High prevalence of anti-HEV antibodies among patients with immunosuppression and hepatic disorders in eastern Poland.

INTRODUCTION: The incidence of hepatitis E virus (HEV) infections in Poland is largely unknown. This study aimed to describe seroprevalence of markers of HEV infection among patients with immunodeficiency of diverse etiology and patients with advanced chronic liver diseases. MATERIAL AND METHODS: Four hundred fifty patients were enrolled; among them, 180 persons were solid organ transplant recipients, 90 patients were HIV-infected and 180 persons had confirmed liver cirrhosis of different etiology. Serum anti-HEV-IgG, IgM antibodies and HEV-antigen were detected by ELISA (Wantai, China). RESULTS: In the group of transplant recipients, serum anti-HEV-IgG antibodies were detected in 40.6%, IgM in 1.1% and HEV-Ag in 2.8% of subjects. In the HIV-infected population 37.7% had anti-HEV-IgG, 1.1% had anti-HEV-IgM and none had HEV-Ag. Among patients with advanced chronic liver diseases the highest prevalence of anti-HEV-IgG was recorded in alcohol-related liver cirrhosis (52.1%) (p = 0.049). In the population of all liver cirrhotics anti-HEV-IgG seroprevalence was 48.3%, anti-HEV-IgM seroprevalence was 5.0% and HEV-Ag seroprevalence was 1.7%. Older age and male gender were significant risk factors associated with increased anti-HEV-IgG prevalence, p = 0.0004 and p = 0.02, respectively. CONCLUSIONS: In this large cohort a high seroprevalence of anti-HEV-IgG was detected in comparison to other European countries, with the highest rates in patients with alcoholic liver disease and in transplant recipients.

Real-world direct-acting antiviral treatment in kidney transplant and hemodialysis patients: the EpiTer-2 multicenter observational study.

BACKGROUND: Patients who undergo hemodialysis (HD) or kidney transplantation (KTx) previously had limited possibilities for treatment of hepatitis C virus (HCV) infection. Direct-acting antivirals (DAA) give these patients a chance of virus eradication and safe transplantation. The aim of this study was to evaluate the effectiveness and safety of DAA in KTx and HD patients in real-world settings. METHODS: Sustained virologic response (SVR) and treatment safety were analyzed in KTx and HD patients from the EpiTer-2 database, which included HCV-infected subjects treated with DAA between 2015 and 2019. Additionally, for KTx patients, changes in creatinine concentration, estimated glomerular filtration rate (eGFR), proteinuria within a year after treatment, and changes in the need for calcineurin inhibitors were assessed. RESULTS: Among 10,152 patients from the EpiTer-2 database 148 were selected, 85 after KTx and 63 undergoing HD. The most common genotype, 1b HCV, was found in 73% and 86% of patients, respectively. Cirrhosis was noted in 10% and 19%, respectively. The most common DAA regimen after KTx was sofosbuvir/ledipasvir (54%), whereas in HD patients it was ombitasvir/paritaprevir/ritonavir +/- dasabuvir (56%). All patients with available follow-up results achieved SVR. No deaths, kidney loss or acute rejection episodes were noted. The most common adverse effects in both groups were anemia and weakness. One year after treatment, creatinine concentration, eGFR and proteinuria remained stable in the majority of patients. CONCLUSION: DAA treatment of HCV infection demonstrated high effectiveness and safety in hemodialyzed patients and patients who had undergone KTx in this real-world study.

The influence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infections on the pregnancy course.

OBJECTIVES: The incidence of HBV infections among the pregnant in Europe falls within the range of 1-7%, whereas it is 1.7-4.3% for HCV. The aim was to assess the course of pregnancy among women infected with HBV or HCV, and the condition of neonates in the fifth minute after the birth. MATERIAL AND METHODS: The study included 157 pregnant individuals infected with HBV, 53 infected with HCV, and 330 healthy pregnant women. None of the women infected with HBV and HCV as well as from the control group were infected with HIV, and none of them took intoxicants. RESULTS: Weight of neonates delivered by healthy women was higher as compared with children born by women infected with HBV or HCV (3.517 vs 3.347 and 3.366). The Apgar score of neonates delivered by women with HBV and HCV infections was lower as compared with the children born by healthy women (9.4 vs 9.3 vs 9.7; p < 0.05). Premature births occurred more often in HBV and HCV-infected women than in the control group (14.6% and 24.5% vs 6.96%; p < 0.05). Miscarriages were significantly more common among the patients with HCV infections as compared with the patients who were healthy (9.4% vs 1.8%; p < 0.05). In comparison with the healthy individuals, this group of patients experienced pruritus (10.5% vs 4.2%; p < 0.05), oedemas (9.4% vs 2.4%; p < 0.05), and hypertension (9.4% vs 1.5%; p < 0.05) more often. An increase in HBV loads was observed between the 6th and 28th-32nd week of pregnancy among the infected with HBV, and then, a decrease was observed in the 6th months after the delivery. CONCLUSIONS: The women infected with HBV without HBsAg (-) and the infected with HCV are subject to common incidence of premature births. Women infected with HCV often experience oedemas, hypertension, and pruritus.

