Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes.

Liver cirrhosis (LC), contributing to more than 1 million of deaths annually, is a major healthcare concern worldwide. Hepatitis B virus (HBV) is a major LC etiological factor, and 15% of patients with chronic HBV infection (CHB) develop LC within 5 years. Recently, novel host genetic determinants were shown to influence HBV lifecycle and CHB course.

Genetic variation in IL-10 influences the progression of hepatitis B infection.

Objectives: The outcomes of hepatitis B virus (HBV) infection vary substantially among affected individuals, providing evidence of the role of host genetic background in the susceptibility to HBV persistence and the dynamics of liver injury progression to cirrhosis and hepatocellular carcinoma (HCC).

Methods: Six single-nucleotide polymorphisms within the interleukin 10 gene (IL10) were genotyped by MALDI-TOF mass spectrometry in 857 patients with chronic HBV infection (CHB), 48 patients with resolved HBV infection, and 100 healthy volunteers. Associations of the selected polymorphisms with susceptibility to chronic HBV infection, liver injury progression, and outcomes were investigated.

Host genetic background affects the course of infection and treatment response in patients with chronic hepatitis B.

Background: Hepatitis B virus (HBV) utilizes proteins encoded by the host to infect hepatocytes and replicate. Recently, several novel host factors have been identified and described as important to the HBV lifecycle. The influence of host genetic background on chronic hepatitis B (CHB) pathogenesis is still poorly understood.

TNF-α polymorphisms affect persistence and progression of HBV infection.

Background: Hepatitis B virus (HBV) infections are a major threat worldwide. Disease progression and outcome is diverse and depends on host genetic background. Recently, a high rate of HBV reactivation in individuals receiving tumor necrosis factor-α (TNF-α) antagonists showed the importance of this cytokine in HBV infection control.

Differences in sequences between HBV-relaxed circular DNA and covalently closed circular DNA.

The hepatitis B virus (HBV) genome exists in two forms: circular covalently closed DNA (cccDNA) and relaxed circular DNA (RCDNA). Here, we investigated the presence of differences in the sequences of both forms in paired samples of serum and liver tissue. The serum and liver biopsy samples were collected at the same time from 67 chronically infected patients.

Association between uridin diphosphate glucuronosylotransferase 1A1 (UGT1A1) gene polymorphism and neonatal hyperbilirubinemia.

Objective: To assess the prevalence of UGT1A1*28 and UGT1A1*60 polymorphisms of UGT1A1 gene and their association with hyperbilirubinemia.

Study Design: The study was performed at a single centre - at the Department of Obstetrics of the Medical University of Gdansk in Poland. DNA was isolated from Guthrie cards of 171 infants.

Interferon lambda polymorphisms associate with body iron indices and hepatic expression of interferon-responsive long non-coding RNA in chronic hepatitis C.

Single nucleotide polymorphisms (SNPs) within DNA region containing interferon lambda 3 (IFNL3) and IFNL4 genes are prognostic factors of treatment response in chronic hepatitis C (CHC). Iron overload, frequently diagnosed in CHC, is associated with unfavorable disease course and a risk of carcinogenesis. Its etiology and relationship with the immune response in CHC are not fully explained.

Association of hepcidin mRNA expression with hepatocyte iron accumulation and effects of antiviral therapy in chronic hepatitis C infection.

Background: Iron overload is frequently observed in patients with chronic hepatitis C (CHC) and is associated with the increased risk of liver fibrosis and carcinogenesis. Hepcidin is a regulator of iron homeostasis and a component of innate immunity. Based on experimental studies, iron overload might be a result of low hepcidin synthesis in CHC.

Liver steatosis correlates with iron overload but not with HFE gene mutations in chronic hepatitis C.

Background: Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non-alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients.

Methods: A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients.

Iron overload and HFE gene mutations in Polish patients with liver cirrhosis.

Background: Increased liver iron stores may contribute to the progression of liver injury and fibrosis, and are associated with a higher risk of hepatocellular carcinoma development. Pre-transplant symptoms of iron overload in patients with liver cirrhosis are associated with higher risk of infectious and malignant complications in liver transplant recipients. HFE gene mutations may be involved in the pathogenesis of liver iron overload and influence the progression of chronic liver diseases of different origins.

Diagnosis and treatment difficulties in 18-year-old male patient with hereditary hemochromatosis, chronic hepatitis B, Gilbert syndrome and ulcerative colitis.

