Urinary metabolomics of HCV patients with severe liver fibrosis before and during the sustained virologic response achieved by direct acting antiviral treatment.

Hepatitis C virus (HCV) infection induces a long-term inflammatory response and oxidative-stress in the liver microenvironment, leading to hepatic fibrosis and metabolic alterations. Direct-acting-antiviral-agents (DAAs) induce HCV-clearance, even though liver damage is only partially restored. In this context, understanding the impact of viral-eradication on liver metabolic activities could allow optimizing the metabolic care of the patient. The present prospective longitudinal study aims at characterizing the urinary metabolic profile of HCV-induced severe liver fibrosis and the metabolic changes induced by DAAs and HCV-clearance by nuclear magnetic resonance-based metabolomics. The urinary metabolic profile of 23 HCV males with severe liver fibrosis and 20 age-matched healthy-controls was analyzed by NMR-based-metabolomics before starting DAAs, at the end-of-therapy, after one and three months of follow-up. The urinary metabolic profile of patients with severe liver fibrosis was associated to pseudouridine, hypoxanthine, methylguanidine and dimethylamine, highlighting a profile related to oxidative damage, and to tyrosine and glutamine, related to a decreased breakdown of aromatic aminoacids and ammonia detoxification, respectively. 1-methylnicotinamide, a catabolic intermediate of nicotinamide-adenine-dinucleotide, was significantly increased in HCV-patients and restored after HCV-clearance, probably due to the reduced hepatic inflammation. 3-hydroxy-3-methylbutyrate, an intermediate of leucine-catabolism which was permanently restored after HCV-clearance, suggested an improvement of skeletal muscle protein synthesis. Finally, 3-hydroxyisobutyrate and 2,3-dihydroxy-2-methylbutyrate, intermediates of valine-catabolism, glycine and choline increased temporarily during therapy, resulting as potential biomarkers of DAAs systemic effects.

Urinary 8-oxo-7,8-dihydroguanosine levels are elevated in HCV-infected patients.

HCV patients are usually under substantial oxidative stress because of viral infection. A total of 177 patients with HCV infection and 198 age- and sex-matched healthy controls were enrolled in this study. We evaluated the urinary levels of 8-oxo-7, 8-dihydro-2'deoxyguanosine (8-oxodGuo) and 8-oxo-7, 8-dihydroguanosine (8-oxoGuo) in patients with HCV infection and explored the factors affecting the urinary 8-oxodGuo or 8-oxoGuo levels. Biomarkers of liver function, cancer, and inflammation were determined. Nonparametric correlations were used to evaluate the correlation between 8-oxoGuo or 8-oxodGuo and various laboratory biochemical indicators. Results showed that the levels of urinary 8-oxoGuo both in male and female patients with HCV infection were significantly higher than those in healthy controls (both p < 0.0001), while the urinary 8-oxodGuo levels only in male patients with HCV infection were significantly higher than those in healthy controls (p < 0.01). Urinary 8-oxoGuo was significantly associated with the white blood cell count, C-reactive protein level, and 8-oxodGuo level (p = 0.016, p = 0.003, and p = 0.000, respectively). Urinary 8-oxodGuo was significantly associated with the white blood cell count and 8-oxoGuo level (p = 0.018 and p = 0.000, respectively). A regression equation of urinary 8-oxoGuo or 8-oxodGuo was also established using the biomarkers in plasma. The results suggested that patients with a high C-reactive protein level are likely to have high urinary 8-oxoGuo levels as well, which may be useful for assessing the level of inflammation and oxidative stress in HCV patients.Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021.1961272 .

Association between hepatitis C virus and opioid use while in buprenorphine treatment: preliminary findings.

