Prevalence of hepatitis B virus MHR mutations and their correlation with genotypes and antiviral therapy in chronically infected patients in Serbia.

Understanding the prevalence and diversity of HBsAg variants in a population is fundamental to assay design and planning vaccination programs. It has been shown that mutations within the S gene, caused by selection or natural variation, can lead to false-negative results in assays for HBsAg, or have clinical implications, such as evading anti-HBV immunoglobulin therapy or vaccine-induced immunity. The region of HBsAg where most of these mutations occur is known as the major hydrophilic region (MHR). The aim of this study was to determine the prevalence and mutational patterns of MHR mutations in patients with chronic hepatitis B, and their correlation with patient characteristics, viral factors and antiviral therapy. The study comprised 164 plasma samples from patients with chronic hepatitis B, of which, 34.8% were on long-term lamivudine monotherapy. Direct sequencing of part of the S/pol gene was used for identification of HBsAg mutations, HBV genotypes, subgenotypes and HBsAg subtypes. The overall frequency of MHR mutations was 22.6%, but it varied significantly between untreated and treated patients (16.8% vs. 33.3%). The most frequent substitution was at position 120 (9.1%) whereas the most common vaccine-escape position, 145, was affected in 1.8% of isolates. The presence of MHR mutations was correlated with genotype D, subgenotype D3, and ayw2/ayw3 HBsAg subtypes and to older age (>40 years). It is concluded that natural viral variability present in a geographical region, duration of infection, and antiviral therapy are among the major factors associated with the occurrence of MHR mutations.

Acute hepatitis E in Montenegro: epidemiology, clinical and laboratory features.

OBJECTIVE: To evaluate the incidence, demographic, clinical and laboratory characteristics of patients with acute viral hepatitis E in Montenegro. MATERIAL AND METHODS: A total of 400 patients with acute viral hepatitis from January 1st, 2000 to December 31st, 2007 were enrolled in the study. Serological tests for hepatitis A, B, C, D, and E viruses, Epstein-Barr virus, cytomegalovirus, and herpes simplex viruses were performed. Standard laboratory tests for liver function were analyzed. The results are presented as absolute numbers, mean +/- SD, range of values, and percent. A P value < 0.05 was considered significant. RESULTS: Twenty-four (6%) patients had clinically and/or serologically confirmed acute hepatitis E. The mean age of the patients was 25 +/- 6 years; 62.5% were males. The majority of the patients (66%) belonged to the 20 to 40 yrs age group (P < 0.05). Seven patients were asymptomatic. Foremost symptoms were loss of appetite (100%), fatigue (94%) and vomiting (75%). The most frequent clinical sign was mild to moderate liver enlargement (94%). Jaundice had 12/17 symptomatic patients. Elevation of alanine aminotransferase was found in 19 patients including two patients without symptoms. The enzyme, gamma glutamyltranspeptidase was increased in all patients. CONCLUSION: Acute hepatitis E in Montenegro emerges as an autochthonous infection with a low incidence. Sub-clinical and anicteric infections may occur. Elevation of gamma glutamyltranspeptidase is an important parameter of the biochemical profile of the disease.

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.

Seroprevalence and risk factors for hepatitis C virus infection among blood donors in Serbia: A multicentre study.

BACKGROUND: The epidemiological characteristics of hepatitis C virus (HCV) infection have not yet been described in Serbia. AIMS: To determine the prevalence of anti-HCV-positive individuals among first-time blood donors and the risk factors for hepatitis C transmission. METHODS: A multicentre case-control study nested within a prospective cohort study was conducted at 10 main transfusion centres in Serbia in 2013 and 27,160 blood donors who gave blood for the first time were included. Blood donors with confirmed anti-HCV positivity and seronegative controls were enrolled to determine the risk factors. RESULTS: Of 27,160 blood donors 52 were anti-HCV-positive; seroprevalence was 0.19%. By univariate analysis, marital status, educational level, drug use, previous transfusion, tattooing, non-use of condoms and number of sexual partners, were risk factors for hepatitis C. In the final multivariate analysis, three factors remained independently predictive: drug use, tattooing and previous blood transfusion. In total, 87.5% of cases had at least one of the risk factors for HCV transmission; 20.9% presumed that they knew when the infection occurred. CONCLUSION: HCV seroprevalence in Serbia is higher than in developed European countries. Preventive measures need to be directed towards drug use and tattooing facilities. The admission questionnaire for blood donors should be improved.

The influence of single and combined IL28B polymorphisms on response to treatment of chronic hepatitis C.

