Risk score based PEG Interferon alpha 2b and Ribavirin treatment response estimation model for genotype 1 chronic hepatitis C patients.

PURPOSE: Attempt to create simple practical algorithm for prospective assessment of PEG interferon/ribavirin related treatment response in individuals with chronic hepatitis C (CHC) basing on the risk factors defined prior to the treatment initiation. MATERIAL/METHODS: Retrospective assessment of 45 female and 39 male previously untreated CHC patients aged 20 to 73 years, with genotype 1, undergoing standard treatment with PEG-IFNa2b+RBV was performed. For the final analysis 78 patients were included (38 effectively treated and 40 treatment failures). Thirty-six sustained virological response (SVR) related factors, which were routinely measured before treatment initiation were compared (including physical, biochemical, serologic and histopathologic). From this group the risk factors of the highest predictive value for treatment failure were selected. Cut-off values for statistical significance were defined for each parameter, with risk score (RS) calculated and compared in the group with and without SVR. RESULTS: Seven factors related to treatment failure were identified: HCV>600000 IU/L, blood platelet count <150000/ul, GGTP>45 IU/ml, total serum protein<7.8 g/dl, glycaemia>105 mg/dl, detectable HBc IgG antibodies and cirrhosis. In the group with RS 1 the likelihood of SVR was 70% (p<0.028), while in patients with RS 3 the response was reduced to 23.8% (p<0.016), with no SVR achieved among patients with RS >3. CONCLUSIONS: Low risk score (0-2) is associated with high probability of treatment success with scores >3 predictive for treatment failure. The presented model is a simple tool for prediction of treatment success for clinical use before PegIFN/RBV treatment initiation among genotype 1 CHC patients.

Introduction of pharmacogenetic screening for the human leucocyte antigen (HLA) B*5701 variant in Polish HIV-infected patients.

OBJECTIVE: Prospective pharmacogenetic screening for the human leucocyte antigen (HLA) B*5701 allele can significantly reduce the number of cases of abacavir-related hypersensitivity among HIV-infected patients treated with this drug. The aim of this study was to establish the frequency of the HLA B*5701 variant in HIV-infected Poles. METHODS: The sequence-specific primer (SSP) test was used to assess the feasibility of the introduction of such testing in clinical practice. For this purpose, 234 randomly selected HIV-positive patients were screened using a low-resolution SSP assay, with HLA B*5701-positive results confirmed using a high-resolution test. RESULTS AND CONCLUSIONS: The HLA B*5701 variant was found in 11 of 234 subjects (4.7%). Testing with the selected method proved quick and reliable.

Sequence variants of chemokine receptor genes and susceptibility to HIV-1 infection.

Genetic susceptibility to HIV infection was previously proven to be influenced by some chemokine receptor polymorphisms clustering on chromosome 3p21. Here the influence of 5 genetic variants was studied: Delta32 CCR5, G(-2459)A CCR5, G190A CCR2, G744A CX3CR1 and C838T CX3CR1. They were screened in a cohort of 168 HIV-1 positive adults [HIV(+) group] and 151 newborns [control group] from northwestern Poland. PCR-RFLP was performed to screen for the variants (except for Delta32 CCR5 polymorphism, where PCR fragment size was sufficient to identify the alleles) and then electrophoresed on agarose gel to determine fragment size. Distribution of genotypes and alleles was not significantly different between the groups except for the CCR5 polymorphisms, with the Delta32 allele and the (-2459)A CCR5 allele more frequent among neonates than in the HIV(+) group. No Delta32/Delta32 homozygotes were found in the HIV(+) group, but 16.1 percent were Delta32/wt heterozygotes. In the control group, 1.3 percent; were Delta32/Delta32 homozygotes and 26.0percent were Delta32/wt heterozygotes. Linkage between the chemokine polymorphisms was calculated using the most informative loci for haplotype reconstruction. Haplotypes containing Delta32 CCR5, 190G CCR2 and 744A CX3CR1 were found to be significantly more common in the control group. This suggests an association between these haplotypes and resistance to HIV-1 infection.

