DYNAMICS OF THE ACUTE VIRAL HEPATITISES MORBIDITY AND RANGE OF MEDICINAL PREPARATIONS FOR TREATMENT IN HOSPITAL ENVIRONMENT IN THE VOLGOGRAD REGION (THE RUSSIAN FEDERATION), 2016–2018

Volume VII, Issue 6, 2019 For citation: L.M. Ganicheva, E.A. Ioannidi, O.A. Panfilova, I.N. Tyurenkov, Yu.S. Knyazeva, N.Sh. Kaysheva. Dynamics of the acute viral hepatitises morbidity and range of medicinal preparations for treatment in hospital environment in the Volgograd region (the Russian Federation), 2016–2018. Pharmacy & Pharmacology. 2019;7(6):356-362. DOI: 10.19163/2307-9266-2019-7-6-356-362 © Л.М. Ганичева, Е.А. Иоанниди, О.А. Панфилова, И.Н. Тюренков, Ю.С. Князева, Н.Ш. Кайшева, 2019 Для цитирования: Л.М. Ганичева, Е.А. Иоанниди, О.А. Панфилова, И.Н. Тюренков, Ю.С. Князева, Н.Ш. Кайшева. Динамика заболеваемости острыми вирусными гепатитами в Волгоградском регионе и ассортимент лекарственных препаратов для стационарного лечения, 2016– 2018 гг. Фармация и фармакология. 2019;7(6):356-362. DOI: 10.19163/2307-9266-2019-7-6-356-362 ДИНАМИКА ЗАБОЛЕВАЕМОСТИ ОСТРЫМИ ВИРУСНЫМИ ГЕПАТИТАМИ В ВОЛГОГРАДСКОМ РЕГИОНЕ И АССОРТИМЕНТ ЛЕКАРСТВЕННЫХ ПРЕПАРАТОВ ДЛЯ СТАЦИОНАРНОГО ЛЕЧЕНИЯ, 2016–2018 ГГ.


INTRODUCTION
Viral hepatitis is a widespread infectious disease that destroys a human liver. According to the World Health Organization, hundreds of millions of people in different countries are infected with viral hepatitises, which exceed the spread of HIV infections. Hepatitis is a medical and social problem both for the Russian Federation and for the whole world. A decrease in the incidence of acute hepatitises, is associated with increased preventive measures and the introduction of vaccination in accordance with the national vaccination calendar 1 . Vaccination against viral hepatitises A (HAV) and B (HBV) has been carried out in Russia for the past 20 years, but a vaccine against viral hepatitis C (HCV) has not been developed due to the severe variability of the virus genome [1,2]. The main reason for the carrier state of this hepatitis virus is the epidemiological problems of countries over the previous 20-25 years. About 650 thousand deaths per year in the world are associated with hepatitis B virus. 2-3% of the Russia population, are infected with hepatitis C. The main routes of HBV and HCV transmission are parenteral, contact (through a skin microtrauma, sexual promiscuity), and the vertical routes (from a mother to a child) [3][4][5][6][7][8][9].
The mechanism of HCV transmission is the fecal-oral route. As the practical data have shown, in the Volgograd Region, the main route of hepatitis B infection is the parenteral route (administration of narcotic substances with non-sterile needles in drug addiction).
when it comes to a single-agent infection. [10,11]. Statistics of the Volgograd region on acute hepatitis A, are not available in the public information sources.
In the Russian Federation in 2012, acute hepatitis B amounted to 1.43 cases per 100 thousand people. Thanks to the vaccination, the morbidity decreased by 30 times in 2000-2012. 90-95% of adults with HBV recover and only 10% have the chronic form. The mortality rate due to acute hepatitis B is less than 1%. In the Volgograd region in 2015, the morbidity of acute hepatitis B was 1.7 times lower than its morbidity rate in the Russian Federation, in 2015 it amounted to 0.78 cases per 100 thousand people, in 2016 it was 0.54 [12,13].
In the Russian Federation in 2012, acute hepatitis C amounted to 1.8 cases per 100 thousand people. 50-80% of the infected people have a chronic form. In the Volgograd region in 2015, the morbidity of acute hepatitis B amounted to 0.66 per 100 thousand people, which is 2.1 times lower than the average rate of this disease in the Russian Federation, and in 2016 it amounted to 0.16 [14].
THE AIM of the study was to investigate the state of affairs in acute viral hepatitises A, B and C in the Volgograd region during the period of 2016-2018: its prevalence, the forms and severity of the disease, the range of medicinal preparations used in hospitals for the acute hepatitises treatment, the dynamics of prices for medicines of the most widely used pharmacological groups based on the state register of medicinal preparations.
Early disease and treatment intelligence plays an important role in preventing health complications and saving budget funds, of both the state and the population.