BACKGROUND: Three single nucleotide polymorphisms (SNPs) near IL28B gene were shown to be highly predictive of sustained virological response (SVR) in patients with chronic hepatitis C virus (HCV) infection. OBJECTIVES: This study attempted to demonstrate the role of single and combined IL28B polymorphisms (rs8099917, rs12979860 and rs12980275) and other host and viral factors in predicting response to treatment, in Caucasian patients infected with HCV genotype 1. STUDY DESIGN: The IL28B genotypes at 3 SNPs were determined in 106 patients who underwent standard 48-week therapy and out of which 55.7% achieved SVR. RESULTS: Patients carrying genotypes CCrs12979860 or AArs12980275 were 3.5 and 3 times more likely to achieve SVR, respectively. Genotypes GGrs8099917 and TTrs12979860 were identified as predictors of treatment failure. The presence of IL28B profiles including at least one of the favourable genotypes was identified as the most important factor associated with SVR, followed by younger age and lower grade of histological activity. Of all patients who achieved SVR, 88.1% was carrying one of these IL28B profiles. The strongest PPV of single SNPs for achieving SVR was observed for CCrs12979860 (76.9%). The presence of GGrs8099917 showed the strongest NPV of 85.7%. The correlation of SNPs with other host and viral factors revealed association of TTrs8099917 and lower AST levels. CONCLUSIONS: Results of this study confirm that all investigated IL28B polymorphisms are associated with treatment response and that presence of any of the favourable IL28B genotypes can be considered independent pretreatment determinant of the effectiveness of therapy.

[Family outbreak of cryptosporidiosis in Serbia: case report].

INTRODUCTION: Cryptosporidiosis is an acute infectious parasitic disease of the gastrointestinal tract, considered as zoonosis underestimated in immunocompetent population. The pathogen is primarily the cause of devastating diarrhea in AIDS patients. Solitary cases and small outbreaks in immunocompetent persons are rarely discovered. There is also a human strain of cryptosporidium. CASE OUTLINE: In December 2010, we examined three family members among whom each successively developed acute gastroenteritis. Their stools were liquid, light brown, without mucus or blood. All of them had abdominal cramps and generalized muscle pains. The daughter had fever and vomited during the first two days. The patients were administered symptomatic therapy. Complaints resolved after 10-17 days, with general condition moderately changed. Cryptosporidium was confirmed in the stool of patients who were second and third to contract the disease. We presumed that the first person released pathogen before the time of examination, although she still had diarrhea. All of them recovered completely. By epidemiologic survey we were unable to presume with certainty the source of infection. CONCLUSION: This is the first description of cryptosporidiosis in immunocompetent individuals in Serbia, which proves that it is present in our country, and that search for it should be included into a routine parasitological check-up of stool. Taking into account the distance in onset time complaints, all combinations are possible; from infection among family members (shortest incubation period) to family members infected from an identical source (different incubation period). Negative finding of the sample collected on the 7th day from the beginning of symptoms does not exclude the diagnosis in this particular situation. Further epidemiologic studies of this disease are necessary as it is clear that it exists in our population. At that moment we were unable to do typization.

[Influence of depression on the quality of life in patients with chronic hepatitis C].

INTRODUCTION: Chronic hepatitis C reduces the quality of life in patients causing fatigue, loss of self-confidence, reduced working capacity, development of depression, emotional problems, and cognitive dysfunction. OBJECTIVE: The aim of the study was to identify the presence of depression in patients with chronic hepatitis C, predicting factors for its expression, and the impact of depression on the quality of life in these patients. METHODS: During the prospective study, we used the Hamilton depression scale to investigate the presence of depression, generic 36-Item Short Form Health Survey (SF-36) and Chronic Liver Diseases Questionnaire (CLDQ) to examine the quality of life in 100 patients with chronic hepatitis C, 30 patients with chronic hepatitis B, 30 patients with chronic liver disease nonviral aetiology and 50 healthy persons. RESULTS: A significantly higher presence of depression, and cognitive dysfunction in patients with chronic hepatitis C were noted as compared to the healthy individuals (p=0.00). In relation to non-viral patients with chronic liver disease, depression was significantly less present (p=0.004). Depression was rare in younger patients. The largest number of patients with chronic hepatitis C was without depression. The presence of depression caused deterioration of the physical and mental components of the quality of life. Multivariate analysis showed that the most significant positive predictive factor for the presence of depression was married life (B=0.278; SE=0.094; p=0.004). CONCLUSION: The presence of depression was more often in patients with chronic hepatitis C viral infection compared to healthy population and was correlated with decline in the quality of life. Depression is more pronounced in the elderly and intravenous drug addicts. The lowest depression is expected in patients who are not married.

