses. By analyzing only the 4 randomized trials, PEP developed in 24.1% of controls, and in 6.1 or 12.0% of the stented patients at the PP or ITT analyses. Risk was significantly lower in the stent group when compared with controls: OR 0.44 (95% CI 0.24–0.81). The absolute risk reduction is 12.0 (95% CI 3.0–21.0), the number needed to treat 8 (95% CI 5–34), and the publication bias 2. ORs for mild to moderate PEP were reduced in the stent group (OR = 0.537, 95% CI 0.283–1.021), as were those for severe PEP (OR = 0.123, 95% CI 0.021–0.726). Non-pancreatic complications were 4.2%, and included early stent migration (1.4%), perforations (0.4%), bleeding (1.4%), and infections (1.0%). Conclusion: Available trials show benefit for pancreatic stenting in the prophylaxis of PEP, but more randomized studies are needed before endorsing a routine use of this endoscopic procedure.

helicobacter pylori Infection May Undergo Spontaneous Eradication in Children: A 2-year Follow-up Study

BACKGROUND Helicobacter pylori infection is generally acquired early in life. However, it is still unknown whether a spontaneous eradication can occur. The purpose of this study was to evaluate whether H. pylori infection can undergo spontaneous eradication in children. METHODS Three hundred and four Italian children (age range, 4.5 to 18.5 years) were tested for H. pylori by means of 13C-urea breath test. Infected children were followed up every 6 months for as long as 2 years. Parents were instructed to record consumption of antibiotics. At each visit, children underwent a repeat 13C-urea breath test. RESULTS Eighty-five out of 304 (27.9%) children were H. pylori infected. Forty-eight out of 85 infected children (56.4%) participated in the follow-up study. After 2 years, 8 (16.6%) infected children had negative results on 13C-urea breath tests; 2 of them were given antibiotics for concomitant infections. One child was negative at 6 months but became positive again at the next 6-month 13C-urea breath test. Forty children remained persistently positive; of them, 10 were treated with a short course of antibiotics. CONCLUSIONS Our findings support the hypothesis that, at least during childhood, H. pylori infection may be a fluctuating disease with spontaneous eradication and possible recurrence.

ABO-mismatch adult living donor liver transplantation using antigen-specific immunoadsorption and quadruple immunosuppression without splenectomy.

ABO‐incompatible (ABO‐I) liver transplantation is a controversial issue because of the generally less favorable outcome as compared to compatible transplants. Encouraging results have been shown by the introduction of new strategies to reduce posttransplant‐specific hemagglutinin (HA) titers with plasmapheresis, reinforced immunosuppression (IS), and the use of splenectomy. We describe a new protocol consisting of daclizumab (DAC) induction, mycophenolate mofetil (MMF)/tacrolimus (TAC)/steroids without splenectomy. Five recipients (mean age of 47 ± 14 yr) undergoing ABO‐I living donor liver transplantation (LDLT) were included in this protocol. Immunoadsorbent columns (Glycosorb ABO) were used for antigen‐specific immunoadsorption (ASI). The median follow‐up was 18.5 ± 10.5 months. ASI was very efficient in lowering HA titers (mean log2 immunoglobulin [Ig] M [IgM] and IgG values before and after ASI were 5.9 ± 2.8 and 1.2 ± 1.4 [P= 0.0038] and 6.5 ± 2.3 and 1.1± 1.9, respectively [P= 0.0001]). Persisting low HA titers were observed over time. No sepsis nor cytomegalovirus infection episodes were recorded. Acute cellular rejection (ACR) occurred in 1 recipient responding to steroid pulse therapy. Two grafts were lost in 2 patients due to technical failure during the first postoperative month. We conclude that ASI using Glycosorb ABO, quadruple immunosuppression including DAC and MMF provide high efficiency to lower HA titers over time, avoiding the need for splenectomy. ABO‐I LDLT can be performed with this adapted IS protocol. Liver Transpl 12:1412‐1417, 2006.

