Dynamics of hospital admissions and all-cause mortality of HIV infected patients in Kazakhstan: data from unified nationwide electronic healthcare system 2014-2019.

Background and objectives: Although global HIV pandemic has stabilized, it continues to rise in Eastern Europe and Central Asia due to exponential growth of newly acquired cases. Based on UNAIDS, there are currently 35,000 people living with HIV (PLWH) in Kazakhstan. This alarming HIV epidemiologic situation mandates urgent investigation of causes, routes of transmission and other characteristics in order to halt the epidemic. We aimed to analyze the data of all hospitalized patients for the period of 2014-2019 who tested positive for HIV from the Unified National Electronic Health System (UNEHS) of Kazakhstan. Methods: This cohort study extracted data for all HIV positive patients during 2014-2019 from UNEHS of Kazakhstan to apply descriptive, Kaplan-Meier estimation, and Cox proportional hazards regression model. Crosscheck of the target population data was conducted with tuberculosis, viral hepatitis, alcohol abuse and intravenous drug user (IDU) cohorts in order to create a comprehensive database. All survival functions and factors associated with mortality were tested for significance. Results: The cohort population (n = 2,213) mean age was 33.3 ± 13.3 years with 1,375 males (62.1%) and 838 females (37.9%). Incidence rate decreased from 2.05 in 2014 to 1.88 in 2019, however, prevalence and mortality continues to escalate every year, the mortality raised significantly from 0.39 in 2014 to 0.97 in 2019. People aged >50 years, males, retired people, patients from tuberculosis hospital profile had much lower survival probabilities than the corresponding groups. Adjusted Cox regression model death hazard showed strong association of HIV patients with tuberculosis coinfection (HR 1.4, 95% CI 1.1; 1.7, p < 0.001). Conclusion: The results of this study demonstrate high rates of HIV mortality, strong association of HIV with TB coinfection, regional, age specific, gender, hospital profile and social status differences that significantly affect HIV prevalence. Since the prevalence of HIV is continuing to increase, more information is necessary for evaluation and implementation of prevention procedures.

Prophylactic Human Papillomavirus Vaccination: From the Origin to the Current State.

Immunization is the most successful method in preventing and controlling infectious diseases, which has helped saving millions of lives worldwide. The discovery of the human papillomavirus (HPV) infection being associated with a variety of benign conditions and cancers has driven the development of prophylactic HPV vaccines. Currently, four HPV vaccines are available on the pharmaceutical market: Cervarix, Gardasil, Gardasil-9, and the recently developed Cecolin. Multiple studies have proven the HPV vaccines' safety and efficacy in preventing HPV-related diseases. Since 2006, when the first HPV vaccine was approved, more than 100 World Health Organization member countries reported the implementation of HPV immunization. However, HPV vaccination dread, concerns about its safety, and associated adverse outcomes have a significant impact on the HPV vaccine implementation campaigns all over the world. Many developed countries have successfully implemented HPV immunization and achieved tremendous progress in preventing HPV-related conditions. However, there are still many countries worldwide which have not created, or have not yet implemented, HPV vaccination campaigns, or have failed due to deficient realization plans associated with establishing successful HPV vaccination programs. Lack of proper HPV information campaigns, negative media reflection, and numerous myths and fake information have led to HPV vaccine rejection in many states. Thus, context-specific health educational interventions on HPV vaccination safety, effectiveness, and benefits are important to increase the vaccines' acceptance for efficacious prevention of HPV-associated conditions.

Epidemiological Characteristics of Chronic Viral Hepatitis in Kazakhstan: Data from Unified Nationwide Electronic Healthcare System 2014-2019.

Background: Viral hepatitis is the leading cause of hepatic cirrhosis and liver-related mortality, yet there are no countrywide epidemiological studies available to date in Kazakhstan. The aim of the study was to perform an estimation of mortality, prevalence and incidence of Hepatitis B and C infections and liver-related complications. Methods: Using centralized healthcare data from the Unified National Electronic Health System (UNEHS) for the period 2014-2019, a total of 82,700 registered patients with chronic viral hepatitis B (HBV), C (HCV) and D (HDV) have been extracted based on ICD -10 codes. Crude rates of incidence, prevalence and mortality, as well as age-, sex- and year-specific rates of incidence and mortality per 100,000 population were estimated. Unadjusted and adjusted hazard ratios were estimated using Cox proportional hazards regression modeling. Results: For the total number of 82,700 patients, 56.6% were represented by chronic HCV infection and 43.4% by HBV infection. The prevalence of coinfection was 10% for HBV+HDV and 3.5% for HBV+HCV. Both HBV and HCV were more prevalent among female patients (56%) and among Kazakh ethnic group (64.8%). Males with HBV had a higher probability of death than females; this trend was stronger among male patients with HCV. Russian ethnic groups infected with HBV had a higher risk of death compared to Kazakh and other ethnic groups. Whereas in HCV-infected patients, Russian ethnic group and other ethnic group had similar risk for death, but higher compared to Kazakhs. Conclusion: During the 2014-2019 period, prevalence, incidence and mortality from chronic HBV and HCV infections increased. Despite the disproportionately higher infection rate among females with chronic viral hepatitis, all-cause mortality was more than two-fold higher among males. Higher death rates in Russian ethnic group compared to other ethnicities need to be evaluated in further studies for other confounding factors and associated comorbidities in this group.

