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Biomedical subjects

A Alberti

Publications and source records attributed to A Alberti.

At least 37 records · Page 2Linked to original sources

Hepatitis C virus quasispecies in the natural course of HCV-related disease in patients with haemophilia.

Patients with haemophilia show high prevalence of hepatitis C infection but low rate of progressive liver disease when they are not co-infected with HIV. The balance between host immune system and hepatitis C virus (HCV) variability seems to play a major role in the evolution of the HCV-related disease. To address this point we have studied, in a group of selected patients with haemophilia, the composition and in some cases the evolution, of the highest variable envelope gene within the hypervariable region 1 (HVR1) of the HCV, which is the region more directly exposed to the host immune response. Five of 12 patients show a very high homogeneity of the HVR1 and four of those had severe progressive liver disease. These results seem to confirm the major role of the immunity in driving the variability of the HCV rather than the high degree of different HCV strains to which haemophiliacs have been in touch with, during their long-term replacement therapy. Our results seem in keeping with other studies on different type of patients, where a low degree of quasispecies variability has been demonstrated in relationship with the progression and the severity of their liver disease.

Adult↗

Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance.

We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins.

Adult↗

Platelet-activating factor (PAF) in internal jugular venous blood of migraine without aura patients assessed during migraine attacks.

The aim of the study was to verify the production of PAF and the activity of PAF acetyl-hydrolase (PAF-AH), the enzyme involved in the catabolism of this phospholipid mediator, in migraine attacks. Their levels were determined during migraine crises in serial samples of internal jugular venous blood taken from five migraine patients without aura, who were admitted to the hospital during the crises. Internal jugular venous blood samples were taken immediately after catheter insertion at 1, 2, and 4 h after attack onset, and within 2 h from its cessation. PAF was purified by high-performance liquid chromatography (HPLC) and determined by radioimmunoassay method. The enzymatic activity of PAF-AH was measured by reverse-phase HPLC, based on the derivatization with 7-diethylaminocoumarin-3-carbonylazide. In the internal jugular venous blood of migraine patients without aura (MO), an increase was observed in PAF levels, which was already evident at the time of catheter insertion (885.6 +/- 82.8) and at the first hour (868.4 +/- 65.24) (ANOVA: P < 0.0001). PAF levels remained elevated through the second (746.8 +/- 82.95), fourth (700.6 +/- 34.93) and sixth hours (644.4 +/- 42.85), and then decreased at the end of the attack, reaching levels significantly lower than those measured at the time of catheter insertion (565.5 +/- 38.34). The activity of PAF-AH showed an opposite trend with higher values at the first hour and significantly lower values at the second and fourth hours from the beginning of the migraine attack (ANOVA: P < 0.02). The increased production of PAF may account for persistent platelet activation during migraine crises, even in the presence of an increased production of nitric oxide (NO) end-products which, on the other hand, should instead intervene in counteracting and limiting platelet activation. Potential sources of PAF production are the endothelial cells from cerebral vessels, stimulated by trigeminal neuropeptides, platelets themselves, and mast cells, as suggested by the neurogenic inflammation model.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications.

BACKGROUND AND AIMS: The natural history of initially compensated cirrhosis due to hepatitis B (HBV) or hepatitis C (HCV) virus is only partially defined. We have investigated morbidity and mortality rates and the hierarchy of complications in compensated viral cirrhosis over a long follow up period. PATIENTS AND METHODS: A cohort of Italian patients with initially compensated cirrhosis of viral aetiology were followed up at six monthly intervals with laboratory tests to identify major complications (ascites, gastrointestinal bleeding, portal-systemic encephalopathy, hepatocellular carcinoma) and to assess the progression of Child's stage and mortality rate due to liver related causes. RESULTS: Between 1986 and 1996, 312 patients (43 HBV positive, 254 HCV positive, and 15 HBV and HCV coinfected) were included. During a median follow up of 93 (range 14-194) months, 102 (32.6%) patients developed at least one complication (HCV positive 31.1%; HBV positive 34.8%; HBV and HCV coinfected 53.3%). Overall, the most frequent complication was hepatocellular carcinoma which occurred in 65 (20.8%) cases, followed by ascites (61 cases, 19.5%), gastrointestinal bleeding (14 cases, 4.5%), and portal-systemic encephalopathy (six cases, 1.9%). Progression of Child's stage was observed in 62 patients (19.8%). Death from liver disease occurred in 58 (18.6%) cases and in 70.7% this was due to hepatocellular carcinoma. Hepatocellular carcinoma was the first complication to develop in 59 cases and represented the most frequent first complication in both HCV and HBV/ HCV related cirrhosis. CONCLUSIONS: These results indicate significant morbidity and mortality during the first decade after diagnosis of compensated cirrhosis due to HBV and/or HCV, and identify hepatocellular carcinoma as the most frequent and life threatening complication, particularly in HCV positive cases.