Tocilizumab for patients with severe COVID-19: a retrospective, multi-center study.

BACKGROUND: Tocilizumab, an inhibitor of the interleukin-6 receptor, may decrease the inflammatory response and control the symptoms of severe coronavirus disease 2019 (COVID-19), but the evidence is scarce. METHODS: This retrospective study included patients with severe COVID-19 requiring oxygen therapy who received tocilizumab in seven centers across Poland. We assessed on-treatment changes in clinical status and inflammatory markers. RESULTS: Twenty-eight patients were included (19 male), with a mean age of 61.7 ± 12.4 years. The mean time from symptom onset to the first tocilizumab dose was 10.5 ± 5.7 days. Clinical status improved within 24 hours in 11 (39%) patients, within one week in 23 (82%) patients, and within two weeks in 25 (89%); one (4%) patient showed no change and two (7%) patients died. Sixteen patients (57%) no longer needed oxygen therapy within a week (p < 0.001). The serum concentrations of C-reactive protein, procalcitonin, and fibrinogen decreased significantly (p ≤ 0.001). Lung changes improved in 21 (84%) patients within two weeks of treatment; 19 had minimal or no changes upon final examination. CONCLUSIONS: Tocilizumab can control the symptoms of severe COVID-19 by reducing the inflammatory response and rapidly improves the clinical status in most patients.

Is an 8-week regimen of glecaprevir/pibrentasvir sufficient for all hepatitis C virus infected patients in the real-world experience?

BACKGROUND AND AIMS: The revolution of the antiviral treatment of hepatitis C virus (HCV) infection resulting in higher effectiveness came with the introduction of direct-acting antivirals with pangenotypic regimens as a final touch. Among them, the combination of glecaprevir (GLE) and pibrentasvir (PIB) provides the opportunity for shortening therapy to 8 weeks in the majority of patients. Because of still insufficient evaluation of this regimen in the real-world experience, our study aimed to assess the efficacy and safety of 8-week GLE/PIB in chronic hepatitis C patients depending on liver fibrosis and genotype (GT). METHODS: The analysis included patients who received GLE/PIB for 8 weeks selected from the EpiTer-2 database, large retrospective national real-world study evaluating antiviral treatment in 12 584 individuals in 22 Polish hepatology centers. RESULTS: A total of 1034 patients with female predominance (52%) were enrolled in the analysis. The majority of them were treatment naïve (94%), presented liver fibrosis (F) of F0-F3 (92%), with the most common GT1b, followed by GT3. The overall sustained virologic response after exclusion of nonvirologic failures was achieved in 95.8% and 98%, respectively (P = 0.19). In multivariate logistic regression HCV GT-3 (beta = 0.07, P = 0.02) and HIV infection (beta = -0.14, P < 0.001) were independent predictors of nonresponse. CONCLUSIONS: We demonstrated high effectiveness of 8-week GLE/PIB treatment in a non-GT3 population irrespective of liver fibrosis stage. Comparable efficacy was achieved in non-cirrhotic patients regardless of the genotype, including GT3 HCV.

Significance of mutations in the region coding for NS3/4 protease in patients infected with HCV genotype 1b.

