Bożena Walewska-Zielecka

Extracellular matrix and cytochrome P450 gene expression can distinguish steatohepatitis from steatosis in mice.

One of the main questions regarding nonalcoholic fatty liver disease is the molecular background of the transition from simple steatosis (SS) to the inflammatory and fibrogenic condition of steatohepatitis (NASH). We examined the gene expression changes during progression from histologically normal liver to SS and NASH in models of obesity caused by hyperphagia or a high‐fat diet. Microarray‐based analysis revealed that the expression of 1445 and 264 probe sets was changed exclusively in SS and NASH samples, respectively, and 1577 probe sets were commonly altered in SS and NASH samples. Functional annotations indicated that transcriptome alterations that were common for NASH and SS, as well as exclusive for NASH, involved extracellular matrix (ECM)‐related processes, although they differed in the type of matrix structure change. The expression of 80 genes was significantly changed in all three comparisons: SS versus control, NASH versus control and NASH versus SS. Of these genes, epithelial membrane protein 1, IKBKB interacting protein and decorin were progressively up‐regulated in both SS and NASH compared to normal tissue. The molecular context of interactions of encoded 80 proteins revealed that they are highly interconnected and significantly enriched for processes involving metabolism by cytochrome P450. Validation of 10 selected mRNAs encoding genes related to ECM and cytochrome P450 with quantitative RT‐PCR analysis showed consistent changes in their expression during NASH development. The expression profile of these genes has the potential to distinguish NASH from SS and normal tissue and may possibly be beneficial in the clinical diagnosis of NASH.

The influence of hepatitis B and C virus coinfection on liver histopathology in children.

AbstractThe influence of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection on liver histology in children remains unknown. We analyzed histopathological features in 70 treatment-naïve children: 10 with HBV/HCV coinfection (case group A), 30 with HBV (control group B), and 30 with HCV (control group C). Liver biopsies were scored for grading and staging according to Knodell’s modified system and were tested for an association with demographic and laboratory data. The mean grade was higher in coinfected children compared to control group C (6.2 ± 3.0 vs. 4.2 ± 2.5, p = 0.04), but not control group B (p = 0.47). A higher proportion of patients with moderate to severe necroinflammation were observed in case group A compared to isolated HCV (p = 0.05). Mean staging did not differ between the case and control groups. Multivariate analysis revealed that HBV/HCV coinfection and aminotransferase activity were independently associated with moderate to severe necroinflammatory activity Conclusion: HBV/HCV coinfection was associated with moderate to severe necroinflammation irrespective of age at biopsy or duration of infection and led to significantly higher necroinflammatory activity than HCV monoinfection. HBV/HCV coinfection did not enhance fibrosis. High aminotransferase levels were positively associated with moderate to severe necroinflammation.

Laboratory-based scoring system for prediction of hepatic inflammatory activity in patients with autoimmune hepatitis

In autoimmune hepatitis (AIH), inflammation is closely related to fibrosis. Although transaminase levels are commonly used to assess hepatic inflammation, they may not relate directly to the histology. We developed a noninvasive diagnostic score as an alternative to liver biopsy to help optimize treatment for AIH and monitor disease progress.

Liver steatosis in children with chronic hepatitis B and C: Prevalence, predictors, and impact on disease progression

Abstract Only scarce data on liver steatosis in children with chronic hepatitis B and C (CHB and CHC) are available. The objective of this study was to evaluate the prevalence, predictors, and impact of hepatic steatosis on children with CHB and CHC. A total of 78 patients aged 11.5 ± 3.4 years were included: 30 (38%) had CHB, and 48 (62%) had CHC. Steatosis was scored on a 5-point scale, as follows: absent; minimal (⩽5% hepatocytes affected), mild (6–33%), moderate (34–66%), and severe (>66%). Stepwise logistic regression was used to determine the factors associated with steatosis and moderate-to-severe steatosis. Steatosis was observed in 4/30 (13%) patients with CHB and 13/48 (27%) patients with CHC (P = 0.17). Moderate-to-severe steatosis was observed in 6/78 (8%) patients: 1/30 (3%) had CHB and 5/48 (10%) had CHC (P = 0.40). The body mass index (BMI) z-score was positively associated with the presence of steatosis in children with CHB (odds ratio [OR] = 3.3, 95% confidence interval [CI]: 1.02–10.64). In CHC, steatosis occurred more frequently in patients with hepatitis C virus genotype 3 compared with other genotypes (P = 0.002). In patients with non-3 genotype hepatitis C virus, steatosis was associated with the stage of fibrosis (OR = 3.35, 95% CI: 1.01–11.07) and inversely associated with the duration of infection (OR = 0.74, 95% CI: 0.55–0.97). Moderate-to-severe steatosis was positively associated with the BMI z-score (OR = 3.62, 95% CI: 1.22–10.75) and stage of fibrosis (OR = 3.89, 95% CI: 1.05–14.47). Steatosis is a common finding in children with chronic viral hepatitis. It is associated with metabolic factors in CHB, whereas in patients with CHC, metabolic and viral factors may have a combined effect, leading to more advanced grades of steatosis in children with higher BMI z-scores. Moderate-to-severe steatosis is a predictor of advanced fibrosis in children with CHC.