BACKGROUND: The prevalence of hepatitis-C-virus (HCV) infections is high among opioid-dependent individuals. Prior research on the simultaneous treatment of both conditions has primarily assessed success as it pertains to HCV. However, it has been noted that favorable substance use therapy outcomes may improve the likelihood of HCV-treatment initiation and success. Therefore, current guidelines for the treatment of HCV among illicit drug users suggest that treatment for addiction be given the highest priority. OBJECTIVES: To determine whether opioid-dependent participants in a clinical trial of buprenorphine-treatment tapering regimens, who tested positive for the HCV antibody, experienced significantly different levels of opioid abstinence than those not infected. METHODS: Data came from the National Drug Abuse Treatment Clinical Trial Network study 0003. 516 eligible opioid-dependent participants were randomized to either a 7-day or 28-day buprenorphine tapering schedule following a 4-week buprenorphine stabilization period. Generalized estimating equations were used to test the research question. RESULTS: Participants with the HCV antibody were significantly less likely to submit opioid-negative urine analyses during and/or immediately following active treatment [OR = 0.69; CI = 0.51-0.93], indicating a higher rate of opioid use among this group. CONCLUSION: Individualized opioid-dependence treatment strategies may be required for opioid-dependent individuals who test positive for the HCV antibody in order to ensure resources for both opioid-dependence and HCV therapies are used efficiently.

Hepameta-- prevalence of hepatitis B/C and metabolic syndrome in population living in separated and segregated Roma settlements: a methodology for a cross-sectional population-based study using community-based approach.

BACKGROUND: Roma represent one of the largest and oldest minorities in Europe. Health of many of them, particularly those living in settlements, is heavily compromised by poor dwelling, low educational level, unemployment, and poverty rooted in generational poverty, segregation and discrimination. The cross-sectional population-based study using community based approach aimed to map the prevalence of viral hepatitis B/C and metabolic syndrome in the population living in separated and segregated Roma settlements and to compare it with the occurrence of the same health indicators in the majority population, considering selected risk and protective factors of these health indicators. METHODS: The sample consisted of 452 Roma (mean age = 34.7; 35.2% men) and 403 non-Roma (mean age = 33.5; 45.9% men) respondents. Data were collected in 2011 via questionnaire, anthropometric measures and analysed blood and urine samples. A methodology used in the study as well as in the following scientific papers is described in the Methods section (i.e. study design, procedures, samples, methods including questionnaire, anthropometric measurements, physical measurements, blood and urine measurements). CONCLUSIONS: There are regions of declining prosperity due to high unemployment, long-term problems with poverty and depleted resources. Populations living in these areas, i.e. in Central and Eastern Europe in Roma settlements, are at risk of poverty, social exclusion and other factors affecting health. Therefore, we should look for successful long-term strategies and tools (e.g. Roma mediators, terrain work) in order to improve the future prospects of these minorities.

Proteomic analysis of serum and urine of HIV-monoinfected and HIV/HCV-coinfected patients undergoing long term treatment with nevirapine.

Nevirapine (NVP) is an effective nonnucleoside reverse transcriptase inhibitor (NNRTI) of particular interest as it is often used in resource limited countries. However, one of the main concerns with the use of NVP is hepatotoxicity and elevation of liver enzymes as a consequence of highly active antiretroviral therapy (HAART) containing NVP is more often reported in HIV patients coinfected with hepatitis C virus than in HIV-monoinfected patients. To discover possible markers of NVP induced hepatotoxicity, serum and urine samples from twenty-five HIV or HIV/HCV patients, all of whom had received NVP continuously for at least four months, and healthy controls were subjected to in-solution or in-gel proteomic analysis. A total of 83 differentially regulated proteins consisted of 34 proteins identified in serum by in-solution analysis, 2 proteins identified from serum in a 2D gel electrophoresis analysis, and 47 proteins identified in urine in an in-solution analysis. Three proteins, namely, haptoglobin, Rho-related BTB domain containing protein 3, and death-associated protein kinase 3, were selected for further validation by Western blot analysis and results showed that haptoglobin has potential for further development as an additional marker of NVP induced hepatotoxicity.

The investigation of specific biochemical markers in monitoring kidney function of drug addicts.