Among possible causes of chronic hepatitis in adolescents most common are infections, autoimmune disorders and metabolic diseases. Thus, diagnostic procedures should be multidirectional. This study reports diagnosis and treatment difficulties in an 18-year-old male patient with hereditary hemochromatosis (HH), ulcerative colitis (UC), chronic hepatitis B (CHB) and Gilbert syndrome.

The role of iron overload and HFE gene mutations in the era of pegylated interferon and ribavirin treatment of chronic hepatitis C.

Background: Iron overload observed in chronic hepatitis C (CHC) has been suggested to be one of the negative prognostic factors influencing liver disease progression and failure of treatment with recombinant interferon in monotherapy or in combination with ribavirin. The aim of this study was to assess occurrence of iron overload in relation to polymorphism of the HFE and the influence of both these factors on efficacy of antiviral treatment with pegylated interferon and ribavirin in patients with CHC.

Material/methods: Liver function tests, serum indices of iron metabolism, and HFE mutations were assayed in 152 patients with CHC from Poland.

The role of MR imaging in detection of hepatic iron overload in patients with cirrhosis of different origins.

Background: There are many pathological conditions with hepatic iron overload. Classical definite diagnostic methods of these disorders are invasive and based on a direct tissue biopsy material. For the last years the role of MR imaging in liver diagnostics has been increasing.

UGT1A1 gene polymorphism as a potential factor inducing iron overload in the pathogenesis of type 1 hereditary hemochromatosis.

Aim Hereditary hemochromatosis is a common genetic disorder characterized by iron overload and subsequent organ damage. It is caused in most cases by HFE gene mutations which penetrance can be affected by many factors. The aim of this study was to establish the role of UGT1A1 gene polymorphism and serum bilirubin concentration in the pathogenesis of hereditary hemochromatosis.

Could iron deposits in hepatocytes serve as a prognostic marker of HFE gene mutations?

Background/aims: The diagnosis of hereditary hemochromatosis (HH) is based on qualitative measurement of tissue iron concentration and genetic tests. The aim of this study was to evaluate the correlation between the presence of iron deposits in the liver and the HFE gene mutations in patients with chronic liver diseases (CLD).

Methodology: The 182 patients, age range 18-71 years, were hospitalized in Gdansk because of CLD.

GUS and PMM1 as suitable reference genes for gene expression analysis in the liver tissue of patients with chronic hepatitis.

Background: The proper application of quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) for the relative quantification of a target gene in gene profiling studies requires reference genes to normalize sample variations. Stable housekeeping genes for this purpose have never been investigated in the liver tissue of patients with chronic hepatitis.

Material/methods: Expression profiles of six functionally distinct housekeeping genes (ACTB, CYCC, GUS, HPRT1, PMM1, POLR2L) were examined by RT-PCR in liver specimens from 12 individuals with chronic hepatitis C or B.

[Housekeeping genes as a reference in quantitative real-time RT-PCR].

The determination of gene expression levels in normal tissue is necessary for the analysis and interpretation of results of gene profiling studies in pathological samples. With the real-time reverse transcription-PCR technique, which enables one to detect the amplification rate during the process, assessment of the amount of gene transcript is fast and accurate. The most important problem in this type of analysis is the variability in the amount of genetic material between samples, caused mostly by changes in the efficiency of mRNA isolation and reverse transcription.

[Hereditary hemochromatosis: the most frequent inherited human disease].

Hereditary hemochromatosis is now recognized as a very common inherited disease of the Caucasian population. It is defined as a disorder of unique clinicopathology caused by mutations of genes that control iron metabolism. Inappropriately increased intestinal iron absorption and accelerated recycling of iron by macrophages lead to progressive body iron accumulation and the generation of oxidative stress in tissues.

[Molecular basis of hereditary hemochromatosis].

Hereditary hemochromatosis (HH) is a genetic metabolic disease characterized by increased intestinal iron absorption and progressive iron loading in the cells of various organs. Human body iron homeostasis involves a number of complicated processes, some of which are not identified yet. Genetic analysis of patients affected by HH recently led to the discovery of many novel proteins and mechanisms that can influence the uptake, transport, storage, and excretion of iron.

HFE gene mutations in Polish patients with disturbances of iron metabolism: an initial assessment.

Hereditary hemochromatosis is one of the most frequent genetic disorders in Europeans, but its prevalence in Poland is still unknown. The aim of the study was an initial assessment of the prevalence of C282Y and H62D HFE gene mutations and their influence on the course of chronic hepatitis C. Forty-one patients were admitted to the Department of Infectious Diseases, Medical University of Gdansk in 2000-2004 because of chronic liver diseases with accompanying disturbances in iron metabolism.