Association between inherited monogenic liver disorders and chronic hepatitis C

Piekuse, Linda; Kreile, Madara; Zariņa, Agnese; Steinberga, Zane; Sondore, Valentina; Keiss, J.; Lāce, Baiba; Krūmiņa, Astrīda

doi:10.4254/wjh.v6.i2.92

Cited by 6 publications

(5 citation statements)

References 34 publications

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“…After pretreatment analysis of liver function tests and biochemical markers commonly used for diagnostic orientation in patients with CHC, we found significant associations of the bilirubin and ferritin levels with UGT1A1 *28 genotype, similar to results by Piekuse L. et al (37) and de Souza et al (5). Hyper bilirubinemia caused by reduced UGT1A1 activity in patients with hepatitis C has been documented in reports of severe ribavirin-induced jaundice, after com mencing pegylated interferon and ribavirin therapy, suggesting usefulness of genotyping for UGT1A1 *28 variant for the decision to continue therapy with ribavirin (38).…”

Section: Discussionsupporting

confidence: 89%

“…Bilirubin levels have also been observed to correlate with the total number of TA repeats (2, 5). The observed association of UGT1A1 *28 allele with serum ferritin levels has been previously documented in few studies which included patients with CHC (37). Serum iron markers (ferritin and transferrin) are suggested as surrogate markers for liver fibrosis and necroinflammatory activity.…”

Section: Discussionmentioning

confidence: 68%

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Significance of UGT1A1*28 Genotype in Patients with Advanced Liver Injury Caused by Chronic Hepatitis C

Jordovic¹,

Bojović

Simonovic-Babic

et al. 2019

Journal of Medical Biochemistry

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SummaryBackground:Chronic hepatitis C (CHC) is a significant cause of liver related morbidity and mortality worldwide. The role of genetics in the host response to hepatitis C virus is not elucidated. Genetic variations inUGT1A1gene are the most common cause of hereditary unconjugated hyperbilirubinemia-Gilbert syndrome. This is the first study investigating the association ofUGT1A1TA repeats promoter genotypes with the degree of liver injury, viremia and biochemical markers in CHC patients with advanced liver injury and late virological relapse.Methods:Genetic testing ofUGT1A1TA repeats promoter genotypes was performed in 42 CHC patients with advanced fibrosis and cirrhosis who achieved sustained virological response and 42 healthy blood donors. CHC patients were evaluated for clinical findings, laboratory tests and imaging.Results:UGT1A1*28 genotype (7/7 TA repeats) was observed in 23.8% CHC patients and 16.7% healthy controls with no significant difference in genotype frequencies (p=0.49). Pretreatment levels of ferritin and bilirubin were associated with the presence ofUGT1A1*28genotype, indicating its potential as a predictive marker. However, in our study, there was no correlation ofUGT1A1*28genotype with the degree of fibrosis or viremia. During antiviral treatment, dose reductions and treatment interruptions, as well as treatment success and occurrence of late virological relapse were not related to the presence ofUGT1A1*28genotype in CHC patients with severe liver injury.Conclusions:Frequencies ofUGT1A1*28genotype are high in both Serbian CHC patients and healthy subjects. The presence ofUGT1A1*28genotype was not associated with ribavirin-related adverse effects and had no effect on long term outcome in CHC patients.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 68%

Significance of UGT1A1*28 Genotype in Patients with Advanced Liver Injury Caused by Chronic Hepatitis C

Jordovic¹,

Bojović

Simonovic-Babic

et al. 2019

Journal of Medical Biochemistry

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“…A recent study on young patients under 10 years of age revealed that zinc monotherapy reduced serum ALT levels ranging from 243 ± 151 to 70 ± 29 IU/L in 1 month. 23 It is also important that copper-overload conditions secondary to chronic cholestasis 24 or chronic liver diseases other than WD 25,26 could be differentiated by the short-term treatment test.…”

