Is Hepatitis B Immunoglobulin Necessary in Prophylaxis of Hepatitis B Recurrence after Liver Transplantation? A Meta-Analysis

Background & Aims

Application of nucleoside analogues and hepatitis B immunoglobulin (HBIG) has reduced hepatitis B virus (HBV) recurrence rate after liver transplantation (LT) dramatically. Recent data suggests therapy without HBIG is also effective. We sought to evaluate the necessity of HBIG in prophylaxis of HBV recurrence after LT.

Methods

A meta-analysis was performed. PubMed/MEDLINE, Web of Knowledge and other databases were searched for eligible literatures. The major end points were recurrence rate, patient survival, and YMDD mutant. Risk difference (RD) or risk ratio (RR) was calculated to synthesize the results.

Results

Nineteen studies with a total of 1484 patients were included in this analysis. Application of HBIG was helpful to reduce HBV recurrence [P<0.001; RD = 0.16; 95% confidence interval (CI)(0.12, 0.20)] and virus mutants [P<0.001; RR = 3.13; 95%CI (1.86–5.26)], it also improved patients'' 1-year [P = 0.03; RD = 0.08; 95%CI (0.01, 0.15)] and 3-year survival rates [P = 0.005; RD = 0.17; 95%CI(0.05, 0.28)]. No significant difference was found for patients'' 5-year survival [P = 0.46; RD = −0.06; 95%CI (−0.21, 0.10)]. Sub-group analysis showed that in patients with positive pre-operative HBV DNA status, HBIG was necessary to reduce HBV recurrence rate (P<0.001; RD = 0.42; 95%CI (0.32, 0.52)). In patients with negative HBV DNA, combined therapy gained no significant advantages (P = 0.18; RD = 0.06; 95%CI (−0.03, 0.14)). Non-Lamivudine (non-LAM) antiviral drugs performed as well as combination therapy in prophylaxis of HBV recurrence after LT (P = 0.37; RD = 0.06; 95%CI (−0.02, 0.14)).

Conclusions

HBIG with nucleoside analogues is helpful to reduce HBV recurrence and virus mutants. The necessity of HBIG in prophylaxis of HBV recurrence after LT when using new potent nucleoside analogues, especially for patients with negative pre-transplant HBV DNA status remains to be evaluated.     

Are older patients less likely to be treated for pancreatic cancer? A systematic review and meta-analysis

Pancreatic cancer is the seventh commonest cause of cancer-related death worldwide. Although prognosis is poor, both surgery and adjuvant chemotherapy improve survival. However, it has been suggested that not all pancreatic cancer patients who may benefit from treatment receive it. This systematic review and meta-analysis investigated the existence of age-related inequalities in receipt of first-line pancreatic cancer treatment. Medline, Embase, Cochrane Library and grey literature were searched for population-based studies investigating treatment receipt, reported by age, for patients with primary pancreatic cancer from inception until 4th June 2020, and updated 5th August 2021. Studies from countries with universal healthcare were included, to minimise influence of health system-related economic factors. A modified version of the Newcastle-Ottawa Scale was used to assess risk of bias. Random-effects meta-analysis was undertaken comparing likelihood of treatment receipt in older versus younger patients. Sensitivity and subgroup analyses were conducted. Eighteen papers were included; 12 independent populations were eligible for meta-analysis. In most studies, < 10% of older patients were treated. Older age (generally ≥65) was significantly associated with reduced receipt of any treatment (OR=0.14, 95% CI 0.10–0.21, n = 12 studies), surgery (OR=0.15, 95% CI 0.09–0.24, n = 9 studies) and chemotherapy as a primary treatment (OR=0.13, 95% CI 0.07–0.24, n = 5 studies). The effect of age was independent of methodological quality, patient population or time-period of patient diagnosis and remained in studies with confounder adjustment. The mean quality score of included studies was 6/8. Inequalities in receipt of healthcare interventions across social groups is a recognised concern internationally. This review shows that older age is significantly, and consistently, associated with non-receipt of treatment in pancreatic cancer. However, there are risks and side-effects associated with pancreatic cancer treatment. Further research on what influences patient and professional treatment decision-making is required to better understand these apparent inequalities.     

Halothane Hepatitis—A Preventable Disease?

Eleven patients with acute hepatitis following multiple anaesthetics with halothane have been seen at two hospitals during the last four years. Six had massive hepatic necrosis and died. Unexplained fever occurred in nine of the patients; two of these and one other had had previous episodes of jaundice after halothane anaesthesia. Thus, in ten patients the disease could have been avoided.     

Are microorganisms everywhere they can be?