INTRODUCTION: An increasingly important issue in the Polish population is drug abuse. It leads to extensive damage of parenchymal organs, including kidney. Establishing early markers of organ damage and their monitoring during rehabilitation therapy is therefore of pivotal importance. This study evaluated the utility of highly specific and selective markers (NGAL, IL-18, a and π-GST isoenzyme, and ß2-M). The influence of opioid drugs and other factors on kidney function (HIV and HCV infections, duration and the kind of drugs abused) was determined. MATERIALS AND METHODS: Urine collected from 83 subjects who abused drugs and 33 healthy volunteers was tested with ELISA using specific antibodies (IBL, Biotron, Bioporto-Diagnostics). HIV infection was confirmed with western-blotting and HCV with PCR. CD4 lymphocytes were quantified with flow cytometry. RFLP and PCR were used to determine the viral load of HIV and HCV (genotype). RESULTS: A significant increase of IL-18, NGAL and ß2M activity in heroin addicts compared to the control group was noted as well as the influence of HIV infection on NGAL and ß2M excretion. A statistically significant (p=0.04) correlation between the viral load and IL-18 concentration was noted while no significant influence of the duration and the kind of drugs abused, the route of intake or the age of addicts was seen. Only the NGAL concentration was sex dependent and significantly higher in women. DISCUSSION: This study showed the specific, clinical utility of IL-18, NGAL, and ß2M in the evaluation of renal function in drug addicts. Early detection of nephropathy with biochemical indicators might help prevent severe conditions that require hospitalization and intensive care.

Distribución de genotipos del virus de hepatitis C en la población Argentina / Distribution of hepatitis C virus genotypes in an Argentine population / Distribuição dos genótipos do vírus da hepatite C na população Argentina

Mundialmente se han identificado 6 genotipos (1 al 6) del virus de la hepa­titis C (HCV). Dichos genotipos se subdividen en diferentes subtipos (a, b, c y otros). La respuesta al tratamiento instaurado depende del genotipo del virus infectante. El objetivo del trabajo fue determinar la frecuencia de los diferentes genotipos del HCV en la población de Argentina. Se estudiaron 510 pacientes infectados con HCV; la genotipificación del virus se realizó utilizando el equipo Versant HCV genotype assay 2.0 (LiPA). Los resultados obtenidos indican que el genotipo predominante del HCV en Argentina es el 1 (67,6%), con una prevalencia similar de subtipos 1a y 1b (33,3% y 34,5%, respectivamente). Se observó también una frecuencia similar de los genotipos 2 y 3 (14,5% cada uno). Con este estudio se actualizan los datos de las frecuencias de los diferentes genotipos de HCV que circulan en Argentina utilizando la nueva versión del reactivo para diagnóstico, el cual permitió una correcta subtipificación de las muestras.

Six hepatitis C virus genotypes have been identified worldwide so far. The­se genotypes have been subclassified into different subtypes (a, b, c and others). It is known that the response to treatment is highly dependent on the genotype involved. The aim of this work was to assess the frequency of occurrence of the different HCV genotypes in the population of Argentina. To this end, 510 infected patients were subjected to HCV genotyping using the commercial kit Versant HCV genotype assay 2.0. Results indicated that the genotype 1 was the most frequent (67.6%), and that subtypes 1a and 1b showed a similar prevalence (33.3% and 34.5%, respectively). Genotypes 2 and 3 also displayed a similar frequency (14.5% and 14.5% respectively). This study provides an update regarding the frequency of all HCV genotypes circulating in Argentina. The results were obtained by the novel version of the genotyping kit, which enabled a correct subtyping of samples.

Globalmente foram identificados 6 genótipos (1 ao 6) do vírus da hepatite C (HCV). Estes genótipos são subdivididos em vários subtipos (a, b, c, etc.). A resposta ao tratamento depende do genótipo do vírus infectante. O objetivo do estudo foi determinar a freqüência dos diferentes genótipos do HCV na população Argentina. Foram estudados 510 pacientes infectados com o HCV, a genotipagem do vírus foi realizada utilizando o kit Versant HCV genotype assay 2.0 (LiPA). Os resultados obtidos indicam que o genótipo predominante na Argentina é o tipo 1 (67,6%), observando-se uma prevalência dos subtipos 1a e 1b (33,3% e 34,5% respectivamente). Observou-se também uma freqüência semelhante do genótipos 2 e 3 (14,5% e 14,5% respectivamente). Este estudo atualiza os dados das freqüências dos diferentes genótipos do HCV em circulação na Argentina usando a nova versão do kit, o que permitiu uma correta subtipagem das amostras.