MATERIALS AND METHODS
In the study, the following methods have been used: comparison, a method of grouping indicators and a structural-logical method. The materials were 175 hepatological department patients' treatment sheets (Volgograd Regional Clinical Infectious Diseases Hospital No.1) and the data of the state register of medicinal preparations of the Russian Federation.
The research design is represented by 4 interconnected stages: 1 -the analysis of the morbidity dynamics of acute viral hepatitises A, B, C; 2 -the analysis of the data on the duration of treatment in hospital environment; 4 -the analysis of the dynamics of prices for the medicinal preparations prescribed for the treatment of acute viral hepatitises.

RESULTS AND DISCUSION
Viral hepatitises are classified according to the form and severity of the disease [15,16]. In the infectious hospital during 2016-2018, the following forms were registered: -the icteric form (moderate and heavy severity level); -the anicteric form (mild and moderate severity level).
At the first stage of the study, the analysis of the morbidity dynamics of the acute viral hepatitises A, B, C (according to the form and severity in the Volgograd region) was carried out (Tab. 1). Methods of comparison and grouping were used. From the data of Tab.1 it follows that acute hepatitis A was the most common -82 (46.9%) cases; acute hepatitis B -48 (27.4%) cases, it occupies the second place; and acute hepatitis C -45 (25.7%) cases it occupies the third place.
In 2016-2018, the dynamics of the acute hepatitis A prevalence was characterized by a significant decrease in the morbidity rate from 59.8 to 12.2%, i.e. by 5 times; the morbidity of icteric moderate forms was decreased from 58.8 to 12.3%, i.e. by 4.5 times, although it should be noted that a single case of an icteric form of heavy severity was detected in 2016.
The dynamics of the acute hepatitis B prevalence in 2016-2018 was characterized by a tendency of a decrease in the morbidity rate from 39.5 to 29.2% (by 1.5 times); a decrease in the icteric form of moderate severity from 31.3 to 25% and in the anicteric form of moderate severity from 2.1 to 4.2% was also found out. A single case of acute hepatic encephalopathy has been detected for the whole period.
The dynamics of the acute hepatitis C prevalence in 2016-2018 was characterized by a tendency of an increase from 20 to 42.2% (by 2 times); there was a growth of the icteric form of moderate severity from 11.1 to 20%, of the anicteric form of mild severity -from 2.2 to 11.1%; and of an anicteric form of moderate severity from 4.4 to 11.1%. Two cases of icteric severity were also detected in 2016 and 2017 per annum.
A decrease in the acute hepatitises A and B morbidity is associated with an active use of the hepatitis vaccines [17]. Vaccination of newborns is carried out from the first days of their lives in accordance with the national calendar of vaccinations. Vaccination has also been prescribed for the adult population 1 .
At the 2nd stage of the study, the data of the duration of treatment in hospital environment were reviewed and summarized. The therapy of acute viral hepatitis takes a different time depending on the type of hepatitis, the form and severity of the disease, and goes with clinical guidelines, standards of specialized medical care for patients with acute viral hepatitises [18]. The icteric form of hepatitis is severer than the anicteric form and, therefore, requires a longer treatment. Using the structural-logical method, we can conclude that among icteric forms of hepatitises, it is more difficult to treat acute severe hepatitis B (the treatment duration is 25±5 days).
The icteric form of acute severe hepatitis, occupies the 2 nd position as its treatment duration is 19±0 days. Acute hepatitises A and B of the icteric form of moderate severity are in the third position; their treatment duration is 17±7 days. A period from 8 to 16 days is required for the treatment of the anicteric form of mild severity of acute hepatitis C; of moderate severity of acute hepatitises C and B; for the icteric form of acute hepatitis C of moderate severity; and for the icteric form of acute severe hepatitis A (Tab. 2). The cases of the anicteric form of moderate severity of acute hepatitises A and a mild degree of acute hepatitises A and B in hospital environment were not registered.
At the next stage of the study, the range groups of medicinal preparations and the frequency of their prescriptions were cleared up. In the treatment of acute viral hepatitises, pathogenetic therapy (hepatoprotectors, enzymes, vitamins, hormonal medicines, medicines for rehydration and detoxification for parenteral use) was used; besides, etiotropic (interferons and their inducers) and symptomatic kinds of therapy were used. These kinds of therapy also go with the clinical recommendations and standards of specialized medical care [19][20][21][22][23]. The use of groups of medicinal preparations in the corresponding types, forms and degrees of severity of acute hepatitises are presented in Tab. 3-5. As it follows from Tab. 3, etiotropic therapy was not used for the icteric form of moderate severity of acute hepatitis A, and only interferons in the function of etiotropic therapy, are added to the main treatment of the icteric form of heavy severity of acute hepatitis A. It should be also noted that vitamins were not used at all in this hospital for the treatment of acute hepatitis A.
As Tab. 4 shows, vitamins were not used in the treatment of acute viral hepatitis B either. In its turn, interferon therapy was not used for the icteric form of heavy severity and the anicteric form of moderate severity of acute hepatitis B. Enzymatic and hormonal medicines were not prescribed for the treatment of acute hepatitis B anicteric forms of moderate severity either.