BACKGROUND: Fast hepatitis C virus (HCV) replication is one of the reasons for frequent changes in viral genome. OBJECTIVES: The objective of this study was to evaluate the frequency and type of mutation in NS3/4 protease in patients with HCV genotype 1b and to determine the effect of the mutation on viral load, fibrosis stage, alanine aminotransferase (ALT) activity, and alpha-fetoprotein (AFP) level. MATERIAL AND METHODS: The study included 46 treatment-naïve patients, infected with HCV genotype 1b. Mutations were analyzed after isolating HCV RNA, and then evaluating the compliance of the amino acid sequence, using 3500 Genetic Analyzer (Applied Biosystems, Foster City, USA). RNA fragment from nucleotide 1-181 encoding NS3/4 protease was subjected to analysis. RESULTS: Mutations were demonstrated in 65% of subjects. Changes in the protease region affecting resistance to treatment (T54, Q80, V158, M175, D186) were detected in 10.8% of patients. Substitution mutation at T72 was found most frequently - in 49.9% of cases. In 13% of patients, mutation at G86 was demonstrated, including G86P in 5 patients and G86S in 1 patient. In the group of patients with T72 mutation, viral load was significantly higher (1.3 × 106 IU/mL vs 1.0 × 105 IU/mL; p = 0.01), AFP level was higher and fibrosis level was lower (1.26 vs 2.17; p = 0.008) compared to the patients without the mutation. Cryoglobulinemia was observed in 74% of patients with mutation at position T72. CONCLUSIONS: Natural mutations of the region coding for NS3/4 protease are found frequently in patients infected with genotype 1b, but they may cause resistance to antiviral agents only in 11% of patients. Changes were most frequently found at position T72. Mutations at position T72 are correlated with the cryoglobulinemia occurrence. This is a substitution mutation, accompanied by a high viral load, high ALT activity and AFP level, which may point to a more unfavorable influence of such a modified virus, compared to wild-type virus, onto pathological processes in the liver.

The Activity of Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in the Sera of Patients with Autoimmune Hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is a progressive inflammatory hepatopathy and an important cause of end-stage liver. The liver cells' destruction is reflected by increased activity of different enzymes in the serum. These enzymes include alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which play a significant role in the metabolism of many biological substances and exist mainly in the liver. In this study we investigated the activity of alcohol dehydrogenase and its isoenzymes and the total activity of ALDH in the sera of patients with autoimmune hepatitis. METHODS: Serum samples were taken for routine biochemical investigation from 32 patients with autoimmune hepatitis and from 40 healthy subjects. Class I and II of ADH and ALDH activity was measured by the spectrofluorometric method. For measurement of class III ADH and total ADH activity we employed the photometric methods. RESULTS: The activity of the class I ADH isoenzyme was significantly higher in the sera of patients with autoimmune hepatitis. The median activity of this isoenzyme in the patients group was approximately 63% (3.94 mU/L) higher than the control level (1.46 mU/L). For this reason, the total ADH activity was also significantly increased. The activities of other ADH isoenzymes and ALDH tested were unchanged. CONCLUSIONS: The activity of total ADH and class I isoenzymes in the sera of patients with autoimmune hepatitis is increased, and it seems to be caused by the release of alcohol dehydrogenase from damaged liver cells.

Activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in sera of patients with hepatitis C.

INTRODUCTION: The changes of enzyme activity in the hepatocytes in the course of different liver diseases are reflected by increase of the corresponding enzyme activity in the plasma. For example, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) correlate with the severity of the condition during cirrhosis. In this study we measured the activity of ADH isoenzymes and ALDH in the sera of patients with hepatitis C. MATERIAL AND METHODS: Serum samples were taken from 60 patients suffering from viral hepatitis C and from 66 control subjects. Total ADH activity and class III and IV isoenzymes were measured by the photometric method and ALDH activity, ADH I and II by the fluorometric method. RESULTS: The ADH activity was significantly higher in patients with hepatitis C than in healthy (p < 0.001). The total activity of ADH was 1284 mU/l in patients, and 745 mU/l (controls). The activity of isoenzymes classes ADH I and ADH II in the hepatitis C group increased respectively 55% (4.24 vs. 1.88 mU/l; p < 0.001) and 47% (26.63 vs. 14.11 mU/l; p < 0.001) in the comparison to the control. There was significant increase in the activity of ADH I isoenzyme (4.96 vs. 3.81 mU/l; p < 0.001) and ADH total (1833 vs. 1105 mU/l; p < 0.001) in patients with high viral load in comparison to patients with low viral load. CONCLUSIONS: The activity of class I and II ADH isoenzymes in the sera of patients with hepatitis C is increased, and it seems to be caused by the release of these isoenzymes from damaged liver cells.

