Characteristics of patients dying from acute viral hepatitis in Serbia.

BACKGROUND/AIMS: Acute viral hepatitis is complicated rarely with severe liver failure due to many factors associated with the etiology, patient age, and time of development of hepatic encephalopathy, etc. The aim of this study was to identify some of the clinical and laboratory features associated with a fatal outcome in patients dying from acute viral hepatitis in Serbia. METHODS: Clinical and laboratory data from 47 patients hospitalized from January 1989 December 2006 were reviewed retrospectively. Serological tests for hepatitis A, B, C, D, and E viruses, herpes simplex viruses, cytomegalovirus, and Epstein-Barr virus were done. Histological features were assessed from 35 liver tissues. The electronic base, SPSS for Windows (version 11.0), was used for statistical analysis. RESULTS: The majority of the patients had alanine aminotransferase (ALT) >20x the normal value, serum bilirubin >300 µmol/L, prothrombin time >25 seconds (s), and white blood cell count >12 x 10(9)/L. Regression analysis revealed activity of alanine aminotransferase >20x the normal value to be associated with fulminant (p=0.015) and serum bilirubin concentration with subfulminant hepatitis (p=0.008). Hepatitis B virus was the most commonly detected virus (70%). Massive hepatocyte necrosis vs. sub-massive with bridging necrosis were found to be independent of clinical presentation. CONCLUSIONS: Hepatitis B virus infection, severe impairment of liver function tests, and confluent hepatocyte necrosis and infection characterize patients dying from acute viral hepatitis in Serbia. High activity of alanine aminotransferase reflects rapid and extensive acute viral liver injury, while deep jaundice is more common in a protracted course of the disease.

Systemic manifestations in the course of meningococcal disease.

BACKGROUND/AIM: Meningococcal disease most often manifests itself as meningitis or sepsis. During the course of these diseases, other clinical events sometimes develop such as pneumonia, pericarditis, arthritis, and they are referred to as extrameningeal or systemic manifestations of the meningococcal disease. The aim of this study was to investigate the type and the incidence of particular extrameningeal/systemic manifestations among patients with meningococcal meningitis and sepsis, including time of their onset and the influence on the disease outcome. METHODS: The retrospective study of the medical records of 246 patients treated for meningococcal disease over the 25-year period in the Institute for Infectious and Tropical Diseases, Belgrade was conducted. The patients, aged 3 months to 82 years both sexes, were divided into two groups. RESULTS: Out of 246 patients extrameningeal/systemic manifestations were found in 42 (17.1%) patients: 35 (14.2%) occurred during meningitis, and seven (2.8%) during sepsis. Pulmonary manifestations (mostly pneumonia) were the most prevalent, found in 12 (4.9%) patients, followed by heart involvement in nine (3.6%) patients (mostly pericarditis, in seven or 2.8% patients). Various ophthalmic manifestations occurred in seven (2.8%), arthritis in 4 (1.6%) and sinusitis in six (2.4%) patients. Otitis, multiple renal embolisms with hematuria, osteomyelitis and thrombophlebitis were evidenced in one patient, each. Most of the systemic manifestations (30 patients or 71.4%), developed within the initial three days of the disease (p < 0.01), suggesting direct pathogenic mechanism induced by meningococci per se, while only three (7.1%) developed after seven days, when immune-mediated disease was more likely. Even though these manifestations complicate and prolong treatment of the meningococcal disease, they had no major influence on the disease outcome. Lethal outcome occurred in 2 (4.76%) patients, both with the meningococcal type of the disease. CONCLUSION: Extrameningeal or systemic manifestations are uncommon complications during the course of both meningococcal meningitis and sepsis. The onset of pneumonia, pericarditis, eye involvement, and arthritis, within the initial seven days of the disease, were most prevalent in the course of meningitis. They had no major influence on the disease outcome.

[The frequency of pathological ultrasonographic findings of the gallbladder in patients with infectious diseases].

INTRODUCTION: The objective of our study was to establish, through retrospective analysis of sonographic findings obtained by portable ultrasound devices, the frequency of pathological findings of the gallbladder and common bile duct in a randomized group of patients with infectious diseases. MATERIAL AND METHODS: During five years (January 1, 2000 - December 31, 2004), gallbladder and common bile duct were examined by ultrasonography in 2691 adult patients (1440 males and 1251 females), mean age 48 +/- 17 years, ranging from 17 to 92 years at the Institute of Infectious and Tropical Diseases in Belgrade. The examination included the measurement of size and shape of the gallbladder, its wall and lumen, as well as measurement of caliber and content of the common bile duct. Conventional portable ultrasound devices, ALOKA SSD-500 and SSD-1000 (B-mod) with convex 3.5 and 5 MHz probes were used. RESULTS: The cholecyst was normal in size (<120 x 50 mm) in 2164 (80.4%), and enlarged in 65 (2.4%) patients. The gallbladder was surgically removed in 163 (6.1%) patients, it was pseudoseptal in 141 (5.2%) and invisible in 44 (1.6%) patients. The gallbladder wall was normal in 2031 (75.5%), thickened in 259 (9.6%) and edematous in 173 (6.4%). Gallbladder calculosis was present in 310 (11.5%), and choledocholithiasis in 13 (0.5%) patients. CONCLUSION: Development of morphological abnormalities of the gallbladder and common bile duct was frequent in non-selected patients with infectious diseases. The majority of them may be detected by portable ultrasound devices, which makes them rather applicable for large clinical-epidemiological studies.

