Elevated levels of soluble glycoprotein V - The plasma marker of platelet activation by thrombin in patients with early stage primary biliary cholangitis (PBC).

PURPOSE: There is a growing body of evidence for a prothrombotic tendency in patients with primary biliary cholangitis (PBC). The aim of the study was to evaluate coagulation disorders in patients with early stage PBC compared to healthy controls and evaluation of their relationship with clinical data, with particular emphasis on minimal hepatic encephalopathy (MHE). PATIENTS AND METHODS: Fifty-one participants (PBC group - 38 patients, all patients but one Child-Pugh A; control group - 13 healthy controls) were included in our prospective, single center study. We assessed the plasma levels of sGPV, plasma procoagulant phospholipids (PPL) and rotational thromboelastometry (ROTEM) profiles in all study participants. Porto-systemic encephalopathy syndrome test was used to assess MHE. RESULTS: The sGPV levels were higher in the PBC group compared to the controls: 36.07 â€‹± â€‹11.32 â€‹ng/mL vs 27.04 â€‹± â€‹11.72 â€‹ng/mL, p â€‹= â€‹0.031. The PPL level was lower in the PBC group compared to controls resulting in increased clotting time in a factor Xa-based coagulation assay: 54.65 (47.83-58.83) sec. vs 45.90 (43.3-50.5) sec., p â€‹= â€‹0.0065. PPL levels were correlated with platelet count (rho â€‹= â€‹-0.46, p â€‹= â€‹0.001). ROTEM parameters did not differ significantly between groups. Coagulation parameters did not differ significantly between patients with and without MHE. CONCLUSIONS: We have showed increased levels of sGPV - a plasma marker of platelet activation by thrombin in patients with early stage PBC compared to healthy controls. We found no relationship between the coagulation disorders and the occurrence of MHE. The PPL level was lower in the PBC group.

Effect of COVID-19 on Anti-S Antibody Response in Healthcare Workers Six Months Post-Vaccination.

The current study aimed to determine to what extent prior COVID-19 infection affects the response of specific antibodies following vaccination. The study involved 173 healthcare professionals who completed the two-dose vaccination course with BNT162b2, including 40 who previously experienced clinical COVID-19. The levels of anti-SARS-CoV-2 S1S2 IgG (anti-S) and, in some cases, anti-SARS-CoV-S-RBD IgG (anti-S-RBD) were determined six months after complete vaccination. A level exceeding the cut-off values for both anti-S and anti-S-RBD was observed in 100% of subjects, but after setting the analysis to 5- and 10-fold cut-off levels, the percentage of subjects meeting this criterion was significantly higher for anti-S-RBD. The 100-fold cut-off level was achieved by only 21% and 16% for anti-S and anti-S-RBD, respectively. Anti-S and anti-S-RBD levels above ten times the positive cut-off were respectively observed in 91% and 100% individuals with a history of COVID-19, while among those without COVID-19, these values were 64% and 90%, respectively. Significantly higher incidence of values above 10 and 100 times the cut-off became apparent among people with a history of COVID-19. In conclusion, vaccination against COVID-19 following infection with the disease provides higher levels of specific antibodies 6 months after vaccination than those of individuals without a history of the disease, which supports the use of a booster dose, particularly for those who have not experienced SARS-CoV-2 infection.

Minimal hepatic encephalopathy may be present despite the absence of non-invasive and elastography evidence of cirrhosis in patients with primary biliary cholangitis.

