Patients at haemodialysis departments constitute a high-risk group for infection by blood-transmitted viral hepatitis. In haemodialysis patients, markers of viral hepatitis C occur at a frequency of 15-70 %. The disease often runs a protracted course with few symptoms. The significant changes in the immune status and the procedure of chronic haemodialysis directly influence the course of infection in this category of patients.
The frequency of exposure markers of associated hepatitis in dialysis patients is significant and has ranged from 10 to 67 % in different studies (1,2). Data on hepatitis, caused by both hepatitis B and C viruses among patients at chronic haemodialysis departments are scarce, but a significant severity and non-favourable prognosis in these patients has been described (3,4). Fabrizi et al. suggested that hepatitis B and C might act synergistically, and lead to the progression of disease. Significant immune status disturbances were registered in patients with infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) combined, compared to patients hepatitis C alone (5). A significant risk of cirrhosis development and decompensation of a liver function in chronic hepatitis patients has been described (6-8).
Materials and methods
The study includes 82 patients treated at the Department of Chronic Haemodialysis, Pavlov’s State Medical University in 1997-1999. Patients in the dialysis unit were tested for viral hepatitis markers. Observation included case history, clinical course of disease and clinical, biochemical and serological indexes. The diagnosis of viral hepatitis was based on generally accepted criteria. Initial serological markers of HBV (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc), HCV (anti-HCV), and CMV (anti-CMV) were determined by immunosorbent assays. Every three months, serological markers (HBsAg, anti-HCV) were monitored with an immunosorbent commercial test-system. RNA HCV was determined once in each patient with PCR.
Clinical and biochemical indexes were estimated monthly, using generally accepted methods of laboratory diagnostics (9,10) including the measurement of the aminotransferase (ALT) activity (reference 0,1-0,68 mmol/ l), thymol test (reference 0-4), total serum protein (65-85 g/l), blood serum albumines (35-45 g/l), fibrinogen (2-4 g/l). Patients’ weight and blood pressure were controlled before and after every course of haemodialysis. Duration of haemodialysis performance and square of used dialysator were registered. Haemodialysis efficiency was evaluated by Kt/V, calculated by the formula Daugirdas-2 (11).
Statistical analysis of obtained data was performed using “Statistica for Windows” V. 5.0 (Statford Firm. Inc., 1995). Data were expressed as mean and 95 % confidence intervals ( 1.96 standard error of the mean) and analysed by unpaired t-test and lined and unlined correlations. Differences were considered as significant when P <0.05.
Results and discussion
Fifty-two of the 82 patients were hospitalised at the department of chronic haemodialysis with hepatitis B and/or hepatitis C. A high frequency of co-infection by several viruses was revealed. Markers of HCV were observed in 45 patients (55 %), markers of HBV in 32 patients (39 %), and anti-CMV in all of the observed patients. The study included patients with different histories of haemodialysis treatment. According to the patient records, the frequency of positive HCV markers and HCV+HBV markers increased during the last 5-year period by a factor 1.5 and 2, respectively. A tendency of conservation or depression of HBV markers was registered (44 % and 42 %, respectively). The maximal risk of infection with viral hepatitis was seen in the first year of haemodialysis. The frequency of viral hepatitis increased with the duration of haemodialysis. The mean duration of the haemodialysis in patients with viral hepatitis B+C was 100 (88-112) months, while in patients with hepatitis C alone it was 42 (38-46) months (p<0,001).
Considering the data suggesting a non-favourable course of patients with associated viral hepatitis B and C in the population and the absence of such data among patients with chronic renal failure and haemodialysis treatment, a comparison of clinical manifestations was made. Based on serological criteria, three patient groups were formed. The first group included patients with HCV monoinfection (n=20), the second group patients with viral hepatitis B+C (n=8), and the third group patients with HCV infection and a history of completed HBV infection (n=16).
During hepatitis infection the main biochemical indexes often remained within the reference values, but changed in relation to a baseline value obtained for that patient during the continuous monitoring of these indexes. Establishing a “normal” baseline for each patient is thus an important aspect of the diagnostic process. The level during hepatitis compared to baseline was evaluated for albumin 38.8 (37.8-39.8) and 40.7 (39.9-41.6) g/l (p<0.01), respectively and fibrinogen 2,4 (1.8-1.9) and 3.2 (2.9-3.6) g/l (p<0.05), respectively. A lower blood albumin level was combined with more severe clinical manifestations of viral hepatitis. In viral hepatitis caused by combined HBV and HCV infections, haemorrhagic syndrome, astheno-vegatative and dyspeptic syndrome and skin itching occurred more frequently.
Viral hepatitis affects the cardio-vascular status of dialysis patients. Among patients with associated viral hepatitis B+C infection compared to hepatitis C monoinfection, the blood pressure (BP) and interdialytic weight gain were both significantly higher (p<0.01), reflecting a tendency of hyperhydratation. The mean systolic BPs in the two groups were 138.0 (132.8-142.3) mm Hg and 126.7 (122.7-130,7) mm Hg, respectively; the mean diastolic BPs 82.8 (80.0-85.6) mm Hg and 78.2 (75.9-80.4), respectively; and the mean interdialytic weight gains 4.0 (3.8-4.2) kg and 3.2 (3.0-3.4) kg, respectively.
At the same time, viral hepatitis influences the results of the haemodialysis procedure decreasing its efficiency more in patients with combined hepatitis B+C infection and less in patients with hepatitis C monoinfection. The level of Kt/V in the exacerbation phase of viral hepatitis B+C was significantly lower than in HCV monoinfection: 1.23 (1.15-1.31) and 1,38 (1,32-1,44) respectively (p<0,001). This was despite an increase in the square of dialysator in an attempt to correct and optimise the dialysis regimen in response to the severity status of the patients.
The increase of the patients’ lifetimes by treating with chronic haemodialysis allowed for an assessment of the protracted course of chronic viral hepatitis including associated forms in these patients. It is well known that maximal changes of immune reactivity of haemodialysis patients occur after 4-5 years from the beginning of the treatment. The comparison of viral hepatitis manifestations in patients with treatment duration less than or more than 5 years allowed us to establish a decrease in clinical and biochemical signs of hepatitis over time, i.e. the disappearance of icteric forms, lower levels of enzymes activity ALT 2.3 (1.9-2.8) and 1.1 (0.8-1.3) mmol/l (p<0.001). At the same time an enhancement of dystrophic processes was seen in hepatitis patients having had more than 5 years of dialysis treatment as compared to patients with dialysis periods less than 5 years. This was observed for a decrease in patients’ weight; for a decrease of albumin levels 38.9 (38.6-39.3) and 41.1 (40.5-41.7), respectively (p<0.005); for total blood-protein 68.7 (68.2-69.2) and 70.0 (68.6-71.4) g/l, respectively (p<0,05); and for increase of interdialytic weight gain 3.9 (3.8-4.1) and 3.2 (3.0-3.3) kg, respectively (p<0.001).
In conclusion, a higher frequency of associated viral hepatitis B and C infection in patients treated by chronic haemodialysis was registered according to an increase of the treatment continuation which probably leads to morphological and functional changes in the liver. These changes can cause a dysfunction of the protein and hormones metabolism which may clinically manifest as hyperhydration, arterial hypertension, disposition to the cholestasis and haemorrhagic manifestations. As a result it can decrease the efficiency of haemodialysis. In the late stages of a haemodialysis the main clinical and biochemical indexes of a viral hepatitis C and B+C infection exacerbation were indicating to dystrophic changes, e.g. a reduction of the patient’s weight after dialysis, a decrease in the total protein and albumin level in blood and an increase of water retention.
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