Diagnosis of liver cancer and cirrhosis by the fluorescence spectra of blood and urine.

Liver cancer or hepato cellular carcinoma (HCC) is a serious malady with only 10% survival rate and is fatal next only to pancreatic cancer. This disease is conventionally detected and diagnosed by ultra sound, CT or MRI scans which are quite expensive. Also the discrimination between cirrhosis and HCC, by these imaging techniques, is poor. The conventional tissue biopsy is quite invasive and painful. In the new diagnostic procedure presented in this paper we have obtained fluorescence emission spectra with excitation at 400 nm and the synchronous emission spectra (Δλ = 10 nm) for a set of blood and urine samples (Normal control N = 25, Liver Malfunction N = 58). Based on the ratio fluorometric parameters, all the three liver maladies (minor inflammation like Hepatitis C, serious diseases like Cirrhosis and hepatoma) could be detected and discriminated with an accuracy of about 80%. Hence this inexpensive, non invasive, optical technique may have significant impact in screening, diagnosis and also prognosis of HCC in large segment of people in the populous Asian countries.

A sensitive and accurate liquid chromatography-tandem mass spectrometry method for quantitative determination of the novel hepatitis C NS5A inhibitor BMS-790052 (daclastasvir) in human plasma and urine.

A liquid-liquid extraction (LLE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods have been developed and validated for the quantification of BMS-790052 (daclastasvir) in human plasma and urine. The samples were extracted with methyl-t-butyl ether (MTBE) before analyzing by an API 4000 mass spectrometer which was operated in a multiple reaction monitoring (MRM) mode for detection of positively charged ions of BMS-790052 and its internal standard, ¹³C10-BMS-790052. The standard curves ranged from 0.050 to 50.0 ng/mL for BMS-790052 in human plasma, and 1.00-1000 ng/mL in human urine. The intra-assay precision (%CV), based on four levels of analytical QCs (low, geometric mean, mid and high), was within 8.6%; inter-assay precision (%CV) was within 6.7% for both plasma and urine methods, and the mean assay accuracy (%Dev) was within ±3.0% for both plasma and urine methods. The ruggedness of this accurate, precise, and selective LLE-LC-MS/MS method has been demonstrated in the successful analysis of several thousand clinical study samples.

Distribution of copper, iron, and zinc in biological samples (scalp hair, serum, blood, and urine) of Pakistani viral hepatitis (A-E) patients and controls.

The aim of the present study was to compare the level of copper (Cu), iron (Fe) and zinc (Zn) in biological samples (serum, blood, urine, and scalp hair) of patients suffering from different viral hepatitis (A, B, C, D, and E; n = 521) of both gender age ranged 31-45 years. For comparative study, 255 age-matched control subjects, of both genders residing in the same city were selected as referents. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and with those values obtained by conventional wet acid digestion method on same CRMs. The results of this study showed that the mean values of Cu and Fe were higher in blood, sera, and scalp hair samples of hepatitis patients, while Zn level was found to be lower than age-matched control subjects. The urinary levels of these elements were found to be higher in the hepatitis patients than in the age-matched healthy controls (p < 0.05). These results are consistent with literature-reported data, confirming that the deficiency of zinc and hepatic iron and copper overload can directly cause lipid peroxidation and eventually hepatic damage.

Feasibility of collecting biologic specimens in population-based surveys: experiences from the epidemiology of hepatitis C in the household, adult population of Puerto Rico study.

The Behavioral Risk Factor Surveillance System (BRFSS) collects data on preventive health practices and risk behaviors that are linked to chronic diseases, injuries, and preventable infectious diseases that affect the adult population in all states and territories in the US. The BRFSS is currently the only survey conducted annually in Puerto Rico in the population aged 18 years and older; however, prevalence estimates are based on self-reports and therefore are subject to reporting errors. Although surveillance data are useful for the purpose of evaluation, program planning and health policy, surveys that collect biological specimens and clinical data provide a more accurate assessment of prevalence and a comprehensive picture of disease distribution and their risk factors. This article summarizes the methodology employed in a population-based study to estimate the seroprevalence of hepatitis C and other viral infections in Puerto Rico and shows the feasibility of combining different modes of data collection in population-based surveys that collect biologic specimens.