Hepatitis C virus genotypes in Serbia and Montenegro: the prevalence and clinical significance.

AIM: To investigate the prevalence of hepatitis C virus (HCV) genotypes in Serbia and Montenegro and their influence on some clinical characteristics in patients with chronic HCV infection. METHODS: A total of 164 patients was investigated. Complete history, route of infection, assessment of alcohol consumption, an abdominal ultrasound, standard biochemical tests and liver biopsy were done. Gene sequencing of 5' NTR type-specific PCR or commercial kits was performed for HCV genotyping and subtyping. The SPSS for Windows (version 10.0) was used for univariate regression analysis with further multivariate analysis. RESULTS: The genotypes 1, 2, 3, 4, 1b3a and 1b4 were present in 57.9%, 3.7%, 23.2%, 6.7%, 6.7% and 1.8% of the patients, respectively. The genotype 1 (mainly the subtype 1b) was found to be independent of age in subjects older than 40 years, high viral load, more severe necro-inflammatory activity, advanced stage of fibrosis, and absence of intravenous drug abuse. The genotype 3a was associated with intravenous drug abuse and the age below 40. Multivariate analysis demonstrated age over 40 and intravenous drug abuse as the positive predictive factors for the genotypes 1b and 3a, respectively. CONCLUSION: In Serbia and Montenegro, the genotypes 1b and 3a predominate in patients with chronic HCV infection. The subtype 1b is characteristic of older patients, while the genotype 3a is common in drug abusers. Association of the subtype 1b with advanced liver disease, higher viral load and histological activity suggests earlier infection with this genotype and eventually its increased pathogenicity.

Older age at the time of liver biopsy is the important risk factor for advanced fibrosis in patients with chronic hepatitis C.

BACKGROUND/AIMS: Progression of chronic hepatitis C depends on the host and viral characteristics, duration of infection, co-infection with other viruses, etc. In this study, some of demographic, epidemiological and viral data as risk factors for a degree of liver fibrosis were evaluated. METHODOLOGY: A total of 144 patients was investigated (89 males, ages from 16-65 years) classified into two groups, with fibrosis scores 0-3 and 4-6, using the Ishak scoring system. Significant variables were entered into univariate logistic regression model and further multivariate analysis was performed. RESULTS: There were 64% and 36% of patients with fibrosis scores 0-3 and 4-6, respectively. Gender, moderate to heavy alcohol abuse and high viral RNA were equally distributed between both groups. In univariate analysis, the age older than 40, history of intravenous drug abuse, and the genotype 1b were independently associated with different fibrosis scores. Multivariate regression analysis revealed ages older than 40 as the positive (p < 0.001), and younger than 40 as the negative predictive factors for fibrosis scores 4-6 and 0-3 (p < 0.001), respectively. CONCLUSIONS: Our results indicate the age over 40 at the time of liver biopsy as the important risk factor for advanced liver disease in chronic hepatitis C according to fibrosis scores.

Histopathology of chronic hepatitis C in relation to virus genotype.

BACKGROUND/AIM: The natural history of hepatitis C virus (HCV) infection is variable and the factors determining the course of the illness are unclear. There are geographical variations in the distribution of different HCV genotypes, and some of them are related to the specific infection routes. Regarding our country, the dominant genotype is genotype 1b. It is unclear and still remains a question whether the distinct histopathological manifestations are related to the particular genotypes of HCV. Thus, the aim of this study was to determine whether the distinct histopathological manifestations of HCV infection might be in relation to the individual virus genotype. METHODS: In this study we examined 126 patients with chronic HCV infection regarding the histopathological features, demographic data, and virus genotype. The observed groups of patients were predominantly infected with HCV genotypes 1b and 3a. RESULTS: In this study we found that the patients infected with HCV genotype 1b had more frequently moderate or severe necroinflammatory activity of the disease, significantly higher grading score as compared with other genotypes (p < 0.0001). A higher degree of fibrosis was, also, more common in the patients infected with genotype 1b of HCV as compared with other genotypes (p < 0.05). There were no significant correlations between the necroinflammatory activity of the disease and the stage of fibrosis in 1b, 4 and mixed genotypes. CONCLUSION: The present data support the hypothesis that distinct genotypes of HCV are associated with the particular histopathological manifestation of the disease.

[Chronic hepatitis C virus infection: is there a correlation between HCV genotypes and the level of viremia?].