Pharmacokinetic parameters of nevirapine and efavirenz in relation to antiretroviral efficacy.

Optimal adherence is essential for successful antiretroviral therapy. We analyzed the relation between minimum plasma drug concentration (Cmin) and total drug exposure over 24 hr (AUC24) with virologic failure for therapy-adherent patients in the nevirapine (NVP) and efavirenz (EFV) groups of the double nonnucleoside study (2NN), which compared the efficacy of NVP and/or EFV together with stavudine and lamivudine. The objective was to find cutoff values of the Cmin and AUC24 below which the risk of virologic failure increased. The relation between Cmin and AUC24 with virologic failure (never a plasma viral load [pVL] < 50 copies/ml or a rebound to two consecutive pVL > 50 copies/ml) was analyzed with proportional hazard analyses. Data were censored at end of study or change of allocated treatment. The risk of virologic failure with NVP (n = 511) started to increase at a Cmin < 3.1 mg/L (hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.89-1.97), but there was no cutoff value below which a statistically significant increased risk occurred. Neither was such a cutoff point identified for the AUC24. The risk of virologic failure with EFV (n = 312) was significantly increased at a Cmin < 1.1 mg/L (HR, 1.95; 95% CI, 1.08-3.54) and an AUC24 < 40 mg x hr x L1 (HR, 1.95; 95% CI, 1.07-3.54). Both cutoff values represent the median values for adherent patients. These associations were driven by patients from Thailand. Adjusting for geographical region made the association between Cmin and AUC24 with virologic failure statistically nonsignificant. The sensitivity of the Cmin values was too low (29% for NVP, 64% for EFV) to be an adequate predictor for virologic failure. We conclude that identifying the Cmin value for the sole purpose of predicting virologic failure in patients who report to be adherent to NVP or EFV is questionable because of the absence of a concentration-response relation (NVP) or the low sensitivity for such a cutoff value (NVP and EFV).

Reasons for stopping antiretrovirals used in an initial highly active antiretroviral regimen: increased incidence of stopping due to toxicity or patient/physician choice in patients with hepatitis C coinfection.

Low adherence and toxicities among HIV-positive patients starting highly active antiretroviral therapy (HAART) can lead to discontinuation of therapy and treatment failure. Little is known about hepatitis C (HCV) status and discontinuation of HAART. Poisson regression was used to determine factors related to discontinuation of any part of an initial HAART regimen due to treatment failure (TF) or toxicities and patient/physician choice (TOX), and to investigate the relationship between HCV and discontinuation of a HAART regimen in 1198 patients staring HAART after 1999 from the EuroSIDA study. At 1 year after starting HAART, 70% of patients remained on their original regimen, 24% had changed, and 6% were off all treatment. The most frequent reason for discontinuation was toxicities (30.4%). There was no change over time in the proportion of patients discontinuing after stratification by reason for discontinuation (p = 0.18). Of patients 190 stopped at least one antiretroviral drug used in their initial HAART regimen due to toxicities; the toxicity reported did not vary according to HCV status (p = 0.90). Anti-HCV seropositive patients had a higher incidence of discontinuation due to TOX (IRR 1.46, 95% CI 1.13-1.88, p = 0.0042) compared to patients without HCV. Patients with HCV were more likely to discontinue all or part of their HAART regimens due to toxicity or patient/physician choice. Managing adverse events must remain a key intervention in maintaining HAART. There is a need for further studies to describe the relationship between HCV, specific antiretrovirals, and different treatment strategies.

Reasons for stopping antiretrovirals used in an initial highly active antiretroviral regimen: increased incidence of stopping due to toxicity or patient/physician choice in patients with hepatitis C coinfection.