PURPOSE: Minimal hepatic encephalopathy (MHE) is an important complication of chronic liver disease (CLD); however, MHE burden in patients with primary biliary cholangitis (PBC) has not been determined yet. Therefore, our study aimed to assess the prevalence of MHE in a typical cohort of middle-aged, patients with PBC suspicion of liver fibrosis and to investigate the relationship between MHE, basic laboratory tests and the stage of liver fibrosis. PATIENTS AND METHODS: Fifty-one patients (38 with PBC and 13 controls), were prospectively enrolled. Portosystemic Encephalopathy-Syndrome test was used to diagnose MHE. Elastography point qualification (ElastPQ) and non-invasive markers (APRI and FIB-4) were used to assess liver fibrosis. The severity of CLD was assessed using the Model of End-Stage Liver Disease (MELD) and Child-Pugh score. RESULTS: MHE was diagnosed in 9 patients (24.3%) with PBC and none in the control group. As many as 44.4% of the patients with MHE had neither advanced fibrosis nor cirrhosis, as demonstrated using non-invasive markers of liver fibrosis or ElastPQ. The MELD score was the only predictor of MHE with cut-off value 8.5 [AUC â€‹= â€‹0.753, CI95% â€‹= â€‹0.569 to 0.938)] with sensitivity of 56%, specificity of 85% and accuracy of the test of 78%. Non-invasive markers of liver fibrosis and ElastPQ did not predict MHE. CONCLUSIONS: MHE may occur in PBC despite no evidence of advanced liver fibrosis or cirrhosis. The slightly elevated MELD score may indicate a substantially increased risk of MHE in patients with PBC.

Endoscopic management of leaks and fistulas after bariatric surgery: a systematic review and meta-analysis.

BACKGROUND: Endoscopic techniques have become the first-line therapy in bariatric surgery-related complications such as leaks and fistulas. We performed a systematic review and meta-analysis on the effectiveness of self-expandable stents, clipping, and tissue sealants in closing of post-bariatric surgery leak/fistula. METHODS: A systematic literature search of the Medline/Scopus databases was performed to identify full-text articles published up to February 2019 on the use of self-expandable stents, clipping, or tissue sealants as primary endoscopic strategies used for leak/fistula closure. Meta-analysis of studies reporting stents was performed with the PRISMA guidelines. RESULTS: Data concerning the efficacy of self-expanding stents in the treatment of leaks/fistulas after bariatric surgery were extracted from 40 studies (493 patients). The overall proportion of successful leak/fistula closure was 92% (95% CI, 90-95%). The overall proportion of stent migration was 23% (95% CI, 19-28%). Seventeen papers (98 patients) reported the use of clipping: the over-the-scope clips (OTSC) system was used in 85 patients with a successful closure rate of 67.1% and a few complications (migration, stenosis, tear). The successful fistula/leak closure using other than OTSC types was achieved in 69.2% of patients. In 10 case series (63 patients), fibrin glue alone was used with a 92.8-100% success rate of fistula closure that usually required repeated sessions at scheduled intervals. The complications of fibrin glue applications were reported in only one study and included pain and fever in 12.5% of patients. CONCLUSIONS: Endoscopic techniques are effective for management of post-bariatric leaks and fistulas in properly selected patients.

Laboratory evidence for hypercoagulability in cirrhotic patients with history of variceal bleeding.

AIM: We aimed to assess the relationship between procoagulant imbalance and the occurrence of variceal bleeding in patients with liver cirrhosis. METHODS: We compared the results of chromogenic assay for the functional evaluation of the Protein C anticoagulant pathway (ThromboPath®), thromboelastometry and the levels of factor VII, VIII, and antithrombin in two groups of cirrhotic patients: Group 1 (n = 25) - patients with moderate or large esophageal or gastric varices, who had never experienced acute gastrointestinal bleeding and Group 2 (n = 24) - patients with a history of variceal bleeding. RESULTS: Despite the differences in MELD score and the results of basic laboratory tests indicating more severe cirrhosis and suggesting a greater risk of bleeding in Group 2, the results of thromboelastometry did not differ significantly between groups. The ThromboPath® test results [ThP B: 67.8 ±â€¯13.4 versus 59.09 ±â€¯12.4%, p = 0.023] and factor VII level [69.04 ±â€¯24.16 vs 53.54 ±â€¯25.06, p = 0.032] confirmed greater plasma procoagulant activity in Group 1 compared to Group 2. However, there were no statistically significant differences in thrombin generation after activation of the protein C. Plasma of patients in Group 2 was more resistant to anticoagulation with protein C compared to Group 1 (PICI%: 65.58 ±â€¯7.24 versus 55.64 ±â€¯13.07%, p = 0.001). CONCLUSION: The results of our study confirm the lack of influence of coagulation disorders on the occurrence of variceal bleeding. Moreover, the results of ThromboPath® assay indicate hypercoagulability in patients with a history of variceal bleeding and more severe liver cirrhosis, compared to patients who have never bled.