A novel approach to genome-wide association analysis identifies genetic associations with primary biliary cholangitis and primary sclerosing cholangitis in Polish patients

BackgroundPrimary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are forms of hepatic autoimmunity, and risk for both diseases has a strong genetic component. This study aimed to define the genetic architecture of PBC and PSC within the Polish population.MethodsSubjects were 443 women with PBC, 120 patients with PSC, and 934 healthy controls recruited from Gastroenterology Departments in various Polish hospitals. Allelotyping employed a pooled-DNA sample-based genome-wide association study (GWAS) approach, using Illumina Human Omni2.5-Exome BeadChips and the following novel selection criteria for risk loci: blocks of at least 10 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium, where the distance between each adjacent SNP pair in the block was less than 30 kb, and each SNP was associated with disease at a significance level of P < 0.005. A selected index SNP from each block was validated using TaqMan SNP genotyping assays.ResultsNineteen and twenty-one SNPs were verified as associated with PBC and PSC, respectively, by individual genotyping; 19 (10/9, PBC/PSC) SNPs reached a stringent (corrected) significance threshold and a further 21 (9/12, PBC/PSC) reached a nominal level of significance (P < 0.05 with odds ratio (OR) > 1.2 or < 0.83), providing suggestive evidence of association. The SNPs mapped to seven (1p31.3, 3q13, 6p21, 7q32.1, 11q23.3, 17q12, 19q13.33) and one (6p21) chromosome region previously associated with PBC and PSC, respectively. The SNP, rs35730843, mapping to the POLR2G gene promoter (P = 1.2 × 10-5, OR = 0.39) demonstrated the highest effect size, and was protective for PBC, whereas for PSC respective SNPs were: rs13191240 in the intron of ADGRB3 gene (P = 0.0095, OR = 0.2) and rs3822659 (P = 0.0051, OR = 0.236) along with rs9686714 (P = 0.00077, OR = 0.2), both located in the WWC1 gene.ConclusionsOur cost-effective GWAS approach followed by individual genotyping confirmed several previously identified associations and discovered new susceptibility loci associated with PBC and/or PSC in Polish patients. However, further functional studies are warranted to understand the roles of these newly identified variants in the development of the two disorders.

Assessment of pain, acceptance of illness, adjustment to life with cancer, and coping strategies in colorectal cancer patients

Introduction Every year more than 15,000 newly diagnosed cases of colorectal carcinoma are recorded in Poland. Aim The objective of the study was an assessment of coping strategies and pain management, acceptance of illness, and adjustment to cancer in patients diagnosed with colorectal carcinoma. The analysis was extended to include the effect of socioeconomic variables on the above-mentioned issues. Material and methods The study included 238 colorectal cancer patients treated on an outpatient basis at the Centre of Oncology, the Maria Skłodowska-Curie Institute in Warsaw in the year 2013. The questionnaire interview comprised demographic questions (socioeconomic variables) and the following four psychometric tests: BPCQ (Beliefs about Pain Control Questionnaire), CSQ (Coping Strategies Questionnaire), AIS questionnaire (Acceptance of Illness Scale), and the Mini-Mac scale (Mental Adjustment to Cancer). Results The source of pain control depends on the respondents level of education. An increase in patient income was associated with a lower mean result in the “power of doctors” subscale. The coping self-statements and increased behavioural activity are the two most frequently selected strategies of coping with pain. The most commonly followed ways of mental adjustment to cancer in the study group were a fighting spirit (23.42) and positive re-evaluation (22.31). Conclusions Colorectal cancer patients believe that the greatest role in pain management is played by internal factors. The locus of pain control depends on the level of education. The study patients feature a constructive way of struggling with disease differentiated by the place of residence, professional status, and income.

Organization of polish and german health care systems in the context of drug policy

Healthcare system in Germany is considered as one of the most effective systems all over Europe. Even in the face the ageing population, German healthcare is placed first in terms of the saturation in advanced medical technologies and access to medicinal products. Differences between the functioning of healthcare systems in Germany and other countries, such as Poland, are reflected by many epidemiological indicators. The main purpose of that article is to present the differences in functioning the Polish and German systems, bearing in mind drug policy and regulations. In the article, there are presented some organizational and financing principles concerning healthcare systems in these countries as well as the healthcare expenditures structures.