[Quality of life in patients with chronic hepatitis C].

INTRODUCTION: Hepatitis C virus often causes chronic liver disease reducing physical, mental and social functions in these patients. OBJECTIVE: The aim of this investigation was analysis of the quality of life in chronic hepatitis C patients compared to patients with other chronic liver diseases and healthy population, as well as investigation of the influence of socio-demographic factors on the quality of life in patients with chronic hepatitis C. METHODS: A generic Short Form-36 (SF-36) questionnaire and Chronic Liver Diseases Questionnaire (CLDQ) were used in this prospective study for the investigation of the quality of life in 160 patients (100 patients with chronic hepatitis C, 30 patients with chronic hepatitis B, 30 patients with non-viral chronic liver diseases) and 50 healthy controls. RESULTS: Reduced quality of life was noted in patients with chronic hepatitis C patients in comparison with healthy controls (p = 0.00). Significant differences in SF-36 were found between patients with chronic hepatitis C and B regarding physical functions, activity, physical pain and emotional functions. Multivariate linear regression analysis revealed ages below 50 years as the most important positive variable in chronic hepatitis C patients for total score of the quality of life and physical component score (B = 14.5; SE = 5.16; p = 0.049; and B = 16.4; SE = 5.94; p = 0.003, respectively). The most important positive variable for the mental component of the quality of life was male gender (B = 15.3; SE = 5.81; p = 0.003). CONCLUSION: Quality of life is reduced in patients with chronic hepatitis C in comparison with healthy population. The quality of life in chronic hepatitis C patients is better than in patients with other non-viral chronic liver diseases. In comparison with patients with chronic hepatitis B, reduction in some domains of the quality of life is noted. Younger age is the most predictable group for the lowest damage of the total quality of life in patients with chronic hepatitis C patients among other sociodemographic characteristics of these patients.

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.

[The efficacy of lamivudine in the treatment of reactivation of chronic hepatitis B virus infection in patients on immunosuppressive therapy].

INTRODUCTION: Reactivation of chronic hepatitis B virus (HBV) infection often occurs in hepatitis B surface antigen (HBsAg) positive patients undergoing immunosuppressive or chemotherapy, but can also occur in HBsAg negative, anti-HB core positive patients. Treatment of HBV reactivation with lamivudin results in favourable outcome in the majority of patients. The aim of the authors was to show the effect of lamivudin therapy to HBV reactivation caused by immunosuppressive therapy. OUTLINE OF CASES: The first patient was a 35-year-old woman with chronic hepatitis B virus infection who underwent prednisolone therapy for pulmonal sarcoidosis. Four months after the beginning of the therapy she presented with jaundice and a significant increase in serum aminotransferase level. Liver biopsy showed chronic viral B hepatitis of strong activity in the stage of rapidly developed cirrhosis. The patient was treated with lamivudine with slow reduction of prednisolone doses, which resulted in full clinical and biochemical recovery. The second patient was a 40-year-old HBsAg negative female with a previous history of resolved acute B hepatitis who received chemotherapy for non-Hodgkin lymphoma. After the third cycle of chemotherapy a significant increase in aminotransferase level occurred, chemotherapy was discontinued, but aminotransferase level still increased. At that moment she was found to be HBsAg positive, and PCR analysis detected a high viral load. Lamivudine treatment resulted in the patient's recovery and allowed further chemotherapy. CONCLUSION: In case of the reactivation of chronic HBV infection during immunosuppressive therapy, it should be stopped and antiviral therapy should be immediately initiated. The use of lamivudine results in rapid suppression of serum HBV DNA, improves the outcome and enables the continuation of immunosuppressive and chemotherapy.

[Comparison of clinical and laboratory characteristics of viral hepatitis A and E in Montenegro].