Blood platelet function abnormalities in cirrhotic patients with esophageal varices in relation to the variceal bleeding history.

Objective: The study aimed at assessing the effect of thrombocytopenia and platelet function abnormalities on the occurrence of variceal bleeding in patients with cirrhosis. Methods: The results of impedance aggregometry, von Willebrand factor antigen level and thromboelastometry (TEM) with and without the addition of a platelet inhibitor (FIBTEM®, EXTEM® test, respectively) were compared in two patient groups: Group 1 (n = 32) - patients with moderate or large esophageal or gastric varices, who had never had symptoms of acute gastrointestinal bleeding and Group 2 (n = 26) - patients with history of variceal bleeding. Results: Standard clotting test indicated more hypocoagulable profile in Group 2 compared to Group 1. However, no differences in any TEM component were observed between groups in EXTEM® test. The contribution of platelets to clot strength was significantly higher in Group 2 than in Group 1 [PLT% = 74.2 (67.5-80.4) versus 68.8 (63.7-76.5) %; p = .039]. The aggregation index was also higher in Group 2 compared to Group 1, although not statistically significant [% of healthy = 96.9 (73.2-140.1) versus 67.6 (52.5-118.8) %, p = .195]. No differences in vWF antigen levels were observed between groups. Conclusions: The results of thromboelastometry and aggregometry indicate increased contribution of platelets in clot formation in patients with a history of variceal bleeding compared to cirrhotic patients who never bled. Comparable effectiveness of hemostasis in both groups is most likely associated with the compensatory role of platelets. Increased platelet activity in this group of patients is probably due to a mechanism independent of the von Willebrand factor antigen level.

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.

Metabolic syndrome in HIV infected adults in Poland.

BACKGROUND: Metabolic syndrome (MS) is usually diagnosed based on the presence of abdominal obesity, elevated blood pres-sure (BP), elevated fasting plasma glucose, high serum triglycerides (TG), and low high-density lipoprotein (HDL) cholesterol levels. Whether HIV is associated with a higher prevalence of MS than in the general population remains unclear. AIM: The aim of the study was to determine the incidence of MS in the population of HIV-infected adults and its association with clinical, virological, and biochemical features. METHODS: Two hundred and seventy HIV-infected Caucasian adult patients were enrolled in the study and evaluated based on clinical records in the years 2013-2015. RESULTS: Metabolic syndrome was diagnosed in 60 of 270 (22%) patients, 47 (24%) males and 13 (17%) females, mostly (72%) aged above 40 years. The percentage of patients with diagnosed MS in specific age groups in comparison to the general Polish population for females aged < 40 years was 7% vs. 4%, and males in the same age - 18% vs. 9%, for females aged 40-59 years - 47% vs. 24.4%, and males - 33% vs. 28.3%. Particular components of MS in the MS population were found as follows: body mass index > 30 kg/m2 in 29%, waist circumference exceeding 94 cm in men and 80 cm in woman - 87.5%, TG ≥ 150 mg/dL - 82%, HDL cholesterol < 40/50 mg/dL (males/females) - 42%, systolic/diastolic BP ≥ 130 mmHg/≥ 85 mmHg - 83%, and fasting glucose > 100 mg/dL - 42%. In stepwise multivariate logistic regression analysis, age (odds ratio [OR] 1.052, 95% con-fidence interval [CI] 1.018-1.088, p = 0.003) and nadir CD4 < 350 cells/mm3 (OR 3.576, 95% CI 1.035-12.355, p = 0.04) were associated with MS. Patients with MS compared with those without this disorder had low, intermediate, high, and very high cardiovascular risk in 10% vs. 23%, 73% vs. 70%, 7% vs. 5%, and 10% vs. 2%, respectively (p = 0.006). CONCLUSIONS: Prevalence of MS in the HIV-infected population is higher than in the general Polish population. Age and low nadir CD4 were found to be associated with MS.