Low adherence and toxicities among HIV-positive patients starting highly active antiretroviral therapy (HAART) can lead to discontinuation of therapy and treatment failure. Little is known about hepatitis C (HCV) status and discontinuation of HAART. Poisson regression was used to determine factors related to discontinuation of any part of an initial HAART regimen due to treatment failure (TF) or toxicities and patient/ physician choice (TOX), and to investigate the relationship between HCV and discontinuation of a HAART regimen in 1198 patients staring HAART after 1999 from the EuroSIDA study. At 1 year after starting HAART, 70% of patients remained on their original regimen, 24% had changed, and 6% were off all treatment. The most frequent reason for discontinuation was toxicities (30.4%). The incidence of any discontinuation was significantly lower after 1999 compared to before [incidence rate ratio (IRR) 0.43; 95% CI 0.35-0.53, p < 0.0001], this pattern was most marked for toxicities (IRR 0.28; 95% CI 0.20-0.39, p < 0.0001) and patient/physician choice (IRR 0.49; 95% CI 0.33-0.73, p < 0.0001). Patients with HCV had a higher incidence of discontinuation due to TOX (IRR 1.46, 95% CI 1.13-1.88, p = 0.0042) compared to patients without HCV. Patients with HCV were more likely to discontinue all or part of their HAART regimens due to toxicity or patient/physician choice. Managing adverse events must remain a key intervention in maintaining HAART. There is a need for further studies to describe the relationship between HCV, specific antiretrovirals, and different treatment strategies.

Natural history of acute symptomatic hepatitis type C.

BACKGROUND: Spontaneous clearance of hepatitis C virus (HCV) after acute hepatitis C, and the course of chronic HCV infection in patients who did not clear the virus, were studied. PATIENTS AND METHODS: Patients with acute C or non-A, non-B hepatitis who were hospitalized between 1988 and 1998 were called for evaluation in 2001. They were tested for anti-HCV, serum HCV-RNA, HCV-RNA in peripheral blood mononuclear cells (PBMC) and liver enzymes. A liver biopsy was performed on chronically infected patients. The course of acute hepatitis C was compared between HCV-RNA-positive and negative subjects to look for factors that might influence spontaneous viral clearance. Factors influencing more progressive liver disease were analyzed in chronic hepatitis C. RESULTS: Out of 159 acute hepatitis C patients, 77 (48.4%) participated in the study, and the median observation time was 8 years. Spontaneous clearance of serum HCV was found in 23 subjects (29.9%), but in two cases HCV-RNA was detected in peripherical blood mononuclear cells (PBMC). Only three patients negative for HCV-RNA in serum and PBMC lost anti-HCV. Severity of acute HCV infection and previous alcohol abuse seemed to influence resolution. In non-alcoholic patients, older age at time of primary infection was a significant predictor of virus clearance. In chronic hepatitis C, more than 75% of patients had minimal or mild activity in biopsy, but 40% had advanced fibrosis. Older age at infection, male gender, alcohol abuse, and higher iron content were connected with advanced fibrosis. CONCLUSION: Studies on HCV infection resolution should include at least PBMC testing for HCV-RNA. A healthy carrier state of HCV can be discussed. A longer observation time increased the likelihood of seroreversion. Fibrosis in chronic hepatitis C probably is not a direct result of inflammatory activity.

Serum iron parameters in patients with alcoholic and chronic cirrhosis and hepatitis.

BACKGROUND: The aim of our study was to asses the serum iron status of patients with various forms of hepatitis and cirrhosis of the liver and to determine the correlation between the degree of hepatocyte damage and the status of serum iron parameters. MATERIAL AND METHODS: The study involved 136 subjects with chronic viral hepatitis type C (group I, n=71) and type B (group II, n=29), alcoholic cirrhosis of the liver (group III, n=15), postinflammatory cirrhosis of the liver (group IV, n=13), and alcoholic hepatitis (group V, n=8). In all these patients, serum alanine (ALT) and aspartate (AST) aminotransferase activity were used as a secondary measure of necroinflammatory activity. The serum iron status measurements included iron concentration (Fe), total iron-binding capacity (TIBC), transferrin saturation, and ferritin concentration. RESULTS: Our study results led us to conclude that the mean value of serum iron concentration did not differ significantly among the analysed groups (p>0.05). The transferrin value - estimated as the total iron-binding capacity (TIBC) - was significantly lower in alcoholic cirrhosis of the liver in comparison to both chronic hepatitis C (p<0.004) and chronic hepatitis B (p<0.04). The transferrin saturation was statistically the higher in group III in comparison with both group I (p<0.0031) and group II (p<0.024). Serum ferritin was significantly higher in cirrhotic patients regardless of etiology, in comparison with patients with chronic viral hepatitis (p<0.045). We found correlation between an increase of both AST and ALT and a higher level of ferritin in patients with chronic hepatitis type C (p<0.005, p<0.02) and type B (p<0.05, p<0.03) and alcoholic hepatitis (p<0.05). CONCLUSIONS: In the course of chronic liver diseases we may observe slight irregularities in iron status relating to both the serum and store pool of this element. The most significant disturbances are seen in patients with alcoholic cirrhosis of the liver.