As it follows from Tab. 5, etiotropic therapy was not used in the icteric form of heavy severity and in the anicteric form of mild severity of acute hepatitis C. In the treatment of the anicteric form of moderate severity, only interferons were used in etiotropic therapy. In the treatment of the anicteric form of mild severity, enzyme medicines, hormonal, rehydration and detoxification medicines were not used. Hormonal medicines were not prescribed for the treatment of the acute hepatitis C anicteric forms of moderate severity either.
Tab.6 contains a range of medicinal preparations used in the treatment of acute viral hepatitis in Volgograd Regional Clinical Infectious Diseases Hospital N 1.
The medicinal preparations referring to pathogenetic and etiotropic therapy, have been examined in detail because they directly affect the outcome of the disease. In Tab.6, the groups of medicinal preparations are indicated in accordance with the anatomical-therapeutic-chemical classification [28]. All the presented medicinal preparations belong to the Vital and Essential Drugs List (dated 2016-2018).
According to Tab. 6, during the period of 2016-2018, rehydration and detoxification medicinal preparations were prescribed most often (47% of the entire range), as well as the group of hepatoprotectors (31.7%). In 2018, unlike the previous years, a group of enzyme medicinal preparations began to be prescribed quite widely.
The final stage of the investigation was devoted to the study of price dynamics for the most commonly prescribed medicines of two pharmacotherapeutic groups: medicines for rehydration and detoxification and hepatoprotectors. Since the presented medicines are included in the list of Vital and Essential Medicines, their prices and wholesale surcharges are fixed and controlled by the state. Tables 7, 8 show the dynamics of prices for rehydration and detoxification medicinal preparations, as well as the group of hepatoprotectors in the period of 2016-2018.
According to Tab. 6, in the period of 2016-2018, the most often prescribed were rehydration and detoxification medicines (47% of the entire range), as well as the group of hepatoprotectors (31.7%). In 2018, unlike the previous years, a group of enzyme medicines began to be prescribed quite widely. Tab. 7, 8 show the dynamics of prices for rehydration and detoxification medicines, as well as the group of hepatoprotectors.
Since the presented medicines are included in the list of Vital and Essential Medicines, their prices and wholesale surcharges are fixed and controlled by the state. From the data of Tab. 7 it follows, that in the study period in the rehydration and detoxification group (11 items taken as 100%) the prices increased for 3 medi-cines (27%), Reamberin ® 200 ml and 400 ml, potassium chloride 4% -10 ml; 2 medicines remained in the same price category: acesol 400 ml and Reamberin ® 250 ml (18%); the prices decreased for 5 medicines: glucose 5% -400 ml, glucose 10% -400ml, Ringer's solution 400ml, Ringer's solution 500ml, sodium chloride 0.9% -400 ml (45%). Remaxol ® 400 ml (1%) belongs to new medicines of 2018, therefore its price dynamics is not possible to trace. A significant decrease in the price of 4medicines (-22-46%), a significant increase in the price of 1 medicine (+81.8%) and a slight increase (+7.5%) for 2 medicines were revealed in comparison with 2016.
Consequently, a larger percentage consists of the medicinal preparations the costs of which have decreased (by 45%). This fact may be associated with an increase in the affordability of medical care, and, accordingly, an increase in medical prescriptions for 2016-2018.
The data of Tab. 8 shows that in the group of 6 hepatoprotectors, the price of 2 medicines did not change (Heptor ® 400 mg and Ursodez ® 500 mg), the price of other medicines went up from 2.1 to 329.8%. However, this fact did not affect the frequency of prescriptions of this group of medicines, which may be due to an increase in the allocation for the purchase of these items for use in hospital environment. Attention should be also paid to the fact thataccording to Tab. 6 and 8, the prices for Heptor ® 400 mg and Ursodez ® 500 mg remained the same in 2016-2018, but their prescription was not registered in 2017 and 2018, which may be due to the lack of their procurement.

CONCLUSION
The studies have shown the following. In the period of 2016-2018, there has been a steady tendency of decreasing in the morbidity of acute hepatitises A and B, but in its turn, there has been an increase in the incidence of acute hepatitis C (it was nicknamed "a gentle killer" because of the hidden course of the disease). The main groups of medicines used in hospital environment for the treatment of acute hepatitises A, B and C depending on the form and severity of the disease, have been identified. 3. A study of the range of medicines, the frequency of medical prescriptions and dosages showed that rehydration and detoxification medicines for parenteral use, and hepatoprotectors are the most commonly prescribed. 4. The dynamics of the prices for the groups of medicines has been studied. It has demonstrated a decrease in prices for rehydration and detoxification medicines (45% of all the numbers of the items) and an increase in prices for medicines of the hepatoprotectors group (66.7% of all the numbers of the items).
The results gained indicate a tendency towards the improvement of medicine provision of patients with acute viral hepatitises, and give an opportunity to consider the ways of their further optimization.