Seroprevalence and risk factors for hepatitis B and hepatitis C in three large regions of Kazakhstan.

BACKGROUND & AIMS: Kazakhstan has implemented comprehensive programs to reduce the incidence of Hepatitis B and Hepatitis C. This study aims to assess seroprevalence and risk factors for HBsAg and anti-HCV positivity in three large regions of Kazakhstan. METHODS: A cross-sectional study was conducted in three regions geographically remote from each other. Participants were randomly selected using a two-stage stratified cluster sampling and were surveyed by a questionnaire based on the WHO STEP survey instrument. Blood samples were collected for HBsAg and anti-HCV testing. RESULTS: A total of 4,620 participants were enrolled. The seroprevalence was 5.5% (95%CI: 3.6%-8.4%) for HBsAg and 5.1% (95%CI: 3.5%-7.5%) for anti-HCV antibodies. Both were more prevalent in the western and northern regions than in the southern. A history of blood transfusion was significantly associated with anti-HCV presence, with odds ratios (ORs) of 2.10 (95%CI: 1.37-3.21) and was borderline associated with HBsAg 1.39 (95%CI: 0.92-2.10), respectively. Having a family member with viral hepatitis was also borderline associated (2.09 (95%CI: 0.97-4.50)) with anti-HCV positivity. CONCLUSIONS: This study found a high-intermediate level of endemicity for HBsAg and a high level of endemicity for anti-HCV antibodies in three large regions of Kazakhstan. We found that history of surgery was not associated with HbsAg neither with anti-HCV seropositivity rates. Blood transfusion was associated with anti-HCV seropositivity, however, to investigate effectiveness of the introduced comprehensive preventive measures in health care settings, there is a need to conduct further epidemiological studies.

Expression profile of the matricellular protein periostin in paediatric inflammatory bowel disease.

The precise role of periostin, an extra-cellular matrix protein, in inflammatory bowel disease (IBD) is unclear. Here, we investigated periostin in paediatric IBD including its relationship with disease activity, clinical outcomes, genomic variation and expression in the colonic tissue. Plasma periostin was analysed using ELISA in 144 paediatric patients and 38 controls. Plasma levels were assessed against validated disease activity indices in IBD and clinical outcomes. An immuno-fluorescence for periostin and detailed isoform-expression analysis in the colonic tissue was performed in 23 individuals. We integrated a whole-gene based burden metric 'GenePy' to assess the impact of variation in POSTN and 23 other genes functionally connected to periostin. We found that plasma periostin levels were significantly increased during remission compared to active Crohn's disease. The immuno-fluorescence analysis demonstrated enhanced peri-cryptal ring patterns in patients compared to controls, present throughout inflamed, as well as macroscopically non-inflamed colonic tissue. Interestingly, the pattern of isoforms remained unchanged during bowel inflammation compared to healthy controls. In addition to its role during the inflammatory processes in IBD, periostin may have an additional prominent role in mucosal repair. Additional studies will be necessary to understand its role in the pathogenesis, repair and fibrosis in IBD.

Effectiveness of pegylated interferon monotherapy in the treatment of chronic hepatitis D virus infection: A meta-analysis.

Chronic HDV infection often is associated with aggressive form of liver disease, compared to chronic HBV mono-infection. However, chronic HDV treatment is challenging because currently there is no approved regimen for affected patients. While standard interferon with/without nucleos(t)ide analogues were reported to be inferior to pegylated interferon (peginterferon) as HDV treatment according to few randomized clinical trials. This meta-analysis will summarize the results of studies on the effectiveness of peginterferon as HDV treatment regimen. An electronic search was performed using PubMed, Cochrane Library, Research Gate, and Medline databases. Studies involving patients who received peginterferon therapy for at least 48 weeks and followed up for 24 weeks post-therapy were included. All analyses were conducted using Review Manager 5.3 designed for Cochrane Reviews. The primary efficacy endpoint was virological response (VR) or HDV-RNA negativity at the end of the follow-up period, whereas secondary efficacy endpoints were biochemical response (BR) or ALT normalization and HBsAg clearance with seroconversion to anti-HBs at the end of follow-up period. Data were abstracted from 13 relevant studies with a total of 475 patients who were treated with peginterferon alpha-2a or -2b. At the end of 24-week post-treatment the pooled VR was achieved in 29% of patients with 95% CI [24%; 34%], BR was reached in 33% of patients [95% CI 27%; 40%] and HBsAg clearance with seroconversion to anti-HBs was achieved in 1% of patients with 95% CI [-0.02; 0.05]. In conclusion, this study showed that peginterferon has limited effectiveness in HDV treatment, since only one-third of chronic HDV patients achieved viral clearance and normalized ALT levels. Morever, HBsAg clearance with seroconversion to anti-HBs has been rarely observed among chronic HDV patients.

Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV.

BACKGROUND: Infection with human immunodeficiency virus (HIV) influences the outcome and natural disease progression of hepatitis C virus (HCV) infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20-46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA) between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance. METHODS: Plasma RNA from HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV was sequenced using Ion Torrent technology. The sequencing results were analyzed to identify transcripts that are associated with HCV clearance by measuring differential gene expression in HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV. RESULTS: We have identified plasma mRNA, the levels of which are significantly elevated (at least 5 fold, False Discovery Rate (FDR) <0.05) before HCV infection in subjects who cleared HCV compared to those who remained chronically infected. Upon further analysis of these differentially expressed genes, before and after HCV infection, we found that before HCV infection 12 genes were uniquely upregulated in the clearance group compared to the chronically infected group. Importantly, a number of these 12 genes and their upstream regulators (such as CCL3, IL17D, LBP, SOCS3, NFKBIL1, IRF) are associated with innate immune response functions. CONCLUSIONS: These results suggest that subjects who spontaneously clear HCV may express these unique genes associated with innate immune functions.

First Case in Kazakhstan of Successful Therapy With 2 Consecutive Direct-Acting Antiviral Regimens in a Patient with Hepatitis C Virus-Induced Decompensated Liver Cirrhosis on a Liver Transplant Wait List.

A 40-year-old man, diagnosed with decompensated liver cirrhosis because of hepatitis C virus, was on the wait list for a liver transplant when he began treatment with the direct-acting antivirals simeprevir 150 mg and sofosbuvir 400 mg. The patient demonstrated end of treatment virologic response at week 12, normal bilirubin, and alanine aminotransferase levels, resolution of ascites, with downgrading to subcompensated liver cirrhosis, and was removed from the liver transplant wait list. However, the patient did not comply with the recommended duration of the antiviral treatment of at least 16 weeks, which resulted in hepatitis C virus relapse at posttreatment week 12. Later, the patient started an alternative regimen that included a combination of ombitasvir 12.5 mg, paritaprevir 75 mg, ritonavir 50 mg, and dasabuvir 250 mg for 24 weeks and achieved a sustained virologic response. However, despite undetectable hepatitis C virus, the patient began to deteriorate again and was again put on the liver transplant wait list. This first described clinical case in Kazakhstan of successful antiviral therapy with 2 consecutive directacting agents demonstrates the importance of virus eradication of pretransplant survival extension and delaying the need for liver transplant.

Liver Transplant Outcomes in a Newly Started Program.

OBJECTIVES: Kazakhstan is experiencing a high demand for liver transplants. More than 1000 patients have end-stage liver disease in the country, and liver transplant is the only viable option for their treatment. MATERIALS AND METHODS: Liver transplant patients, treated from February 2013 to December 2014, were included in this retrospective analysis. RESULTS: From February 2013 to December 2014, seven patients received a liver transplant in our center (1 pediatric patient was excluded). Deceased liver recipients' (n = 3) median age was 52 years and median Model for End-Stage Liver Disease score 9. The indication for transplant was uncontrolled portal hypertension due to autoimmune liver disease. Cadaveric donors' median age was 45 years. Recipients' intensive care unit stay was > 5 days, time on inotropic support was > 3 days. Mean cold ischemic time was > 6 hours, and secondary ischemic time was 67 minutes. One patient in the deceased donor transplant group died during postoperative week 1 from hepatic artery thrombosis. Living donor liver recipients' (n = 3) median age was 47 years (43-48 y) and median Model for End-Stage Liver Disease score was 17 (range 14-20). Liver disease was hepatitis virus related (hepatitis C virus in 1 patient and hepatitis B and D virus in 2 patients). Mean cold ischemic time was 0.43 hours, and mean secondary ischemic time was 64 minutes. One recipient in the living donor liver group died early in the postoperative period from hemorrhage. CONCLUSIONS: Our experience was insufficient to adequately assess morbidity and survival rates in patients for whom the longest follow-up was 25 months. However, no episodes of rejection were observed. Survival rates between living and deceased donor recipients were equivalent, although cadaveric-donor liver conditions were imperfect. This analysis demonstrates the necessity for timely diagnosis of surgical complications, which accounted for all mortality incidence in our series.