[Autoimmune hepatitis: pathogenesis, clinical features and treatment]. / Autoimmunologiczne zapalenie watroby: patogeneza, obraz kliniczny i leczenie.

Autoimmune hepatitis (AIH) is a chronic liver disease of unknown etiology. The incidence of AIH keeps rising, most probably because of increasing availability of the diagnostic tools permitting thorough differential diagnosis amongst liver diseases presenting histologically as chronic active hepatitis. In this review we focus on clinical aspects of autoimmune hepatitis and discuss pathogenesis, clinical features and treatment of AIH.

Parasitic cysts of the liver - practical approach to diagnosis and differentiation.

BACKGROUND: The aim of the study was to determine the incidence of parasitic liver cysts. MATERIAL AND METHODS: In 1996-2000 at the Department of Infectious Diseases parasitic liver cysts were diagnosed in 31 patients. The diagnosis was based on imaging examinations (ultrasound, computerised tomography), serological reactions (ELISA, IHA) and histopathological investigation of the specimens obtained through fine-needle aspiration biopsy. RESULTS AND CONCLUSION: The latter followed the pre-treatment with antiparasitic drug and no significant complications were observed. On the basis of the criteria developed by our team (evident, highly probable and probable diagnosis), hydatid disease of the liver was diagnosed in 8 patients (25.8%). The remaining subjects, excluding one patient who underwent surgical treatment, received repeated treatment with imidazole derivatives (Zentel or Vermox).

[Effectiveness of antiviral treatment of patients with chronic hepatitis C (a Polish multicenter study)]. / Efektywnosc leczenia przeciwwirusowego przewleklego zapalenia watroby typu C (wieloosrodkowe badania pòlskie).

Interferon alpha (INF) is routine treatment in patients with chronic hepatitis C. Many controlled investigations were evaluated to establish the optimal schedule of treatment with sustained virological and biochemical response. Recently, multicentre meta-analyses suggest that combination therapy (INF + Ribavirin) was more effective than treatment with interferon alone. The aim of this study was to compare the efficacy of four schedules of antiviral treatment in 445 patients with chronic hepatitis C. Combination therapy (INF + Ribavirin) given for 6 mo. and monotherapy (INF) for 18 mo. were more effective than interferon alone given for 6 mo. Treatment with INF alone for 6 mo. was demonstrated to be insufficient.

Hospital-treated infectious diseases in Western Pomeranian region in a 5-year surveillance: importance for travellers.

Retrospective analysis of the incidence of infectious diseases in the five-year period 1994-1998 as recorded by the Department of Infectious Diseases of the Pomeranian Medical School, has been presented. In this period contagious diseases were diagnosed in 3,863 adults with mean age of 42.8 +/- 33.5 y. Most patients still had viral liver diseases, but we observe some major changes in the epidemiology of infectious diseases in our region. There is an increased number of hospitalisations due to chronic hepatitis and liver cirrhosis as well as due to symptomatic HIV infections, whereas some acute diseases namely acute hepatitis B and infectious intoxication show decreasing tendency.

[Pneumonia in HIV-infected patients: clinical observations]. / Zapalenie pluc u osób zakazonych HIV--obserwacje kliniczne.