Aflatoxin B1 albumin adducts in plasma and aflatoxin M1 in urine are associated with plasma concentrations of vitamins A and E.

BACKGROUND: Although aflatoxin exposure has been associated with micronutrient deficiency in animals, there are few investigations on the effects of aflatoxin exposure on micronutrient metabolism in humans. OBJECTIVE: To examine the relationship between aflatoxin B1 (AFB1) albumin adducts (AF-ALB) in plasma and the aflatoxin M1 (AFM1) metabolite in urine and plasma concentrations of retinol (vitamin A) and alpha-tocopherol (vitamin E) in Ghanaians. METHODS: A cross-sectional study of 147 adult participants was conducted. Blood and urine samples were tested for aflatoxin and vitamins A and E levels. RESULTS: Multivariable analysis showed that participants with high AF-ALB (>or=0.80 pmol/mg albumin) had increased odds of having vitamin A deficiency compared to those with lower AF-ALB [Odds Ratio (OR)=2.61; CI=1.03-6.58; p=0.04]. Participants with high AF-ALB also showed increased odds of having vitamin E deficiency but this was not statistically significant (OR=2.4; CI=0.96-6.05; p=0.06). Conversely, those with higher AFM1 values had a statistically nonsignificant reduced odds of having vitamin A deficiency (OR=0.31; CI=0.09-1.02; p=0.05) and a statistically significant reduced odds of having vitamin E deficiency (OR=0.31; CI=0.10-0.97; p=0.04). Participants with high AF-ALB or high AFM1 (>or=437.95 pg/dL creatinine) were almost 6 times more likely to be hepatitis B virus surface antigen (HBsAg)-positive (OR=5.88; CI=1.71-20.14; p=0.005) and (OR=5.84; CI=1.15-29.54; p=0.03) respectively. CONCLUSIONS: These data indicate that aflatoxin may modify plasma micronutrient status. Thus, preventing aflatoxin exposure may reduce vitamin A and E deficiencies.

Clinical study of urinary sulfated bile acids in patients with hepatitis C virus.

BACKGROUND/AIMS: Sulfation is considered to be a detoxifying mechanism for bile acids, which allows the sulfated bile acids to be eliminated in the urine (urinary sulfated bile acids: USBA) by enhancing renal clearance when serum bile acids increase due to hepatobiliary disease. We measured urinary sulfated bile acids in patients positive for hepatitis C virus and studied the relation between USBA and standard liver function tests. METHODOLOGY: Seventy-eight outpatients could be followed for at least one year were enrolled in this study. Blood and urine samples were simultaneously obtained from the patients. The measured urinary sulfated bile acids levels were adjusted for the urinary creatinine concentration and the normal value was defined <8 micromol/g creatinine. RESULTS: Among the 78 patients, the mean USBA level of 26 carriers, 37 patients with chronic hepatitis C, 9 with liver cirrhosis, and 6 with hepatocellular carcinoma were 6.0 +/- 6.1 micromol/g creatinine (mean +/- SD), 27.9 +/- 35.8, 33.1+/- 22.7, and 50.6 +/- 47.3, respectively. The mean urinary sulfated bile acids level was correlated with the clinical progression of these liver diseases. CONCLUSIONS: Urinary sulfated bile acids are considered to be a useful diagnostic indicator of impaired liver function, and can also be used to assess the severity of hepatic disease.

Electrophoretic methods for analysis of urinary polypeptides in IgA-associated renal diseases.