Serum Cytokeratin 18 M30 Levels in Chronic Hepatitis B Reflect Both Phase and Histological Activities of Disease.

Chronic hepatitis B has highly a dynamic course with significant fluctuations of HBV-DNA and ALT impeding assessment of disease activity. New biomarkers of inflammatory versus noninflammatory stages of HBV infection are urgently needed. Cytokeratin 18 epitope M30 (M30 CK-18) is a sensitive marker of cell death. We aimed to investigate an association between serum M30 CK-18 and histological activity and phase of HBV infection. 150 Caucasian patients with HBV-infection were included in the study. Serum M30 CK-18 levels reflected phase of disease, being significantly higher in both HBeAg(+) and HBeAg(-) hepatitis B in comparison to HBsAg(+) carrier groups. The highest serum M30 CK-18 levels were observed in subjects with the most advanced stages of HBV. Moreover, its serum concentrations correlated with both inflammatory activity and fibrosis advancement (ANOVA P < 0.001). Importantly, serum M30 CK-18 levels were able to discriminate patients with mild versus moderate-advanced fibrosis (AUC: 0.86) and mild versus active liver inflammation (AUC: 0.79). M30 CK-18 serum concentration has good sensitivity and specificity in discriminating mild versus moderate/severe fibrosis and inflammation even in patients with normal ALT activity. This study suggests M30 CK-18 as a potential noninvasive marker of disease activity and also a marker of phase of persistent HBV infection.

Hypertension, dyslipidaemia, and cardiovascular risk in HIV-infected adults in Poland.

BACKGROUND: The prevalence of cardiovascular diseases (CVD) in HIV-infected patients increases with aging and duration of the disease. Hypertension, high cholesterol level obesity, diabetes, tobacco exposure, and use of alcohol are among the traditional risk factors that contribute to CVD. AIM: The aim of the study was to determinate the incidence of hypertension, lipid disturbances, and CVD risk in dependence on clinical, viral, and biochemical factors. METHODS: A total of 417 HIV-infected Caucasian adult patients from the four clinical centres in Poland were enrolled and analysed on the basis of available medical data from the years 2013-2015. RESULTS: Hypertension was diagnosed in 28% of all patients and in the age ranges: < 40 years, 41-60 years and > 60 years in 18%, 43%, and 53%, respectively. The percentage of optimal, normal, and high normal blood pressure was: 28%, 14%, and 30%, respectively. Hypertension grade 1, 2, and 3 was observed in 58%, 35%, and 7% of patients, respectively. Factors associated with hypertension were: increasing age, male sex, increased body mass index, hypercholesterolaemia, hypo-high density lipoprotein (HDL), hypertriglyceridaemia and duration of HIV infection more than 10 years. Hypercholesterolaemia, suboptimal level of HDL, elevated low-density lipoprotein, and hypertriglyceridaemia were observed in 37%, 20.5%, 31%, and 52%, respectively. Hypertriglyceridaemia was associated with protease inhibitor-based highly active antiretroviral therapy. HCV infection was negatively associated with hypercholesterolaemia. Cigarette smoking was reported in 55% of cases. CONCLUSIONS: Incidence of hypertension in particular age groups of HIV infected people is higher than in the general Polish population. Hypertension is influenced by traditional risk factors and duration of HIV infection but not antiretroviral treatment. HIV/HCV coinfection appears to be protective against hypercholesterolaemia.

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.

Influence of HCV and HIV on development of cryoglobulinemia.

