CLINICAL AND LABORATORY FEATURES OF CHRONIC VIRAL HEPATITIS C IN THE ELDERLY

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CLINICAL AND LABORATORY FEATURES OF CHRONIC VIRAL HEPATITIS C IN THE ELDERLY
M. G. Pavlova
Voronezh State Medical University named after N. N. Burdenko, Voronezh, Russia
Department of Infectious Diseases

Relevance. By improving the quality of life and empowerment of medicine in most countries, increasing life expectancy, leading to an increase in the share of elderly in the population, which in turn leads to an increase in the number of age-related pathologies. According to the International Classification of Gerontologists and WHO documents, people aged 60 to 74 years are classified as elderly. Elderly people over 60 years of age are the fastest growing group of the Russian population [1]. The share of elderly people in Russia according to ROSSTAT in 2019 has already reached 25% of the population and amounted to 37 million people [2].
No less urgent is the problem of chronic viral hepatitis C (HCV). It is estimated that about 5 million people in Russia are infected with the hepatitis C virus (HCV), and there is an increase in the prevalence of HCV infection with age [3]. In addition, the progression of the disease in older patients is faster than in younger patients [3].
Goal. Determination of clinical and laboratory features of the course of CVS in elderly patients.
Materials and methods. A retrospective study of 274 case histories of patients with chronic viral hepatitis C, aged from 18 to 75 years, who were on inpatient and/or outpatient treatment in the BUZ VOKIB of Voronezh and in the BUZ VOKTSPBS of Voronezh in 2018-2019 was conducted.
The criteria for inclusion of patients in the study were: 1) the presence of confirmed chronic viral hepatitis C in the replication phase (according to ELISA and PCR) and 2) age from 18 to 75 years.
Patients with tuberculosis, HIV infection, autoimmune diseases, cancer, chronic lung and cardiovascular diseases in the decompensation stage, renal failure, pregnant women and women during lactation were not included in the study.
In the course of the study, the examined patients with chronic viral hepatitis C were divided into 2 groups according to their age: elderly patients (over 60 years old) – 73 people and patients under 60 years old (comparison group) – 201 people.
Among the 73 examined elderly patients with HCV, there were 47 women (64.4%) and 26 men (35.6%). Among 201 examined patients with HCV under 60 years of age, there were 70 women (34.8%) and 131 men (65.2%). The
average age in the group of elderly patients with HCV was 65.8±5.8 years, and in the group of patients with HCV under 60 years of age - 44.0±8.6 years.
All patients underwent standard general clinical examination (UAC, OAM, biochemical blood test, ECG), serological examination by ELISA for markers of viral hepatitis A, B, C, D, anti-CMV-IgM, anti-EBV-IgM, liver ultrasound, FGDS, qualitative and quantitative PCR for HCV RNA, HCV genotyping, liver fibroelastometry.
A statistical analysis of quantitative signs was carried out using the Student's t-test - the significance level α = 0.05, the probability of error p<0.05 - an acceptable value for conducting medical scientific research. In the absence of a normal distribution, the Mann-Whitney test was used to compare the two samples. The average values were represented by the median, since the distribution of the studied values was not normal, and the extreme values of the variable have a much lower value on the median than on the arithmetic mean. The average values were presented together with the standard deviation. To study the statistical significance of the differences in the results, the SPSS Statistics 25 and Microsoft Excel programs were used.
Results.
Men (65.2%) predominated among patients with HCV younger than 60 years, while women (64.4%, P<0.05) dominated in the group of patients with HCV older than 60 years.
In the clinical picture, elderly patients with HCV compared to patients under 60 years of age were significantly more likely to have general weakness (80.8% vs. 65.7%, P<0.05) and severity in the right hypochondrium (71.2% vs. 37.8%, P<0.05). Also, splenomegaly was significantly more frequently detected in elderly patients (15.1% vs. 4.5%, P<0.05). Symptoms such as dyspepsia (34.2% vs. 29.4%) and pruritus (4.1% vs. 3.0%) were more common in elderly patients with CVS, but these differences were not significant (P>0.05).
The distribution of HCV genotypes in different age groups differed. In patients older than 60 years, 3 the virus genotype was found only in 19.2% of patients, while in patients younger than 60 years, this genotype was recorded 2 times more often - in 38.3% of patients, and this difference was significant (P<0.05). Accordingly, HCV genotypes 1 and 2 were slightly less common in elderly patients (68.5% and 9.6%, respectively) than in patients younger than 60 years (55.2% and 6.5%, respectively), but these differences were not significant (P>0.05).
The frequency of concomitant diseases was significantly higher in elderly patients with CVS: on average, one elderly patient had 4-5 concomitant diseases compared to 1-2 diseases in young patients. The main concomitant pathology in the elderly was hypertension, cardiovascular diseases, type 2 diabetes, chronic cholecystitis and / or chronic pancreatitis, joint diseases.
When comparing the biochemical parameters of the blood, it was found that in elderly patients with CVS, significantly more often than in patients younger than 60 years, there was an increase in the activity of alkaline phosphatase (52.1% vs. 41.8%, P<0.05), GGTP (56.2% vs. 31.8%, P<0.05) and total blood cholesterol (31.5% vs. 21.9%, P<0.05), although the differences in the average values of these enzymes were unreliable.