We evaluated the utility of SDS-PAGE/Western blot and CE coupled with MS (CE-MS) for detection of urinary polypeptide biomarkers of renal disease in patients with IgA-associated glomerulonephritides. In a reference cohort of 402 patients with various renal disorders and 207 healthy controls, we defined CE-MS patterns of renal damage and IgA nephropathy (IgAN). In a blinded analysis of a separate cohort of patients with IgAN (n = 10), Henoch-Schoenlein purpura (HSP) with nephritis (n = 10), and IgA-associated glomerulonephritis due to hepatitis C virus (HCV)-induced cirrhosis (n = 9), and healthy controls (n = 12), we compared SDS-PAGE/Western blot and CE-MS against clinical urinalysis for detection of urinary proteins/polypeptides. Urinalysis indicated proteinuria for 50, 90, and 33% of patients, respectively, and for none of the healthy controls. SDS-PAGE/Western blot showed urinary polypeptides abnormality for 90, 80, and 67% of patients, respectively, and for none of the healthy controls. CE-MS indicated a Renal Damage Pattern in 80, 80, and 100 of patients, respectively, and in 17% of healthy controls, with the more specific IgAN Pattern in 90, 90, and 1%, respectively, and in none of the healthy controls. Based on differences in CE-MS patterns, the disease mechanisms may differ among various IgA-associated glomerulonephritides. These exploratory findings should be evaluated in a prospective study with contemporaneous renal biopsy and urinary testing. If validated, it may be feasible to adapt the CE-MS methodology to develop novel tests to detect renal injury at earlier stages, assess clinical manifestations, and monitor responses to therapy in patients with IgA-associated renal diseases.

Viral hepatitis and proteinuria in an area endemic for hepatitis B and C infections: another chain of link?

BACKGROUND AND OBJECTIVES: Virus hepatitis may lead to nephropathy as one of its multiple extrahepatic manifestations. Proteinuria by dipstick, a simple test in practice, is a useful and cardinal sign of underlying renal abnormalities. The aim of this study was to elucidate the impact of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections on the occurrence of proteinuria amongst adults. DESIGN AND SETTING: A prospective, cross-sectional, community-based study was conducted in an HBV/HCV endemic area of southern Taiwan. Eligible subjects aged 40-65 years (n=9934) underwent testing of hepatitis B surface antigen (HBsAg), HCV antibody (anti-HCV) and other related biochemical profiles. Urinalysis with repeated dipstick for proteinuria detection was performed. RESULTS: Anti-HCV-positive rate amongst proteinuria subjects was significantly higher than nonproteinuria subjects (9.6% vs. 6.2%, P<0.001). By contrast, HBsAg-positive rate did not differ between subjects with and without proteinuria (13.0% vs. 13.8%, P=0.57). Prevalence of proteinuria amongst anti-HCV-positive subjects (10.2%) was significantly higher than that in HBsAg-positive subjects (6.4%, P=0.004) and in HBsAg-negative or anti-HCV-negative subjects (7.0%, P=0.004). The difference persisted even after excluding diabetics. Multivariate logistic regression analyses showed that diabetes was the most important significant factor associated with proteinuria, followed by hypertension, anti-HCV seropositivity, body mass index, age and triglyceride levels. CONCLUSION: We demonstrated the significant association between proteinuria and HCV, but not HBV, infection in this HBV/HCV-endemic area.

Urinary porphyrin excretion in hepatitis C infection.

A high prevalence of hepatitis C virus infection in porphyria cutanea tarda in some populations suggests a close link between viral hepatitis and alteration of porphyrin metabolism. Moreover, there is evidence of a role of porphyrinopathies in hepatocarcinogenesis. The aim of our study was to obtain data on the prevalence and patterns of heme metabolism alterations in patients with chronic hepatitis C virus infection. Urinary porphyrin excretion was prospectively studied in 100 consecutive outpatients with chronic hepatitis C infection without signs of photosensitivity, using an ion-pair high-performance liquid chromatography method. Increased total porphyrin excretion was found in 41 patients, with predominant excretion of coproporphyrins (whole study group: mean 146 microg/g creatinine, interquartile range 76-186; normal < 150), in 10 patients excretion exceeded 300 microg/g creatinine. In the majority of all patients studied (75/100) an increased ratio of the relatively hydrophobic coproporphyrin isomer I to isomer III was found. In just one case, urinary porphyrin pattern characteristic for chronic hepatic porphyria was present (uroporphyrin > coproporphyrin, heptacarboxyporphyrin III increased) but the total porphyrin excretion was only slightly elevated in this case. In the whole group, total urinary porphyrin excretion correlated well with serum bilirubin and was inversely correlated with albumin and thrombin time. In conclusion, secondary coproporphyrinuria occurs frequently in heptatitis C infection, whereas in Germany, preclinical porphyria cutanea tarda seems to be rare in these patients.

