Prevalence of serological markers for hepatitis and potential associated factors in patients with diabetes mellitus

ABSTRACT Objective: to estimate the prevalence of serological markers for hepatitis B and C in patients with diabetes mellitus and analyze potential associated factors. Method: a cross-sectional study with 255 patients with diabetes mellitus. Demographic, clinical, and risk behavior factors for hepatitis B and C were selected. The markers HBsAg, Anti-HBc IgG, Anti-HBc IgM, Anti-HBs, and Anti-HCV were investigated. A questionnaire and venous blood collection and inferential statistical analysis were used. Results: 16.8% of the patients had a total reactive Anti-HBc marker, 8.2% an isolated Anti-HBs, and 75% were non-reactive for all hepatitis B markers. No case of reactive HBsAg was found and 3.3% of the patients had a reactive anti-HCV marker. The prevalence of prior hepatitis B virus infection was directly associated with the time of diabetes mellitus and the prevalence of hepatitis C virus infection was not associated with the investigated variables. The prevalence of hepatitis B and C infection in patients with diabetes mellitus was higher when compared to the national, with values of 16.8% and 3.3%, respectively. Conclusion: the results suggest that patients with diabetes are a population of higher vulnerability to hepatitis B and C, leading to the adoption of preventive measures of their occurrence.


Introduction
The international literature shows outbreaks of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in the hospital, outpatient, and long-term care facilities.
Infection cases have been shown to be more frequent in patients with diabetes mellitus (DM) than in those without the disease, suggesting that patients with DM are potentially more susceptible to HBV and HCV infection as a result of treatment and control procedures of the disease, in particular, the monitoring of capillary glycemia (1)(2)(3)(4)(5)(6)(7)(8) .
These outbreaks occur when infection control standards during capillary glycemia monitoring are neglected, such as the sharing of lancet pens, lancets, and glucometers without the proper disinfection process due to the transmission of microorganisms through the blood. HBV and HCV can survive on surfaces such as lancet pens, lancets, and glucometers on average for five to seven days, even in the absence of visible blood. During this period, the virus can cause infection if it reaches the bloodstream of a susceptible person (9)(10) .
There is evidence that the severity and lethality related to HBV and HCV infection are higher in patients with DM than in those without the disease. Studies show that in patients infected with HBV and HCV, the presence of DM can accelerate the progression of liver disease, lead to cirrhosis, hepatocellular carcinoma, and death (11)(12) . In addition, HBV and HCV infection may negatively influence the glycemic control of patients with DM, increasing the risk of hyperglycemia (13)(14)(15) .
However, in Brazil, there is a shortage of studies regarding the behavior of hepatitis B and C in patients with DM. Regarding hepatitis C, four studies were identified in patients with DM (16)(17)(18) . One of them showed a high prevalence of hepatitis C in patients with type 2 diabetes mellitus (DM2) when compared to blood donors without DM (16) . Another study also found a high prevalence of hepatitis C in patients with DM2 (18) . On the other hand, studies did not identify a difference in the prevalence of hepatitis C in patients with and without DM (14) and cases of hepatitis C in investigated patients with DM2 (17) .
A study on the occurrence of hepatitis showed the magnitude of the prevalence of Hepatitis A, B, and C Virus Infections in the Brazilian macro-regions and represented a major step in coping with hepatitis in Brazil (19) . However, the behavior of the disease in individuals with DM and risk factors related to infection in this population is unknown.  Arrelias CCA, Rodrigues FB, Torquato MTCG, Teixeira CRS, Rodrigues FFL, Zanetti ML.
The data collection instrument was pre-tested with ten patients in order to identify possible adjustments in the sequence of questions, test the approach to the patient, as well as estimate the time of application of the questionnaire.
For data collection, the researcher had the collaboration of a student of Scientific Initiation previously qualified in order to standardize it. After the application of the pre-test, the questionnaire was maintained with no need for adjustments regarding its form and content. The ten patients were

