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.

UNLABELLED: 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.

Retroperitoneal neurilemoma diagnosed by endosonographically guided fine needle aspiration.

Retroperitoneal neurilemoma is an often asymptomatic benign tumor that is usually discovered incidentally. We report a case of retroperitoneal neurilemoma diagnosed via endosonographically guided fine needle aspiration and emphasize the importance of obtaining a definite diagnosis before surgical treatment.

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

OBJECTIVES: We evaluated the influence of tumor necrosis factor-alpha (TNF-alpha) promoter gene polymorphisms on clearance of hepatitis B virus (HBV) and outcome of HBV chronic hepatitis. METHODS: Four TNF-alpha promoter polymorphisms (T-1031C, C-863A, G-308A, and G-238A) were evaluated by direct sequencing in 184 chronic HBV carriers hepatitis B surface antigen (HBsAg) positive and 96 controls with documented sero-clearance (HBsAg negativity, positivity for anti-HBs and anti-HBc IgG). Frequencies of single-nucleotide polymorphisms (SNPs) and haplotypes in the control group were compared with those of the chronic carrier group and with clinically defined subgroups of the latter: asymptomatic carriers, patients with compensated hepatitis, decompensated cirrhotics, and patients with hepatocellular carcinoma. Furthermore, subgroups of chronic carriers were compared among them. RESULTS: In the chronic carrier group, the -308 G allele was more frequent in those with a family history of HBV infection (96% vs 88% of those with non-familial transmission). The G/G genotype at position -308 was found in all chronic carriers with decompensated cirrhosis but in only 78% of controls (P=0.01) and was more frequent in decompensated cirrhotics than in the other subgroups. The distribution of TNF-alpha gene polymorphisms in the carrier group was not significantly different from that in the sero-clearance control group. TNF-alpha SNPs at positions -1031/-863 and -863/-238 were in linkage disequilibrium. The TCGG haplotype (-T1031, -C863, -G308, -G238) was significantly associated with end-stage liver disease. CONCLUSION: The TNF-alpha promoter polymorphisms do not appear to be determinant of HBV sero-clearance in southern Italians. The genotype -308G/G and haplotype TCGG are associated with an unfavorable prognosis in patients with chronic HBV infection.

[Transabdominal US-guided FNAB in the diagnosis of gastric GIST]. / Diagnosi di tumore stromale gastrico mediante biopsia con ago sottile guidata da ecografia transaddominale.

Immunohistochemical staining for CD 117 and morphologic features like mitotic activity are crucial respectively in diagnosing GI stromal tumours and in defining the risk of malignant behaviour in GISTs. In the case reported both requirements have been fulfilled through specimens obtained by transabdominal US-guided FNAB of a gastric submucosal tumour.

Diagnosis of hepatocellular carcinoma complicating liver cirrhosis: utility of repeat ultrasound-guided biopsy after unsuccessful first sampling.

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).

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.