INTRODUCTION: Hepatitis E has many similarities in with hepatitis A concerning clinical picture, route of transmission and nonexistence of chronicity. Comparison of clinical and laboratory parameters of patients with hepatitis A and E to estimate characteristics of these diseases. MATERIAL AND METHODS: Total of 54 patients divided into two groups was investigated: 27 had hepatitis A, others had hepatitis E. Detailed history past, clinical examination, liver function tests and ultrasonography of the upper abdomen, were done in all patients. Aetiology of viral hepatitis was investigated serologically by enzyme immunoassay (ELISA) using commercial kits for following viruses: Hepatitis A-E viruses, cytomegalovirus, and Epstein-Barr virus. RESULTS: Asymptomatic infections (29.6%) and clinical forms without jaundice (59.3%) were more frequent in patients with hepatitis E. Splenomegaly was found more frequent in patients with hepatitis A than in hepatitis E (66.7% vs. 33.3%). Patients with hepatitis E had significantly lower activity of aminotransferases than patients with hepatitis A. A significant increase of gamma-glutamyltranspeptidase was found in patients with hepatitis E (mean value: 120 IU/L). DISCUSSION: Our results are in concordance with other reports that hepatitis E virus infection is more common asymptomatic disease than hepatitis A. In addition, hepatocyte necrosis in hepatitis E is less extensive than in hepatitis A measured by the activity of aminotransferases. Contrary to that the value of gamma-glutamyltranspeptidase is more increased in hepatitis E than in hepatitis A without exact explanation so far: CONCLUSION: Viral hepatitis E and A have differences in some clinical features and laboratory parameters although both diseases principally have resolved without consequences after 6-8 weeks.

Epidemiological characteristics and clinical manifestations of acute non-A-E hepatitis.

BACKGROUND/AIM: Acute non-A, non-B, non-C, non-D, non-E hepatitis (non-A-E AH) is an acute disease of the liver of unknown etiology for which one or more new, so far undetected, hepatotropic viruses may be responsible. The frequency of non-A-E AH ranges from 3.8% to 33.9%, and therefore it has a significant place within current infectology and hepatology. The aim of our study was to establish the frequency, clinical and biochemical characteristics, natural course and outcome of non-A-E AH and compare them with control groups affected by acute viral hepatitis A, B and C. METHODS: This descriptive-analytic prospective study included 31 patients with non-A-E AH treated at the Institute of Infectious and Tropical Diseases, Clinical Center of Serbia, Belgrade, from 2003 to 2008. They were followed up during the period not less than 6 months. The controls involved randomly selected patients, treated at the same time with a definite diagnosis of acute viral hepatitis A, B and C. Statistical data analysis used Mann-Whitney U-test, Student's t-test and variance analysis. The value of p < 0.05 was considered statistically significant. RESULTS: The frequency of non-A-E AH was 7.6%. Almost no difference was found between sexes (male/female ratio was 1:1.07); it was developed in all age groups, with the highest incidence in the middle age (mean age was 38.32 +/- 15.3 years). It appeared equally throughout the whole year. Out of risk factors, inoculation risk was predominant (before all, dental interventions), mostly involving urban population living in comfortable conditions. The duration of incubation varied much ranging from 20 to 180 days (median 60 days). By clinical course, moderate and icteric forms were most common, mostly corresponding to acute hepatitis A and C. On the other hand, by duration of the disease (mean duration was 67.1 +/- 27.1) and chronic transformation, non-A-E AH resembled to acute hepatitis B. Progression to chronicity was recorded in 9.68% of the patients. There was no fulminant neither cholestatic form of the disease. CONCLUSION: Based on the results obtained in this study, it is probable that there are some so far undetected primary hepatotropic viruses in our environment.

Treatment of subacute hepatitis B with lamivudine: a pilot study in Serbia.

BACKGROUND/AIM: The incidence of acute hepatitis B viral (HBV) infection in adults has increased in recent years in Serbia. Most icteric patients with acute hepatitis B resolve their infection and do not require treatment. Fulminant hepatitis B is a severe form of acute infection complicated by encephalopathy and liver failure. Subgroups of fulminant hepatitis B including hyperacute, acute and subacute are defined by the interval between jaundice and encephalopathy. Fulminant hepatic failure or subacute hepatitis B infection we observed in about 1% of all cases. In cases of fulminant hepatic failure or subacute form of HBV infection orthotopic liver transplantation can be life-saving operation, but in our country this procedure is difficult to achieve. Lamivudine has been established as a safe and effective antiviral agent for the treatment of chronic HBV hepatitis. METHODS: In our pilot study performed at the Institute of Infectious and Tropical Diseases in Belgrade, Serbia in the period between 2002 and 2006 we treated 10 patients with clinically verified subacute HBV infection with lamivudine, 100 mg orally per day. RESULTS: The most of the treated patients (9/10; 90%) survived subacute form of hepatitis B. After a few weeks of the treatment serum aminotransferase levels and other liver-function tests were normalized. Also, after a four-month lamivudine treatment all the patients lost HBsAg. Lamivudine was discontinued after six months in all the patients. In addition, six months after lamivudine was discontinued the patients remained well with normal results on liver-function tests. CONCLUSION: The obtained results suggest significant efficacy of lamivudine in patients with subacute hepatitis B. Also, we suggest that lamivudine therapy should be administered early in progression of subacute disease since it could be life-saving treatment in some patients, especially in the countries (like Serbia) where orthotopic liver transplantation is difficult to achieve.

