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The treatment of HIV infection in Latvia by using highly active antiretroviral therapy (HAART) was started in 1996. The prevalence and tendencies of HIV drug resistance among treated and treatment-naive patients in Latvia in the years 2006-2007 were evaluated in this study. Data of HIV genotyping, performed in 132 HIV-1 infected during years 2006-2007 by TRUGENE HIV-1 genotyping assay (BayerHealthCare-diagnostics) are included in the study.Analysis of data showed that in the group of treatment-naive individuals majority carried wild type virus. Prevalence of resistance-associated mutations (RAMs) in the treatment-naive group according to IAS list was 28%. In most cases it was NRTI mutation A62V that is associated with multinucleoside resistance caused by Q151M, its effect in the absence of Q151M is not known. By many authors A62V is supposed to be a result of polymorphism in RT gene and is excluded from the list of resistance mutations. High prevalence of A62V is typical for HIV-1 subtype A. As majority of treatment-naive cases (89%) in this study were with HIV-1 subtypes A or AE, we excluded A62V mutation and estimated RAMs prevalence in group of treatment-naive HIV-infected individuals as 7%. Minor PI mutations were not included in analyses. In Europe published rates generally very between 5% and 15%.In the group of treatment-experienced HIV infected people 25/75 were with HIV-1 subtype B, the rest part -with non-B subtypes: A/AE (35/75), CRF -01AE (7/75), B/AE (4/75) and others. In treatment-experienced patients RAMs prevalence was estimated as 58.6%. Most frequently RAMs were found for nucleoside reverse trans criptase inhibitors (NRTI) (49.3%) followed by non-nucleoside reverse transcriptase inhibitors (NNRTI) (22.6%) and protease inhibitors (PI) (16%).In the group of NRTI mutations M184V (26/75; 34.6%), A62V (12/75; 16.0%) and T215Y (8/75; 10.6%), in NNRTI mutations K103N (10/75; 13.3%), G190S (6/75; 8.0%), in PI group mutations L90M (6/75; 8.0%) and M461/L (6/75; 8.0%) occurred most frequently.The following drug susceptibility was predicted according to the Trugen expert interpretations: in 33/75 (44%) patients no evidence of resistance, in 21/75 (28%) patients resistance to 1 drug class (NRTI -16/75 NNRTI -4/75, PI -1/75), in 17 patients (22.6%) resistance to 2 drug classes (NRTI+NNRTI -9/75, NRTI+PI -7/75, NNRTI+PI -1/75) and in 3/75 (4%) patients resistance to all 3 classes of drugs (NRTI+NNRTI+PI).We conclude, that prevalence of RAMs in treatment-naive HIV infected persons in Latvia is comparable with prevalence in Europe. The origin of predominated mutation A62V associated with NRTI at present is not clear. In more than half of treated HIV infected patients HIV resistance to at least one HAART class was predicted. NRTI+NNRTI 12.0% no evidence of resistance 44.0% NRTI 21.3% NRTI+PI 9.3% 3 classes 4.0% NNRTI+PI 1.3% PI 1.3% NNRTI 5.3%

AIM:To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS:This study included 86 patients with chronic hepatitis C (55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene (mutation): ATP7B (H1069Q), HFE (C282Y, H63D), UGT1A1 (TA)7, and SERPINA1 (PiZ)] were detected by polymerase chain reaction (PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing. RESULTS:The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61 (76%), 7 (9%), and 12 (15%) patients, respectively. Among all 86 patients, 50 (58%) reached an early viral response and 70 (81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Casecontrol analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls (patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The (TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels (beta regression coefficient = -295.7, P = 0.0087). CONCLUSION:Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail.

Novel Laboratory Tests in Assessment of Liver Function in Acute and Chronic Liver Diseases Liver biopsy in clinical practice has been widely used for the diagnosis and management of patients with liver diseases, particularly, with chronic liver diseases. However, liver biopsy is an invasive method with potential complications, sampling and interpretation errors. Therefore, noninvasive tests are being developed and introduced to replace liver biopsy. The aim of the present study was to identify the new noninvasive methods to be used for the assessment of liver structure and function, by use of the appropriate serum surrogate markers and to evaluate the clinical diagnostic and prognostic accuracy of these methods, including immunogenetic methods, in cases of acute and chronic liver diseases. The obtained data showed that serum markers of apoptosis (cytokeratin-18 neoepitope and citochrome c) and fibrosis (hyaluronic acid) should be included in viral and toxic liver damage management algorithms. The punctual identification of immunogenetic factors (HLA class II antigens) may prove to be useful in predicting disease evolution, and in guiding the appropriate therapy for patients with poor prognosis.

Alcohol metabolism causes cellular damage by changing the redox status of cells. In this study, we investigated the relationship between genetic markers in genes coding for enzymes involved in cellular redox stabilization and their potential role in the clinical outcome of acute alcohol-induced hepatitis. Study subjects comprised 60 patients with acute alcohol-induced hepatitis. The control group consisted of 122 healthy non-related individuals. Eight genetic markers of the genes UGT1A1, GSTA1, GSTP1, NAT2, GSTT1 and GSTM1 were genotyped. GSTT1 null genotype was identified as a risk allele for alcohol-toxic hepatitis progression (OR 2.146, P=0.013). It was also found to correlate negatively with the level of prothrombin (β= −11.05, P=0.037) and positively with hyaluronic acid (β=170.4, P=0.014). NAT2 gene alleles rs1799929 and rs1799930 showed opposing associations with the activity of the biochemical markers γ-glutamyltransferase and alkaline phosphatase; rs1799929 was negatively correlated with γ-glutamyltransferase (β=−261.3, P=0.018) and alkaline phosphatase (β= −270.5, P=0.032), whereas rs1799930 was positively correlated with Γ-glutamyltransferase (β=325.8, P=0.011) and alkaline phosphatase (β=374.8, P=0.011). Enzymes of the glutathione S-transferase family and NAT2 enzyme play an important role in the detoxification process in the liver and demonstrate an impact on the clinical outcome of acute alcohol-induced hepatitis.