OBJECTIVES: To determine the occurrence of pneumonias in HIV-infected patients in our hospital during 1990-1999; to evaluate the clinical significance of pneumonias in HIV-seropositive patients; to estimate the ethiology of pulmonary infection. MATERIALS AND METHODS: One hundred and two HIV-infected patients, 17 (16.6%) female and 85 (83.3%) male with mean age of 29 +/- 4.5 yrs, were retrospectively analysed. All patients had a physical examination particularly concerning the clinical symptoms of pulmonary infection, X-ray exam and tuberculin skin test (PPD). The stage of HIV infection according to the 1993 CDC classification was determined. All patients had the microbiology test of sputum (Pc, TB, fungi, other pathogen). In some cases the bronchofiberoskopy with bronchoalveolar lavage (BAL) was performed. RESULTS: One hundred and two HIV-positive patients had 129 episodes of pneumonia. We determine the bacterial ethiology in 94/129 (72.9%) cases--TB in 11/129 (8.5%) cases. Fourteen patients had 23 episodes of Pneumocystis carinii pneumonia (PcP). Three patients had CMV--pneumonitis, detected post mortem. In seven cases the ethiology of pulmonary infection was unknown. In summary the ethiology of pneumonia was determined in 58/129 (44.9%) cases. Thirty three patients were died. The pulmonary infections were main cause of death in 23 (67.7%) persons. CONCLUSIONS: In the era of high active antiretroviral therapy (HAART) the pulmonary infections in HIV-positive patients are the main cause of death as before. The PPD test is useless in HIV-positive patients. We make a note the increase cases of TB in HIV-infected patients during the time of observations.

HLA class II genotypes associated with chronic hepatitis C virus infection and response to alpha-interferon treatment in Poland.

AIMS/BACKGROUND: Recent evidence suggests that spontaneous clearance of hepatitis C virus (HCV) may be associated with the HLA DQB1*0301 allele but there is still some debate over the role of other alleles and HLA haplotypes in HCV infection. As this may best be resolved by studying genetically different populations, we have investigated HLA class II-encoded susceptibility and resistance to HCV infection in a relatively sedentary population of patients from northwestern Poland. METHODS: The distributions of HLA class II DRB1, DQA1, DQB1 and DPB1 alleles were determined by standard PCR-protocol in 129 unrelated patients with chronic hepatitis C (anti-HCV and HCV-RNA positive) and 103 healthy unrelated racially-matched control subjects. Fifty-five patients were treated with alpha-interferon (5 MIU thrice weekly for 6 months) out of whom 29 showed a complete response and 26 were non-responders. RESULTS: A significantly reduced frequency of the DQB1*0301 allele in the patients was observed (24.0% vs. 38.8%; p=0.015). Additionally, two different DR-DQ haplotypes were found to be associated with chronic HCV infection: DRB1*1501-DQA1*01-DQB1*0602 (24.0% vs. 12.6%; p= 0.027) and DRB1*0701-DQA1*0201-DQB1*02 (31.8 vs. 12.6%; p=0.0006), the latter difference being most pronounced in those patients who responded to alpha-interferon treatment (41.4% vs. 12.6%; p=0.00048). CONCLUSIONS: The results confirm the negative association between chronic HCV and DQB1*0301 and identify two novel genetic associations. In particular, the DRB1*0701-DQA1*0201-DQB1*02 haplotype is associated with both chronic infection and response to alpha-interferon. Interestingly, the same haplotype is reportedly associated with non-response to hepatitis B vaccination.

[Anthrax in man with reference to alimentary infection and environmental conditions]. / Waglik czlowieka ze specjalnym uwzglednieniem zakazen pokarmowych oraz uwarunkowan srodowiskowych.

Based on already published data, the following issues have been covered in the present review: epidemiology, epizootiology and the occurrence of anthrax in man with reference to current data. Moreover, in the paper are presented some problems of intestinal anthrax with emphasis on environment conditions, pathogenesis, prevention and treatment of this clinical form.

