Proton pump inhibitors are not associated with fundic gland polyps - a systematic review that takes into consideration all known confounders.

Sporadic fundic gland polyps (FGPs) progress, albeit rarely, to dysplasia and cancer. Two meta-analyses, including 8 and 11 studies, concluded that proton pump inhibitors (PPIs) were associated with FGPs. Intervention is considered unnecessary when FGPs have a background of PPIs use. Both meta-analyses, however, disregarded known confounders: age, sex, endoscopy indications, study design (prospective or retrospective), duration of PPI use, and H. pylori infection. Confounders are known to invalidate meta-analyses. We followed PRIXMA guidelines and searched the literature for studies on FGPs in PPI-users and PPI-nonusers. In the 22 studies searched, we compared FGPs in PPI-users (n = 6534) and PPI-nonusers (n = 41 115). Heterogeneity was significant (Cochran Q = 277.8, P < 0.0001; I2 = 92.8%), annulling meta-analysis performed by blanket tallying. To offset the above confounders, we matched PPI-users and PPI-nonusers by (a) age and sex (n = 4300 and 29 307, respectively) and (b) their propensity scores derived from the confounders (n = 2950 and 4729, respectively). After both matching, FGPs were not significantly different between PPI-users and PPI-nonusers [odds ratio (OR) = 1.1, P = 0.3078; OR = 0.9, P = 0.3258, respectively]. Furthermore, FGP frequency did not correlate with increasing duration of PPI use (Pearson and Spearman correlation coefficients = 0.1162, 0.0386, P < 0.6064, 0.8646, respectively); it was not significantly different between any of the duration periods of observation, namely, <10, 10-20, 20-40, >40 months, nor was it significantly different between PPI-users and PPI-nonusers within each duration period (P > 0.05). We conclude that PPIs are not associated with FGPs, implying that a background history of PPI use is not a justification for nonintervention in the management of FGPs.

Occult hepatitis B virus infection of donor and recipient origin after liver transplantation despite nucleoside analogue prophylaxis.

Liver grafts from donors positive for antibody to hepatitis B core antigen (anti-HBc) may be used for transplantation in patients with hepatitis B virus (HBV)-related liver disease, and an occult HBV infection may develop from either source. Liver biopsy was performed for 31 patients who remained seronegative for hepatitis B surface antigen for a median of 44.5 months (range = 13.6-126.4 months) and received nucleoside analogue prophylaxis post-transplant. Nineteen of these recipients (61%) had received anti-HBc-positive grafts. Intrahepatic total HBV DNA and covalently closed circular DNA (cccDNA) levels were quantified, and the sequence was analyzed. Intrahepatic total HBV DNA and cccDNA were detectable in 26 (84%) and 16 (52%) of the 31 recipients, respectively, and they were more common when the donor was positive for anti-HBc (95% versus 67%, P = 0.038). The intrahepatic HBV DNA level correlated with the recipient pretransplant serum HBV DNA level (P = 0.06), and the intrahepatic HBV cccDNA level correlated with the donor intrahepatic HBV cccDNA level (P = 0.06). A phylogenetic analysis of the isolated HBV DNA sequence revealed HBV infections of both donor and recipient origins. In conclusion, an occult HBV infection after liver transplantation can originate from both the donor and recipient despite prolonged nucleoside analogue prophylaxis. The presence of intrahepatic HBV cccDNA is attributable more to the persistence of preexisting intrahepatic HBV cccDNA from a donor with previous exposure.

Tumor necrosis factor-alpha-induced protein 1 and immunity to hepatitis B virus.

AIM: To compare the gene expression profile in a pair of HBV-infected twins. METHODS: The gene expression profile was compared in a pair of HBV-infected twins. RESULTS: The twins displayed different disease outcomes. One acquired natural immunity against HBV, whereas the other became a chronic HBV carrier. Eighty-eight and forty-six genes were found to be up- or down-regulated in their PBMCs, respectively. Tumor necrosis factor-alpha-induced protein 1 (TNF-alphaIP1) that expressed at a higher level in the HBV-immune twins was identified and four pairs of siblings with HBV immunity by RT-PCR. However, upon HBV core antigen stimulation, TNF-alphaIP1 was downregulated in PBMCs from subjects with immunity, whereas it was slightly upregulated in HBV carriers. Bioinformatics analysis revealed a K+ channel tetramerization domain in TNF-alphaIP1 that shares a significant homology with some human, mouse, and C elegan proteins. CONCLUSION: TNF-alphaIP1 may play a role in the innate immunity against HBV.

Interleukin 17A promotes hepatocellular carcinoma metastasis via NF-kB induced matrix metalloproteinases 2 and 9 expression.

BACKGROUND:  IL-17A is a pro-inflammatory cytokine that plays important role in inflammatory disease pathology and tumor microenvironment. The aim of this study is to investigate the effect of IL-17A on the progression of hepatocellular carcinoma (HCC). METHODOLOGY AND PRINCIPAL FINDING: Expression pattern of IL-17A in clinical HCC samples (n = 43) was determined by immunohistochemistry staining. Transcript levels of MMP2, MMP9 and IL-17A were measured in another 50 pairs (including tumor and related non-tumor tissues) HCC samples. Cell growth, focus formation, cell migration, invasion and western blot assays were used to characterize the functional and signaling mechanisms in IL-17A-treated HCC. Association study was used to identify clinical significance of IL-17A in HCC. Compared with paired non-tumor tissue, higher frequency of IL-17A-positive cells was detected in tumor tissues in HCCs with metastasis, and the frequency of IL-17A-positive cells was also significantly associated with poor prognosis of HCC (P = 0.01). Functional study found that IL-17A could promote HCC cell migration and invasion. Further molecular analysis also showed that IL-17A could upregulate MMP2 and MMP9 expression via NF-κB signaling activation. CONCLUSIONS:  IL-17A could promote HCC metastasis by the upregulation of MMP2 and MMP9 expression via activating NF-κB signaling pathway.

Development of antibody to hepatitis B surface antigen after liver transplantation for chronic hepatitis B.

Patients with chronic hepatitis B virus (HBV) infection have a defective HBV-specific immune response, and the spontaneous development of antibody against hepatitis B surface antigen (anti-HBs) after liver transplantation has not been observed. We report the spontaneous production of anti-HBs in 21 of 50 (42%) patients receiving lamivudine monoprophylaxis after liver transplantation. Seroconversion to anti-HBs status (>10 mIU/mL) was found at a median of 8 days (range, 1 to 43 days) after transplantation. In each case, serial serum samples showed a >100% increase in antibody titer as compared with that of day 7 after transplantation in the absence of any blood product transfusion. The anti-HBs titer increased to a maximum within 3 months, and the peak titer was <100 mIU/mL in 10 patients, 100 to 1000 mIU/mL in 5 patients, and >1,000 mIU/mL in 6 patients. In 12 patients, anti-HBs disappeared from serum at a median of 201 days (range, 24 to 414 days), whereas the other 9 patients remained positive for anti-HBs at a median of 221 days (range, 94 to 1,025 days) after transplantation. Patients in whom anti-HBs in serum developed had a more rapid clearance of serum hepatitis B surface antigen (HBsAg) (log rank test, P =.011). Using logistic regression analysis, the only predictor of anti-HBs production was an HBV-immune donor (odds ratio, 18.9; 95% confidence interval, 3.2 to 112.4; P =.001). In conclusion, patients who undergo liver transplantation for chronic hepatitis B using lamivudine prophylaxis may develop anti-HBs spontaneously. The antibody is likely to be of donor origin, suggesting the possibility of adoptive immunity transfer through a liver graft.