Baas-Becking is famously attributed with the conjecture that ‘everything is everywhere, but the environment selects’. Although this aphorism is largely challenged by microbial biogeographical data, even weak versions of the claim leave unanswered the question about whether all environments that could theoretically support life contain life. In the last decade, the discovery of thermally sterilized habitable environments disconnected from inhabited regions, and habitats within organisms such as the sterile, but habitable human fetal gut, suggest the existence of a diversity of macroscopic habitable environments apparently devoid of actively metabolizing or reproducing life. Less clear is the status of such environments at the micron scale, for example, between colonies of organisms within rock interstices or on and within other substrates. I discuss recent evidence for these types of environments. These environments have practical uses in: (i) being negative controls for understanding the role of microbial processes in geochemical cycles and geological processes, (ii) yielding insights into the extent to which the biosphere extends into all spaces it theoretically can, (iii) suggesting caution in interpreting the results of life detection instrumentation, and (iv) being useful for establishing the conditions for the origin of life and its prevalence on other planetary bodies.     

Are acidic and basic groups in buried proteins predicted to be ionized?

Ionizable residues play essential roles in proteins, modulating protein stability, fold and function. Asp, Glu, Arg, and Lys make up about a quarter of the residues in an average protein. Multi-conformation continuum electrostatic (MCCE) calculations were used to predict the ionization states of all acidic and basic residues in 490 proteins. Of all 36,192 ionizable residues, 93.5% were predicted to be ionized. Thirty-five percent have lost 4.08 kcal/mol solvation energy (DeltaDeltaG(rxn)) sufficient to shift a pK(a) by three pH units in the absence of other interactions and 17% have DeltaDeltaG(rxn) sufficient to shift pK(a) by five pH units. Overall 85% of these buried residues (DeltaDeltaG(rxn)>5DeltapK units) are ionized, including 92% of the Arg, 86% of the Asp, 77% of the Glu, and 75% of the Lys. Ion-pair interactions stabilize the ionization of both acids and bases. The backbone dipoles stabilize anions more than cations. The interactions with polar side-chains are also different for acids and bases. Asn and Gln stabilize all charges, Ser and Thr stabilize only acids while Tyr rarely stabilize Lys. Thus, hydroxyls are better hydrogen bond donors than acceptors. Buried ionized residues are more likely to be conserved than those on the surface. There are 3.95 residues buried per 100 residues in an average protein.     

To be folded or to be unfolded?

The lack of ordered structure in “natively unfolded” proteins raises a general question: Are there intrinsic properties of amino acid residues that are responsible for the absence of fixed structure at physiological conditions? In this article, we demonstrate that the competence of a protein to be folded or to be unfolded may be determined by the property of amino acid residues to form a sufficient number of contacts in a globular state. The expected average number of contacts per residue calculated from the amino acid sequence alone (using the average number of contacts for 20 amino acid residues in globular proteins) can be used as one of the simple indicators of natively unfolded proteins. The prediction accuracy for the sets of 80 folded and 90 natively unfolded proteins reaches 89% if the expected average number of contacts is used as a parameter and 83% in the case of hydrophobicity. An optimal set of artificial parameters for 20 amino acid residues obtained by Monte Carlo algorithm to maximally separate the sets of 90 natively unfolded and 80 folded proteins demonstrates the upper limit for prediction accuracy, which is 95%.     

To be or not to be ubiquitinated?

Levels of p21, a cyclin-dependent kinase (CDK) inhibitor, are controlled in part at the post-translational level by protein degradation. Although the signaling pathways leading to p21 degradation have not yet been fully elucidated, it is evident that p21 ubiquitination is an essential factor in its degradation. We discuss that, with the only notable exception of ornithine decarboxylase, ubiquitination appears to be a prerequisite for proteasomal degradation rather than an unnecessary byproduct of such proteolysis.     

Are islands more susceptible to be invaded than continents? Birds say no

Island communities are generally viewed as being more susceptible to invasion than those of mainland areas, yet empirical evidence is almost lacking. A species-by-species examination of introduced birds in two independent island-mainland comparisons is not consistent with this hypothesis. In the New Zealand-mainland Australia comparison. 16 species were successful in both regions. 19 always failed and only eight had mixed outcomes. Mixed results were observed less often than expected by chance, and in only 5 cases was the relationship in the predicted direction. This result is not biased by differences in introduction effort because, within species, the number of individuals released in New Zealand did not differ significantly from those released in mainland Australia. A similar result emerged in the Hawaiian islands-mainland USA comparison: among the 35 species considered, 15 were successful in both regions, seven always failed and 13 had mixed outcomes. In this occasion, the results fit well to those expected by chance, and in only seven cases was the relationship in the direction predicted. I therefore conclude that, if true, the view that islands are less resistant than continents to invasions is far from universal.