[Profile of liver diseases from personal observations]. / Profil chorób watroby w obserwacjach wlasnych.

In this paper a cohort study from Infectious Diseases Department in Szczecin the etiology and dynamics of liver diseases in hospitalized patients from 1994 to 1996 are presented. The number of patients is increased during this period. Chronic liver diseases are common and predominately are cause of by hepatitis B virus. Men from urban environmental are most often stricken with sickness.

[Herpes zoster--clinical aspects]. / Pólpasiec--aspekty kliniczne.

Clinical course of herpes zoster was assessed in 119 immuno-competent and in 28 immuno-compromised hosts. Complications of herpes zoster were observed in one third cases. However, the frequency of post-herpetic neuralgia was lower than that seen by other authors. Despite severe underlying diseases in compromised hosts, good outcome of herpes zoster was obtained. It may be related to the use of aciclovir in all these cases. Early and rational treatment with aciclovir is important for decreasing of the frequency of severe complications of herpes zoster.

[Amebic liver abscess--personal observations]. / Ropien pelzakowy watroby--obserwacje wlasne.

In the period of 1989-1995 seven patients with amebic liver abscess were observed in Clinic of Infectious Diseases of Pomeranian Medical School in Szczecin. The diagnosis has been made on the base of epidemiological data, presence of intrahepatic defect by a scanning procedure of liver (ultrasonography, CT, scintigraphy) and positive serologic test for amebiasis. All patients were male of Polish nationality, 29-57 years old, who became ill after travel to Africa or India. Intestinal amebiasis was present only in two cases. Five patients had acute onset of disease and two chronic. The most common complaints included fever, abdominal pain, anorexia. A cough, chest pain, diarrhea or weight lose were less common. At physical examination paleness of skin, subjaundice, abdominal tenderness, hepatomegaly and sometimes pleural effusion have been observed. Laboratory tests revealed high RBS, leucocytosis and mild anemia. Slightly higher serum level of bilirubin, alkaline phosphatase were transient. Trophozoits of Entamoeba histolytica have been found in stool specimens of one only patient. Amebic antibodies tested with indirect hemagglutination (IHA) were present in all cases. Visual technics have shown abscess of 3 to 9 cm in diameter located at right liver lobe. Six patients have been treated with both chemotherapy (metronidazole or/and dehydroemetine) and "skin needle" aspiration. In two cases recrudescence of abscess has been observed after one and three years respectively. These two patients have been undergone second course of treatment with using not only needle aspiration and metronidazole/dehydroemetine but luminal agents as well.

[Observation of patients with malaria hospitalized during the years 1980-1993 in the Clinic of Infectious Diseases in Szczecin]. / Obserwacje chorych na zimnice hospitalizowanych w latach 1980-1993 w Klinice Chorób Zakaznych w Szczecinie.

Thirty five patients with imported malaria were hospitalised in a period of 1980-93 in Department of Infectious Diseases of Pomeranian Medical School, Szczecin, Poland. The diagnosis of malaria was established on a base of clinical feature, the presence of Plasmodium in peripharal blood smears and, in some cases, on positive serological tests. Thirty two patients were Polish citizens, and three persons were foreigners. Malaria was caused mostly by invasion of Plasmodium falciparum (62.8), then P. vivax (31, 4), in 1 case--P. ovale and 1 case--mixed invasion occurred (P. falciparum and P. vivax). The majority of cases caused by P. falciparum were imported from Central Africa. Invasions of P. vivax were brought from North Africa, India and Middle East. Malaria in Polish patients was connected with occupational exposure and lack of proper antimalarial prophylaxis was obvious. A clinical course of disease was serious, with one mortal case. Fever, headache, abdominal pain, weakness, jaundice, insomnia were main complaints. Anemia, leucopenia, thrombocytopenia, hyperbilirubinemia, hypertransaminasemia and high serum concentration of urea were observed. A level of parasitemia in peripheral blood varied from minimal to very high (22.5%) in cases of P. falciparum invasions. In treatment chloroquine, fansidar, quinine, primaquine, halfan were used.