The natural history of cancers associated with virus exposure is intriguing, since only a minority of human tissues infected with these viruses inevitably progress to cancer. However, the molecular reasons why the infection is controlled or instead progresses to subsequent stages of tumorigenesis are largely unknown. In this article, we provide the first complete DNA methylomes of double-stranded DNA viruses associated with human cancer that might provide important clues to help us understand the described process. Using bisulfite genomic sequencing of multiple clones, we have obtained the DNA methylation status of every CpG dinucleotide in the genome of the Human Papilloma Viruses 16 and 18 and Human Hepatitis B Virus, and in all the transcription start sites of the Epstein-Barr Virus. These viruses are associated with infectious diseases (such as hepatitis B and infectious mononucleosis) and the development of human tumors (cervical, hepatic, and nasopharyngeal cancers, and lymphoma), and are responsible for 1 million deaths worldwide every year. The DNA methylomes presented provide evidence of the dynamic nature of the epigenome in contrast to the genome. We observed that the DNA methylome of these viruses evolves from an unmethylated to a highly methylated genome in association with the progression of the disease, from asymptomatic healthy carriers, through chronically infected tissues and pre-malignant lesions, to the full-blown invasive tumor. The observed DNA methylation changes have a major functional impact on the biological behavior of the viruses.

Hepatitis E virus (HEV) is responsible for a small number of acute hepatitis in developed countries. In this setting, HEV infection seems to be a zoonosis, although this has not been completely demonstrated. High morbidity and mortality associated with severe acute infections have been described, as well as the possible role of ribavirin therapy in those cases. We describe a case of acute hepatitis after pork meat ingestion in a patient with Waldeström macroglobulinemia with immunoglobulin A deficiency. Acute hepatitis E was diagnosed based on positive IgM anti-HEV antibodies and HEV RNA detected by real-time PCR. Because of clinical and analytical worsening, ribavirin was initiated, achieving sustained virologic response after 12 weeks of treatment. The phylogenetic analysis revealed the same HEV strain genotype 3 in both plasma and consumed meat samples, proving the zoonotic transmission. Regarding immunocompromised patients, acute hepatitis E can be associated to high morbidity and mortality rate, so dietetic recommendations may be needed to avoid the virus transmission.

α₁-Antitrypsin (AT) deficiency is a hereditary disorder that may lead to early-onset emphysema, and chronic liver disease later in life. Although there are validated methods for testing, the vast majority of α₁-AT-deficient individuals remain undiagnosed. Recommendations have been published for the testing and diagnosis of α₁-AT deficiency; however, guidelines on best practice are not well established.In our article, we review the developments in diagnostic techniques that have taken place in recent years, and describe the practices used in our three European centres. The determination of the level of α₁-AT and genotyping are reported as the main diagnostic steps, whereas isoelectric focusing (also referred to as phenotyping) is reserved for confirmatory analysis.The following recommendations for best practice are put forward: detection of all PiZZ and other severe deficiency individuals; automated genotyping; preparation of reference standards; quality control programmes; development of standard operating procedure documents; and standardised methods for the collection of dried blood samples. Closer cooperation between laboratories and the sharing of knowledge are recommended, with the objectives of improving the efficiency of the diagnosis of severe α₁-AT deficiency, increasing the numbers of individuals who are detected with the disorder, and assisting the establishment of new patient identification programmes.