Reduced quality of life in patients with chronic viral liver disease as assessed by SF12 questionnaire.

BACKGROUND & AIM: Quality of life may be reduced in patients with chronic liver diseases. The purpose of this study was to assess the impact of chronic viral liver disease on health-related quality of life (HRQOL). PATIENTS AND METHODS: Quality of life was prospectively investigated in 227 patients with chronic viral liver disease and 75 controls. The generic Short Form 12 questionnaire was applied to measure the HRQOL: Mental and physical component scores were expressed as numeric and categorical values (presence/absence of disability). The electronic database (SPSS for Windows) was used for statistical analysis with 95% confidence intervals. RESULTS: Mental and physical numeric and categorical scores for the absence of disability were significantly worse in patients compared with controls. Patients were a negative predictive factor for the absence of disability on both mental and physical components while the physical component was the significant factor in multivariate regression analysis (p =0.000). There was no difference in HRQOL scores among patients with hepatitis C or B virus infection. Mental and physical numeric scores were lower in patients with cirrhosis. Liver cirrhosis predicted lower components of the absence of disability in comparison to chronic hepatitis more influencing the physical component (p =0.003). CONCLUSIONS: Chronic viral liver disease reduces and predicts a lower quality of life in comparison to a healthy population impairing more the physical component. Hepatitis viruses do not influence differently the quality of life. Liver cirrhosis has a higher negative impact on the quality of life than chronic hepatitis, especially relating to a physical component.

Liver enlargement associated with opportunistic infections in patients with human immunodeficiency virus infection.

BACKGROUND AND AIM: Liver disease is commonly present in human immunodeficiency virus (HIV) infection. The aim was to determine the frequency of liver enlargement and its association with opportunistic infections in patients with HIV infection. PATIENTS AND METHODS: A total of 400 HIV-infected patients were investigated. Commercial kits (Ortho EIA; BioRad, ELISA) were used for detection of serum specific antibodies to HIV, hepatitis C virus, surface antigen of hepatitis B virus, and cytomegalovirus. Liver tissues were stained for various microorganisms. The electronic data base SPSS for Windows (version 10.0) was used for statistical analysis. A p <0.05 was considered significant. RESULTS: Ultrasonographic screening revealed liver enlargement in 63.75% of HIV patients. In 40.7% the right lobe size varied from 140 mm to 160 mm. Of those with hepatomegaly, 60.7% had AIDS. Hepatitis C and B viruses and Mycobacterium tuberculosis were detected in 50%, 29% and 18% of patients, respectively. Histological changes were mostly non-specific. Liver pathology depended on the degree of cellular immune deficiency, particularly in patients with HBV co-infection. In a minority of patients (32.5%), the histology revealed granulomatous hepatitis. Liver function tests were abnormal in 46%. CONCLUSION: Liver enlargement is common in HIV-infected patients mostly in association with hepatitis C and B viruses and Mycobacterium tuberculosis.

[The role of interferon in the treatment of acute hepatitis C].

INTRODUCTION: Progression from acute to chronic HCV infection occurs in 50% to 84% of cases. Even the latest approach--combination therapy with pegilated interferon alfa 2-a or 2b and ribavirin--eliminates the virus in only 54% to 56% of cases with chronic infection. The aim of this study is to determine whether treatment during the acute phase prevents the development of chronic infection. MATERIAL AND METHODS: Between 2001 and 2004, 27 patients with the diagnosis of acute hepatitis C were treated at the hepatology Department of Institute of Infectious and Tropical Diseases. Among them, 19 were treated with recombinant interferon alfa 2-a. Acute hepatitis C was defined by clinical and laboratory test results and by exclusion of other causes of acute liver disease. RESULTS: The mean age of our patients was 32.7 years, whereas the mean incubation time was 61.7 days. The mean serum aminotransferase levels were 1119 U/l and the mean total bilirubin levels were 106 mmol/l. At the end of therapy, 81.8% of patients had undetectable levels of HCV RNA, but 94.7% of patients had normal serum alanine aminotransferase levels. At the end of folow up, 84.6% of patients had normal alanine antimiransferase levels and 83.3% of patients had undetectable levels of HCV RNA. One patient had undetectable antibody to HCV the end of follow-up. CONCLUSION: The results reported here demonstrate that in the acute phase of HCV infection, interferon treatment is associated with a high rate of virological and biochemical response. We concluded that early treatment of acute heptitis C may prevent chronic hepatitis C.

[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.