Toxic hepatitis caused by the excretions of the Phyllomedusa bicolor frog - a case report.

The Kambô ritual consists of various types of skin scarification and subsequent application of Phyllomedusa bicolor secretion to the fresh wounds. In Europe, the ritual of Kambô is becoming more popular, but its use can lead to serious multiple organ damage, sometimes life-threatening. Our manuscript shows a patient with toxic liver damage probably associated with the Kambô ritual.

Serum Concentrations of Th17-Associated Interleukins and Autoimmune Phenomena are Associated with the Degree of Liver Damage in Alcoholic Liver Disease.

BACKGROUND AND AIMS: Recent reports suggest an involvement of Th17 responses in inflammatory and autoimmune reactions in alcoholic liver disease (ALD). Our study aimed to assess serum levels of Th17-interleukins in ALD with regard to the frequency of liver-specific autoantibodies and degree of liver damage. METHODS: Ninety-five patients with ALD were enrolled. Serum concentrations of IL-17F, IL-17A, IL-22 were assessed by ELISA. The presence of autoantibodies AMA-M2, SLA/LP, LKM-1, LC1, anti-F-actin, anti-desmin and anti-myosin in serum was assessed by immunoblotting, ANA antibodies were detected by ELISA. The results were analysed with regard to the degree of hepatic damage. RESULTS: Serum IL-17F was significantly elevated in ALD patients compared to controls (p=0.03). There was a correlation between serum IL-17F and degree of liver failure evaluated by the MELD score (rs=0.23, p=0.03). Serum IL-22 also correlated with MELD score (rs=0.32, p=0.007) and CTP score (rs=0.28, p=0.02). Anti-F-actin antibodies were present in 19% and ANA-antibodies in 11% of the patients in the study group, and in no subjects in the control group. The prevalence of anti-F-actin autoantibodies was higher in subjects with more advanced liver diseases but also independently associated with IL-17A in the regression analysis. Furthermore, serum IL-22 in anti-F-actin(+)-patients was significantly higher compared to anti-F-actin(-)-patients (p=0.03). CONCLUSIONS: Elevation of serum IL-17A, IL-17F, IL-22 correlated with the progression of liver damage and also with presence of F-actin in ALD. Alcoholic liver disease may trigger autoimmunity and formation of autoantibodies, especially anti-F-actin, with possible engagement of Th17-related cytokines in this process.

Helicobacter pylori infection among patients with liver cirrhosis.

BACKGROUND AND AIM: Inflammatory changes in the stomach caused by Helicobacter pylori indirectly and directly affect liver function. Moreover, the bacteria may worsen the course of the liver cirrhosis. The study aimed at evaluating the incidence of H. pylori infection among patients with liver cirrhosis, depending on the etiology and injury stage, scored according to Child-Pugh classification. Stage of esophageal varices and endoscopic inflammatory lesions in the stomach were evaluated, depending on the presence of H. pylori infection. PATIENTS AND METHODS: The study included 147 patients with liver cirrhosis: 42 were infected with hepatitis C virus, 31 were infected with hepatitis B virus, 56 had alcoholic liver cirrhosis, and 18 had primary biliary cirrhosis. Diagnosis of H. pylori infection was performed based on the presence of immunoglobulin G antibodies in serum. RESULTS: H. pylori infection was found in 46.9% of patients. The incidence of H. pylori infection among patients with postinflammatory liver cirrhosis was significantly higher (P=0.001), as compared with patients with alcoholic liver cirrhosis. Ammonia concentration was significantly higher in patients infected with H. pylori, compared with noninfected individuals (129 vs. 112 µmol/l; P=0.002). Incidence of H. pylori infection in patients without esophageal varices was significantly lower compared with patients with esophageal varices (14 vs. 60%; P<0.001). CONCLUSION: H. pylori infection is significantly more frequent among patients with postinflammatory liver cirrhosis (infected with hepatitis C virus or hepatitis B virus) than in patients with alcoholic liver cirrhosis or primary biliary cirrhosis. H. pylori infection correlates with elevated concentration of blood ammonia and the incidence of esophageal varices.

Serum Alcohol Dehydrogenase and Aldehyde Dehydrogenase Activity in the Course of Hepatitis C.