Cryoglobulinemic syndrome refers to a systemic inflammatory process that involves small and medium-sized vessels accompanied by multi-organ damage. The aim of the present study was to determine the incidence of cryoglobulinemia among patients infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HCV/HIV co-infection, as well as evaluation of cryoglobulinemia type. The association was evaluated between cryoglobulinemia and clinical symptoms, selected biochemical measures of liver and kidney function, virologic measures, as well as histopathological changes in the liver. One hundred and forty-one patients were enrolled (59 HCV mono-infected, 48 HIV mono-infected, and 34 HCV/HIV co-infected). Cryoglobulinemia was nearly five times less frequent among HIV mono-infected patients (10%) than HCV mono-infected (53%) and HCV/HIV co-infected patients (59%). Cryoglobulinemia was more frequent in patients infected with genotype 1 HCV than genotype 3 (63% vs. 46%, p=0.12). There was a lower incidence of cryoglobulinemia in HIV mono-infected patients treated with antiretroviral drugs (p=0.04). Cryoglobulinemia correlated with ALT activity (p=0.01) and HIV viral load (p<0.001). Symptoms were significantly more frequent among cryoglobulinemic patients than those without cryoglobulinemia (38% vs. 9%, p<0.001). The most common symptoms related to cryoglobulinemia, regardless of cryoglobulinemia type, were fatigue (38%), arthralgia (20%), polineuropathy (18%), and skin lesions (14%). In conclusion, HCV mono-infection and HCV/HIV co-infection, regardless of HCV genotype, are potent stimulators of cryoglobulinemia, with its symptomatic form occurring in about 40% of cases. Effective antiretroviral therapy seems to be protective against cryoglobulinemia development in HIV mono-infected patients.

Impact of rs12979860 polymorphism on liver morphology in chronic HCV infection.

AIM OF THE STUDY: To determine distribution of rs12979860 genotypes, their correlations with viral load as well as inflammatory activity and stage of liver fibrosis in patients infected with HCV genotype 1. MATERIAL AND METHODS: The study included 132 patients infected with HCV genotype 1b. Serum viral loads were obtained with the PCR method. Rs12979860 polymorphisms were determined by sequencing of PCR products. Liver biopsy was performed in all patients. RESULTS: CT, TT and CC alleles of rs12979860 polymorphism were detected in 58%, 20% and 22% of patients respectively. The highest viral load was observed in the TT and the lowest in the CC group (72.0 × 106 IU/ml vs. 2.1 × 106 IU/ml, p < 0.005). A significant correlation was demonstrated between patient's age and inflammatory activity as well as degree of liver fibrosis. No association was found between liver histopathology and HCV viral load or rs12979860 genotypes. CONCLUSIONS: There is an association between HCV viral load and rs12979860 polymorphism. Inflammatory activity and stage of liver fibrosis depend on age, but there is no relationship with rs12979860 genotypes and HCV viral load.

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.

Exacerbation of chronic hepatitis B during chemotherapy due to testicular seminoma.

Chronic hepatitis B is often asymptomatic until it progresses to advanced stage. The natural course of disease includes flares and periods of decreased inflammatory activity. Immune decline status is proven risk factor for exacerbation of viral hepatitis. Anticancer chemotherapy in chronic HBsAg carriers is known to promote viral replication. Return of immunocompetence after withdrawal of immunosuppressant might result in liver damage. We describe case of a patient with chronic HBV infection who developed hepatitis flare subsequently to the cessation of anti-viral treatment and introduction of chemotherapy due to testicular seminoma. Patients with history of HBV infection who receive immunosuppressive treatment are at risk of HBV reactivation or exacerbation of hepatitis. During immunosuppressive treatment enhanced HBV replication and inhibition of CTL without evident liver injury is observed. Restoration of immune system after withdrawal of immunosuppressant allows recognizing increased expression of HBV antigens in hepatocytes. Intensive elimination of infected hepatocytes could occur resulting in liver tissue necrosis, active hepatitis and liver decompensation. It is recommended for HBV infected patients on immunosuppressive treatment to receive antiviral therapy, particularly with the lowest risk for the selection of mutations, regardless the stage of infection.