INTRODUCTION: Hepatitis C virus (HCV) RNA status and HCV genotypes have become extremely important for exact diagnosis, prognosis, duration of treatment and monitoring of antiviral therapy of chronic HCV infection. MATERIAL AND METHODS: For the purpose of precise and objective assessment of virologic analyses, such as the determination of the number of virus copies and virus genotypes, 110 patients with chronic HCV infection were tested Genotyping of HCV isolates and HCV RNA quantification were performed by using the PCR method. Genotype 1b infection was verified in 49.1% of patients, genotype 3a infection was found in 28.2%, genotype 4 in 9.1%, genotype 2 in 4.5%, while mixed genotype infections were diagnosed in 9.1% of cases. RESULTS: Patients infected by genotype 1b had significantly higher serum HCV RNA level in relation to patients infected by other genotypes (p < 0.05). Over 70% of patients infected by genotype 1b had more than 2 x 10(6) virus copies in 1 ml of blood, while in genotypes 2, 3a and 4, the percentage was 40%, 38.5% and 30%, respectively. Male patients had approximately 7.7 x 10(6) virus copies in 1 ml of blood, which was significantly higher in comparison with female patients (2.3 x 10(6) copies/ml; p < 0.05). CONCLUSION: Our results are in concordance with the results of other authors reporting that genotype 1b is predominant in Europe, as well as significantly higher incidence of viremia in patients with genotype 1b infection in relation to other HCV genotypes. Based on these results, we can conclude that our patients, most commonly, present with severe clinical course of chronic HCV infection and require longer treatment (48 weeks), which causes economic problems.

[Abnormal ultrasonographic findings of the kidneys obtained with a portable echosonographic device in the patients with infectious diseases--a five-year study].

BACKGROUND/AIM: Ultrasonographic kidney changes might be a part of the clinical picture, or consequence of the various infections diseases. The aim of this study was to establish ultrasonographic findings obtained by portable devices, the frequency of abnormal findings of the kidneys in the non-selected group of the patients with infections diseases. METHODS: Over a five-year period (January 1, 2000-December 31, 2004), the kidneys were examined by ultrasonography in 2,718 patients, 1,452 males and 1,266 females, mean age 47.52 +/- 17 years, (16-92 years). The examination included the measurement of the size of the kidneys, evaluation of the condition of parenchyma and pyelo-calix, detection of simple cysts, calculi and tumor. The conventional portable ultrasonographic devices ALOKA SSD-500 and SSD-1000 (B-mode) with a convex 3.5 and 5 MHz sonde were used. RESULTS: The size of kidneys was normal in 95% of the patients, while they were enlarged in 1.3% and reduced in 1.5% of the patients. A normal ultrasonographic recording was noted in 68.9% of the patients, double pelvis in 0.1%, while hydronephrosis was revealed in 0.9% of the patients. A reduced renal parenchyma was observed in 16.1% of the patients. Nephrolithiasis was found in 10.9% of the patients, and simple cysts of kidneys in 8.9% of the patients. The finding of polycystic kidneys was seen in 0.5% of the patients. An ultrasonographic recording of angiomyolipoma was noted in 0.4% of the patients, and the finding of other tumors in 0.1% of the patients. Adrenal tumors were found in 0.1% of the patients. CONCLUSION: Portable ultrasonographic units may be highly useful for the standard morphological diagnostics of renal changes during infections, as well as in clinical-epidemiological studies and screening of hereditary and the acquired diseases of this organ.

[Effects of interferons on hepatitis C virus infection].

INTRODUCTION: The consequences of hepatitis C virus infections (chronic hepatitis, liver cirrhosis and hepatocellular carcinoma) are one of the major problems in clinical medicine. The persistence of infection in spite of high specific antibody titre suggests that the virus has the abillity to "escape" the immunological response. INTERFERON THERAPY: Interferons are important components of the early host response to infection. They have antiviral, antiproliferative, and immunomodulatory activities. Many viruses have developed the ability to "annul" or alleviate the action of interferon by preventing its synthesis or by interfering with signaling pathways in the cells. During acute infection some of the non-structural proteins of HCV block regulatory factors that are responsible for the synthesis of endogenous infection. Within a cell, interferon induces a number of genes to produce proteins that prevent virus replication. Among them, the most important are RNA-dependent protein kinase and the eukaryotic initiation factor. However, viral proteins, especially viral envelope proteins and nonstructural protein 5A, prevent their phosphorylation and activation which enhance virus replication. These are the facts that have to be considered when using IFN in chronic hepatitis C patients.

[Treatment options for chronic hepatitis C virus infection].

INTRODUCTION: The incidence of chronic hepatitis C virus (HCV) infection is rather high. Its most frequent consequences are chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. TREATMENT OF CHRONIC HCV INFECTION: In treatment of chronic HCV infection, interferons have antiviral, anriproliferative, and immunoregulatory action. Within the cell, they induce protein synthesis, inhibiting viral replication. The most important among them are RNA dependent protein kinase, and eukaryotic initiation factor. However, viral proteins prevent their phosphorylation and activation. In order to overcome this problem, treatment is prolonged, higher doses of lFN are used, as well as induction therapy. The optimal period for viral response is 52 weeks, while induction therapy has shown controversial results.