BACKGROUND: Hepatistis C virus (HCV) affects approximately 170 million people, and it is the leading cause of the chronic liver disease. The destruction of liver cells is reflected by an increase of different enzyme activities in the serum. These enzymes include alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which play a significant role in the metabolism of many biological substances and exist mainly in the liver. In this study we investigated the activity of alcohol dehydrogenase and its isoenzymes and the total activity of ALDH in the sera of patients with hepatitis C. METHODS: Serum samples were taken for routine biochemical investigations from 50 patients with hepatitis C and from 50 healthy subjects. The activity of class I and II ADH isoenzymes and ALDH activity were measured by spectrofluorometric methods. For the measurement of total ADH activity and activity of class III and IV isoenzymes, the photometric methods were used. RESULTS: The analysis of our results shows a statistically significant increase in the activity of ADH I and ADH II (2.5-fold and 2-fold, respectively). Activities of both classes of alcohol dehydrogenase isoenzymes have good correlation with alanine and aspartate aminotransferase. The observed increase in total alcohol dehydrogenase activity was not very high but confirmed the elevation of class I and II isoenzyme activity. CONCLUSIONS: We can state that the activity of class I and II alcohol dehydrogenase isoenzymes in the sera of patients with hepatitis C is increased and it seems to be caused by the release of these isoenzymes from damaged liver cells.

The occurrence of autoantibodies in patients with chronic HCV infection, including patients dialyzed and after kidney transplantation.

INTRODUCTION: There are reports suggesting that hepatitis C virus (HCV) may stimulate the autoimmune process. Studies have been undertaken to evaluate the occurrence and type of autoantibodies in HCV-infected patients with and without immunosuppression. Results were analyzed according to HCV genotype, intensity of inflammation and liver fibrosis stage. MATERIAL AND METHODS: The study included 105 patients chronically infected with HCV, including 25 with immunological suppression administered for kidney disease or kidney transplantation. Blood samples were tested by immunoblotting for the presence of AMA-M2, SLA/LP, LKM-1, LC1, anti-F-actin, anti-desmin, anti-myosin, anti-gp210 and anti-sp100 autoantibodies, and ANA. All the patients were scored for autoimmune hepatitis. RESULTS: Autoantibodies were detected in 32.5% of patients without immunosuppression and in 16% with immunosuppression. Single types of autoantibodies were identified in 26% of patients. The most frequent ones were ANA (19%) and AMA-M2 (5.7%). The presence of antibodies in patients with genotype 1 was significantly higher in comparison to their occurrence in genotype 3. Autoimmune hepatitis was not diagnosed in any of the patients. Immunoglobulin G level was significantly higher in patients with detectable autoantibodies, compared to patients without antibodies (1.89 vs. 1.28 g/dl, p < 0.001). No correlation between fibrosis stage or intensity of inflammatory state and the frequency of antibodies was found. CONCLUSIONS: The antibodies are significantly more frequent in patients without immunosuppression and in patients infected with genotype 1 than genotype 3. The presence of these autoantibodies is not associated with the development of autoimmune hepatitis. Higher level of immunoglobulin G in the serum correlates with the presence of autoantibodies.

Serum cytochrome c and m30-neoepitope of cytokeratin-18 in chronic hepatitis C.

BACKGROUND & AIMS: Cytochrome c (CYC) and M30-neoepitope of cytokeratin-18 (M30-CK18) are involved at different levels in apoptotic pathways. We aimed to evaluate an association between serum CYC, M30-CK18 and disease activity as well response to therapy in chronic hepatitis C (CHC). METHODS: Seventy CHC patients were enrolled in this study. Forty five of them completed pegylated interferon plus ribavirin therapy. Histopathological evaluation of hepatic inflammatory activity and fibrosis, as well as blood liver function tests, was performed. Serum concentrations of M30-CK18 and CYC were measured by ELISA. RESULTS: Median serum concentration of M30-CK18 was higher in CHC patients [283 U/L] vs. control [113 U/L] (P = 0.0003) and was associated with inflammatory activity and liver fibrosis (P < 0.001). Serum M30-CK18 positively correlated with serum activity of ALT and GGT. CYC was not detected in sera of control group, whereas in CHC, 41.43% patients had detectable CYC in serum samples [0.60 ng/ml]. Detectable baseline serum CYC had been negatively associated with sustained virological response (SVR). In patients with detectable CYC, SVR rate was 20% vs. 60% in patients with undetectable CYC (P = 0.007). CONCLUSIONS: Elevated serum M30-CK18, as an indicator of enhanced apoptosis of hepatocytes, parallels active hepatic inflammation and fibrosis but also biochemical activity in CHC; thus, it may serve as a comprehensive non-invasive marker of disease activity. On the other hand, detection of serum CYC at baseline may be negatively associated with treatment response to pegylated interferon plus ribavirin in CHC.