Sustained response to interferon-alpha or to interferon-alpha plus ribavirin in hepatitis C virus-associated symptomatic mixed cryoglobulinaemia.

BACKGROUND: Hepatitis C virus (HCV) infection has been associated with mixed cryoglobulinaemia. AIM: To investigate the efficacy of anti-viral therapy on the eradication of HCV and its clinical manifestations in patients with HCV-associated symptomatic mixed cryoglobulinaemia. PATIENTS AND METHODS: 18 out of 32 patients with symptomatic mixed cryoglobulinaemia (MC group) received a 12-month course of interferon (3 MU three times a week, subcutaneously). Nonresponders or relapsers to this therapy were treated with interferon plus ribavirin (1200 mg/day, orally) for 12-months. 226 patients with HCV infection and without cryoglobulins were studied in comparison (Hepatitis C group). Serial quantification of serum HCV-RNA and cryoglobulins were performed. RESULTS: In the MC group, 10 out of 18 patients (55%) receiving interferon showed an end of treatment response, but at the end of follow-up, only five (28%) patients had a sustained response. In the hepatitis C group, 91 patients (47%) showed an end of treatment response but only 42 (20%) a sustained response. In the MC group alanine transaminase, cryocrit and rheumatoid factor decreased significantly in responders, with an improvement or disappearance of the MC-associated clinical manifestations. Alanine transaminase, cryocrit and rheumatoid factor increased in the relapsers and the clinical manifestations reappeared. Nonresponders and relapsers to interferon in the MC group were retreated with interferon plus ribavirin. Five out of eight nonresponders showed a end of treatment response but it was sustained in three of them. In the relapsers, treatment with combined therapy achieved a sustained response in four out of the five patients (80%). CONCLUSIONS: Interferon as monotherapy or combined with ribavirin is a safe and effective treatment in patients with HCV-associated MC. The presence of cryoglobulins does not affect the response to anti-viral treatment in patients with HCV infection. The eradication of HCV is associated with an improvement or disappearance of MC-associated clinical manifestations.

HCV antibodies in saliva and urine.

Infection with hepatitis C virus (HCV) is usually established by detection of serum antibodies (anti-HCV). This study was conducted in order to evaluate whether saliva and urine may substitute serum for anti-HCV detection. Serum, saliva, and urine were obtained simultaneously from 141 patients with a variety of liver diseases and from 52 patients with autoimmune diseases (systemic lupus erythematosus n = 27 and rheumatoid arthritis n = 25). The cell free fraction of saliva and urine samples was tested for anti-HCV using a modification of a serum anti-HCV kit. Western blot analysis was used as a confirmation method. Of the patients with liver diseases, 73 were anti-HCV-seropositive. Salivary and urinary anti-HCV could be detected in 66 (90%) and 36 (49%) of the anti-HCV-seropositive patients, respectively. The presence of anti-HCV in saliva or urine was not related to the severity of liver disease. All the anti-HCV-seronegative liver patients were negative for salivary anti-HCV and 22 (32%) had urinary anti-HCV. The patients with autoimmune diseases were all anti-HCV-seronegative. None had detectable salivary anti-HCV while 33 (63%) were positive for urinary anti-HCV. Western Blot analysis confirmed the presence of anti-HCV in all serum and saliva samples tested but only in 2/12 urine samples. The results suggest that saliva, but not urine, may serve as a substitute for serum for the determination of anti-HCV positivity.

[Renal manifestations of viral diseases]. / Manifestations rénales des affections virales.

Like bacterial diseases viral diseases may also be accompanied by functional renal disorders or abnormalities of the urinary sediment. Thus, to find a hematuria or an isolated proteinuria in the context of influenza or hepatitis is not rare at all. In certain cases viral affections may even be accompanied by a nephrotic syndrome. This article aims at the discussion of multiple renal disorders appearing in the context of hepatitis B and C and AIDS.