Intrafamilial transmission of hepatitis delta virus: molecular evidence

BACKGROUND/AIMS Epidemiologic studies have suggested that transmission of hepatitis delta virus (HDV) occurs by intrafamilial routes in some populations in southern Italy, where HDV infection is endemic. To further evaluate intrafamilial transmission of HDV, we obtained the partial sequence of the viral genome from HDV-RNA positive members of families in which two or more immediate family members were positive for HDV-RNA. METHODS The region analyzed was the semi-conserved region from nucleotides 908 to 1265. Sequences obtained from family members were compared with those obtained from a control group of 20 unrelated patients. RESULTS The mean genetic divergence among HDV isolates was 2.8 +/- 1.7% within the 9 families analyzed, and 7.6 +/- 2.2% among the control group of unrelated individuals (p < 0.0001). A Receiver Operating Characteristic curve and Youden Index were used to define a cut-off value of 3.5% to discriminate sequence variations calculated within families and in the control group. CONCLUSIONS The data indicate that in most family units, HDV-infected members harbored nearly identical strains of HDV, and provide molecular support that HDV infection can be transmitted within the family. Such spreading among family members highlights the role of inapparent transmission through personal contacts.

Gastric emptying of solids in patients with nonobstructive Crohn's disease is sometimes delayed.

To date, only a few studies of gastric emptying in Crohns disease have been published in the literature. This might be clinically important because slow-release drug formulations are increasingly available for treatment. Studies in children with gastric involvement suggest that gastric emptying may be delayed in this condition. We studied the scintigraphic gastric emptying of 21 adult patients with nonobstructive Crohns disease and without gastric or duodenal involvement by the disease, compared with that of 20 healthy volunteers. Overall, no significant differences were found, but subgroup analysis showed that symptomatic patients [half-time (t1/2) 133 +/- 75.9] and those with colonic involvement (t1/2 127.2 +/- 64) had a significantly (p < 0.01) delayed gastric emptying over controls (t1/2 85.5 +/- 15.4). Such a difference was also observed between symptomatic and asymptomatic patients (p < 0.05). We conclude that gastric emptying is slowed in symptomatic patients with nonobstructive Crohns disease and in those with colonic involvement. This may have therapeutic implications.

Ultrasonographic and biochemical parameters in the non‐invasive evaluation of liver fibrosis in hepatitis C virus chronic hepatitis

Background : Prior studies suggest that platelet counts of <140 000/μL can discriminate patients with different stages of fibrosis.

Antineutrophil cytoplasmic antibodies in inflammatory bowel disease: clinical role and review of the literature.

PURPOSE: Perinuclear antineutrophil cytoplasmic antibodies have been found consistently in patients with ulcerative colitis; however, their pathogenetic and clinical role is still uncertain. In this study we tested the prevalence of perinuclear antineutrophil cytoplasmic antibodies in a large population of patients with ulcerative colitis and Crohns disease, with particular attention to the possible correlation with clinical features. METHODS: Perinuclear antineutrophil cytoplasmic antibody reactivity was investigated with indirect immunofluorescence in 279 patients with ulcerative colitis, 110 patients with Crohns disease, and 252 unrelated healthy subjects. RESULTS: Perinuclear antineutrophil cytoplasmic antibodies were found in 84 of 279 patients with ulcerative colitis (30 percent), 10 of 110 patients with Crohns disease (9 percent), and 2 of 252 healthy subjects (<1 percent;P<0.001), respectively. Perinuclear antineutrophil cytoplasmic antibodies were significantly more frequent in patients with ulcerative colitis with higher relapse rate (43vs. 27 percent;P<0.002), and patients with Crohns disease with colitis (27vs. 2.5 percent;P<0.0003). Perinuclear antineutrophil cytoplasmic antibodies were also significantly less frequent in patients with ulcerative colitis in remission (18vs. 34 percent;P<0.0025). CONCLUSIONS: In this study we confirm the relative specific of perinuclear antineutrophil cytoplasmic antibodies, either for ulcerative colitis or for Crohns disease involving the colon. Perinuclear antineutrophil cytoplasmic antibodies were more frequently found in patients with ulcerative colitis with a more aggressive clinical behavior; however, their presence had a limited value in identifying homogeneous subgroups of patients in our population.