Epidemiological features of patients infected with HCV genotype 4 in Poland: Epidemiology of HCV genotype 4 in Poland.

BACKGROUND: Hepatitis C genotype 4 (HCV-4) is considered to be rare outside northern Africa and southern Europe. OBJECTIVES: To describe the epidemiological characteristics of patients infected with HCV-4 in Poland. PATIENTS AND METHODS: The study group included 290 patients with HCV-related chronic liver disease and intravenous drug users with HCV infection recruited in years 2002-2006 in Podlaskie region, north-eastern Poland. In all cases, HCV infection was confirmed by HCV-RNA detection by qualitative nested RT-PCR. HCV genotype was determined by 5'UTR sequencing and comparison with known genotype-specific sequences. RESULTS: HCV 4 was found in 45 (15.5%) of 290 HCV-infected and HCV RNA-positive individuals. 60% of HCV 4 infections occurred in intravenous drug users; 51% of HCV 4-infected patients were also HIV-positive. Among 119 patients whose source of infection was other than drug use, there were 16 (10.5%) HCV 4 cases. Seven (46%) of 13 HCV 4-positive and HIV-negative patients who received combined antiviral treatment had sustained viral response. CONCLUSIONS: HCV 4 exists in eastern Poland, and the infection is frequently related to intravenous drug use and accompanied by HIV infection. HCV 4 also causes a proportion of non-drug-related HCV infections.

Does HAART improve renal function? An association between serum cystatin C concentration, HIV viral load and HAART duration.

AIM: The prevalence of renal disease in human HIV-infected individuals varies between 2% and 10%. Many reports have demonstrated the beneficial effect of antiretroviral (ARV) therapy on slowing the progression of renal diseases. The aim of our cross-sectional study was to determine serum cystatin C concentration in different stages of HIV infection and the relationship between cystatin C concentration and ARV treatment. METHODS: Cystatin C concentration was measured in the sera of 77 HIV-1-infected individuals and 18 HIV-seronegative volunteers. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease Study formula. RESULTS: HIV infection resulted in a significant increase in serum cystatin C concentration compared with healthy individuals (933.4 +/- 32.1 vs 621.1 +/- 56.8 ng/ml, P < 0.001). There were no significant differences in urea, creatinine and GFR between those groups. On multivariate analyses serum cystatin C was independently associated with highly active antiretroviral therapy (HAART) duration (beta = -0.34, P = 0.04) and HIV viral load (beta = 0.33, P = 0.04), whereas there were no significant relationships with age, body mass index, HIV duration, CD4+ and CD8+ T-cell counts and serum high sensitivity C-reactive protein concentration. CONCLUSIONS: Our initial observations indicate that serum cystatin C, which may reflect mild renal dysfunction, is increased during HIV-infection and is associated with HIV viral load. Long-lasting HAART seems to decrease cystatin C concentration, thus potentially improves renal function.

Plasma transforming growth factor beta1, metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 in acute viral hepatitis type B.

AIM: Antiproliferative, pro-apoptotic and immunosuppressive activity effects suggest crucial role of transforming growth factor (TGF)-beta1, metalloproteinase (MMP)-1 and its tissue inhibitor (TIMP)-1 in the pathogenesis of acute liver injury that in some patients precede development of chronic liver diseases and fibrogenesis. The aim of this study was to evaluate effect of acute HBV infection on plasma TGF-beta1, MMP-1 and TIMP-1 levels. METHODS: TGF-beta1, MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 39 patients with acute viral hepatitis type B. Baseline measurement was performed within the first week of jaundice and then weekly up to the fourth week of the disease. Results were compared to baseline and normal values and to liver function tests. RESULTS: Plasma concentrations of TGF-beta1, TIMP-1 and MMP-1 were significantly elevated in the first week of acute viral B hepatitis in comparison to normal. Analysis of individual values demonstrated significant positive correlation between plasma concentrations of TGF-beta1 and TIMP-1. There was no correlation between MMP-1 and TGF-beta1 or TIMP-1. Significant correlation was demonstrated between both TGF-beta1 and ALT or AST as well as between TIMP-1 and ALT, AST or bilirubin. Elevated baseline levels of both TGF-beta1 and TIMP-1 decreased gradually in consecutive weeks of the disease. TGF-beta1 but not TIMP-1 plasma concentrations were significantly lower in 3rd and 4th week than baseline values. MMP-1 concentration remained on baseline level in the 2nd week of the disease. However in the 3rd week its values increased suddenly but the significant difference in comparison to baseline was observed only in 4th week. CONCLUSIONS: These results indicate important role of TGF-beta1, TIMP-1 and MMP-1 in acute viral hepatitis, that seems to be connected first of all with hepatocytes damage. Their role in extracellular matrix metabolism during acute liver injury needs further evaluation.