Section: Discussionmentioning

confidence: 99%

Alanine Aminotransferase as the First Test Parameter for Wilson’s Disease

Hayashi

Watanabe

Inui³

et al. 2019

Journal of Clinical and Translational Hepatology

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Background and Aims: The liver is the first organ affected by toxic copper in the classical and severe hepatic forms of Wilson's disease (WD). Because their associated chronic liver damage is mostly asymptomatic, an intervention using a special test including serum alanine aminotransferase (ALT) activity is needed for detecting WD. Methods: Using the modified international criteria for the diagnosis of WD, 45 patients were selected from the collective databases of our institutions, and 7 infants were reviewed from the literature. Two patients had the severe hepatic form, with normoceruloplasminemia and no mutations in ATP7B. The rapid ALT change during hemolytic anemia was adjusted for a baseline. The diagnostic potential of the ALT test was assessed from the age-dependent natural course of the liver damage of WD. Results: The natural course had three stages. ALTs were still low in some infants younger than 4 years-old. They were high in all children between the ages of 4 and 8 years-old; then, they reduced to low levels in some patients over 9 years of age. The high ALT stage represents chronic active hepatitis, and the subsequent low ALT stage is due to silent cirrhosis. The hepatic copper content is a reliable but invasive test, while urinary copper secretion is an alternative, non-invasive test for copper toxicosis of WD. The serum ceruloplasmin and ATP7B analyses are subtype tests of WD. The response to anti-copper regimens is the final test result. Conclusions: ALT could be the first parameter to test to detect WD in children between the ages of 4 and 8 years.

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“…These data demonstrate a gene-by-environment interaction between hepatitis C and AATD risk alleles. Previous studies have investigated whether there is an enrichment of individuals with AATD risk alleles within a population of patients with liver disease and have been inconclusive; some show no association between AATD risk alleles [21][22][23] and liver disease and others demonstrate an enrichment of these alleles in patients with hepatitis C related liver disease [18][19][20]24]. A recently published prospective study of individuals with chronic hepatitis C infection showed that there was no difference in the prevalence of Z allele heterozygotes in patients with cirrhosis compared with those without cirrhosis in two cohorts [49].…”

Section: Discussionmentioning

confidence: 99%

“…There are known environmental exposures that can exacerbate or accelerate tissue damage secondary to AATD in both heterozygotes and homozygotes including smoking, environmental pollution, respiratory infections, obesity, non-steroidal anti-inflammatory drugs, and alcohol [13][14][15][16][17]. There are additional environmental factors, like viral hepatitis, whose impact on exacerbating AATD-related tissue damage is debated [13,[18][19][20][21][22][23][24]. Early AATD diagnosis can lead to an avoidance of these environmental exposures and an attenuation of symptom manifestation [12,25].…”

Section: Introductionmentioning

confidence: 99%

Population genetic testing and SERPINA1 sequencing identifies unidentified alpha-1 antitrypsin deficiency alleles and gene-environment interaction with hepatitis C infection

Schuler,

Bastarache,

Wang

et al. 2023

PLoS ONE

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Alpha-1 antitrypsin deficiency (AATD), a relatively common autosomal recessive genetic disorder, is underdiagnosed in symptomatic individuals. We sought to compare the risk of liver transplantation associated with hepatitis C infection with AATD heterozygotes and homozygotes and determine if SERPINA1 sequencing would identify undiagnosed AATD. We performed a retrospective cohort study in a deidentified Electronic Health Record (EHR)-linked DNA biobank with 72,027 individuals genotyped for the M, Z, and S alleles in SERPINA1. We investigated liver transplantation frequency by genotype group and compared with hepatitis C infection. We performed SERPINA1 sequencing in carriers of pathogenic AATD alleles who underwent liver transplantation. Liver transplantation was associated with the Z allele (ZZ: odds ratio [OR] = 1.31, p<2e-16; MZ: OR = 1.02, p = 1.2e-13) and with hepatitis C (OR = 1.20, p<2e-16). For liver transplantation, there was a significant interaction between genotype and hepatitis C (ZZ: interaction OR = 1.23, p = 4.7e-4; MZ: interaction OR = 1.11, p = 6.9e-13). Sequencing uncovered a second, rare, pathogenic SERPINA1 variant in six of 133 individuals with liver transplants and without hepatitis C. Liver transplantation was more common in individuals with AATD risk alleles (including heterozygotes), and AATD and hepatitis C demonstrated evidence of a gene-environment interaction in relation to liver transplantation. The current AATD screening strategy may miss diagnoses whereas SERPINA1 sequencing may increase diagnostic yield for AATD, stratify risk for liver disease, and inform clinical management for individuals with AATD risk alleles and liver disease risk factors.

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Association between inherited monogenic liver disorders and chronic hepatitis C

Cited by 6 publications

References 34 publications

Significance of UGT1A1*28 Genotype in Patients with Advanced Liver Injury Caused by Chronic Hepatitis C

Significance of UGT1A1*28 Genotype in Patients with Advanced Liver Injury Caused by Chronic Hepatitis C

Alanine Aminotransferase as the First Test Parameter for Wilson’s Disease

Population genetic testing and SERPINA1 sequencing identifies unidentified alpha-1 antitrypsin deficiency alleles and gene-environment interaction with hepatitis C infection

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