Domenico Facciorusso

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.

Lamivudine/interferon combination therapy in anti-HBe positive chronic hepatitis B patients: a controlled pilot study

BACKGROUND/AIMS In this study, lamivudine-interferon (LAM/IFN) combination therapy was compared to LAM monotherapy to verify if the combination treatment might improve efficacy and reduce the emergence of LAM-resistant mutants. METHODS Fifty patients with anti-HBe-positive chronic hepatitis B were treated for 12 months with LAM at 100mg/day (26 pts) or with IFN at 5MU t.i.w.+LAM 100mg/day (24 pts). Serum ALT, HBV DNA and IgM anti-HBc were monitored during treatment and a 6-month follow-up. The polymerase gene was amplified by PCR and the region coding for YMDD motif was directly sequenced. RESULTS All patients normalized ALT and cleared HBV DNA during treatment. The response was maintained until the end of therapy in the LAM/IFN group, while in 5/26 initial responders treated with LAM alone, a virological and biochemical breakthrough was observed after 6-10 months, and selection for YMDD variants resulted. After therapy discontinuation, most patients relapsed; the response rate after 6 months was 17% in the LAM/IFN group and 19% in the LAM group. CONCLUSIONS In anti-HBe-positive chronic hepatitis B, a 12-month course of LAM/IFN combination therapy is as beneficial as LAM monotherapy, however, the combination regimen appeared to prevent or delay the emergence of YMDD variants.

Inosine Triphosphatase Genetic Variants are Protective Against Anemia During Antiviral Therapy for HCV2/3 But Do Not Decrease Dose Reductions of RBV Or Increase SVR

Two functional variants in the inosine triphosphatase (ITPA) gene causing inosine triphosphatase (ITPase) deficiency protect against ribavirin (RBV)‐induced hemolytic anemia and the need for RBV dose reduction in patients with genotype 1 hepatitis C virus (HCV). No data are available for genotype 2/3 HCV. We evaluated the association between the casual ITPA variants and on‐treatment anemia in a well‐characterized cohort of genotype 2/3 patients treated with variable‐duration pegylated interferon alfa‐2b (PEG‐IFN‐α2b) and RBV. Two hundred thirty‐eight Caucasian patients were included in this retrospective study [185 (78%) with genotype 2 and 53 (22%) with genotype 3]. Patients were treated with PEG‐IFN‐α2b plus weight‐based RBV (1000/1200 mg) for 12 (n = 109) or 24 weeks (n = 129). The ITPA polymorphisms rs1127354 and rs7270101 were genotyped, and an ITPase deficiency variable was defined that combined both ITPA variants according to their effect on ITPase activity. The primary endpoint was hemoglobin (Hb) reduction in week 4. We also considered Hb reduction over the course of therapy, the need for RBV dose modification, and the rate of sustained virological response (SVR). The ITPA variants were strongly and independently associated with protection from week 4 anemia (P = 10−6 for rs1127354 and P = 10−7 for rs7270101). Combining the variants into the ITPase deficiency variable increased the strength of association (P = 10−11). ITPase deficiency protected against anemia throughout treatment. ITPase deficiency was associated with a delayed time to an Hb level < 10 g/dL (hazard ratio = 0.25, 95% confidence interval = 0.08‐0.84, P = 0.025) but not with the rate of RBV dose modification (required per protocol at Hb < 9.5 g/dL). There was no association between the ITPA variants and SVR. Conclusion: Two ITPA variants were strongly associated with protection against treatment‐related anemia in patients with genotype 2/3 HCV, but they did not decrease the need for RBV dose reduction or increase the rate of SVR. (HEPATOLOGY 2011;53:389‐395.)

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.

Tumor necrosis factor gene polymorphisms and clearance or progression of hepatitis B virus infection

Abstract: Objectives: We evaluated the influence of tumor necrosis factor‐α (TNF‐α) promoter gene polymorphisms on clearance of hepatitis B virus (HBV) and outcome of HBV chronic hepatitis.

External Validation of Biochemical Indices for Noninvasive Evaluation of Liver Fibrosis in HCV Chronic Hepatitis

External Validation of Biochemical Indices for Noninvasive Evaluation of Liver Fibrosis in HCV Chronic Hepatitis

Diagnosis of Hepatocellular Carcinoma Complicating Liver Cirrhosis: Utility of Repeat Ultrasound-Guided Biopsy after Unsuccessful First Sampling

Abstract Purpose: To evaluate the utility of a second ultrasound-guided fine-needle biopsy of liver nodules thought to be hepatocellular carcinoma when the original biopsy has failed to provide a reliable diagnosis. Methods: Thirty-seven cirrhotic patients underwent ultrasound-guided fine-needle biopsy of liver nodules that were subsequently diagnosed as hepatocellular carcinoma. Each biopsy involved a single puncture with a 20 G cutting needle, which yielded pathologic material used both for cytologic and histologic studies. In 23 cases (mean diameter of nodules 48 mm) the biopsy furnished exclusively necrotic material (non-diagnostic subgroup); in the other 14 cases (mean diameter 26 mm) the biopsy yielded no neoplastic elements (false-negative subgroup). All 37 nodules were subjected to repeat biopsies performed in the same manner. Results: The repeat biopsies provided a diagnosis of hepatocellular carcinoma in six of the 23 patients from the non-diagnostic subgroup and in seven of the 14 in the false-negative subgroup. Overall, repeat biopsy produced a diagnostic gain of 35.1%. Conclusion: The chance of success with repeat biopsy of hepatocellular carcinoma is limited and may depend to some extent on the characteristics of the lesions (i.e., areas of necrosis in large nodules, well-differentiated cellular populations in small ones).

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.

Hepatic hydrothorax. Diagnosis and management.

Twelve cases of right hepatic hydrothorax are reported. Tc-99m SC that was injected intraperitoneally and intrapleurally provided evidence of a one-way flow of fluid from the peritoneal to the pleural cavity. Eight patients, whose hydrothorax was refractory to sodium restriction, diuretics and repeated thoracenteses, were treated by endopleural tetracycline instillation. The pathogenetic role of the diaphragmatic defect and the diagnostic usefulness of radionuclide imaging are stressed.

Re‐treatment of patients with anti‐HBe‐positive chronic hepatitis B who relapsed after an initial course of lamivudine

Aim : To evaluate the efficacy of a long‐term course of lamivudine monotherapy in patients with anti‐HBe‐positive chronic hepatitis B who relapsed after the first course of either lamivudine/interferon (n = 16; Group 1) or lamivudine (n = 20; Group 2).