Effect of pegylated interferon alpha 2b plus ribavirin treatment on plasma transforming growth factor-beta1, metalloproteinase-1, and tissue metalloproteinase inhibitor-1 in patients with chronic hepatitis C.

AIM: To evaluate the effect of antiviral treatment on plasma levels of transforming growth factor-beta1 (TGF-beta1), metalloproteinase 1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with chronic hepatitis C. METHODS: TGF-beta1, MMP-1, and TIMP-1 plasma concentrations were measured by an enzyme immunoassay in 28 patients, during 48 wk of treatment with pegylated interferon-alpha 2b (PEG-IFN-alpha2b) plus ribavirin (RBV) and after 24 wk of follow-up. Patients were divided into two groups: responders (R) and non-responders (NR) related to achieved sustained virologic response. Normal values were evaluated in plasma samples of 13 healthy volunteers. RESULTS: Baseline plasma concentrations of TGF-beta1 and TIMP-1 (30.9+/-3.7 and 1 506+/-61 ng/mL respectively) measured in all subjects significantly exceeded the normal values (TGF-beta1: 18.3+/-1.6 ng/mL and TIMP-1: 1 102+/-67 ng/mL). In contrast, pretreatment MMP-1 mean level (6.5+/-0.9 ng/mL) was significantly lower than normal values (11.9+/-0.9 ng/mL). Response to the treatment was observed in 12 patients (43%). TGF-beta1 mean concentration measured during the treatment phase decreased to the control level in both groups. However at wk 72, values of NR patients increased and became significantly higher than in R group. TIMP-1 concentrations in R group decreased during the treatment to the level similar to normal. In NR group, TIMP-1 remained significantly elevated during treatment and follow-up phase and significant difference between both groups was demonstrated at wk 48 and 72. MMP-1 levels were significantly decreased in both groups at baseline. Treatment caused rise of its concentration only in the R group, whereas values in NR group remained on the level similar to baseline. Statistically significant difference between groups was noted at wk 48 and 72. CONCLUSION: These findings support the usefulness of TGF-beta1, TIMP-1, and MMP-1 in the management of chronic hepatitis C. Elevated TIMP-1 and low MMP-1 plasma concentrations during antiviral therapy may indicate medication failure.

[Prevalence of HLA class I and II antigens and extra-bowel manifestations in ulcerative colitis]. / Wystepowanie antygenów HLA klasy I i II oraz pozajelitowych uszkodzen narzadowych u chorych na wrzodziejace zapalenie jelita grubego.

HLA class I and II antigens are common among patients with ulcerative colitis. They can be involved in the autoaggressive mechanisms of the disease. The aim of the study was to evaluate the prevalence of HLA B and HLA DR antigens and estimate the correlation to extra-bowel manifestations of the disease. 50 patients with ulcerative colitis and 20 healthy controls were examined. HLA-B27, -B7, -B40, -DR1, -DR2, -DR3, -DR4 and -DR7 were determined using monoclonal antibodies in microlymphocytotoxic method. HLA I and/or HLA II antigens were detected in 36% of patients: HLA I in 28% and HLA II 16%. 46% of the patients were demonstrating joint changes, with 65% of them presenting HLA molecules. 16% of the examined patients presented symptoms of intrahepatic cholestasis; with 67% having HLA I/II molecules. The difference from the control group was statistically significant, only 25% of healthy persons presented HLA I/II antigens. The incidence of joint involvement and cholestasis was higher in ulcerative colitis patients with HLA class I and/or HLA II.