Results
The demographic and clinical characteristics of the 255 (100%) investigated patients are described in Table 1

Discussion
When comparing the obtained results with the population-based survey conducted in Brazil, the prevalence of HBV exposure (16.8%) was higher than the national prevalence (11.6%) in the general population from 20 to 69 years. Regarding the prevalence of acute or chronic infection, the prevalence found was lower than the national prevalence, with a value of 0.6% (19) . This result suggests that the prevalence of HBV exposure is higher in individuals with DM when compared to those without the disease (5) .
The association of exposure to HBV and a longer time of DM can be interpreted as a cumulative risk of exposure to the virus probably attributed to the disease management since DM does not progress to hepatitis B or C. The association of exposure to HBV and a longer time of DM were reported in Poland (26) , Turkey (28) , and Nigeria (30) .
On the other hand, a study carried out in Italy found no association of infection and time of DM (27) .
In accordance with another study (27) , the present study also did not find an association of HBV infection with The prevalence of HCV infection was 3.3% higher than the national prevalence for the general population from 20 to 69 years old, which was 1.6% (24,27) , as well as national studies with specific populations such as the deaf, military males, and workers collecting household waste (31)(32)(33) . On the other hand, a study that investigated the prevalence of HCV infection in elderly patients in southern Brazil found a prevalence of 2.2% (34) .
The prevalence of hepatitis C in patients investigated in our study was also higher than that found in three national studies with patients with DM (16)(17) . The difference in the observed prevalence can be attributed to the composition of the sample regarding the age group. An old age is considered a risk factor for exposure to HCV infection (20)(21) . The time of DM found in these studies was also lower than that found in our study, which may also justify the difference in the observed prevalence.
On the other hand, a study carried out in southern Brazil showed that the prevalence was four times higher in patients with DM2 undergoing outpatient care (18) . The time of DM of the investigated outpatients is higher when compared to those of our study, which may have contributed to a higher prevalence of infection.
International studies investigating the prevalence of HCV exposure in patients with DM in an outpatient clinic or hospital found a lower (7,24,30) , similar (23,28) , and higher (8,22,25,27,29) prevalence in relation to our results.
Since the 1990s studies have shown a higher prevalence of hepatitis C in patients with DM when compared to those without this disease (7)(8)16,23,27) . When comparing the prevalence of hepatitis C in patients with DM found in our study (3.3%) and the prevalence observed in the general Brazilian population (1.4%) (19) , we also observed a higher prevalence of infection in patients with DM.
However, in our study, although we found a prevalence of HCV infection higher than that of the Brazilian population, we did not observe an association of HCV infection with demographic variables, variables related to insulin use, monitoring of capillary glycemia, and history of medical, surgical, diagnostic, and therapeutic interventions, which is in agreement with national studies (16)(17)(18) .
Other studies reported in the international literature found as variables associated with infection only recognized risk factors for hepatitis C such as the history of blood transfusion, sharing of sharps, multiple sexual partners, and changes in liver enzyme levels (16,18,23,25,29) .
A study carried out in France found a significant difference in the prevalence of HCV infection in patients with (3.1%) and without DM (0.04%). However, the hypothesis that the type of treatment for DM, previous hospitalizations, and lancet use pen for monitoring the capillary glycemia are associated with HCV infection in patients with DM has not been confirmed (35) .
These results lead to the assumption that HCV infection may present as a risk factor for the development of DM, as investigated in other studies (36)(37) . Studies have shown that HCV infection is followed by defects in the insulin-signaling pathway in the liver, which may contribute to insulin resistance and DM (37) . However, HCV-induced insulin resistance mechanisms are still partially understood (14,38) . Another study shows that liver inflammation is a possible risk factor for pre-diabetes in the context of HCV infection (39) .
In summary, when considering the higher prevalence of HBV exposure and its relation to the time of DM, it is suggested to deepen new investigations related to diabetes management that may contribute to HBV infection. The absence of association of HCV infection with the studied variables can be attributed to the relatively low number