Clinical Applicability of Whole-Exome Sequencing Exemplified by a Study in Young Adults with the Advanced Cryptogenic Cholestatic Liver Diseases

Background The proper use of new medical tests in clinical practice requires the establishment of their value and range of diagnostic usefulness. While whole-exome sequencing (WES) has already entered the medical practice, recognizing its diagnostic usefulness in multifactorial diseases has not yet been achieved. Aims The objective of this study was to establish usability of WES in determining genetic background of chronic cholestatic liver disease (CLD) in young patients. Methods WES was performed on six young patients (between 17 and 22 years old) with advanced fibrosis or cirrhosis due to CLD and their immediate families. Sequencing was performed on an Ion Proton sequencer. Results On average, 19,673 variants were identified, of which from 7 to 14 variants of an individual were nonsynonymous, homozygous, recessively inherited, and considered in silico as pathogenic. Although monogenic cause of CLD has not been determined, several heterozygous rare variants and polymorphisms were uncovered in genes previously known to be associated with CLD, including ATP8B1, ABCB11, RXRA, and ABCC4, indicative of multifactorial genetic background. Conclusions WES is a potentially useful diagnostic tool in determining genetic background of multifactorial diseases, but its main limitation results from the lack of opportunities for direct linkage between the uncovered genetic variants and molecular mechanisms of disease.

Diagnosis of hepatitis C virus infection in pregnant women in the healthcare system in Poland: Is it worth the effort?

AbstractThe hepatitis C virus (HCV) is globally recognized as a serious public health concern. Current statistics indicate that approximately 2% of people worldwide and 1.9% of people in Poland suffer from HCV infection.This study was conducted to assess the anti-HCV seroprevalence in pregnant women in Poland and subsequently provide recommendations on the rationale for obligatory screening.A total of 42,274 women participated in our study, of which 16,130 were pregnant. We were granted access to their health data stored in the form of electronic medical records kept by the network of outpatient clinics throughout Poland.The lowest rate of positive anti-HCV test results was found in women ages 25 to 34 (0.73%); however, younger and older age groups had similar rates (15–24 = 0.86%; 35–44 = 0.84%). Additional analysis of data from the period between 2011 and 2014 revealed a downward trend in the proportion of positive anti-HCV tests among pregnant women (mean positive anti-HCV = −0.001 × year + 1.9451; R2 = 0.7274). Regardless of the gradual increase in the number of female patients undergoing screening between 2004 and 2015, there has been a constant decrease in the rate of positive cases. The rate of pregnant women potentially infected with HCV was twice as lower than that in a control group of women undergoing tests for other medical circumstances: 0.76% vs 1.67% (P < 0.0001).Analysis of real-world data of female patients in Poland provides evidence that screening based on an individuals medical history and behavioral risk factors in clinical circumstances would be more effective than obligatory testing of all pregnant women.

Immunity to hepatitis A virus among working professionals in Poland – Results of a 3-year serological survey 2013–2015

INTRODUCTION Hepatitis A (HA) is caused by infection with the hepatitis A virus (HAV). The differential etiological diagnosis of acute hepatitis is based on a positive result of the serological test detecting IgM class anti-HAV. For epidemiological studies on past infection and seroprevalence of HAV in populations, the tests measuring IgG class anti-HAV or total anti-HAV are used. Since the 1990s, specific prophylaxis is possible by vaccination against HA. In Poland, vaccination is recommended and in majority is performed at own cost. MATERIAL AND METHODS Database was obtained from electronic medical records of the 2 major private health care providers networks (Luxmed and Medicover) operating in Poland. During a 3-year period (2013-2015), 1,124 persons with unknown status of anti-HA vaccination were tested for the presence of total anti-HAV. Objective. The aim of the study was to evaluate the seroprevalence of anti-HAV among working professionals in Poland. RESULTS Anti-HAV were detected in 603 (53.6%) persons, while 521 (46.3%) tested negative. The study group was divided into 2 subgroups: 25-44 and 45-64-years-old. For detailed statistical analysis, the presence of anti-HAV was considered as a dependent variable, and its predictors were gender, age and the year of the test performance. The presence of anti-HAV was significantly more prevalent in older age group. The lack of specific antibodies was more prevalent in younger age group. CONCLUSIONS Results of the study show increasing susceptibility to HAV infection in the younger age group, compared with the older age group of corporate professional employees in large cities in Poland. Since the epidemiological situation of HA is currently changing with increasing number of symptomatic cases of HA, it is suggested that employers might consider including an additional procedure of vaccination against HA into their private health insurance portfolio.