Prevalence of cryoglobulinaemia in hepatitis C virus- and hepatitis C virus/human immunodeficiency virus-infected individuals: implications for renal function.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) demonstrate an affinity towards lymphocytes B, stimulating the production of cryoglobulins. Deposits of cryoprecipitates contribute to glomerulonephritis and renal failure. The presence of cryoglobulins was investigated in the sera of HCV-monoinfected and HCV/HIV-coinfected individuals. Associations between types of cryoglobulins and HCV genotypes, viral load and renal function tests were also evaluated. PATIENTS AND METHODS: Seventy-seven patients were enrolled in this study. Forty-four were HCV infected and 33 were HCV/HIV coinfected. Cryoglobulins were detected in the sera by electrophoresis and immunofixation. Serum urea and creatinine concentration, glomerular filtration rate (GFR) and serum cystatin C concentration (CC) were analysed to evaluate renal function. The control group included 16 healthy individuals. RESULTS: The occurrence of cryoglobulinaemia in HCV-monoinfected patients was 55%, whereas in HCV/HIV-coinfected patients it was 64%. Mixed cryoglobulinaemia type II was determined in 34%, whereas type III in 25%. The prevalence of cryoglobulinaemia was significantly higher in infection with HCV genotype 1 vs. genotype 3 (65 vs. 50%; P<0.01). The most frequently occurring heavy chains were gamma-type (96%). Light chains, the kappa-type, were detected in all patients. The CC concentration was significantly higher in HCV/HIV-coinfected patients compared with controls (718 vs. 392 ng/ml; P<0.005) or HCV-monoinfected patients (508 ng/ml; P<0.007). There was correlation between the serum CC concentration and the incidence of cryoglobulinaemia (R=0.44; P<0.00015), which was particularly evident in HCV monoinfection (R=0.43; P<0.0034). CONCLUSIONS: Genotype-1 infection is an important risk factor for cryoglobulinaemia. Standard renal function tests are not sufficient for the prediction of renal failure in HCV-infected patients. Serum CC concentration allows to establish an early diagnosis of renal insufficiency related to cryoglobulinaemia.

[Influence of cryoglobulinaemia on renal function in patients with chronic HCV infection]. / Wplyw krioglobulinemii na funkcje nerek wsród osób przewlekle zakazonych HCV.

UNLABELLED: HCV infection is a common cause of cryoglobulinaemia, characterized by existence of antibodies that show reversible precipitation at low temperatures. Deposition of cryoglobulines in glomerular vessels tends to induce development of membranous, or less commonly, mesangial glomerulonephritis with renal insufficiency as final consequence. Objective was investigating the existence of cryoglobulinaemia, its types and relation with renal impairment in patients chronically infected with hepatitis C virus. METHODS: The research included 36 patients (9 women and 27 men) chronically infected with hepatitis C virus at the average age 38 years. Existence and types of cryoglobulines in serum were measured using electrophoresis and then immunofixation on cryogel by the method of Bence Jones (Sebia, France). Renal functioning was estimated with reference to serum urea and creatinine concentrations, glomerular filtration rate (GFR) and serum cystatin C concentration with immunoenzymatic method. RESULTS: Cryoglobulinaemia was significantly more common among patients infected with genotype 1 than 3 (71% vs. 39%; p<0.05). Types II and III of cryoglobulinaemia existed in equal frequency. The most common heavy chains were gamma immunoglobulins (42%) and the light ones--kappa (54%). Urea and creatinine concentration were normal in all patients. Three patients diagnosed with cryoglobulinaemia and infected with genotype 1 had abnormal GFR. There was dependency between cryoglobulinaemia and elevated cystatin C concentration (R=0.4; p<0.013).