At the same time, the frequency of detection of hyperfermentemia did not significantly differ in different age groups, amounting to 99% and 98.5%, respectively, in elderly patients and patients under 60 years of age (P>0.05). As for the average activity of cytolytic enzymes (ALT, AST), it, as in the case of the average activity of cholestasis markers, also did not significantly differ in patients of the compared groups (100.451.8 vs. 94.735.0 for ALT, P>0.05; and 90.446.9 vs. 72.129.9 for AST, P>0.05).
Increased thymol sample and the level of gamma-globulins in elderly patients with chronic HCV were observed approximately 1.5 times more likely than patients younger than 60 years, although the differences of the average values of these indicators were unreliable (P>0.05).
Thus, a biochemical picture of chronic HCV in older patients was characterized by 1.5-2 times more frequent detection of markers of cholestasis, a more pronounced dysproteinemia, with significant differences in the frequency and severity of cytolytic syndrome have been identified.
Among elderly patients with chronic HCV and patients younger than 60 years, the frequency of detection of HCV RNA were generally comparable: 75,3% and 69.7%, respectively (P>0.05).
The level of viremia HCV RNA in elderly patients was on average 2 times higher and amounted to an average of 1,28х107 copies/ml compared to 6,29х10⁶ copies/ml in patients with chronic HCV younger than 60 years, and this difference was highly significant (P<0.01).
High levels of liver fibrosis (F3 and F4 on the METAVIR scale) were 3 times more frequent in elderly patients (24.7% and 35.6%, respectively) compared to 11.4% and 14.4% for patients younger than 60 years (P<0.01). In contrast, the absence of liver fibrosis (F0) in the elderly was significantly less common than in patients under the age of 60 (6.8% vs. 34.3%, P<0.01). A similar situation was observed for fibrosis of minimal severity (F1) – it occurred only in 16.4% of elderly patients and, on the contrary, was registered in 22.9% of patients under 60 years of age (P=0.06).
Discussion.
During the period under review, among all patients with chronic viral hepatitis C, the proportion of patients over 60 years of age was slightly more than 25%, which is generally consistent with the share of the elderly population in the general population structure of Russia. The prevalence of women in the group of patients with HCV over 60 years of age is explained by the age structure of the population with a predominance of women in the structure of the elderly population worldwide, so the result is also not unexpected.
In the course of our study, we found that among elderly patients with chronic viral hepatitis C, such manifestations as general weakness, severity and/or pain in the right hypochondrium, splenomegaly, more frequent detection of markers of cholestasis (increased activity of alkaline phosphatase, GGTP), more pronounced dysproteinemia were more common. These manifestations could be associated with a three-fold higher frequency of severe liver fibrosis and cirrhosis in elderly patients (F3-F4), which was found in the course of our work.
Cholestasis is one of the manifestations of chronic viral hepatitis C in both the young and the elderly. Possible reasons for the more frequent presence of markers of cholestasis in elderly patients with CVS could be both concomitant diseases of the biliary tract, which were significantly more often recorded in old age, and age-related morphological changes in the biliary system, which has been repeatedly documented by many researchers [4].
In turn, the cause of more frequent and pronounced liver fibrosis in elderly patients with HCV is obviously a long duration of the disease, but it was impossible to accurately name this cause of more advanced fibrosis as the main one, in most cases, due to the high frequency of asymptomatic onset of the disease. However, the more frequent detection of high fibrosis rates in elderly patients indirectly indicates a longer course of the disease. Another possible explanation for the more frequent and pronounced fibrosis in the elderly may be a faster progression of fibrosis at this age, as reported by a number of authors [5, 6].
Twice as rare registration of HCV genotype 3 in elderly patients with HCV is also consistent with the literature data [7], according to which the more aggressive HCV genotype 1 prevails in patients infected several decades ago (i.e., in older patients). Accordingly, the frequency of detection in the group of elderly patients of other genotypes of the virus (2nd and 3rd) becomes less.
As for the higher level of viremia in elderly patients, a possible explanation is a much more frequent decrease in the level of T-helpers ("age-related immunodeficiency"), and, as a result, an increase in the number of virions in the body against the background of a weaker immune response.
Conclusions.
In the course of our study, it was found that HCV in elderly patients has a number of clinical and laboratory differences compared to patients under 60 years of age. Thus, in elderly patients with HCV, general weakness, severity and/or pain in the right hypochondrium, high levels of liver fibrosis and cirrhosis, splenomegaly, as well as the frequency and number of concomitant diseases were significantly more common. In elderly patients with HCV, markers of cholestasis were detected twice as often, dysproteinemia was significantly more pronounced, HCV genotype 3 was twice as rare, and the level of HCV RNA viremia was 2 times higher.

About the authors

Maria G. Pavlova

Author for correspondence.
Email: masha_pavlova_98@mail.ru
ORCID iD: 0000-0003-0818-4249
SPIN-code: 9937-9851
Russian Federation, 10 Studentskaya Street, Voronezh, Russia, 394036

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