Naturally-occurring mutations associated with resistance to nucleoside/nucleotide analogues (NA) can be detected in a group of treatment-naive individuals chronically infected with hepatitis B virus (HBV). Genotypic resistance testing prior to the initiation of NA therapy may facilitate the selection of optimal drug regime and help to prevent early emergence of clinical resistance. In this study, presence of resistance mutations in treatment-naive individuals with chronic hepatitis B (CHB) was investigated in Hacettepe University Hospital, a referral center in Ankara province, Turkey. A total of 42 patients (17 female, 25 male; age range: 18-62 years) diagnosed as CHB were enrolled in the study with informed consent. All of the patients were negative for hepatitis C and D viruses and human immunodeficiency virus coinfections, and none had a history of interferon or NA treatment. HBV viral load, HBV markers and hepatic enzymes in patients were determined via standardized commercial assays. For the detection of NA resistance mutations, a partial sequence of approximately 250 nucleotides, harboring the frequently-observed sites for NA resistance was amplified via nested PCR and characterized by direct sequencing of the amplicons. The sequences were handled and interpreted for the presence of mutations via various softwares and a web-based virtual phenotyping tool. Well-characterized sequences were obtained in 30 out of 42 samples (71.4%). All circulating HBV strains were observed as genotype D. Nucleotide variations were detected in 19 individuals (63.5%) that comprise silent mutations without amino acid substitution in 8 (26.6%), mutations with undetermined significance in 7 (23.3%) and mutations associated with NA resistance in 3 (10%) patients. Mutations conferring resistance to entecavir + lamivudine (S202G, M204V, L180M, T184N) were identified in one patient whereas L180P, A181Q and A194V substitutions associated with probable lamivudin + adefovir and tenofovir resistance, respectively, were detected in other patients. All patients with resistance mutations were HBsAg and HBeAg positive, anti-HBe negative and had viral loads exceeding 3 x 10(7) IU/ml. In two patients, the route for HBV transmission was vertical. Since no follow-up samples were available from individuals with resistance mutations, alterations in serological markers, viral load and mutation patterns could not be monitored. In conclusion, the presence of NA resistance mutations were revealed in treatment-naive CHB cases in a referral hospital in Turkey. The impact and cost-effectivity of detecting naturally-occurring resistance mutations for clinical follow-up prior to the antiviral therapy need to be elucidated by prospective studies.

Gastrointestinal (GI) cancers are the most common causes of global cancer burden and cancer-related deaths. Chronic inflammation is a hallmark feature of GI tumors and plays an important role in tumor initiation, progression, and therapeutic response. The genetic makeup of cancer cell, as well as epigenetic alterations, and biological processes constitute an inflammatory tumor microenvironment (TME) that provides an essential nich for cancer initiation and progression. Cancer-associated inflammation, a key component of TME, displays protumoral or antitumoral activity depending on the composition, spatial distribution, and functional status of the immune cells involved, thus adversely affecting response to cancer treatment and clinical outcomes, whereas acute inflammation supports T-cell priming, activation, and infiltration into malignant tissues, thereby conferring anti-tumoral immunity. Inflammatory cells and proinflammatory molecules within the TME act as a bridge between inflammation and cancer. The majority of cells involved in the inflammatory process in the TME are innate immune cells, which play a critical role in shapping both the cellular composition of the TME and the plasticity of cancer cells and stromal cells. Activation of innate immune cells in the TME initiates the production of inflammatory, regenerative, and anti-inflammatory soluble molecules, resulting in adaptive immune response to the cancer. Additionally, aberrant activation of intracellular signaling pathways, inflammatory molecules, and metabolites have critical roles in the development and healing of inflammation during carcinogenesis. Cancer-associated inflammation may inhibit the effectiveness of anti-cancer agents by causing enzymatic degradation of drugs and modulating the immun activity, thus affecting survival of patient. In this review article, we highlight the genetic and cellular mechanisms involved in the formation of the inflammatory component of the TME in GI cancers, the soluble molecules, the cancer cell-immune cell interactions, and the implications of all these for clinical outcomes. We also comprehensively address the mechanisms linking chronic inflammation to cancer, with a focus on the most frequent GI cancers.