Adult↗

Genotoxicity of surface water treated with different disinfectants using in situ plant tests.

Disinfection of surface drinking water, in particular water chlorination, results in many by-products with potential genotoxic and/or carcinogenic activity. In the present study, we evaluated the genotoxicity of surface water after treatment with different disinfectants by means of in situ plant genotoxicity assays (micronucleus and chromosomal aberration tests) which can detect both clastogenic and aneugenic effects. The study was carried out at a pilot plant using lake water after sedimentation and filtration. This water supplied four stainless steel basins: three basins were disinfected with sodium hypochlorite, chlorine dioxide, and peracetic acid and the fourth basin containing untreated lake water was used as a control. Plants were exposed in situ in the basins. The study was carried out using water collected in different seasons over a period of about 1 year in order to assess the treatments in different physical and chemical lake water conditions. The micronucleus test in root cells of Vicia faba (Vicia faba/MCN test) revealed genotoxicity in many samples of disinfected water. The micronucleus test in Tradescantia pollen cells and the chromosome aberration test in root cells of Allium cepa showed genotoxic effects only in some disinfected samples, but also revealed genotoxicity in raw water. The results of the study indicated that the Vicia faba/MCN test was the most sensitive plant assay for disinfected water and that peracetic acid disinfection produced similar or lower genotoxicity than sodium hypochlorite or chlorine dioxide treatment.

Chlorine Compounds↗

Hepatitis reactivation and liver failure in haemopoietic stem cell transplants for hepatitis B virus (HBV)/hepatitis C virus (HCV) positive recipients: a retrospective study by the Italian group for blood and marrow transplantation.

Hepatitis B virus/hepatitis C virus (HBV/HCV) positive patients undergoing haemopoietic stem cell transplantation (HSCT) are at risk of hepatitis reactivation and fatal liver failure: we have conducted a retrospective study to assess the risk in 20 Italian transplant centres. A total of 90 patients infected with HBV (n=33) or HCV (n=57) receiving allogeneic (n=36) or autologous (n=54) haemotopoietic stem cell transplant (HSCT) between 1996 and 2000 were reviewed. The biochemical profiles and outcomes of infection-related liver disease were also analysed. The risk of death at 2 years was comparable when considering type of infection (3% for HBV vs 8% for HCV, P=0.6) or type of HSCT (7% for allogeneic vs 5% for autologous HHSCT, P=0.34). Hepatitis reactivation followed by resolution was more frequent in HCV+ than in HBV+ patients receiving an allograft (100% vs 16%, P=0.004). In HBV+ cases, risk of reactivation was comparable after autologous or allogeneic transplantation (66 vs 81%, P=0.3), but liver disease was more severe and occurred earlier in the autologous group. Our results indicate that HBV and HCV infection should not be taken as an absolute contraindication for HSCT and the risk of life-threatening liver complications are similar after allogeneic or autologous transplants.

Adult↗

Glutamate and nitric oxide pathway in chronic daily headache: evidence from cerebrospinal fluid.

A central sensitization has been advocated to explain chronic daily headache (CDH) due to sustained peripheral sensitization of allogenic structures responsible for sustained trigeminovascular system activation. Several mechanisms have been suggested to underlie central sensitization, but have been poorly investigated in CDH. They involve N-methyl-D-aspartate (NMDA) receptor activation and nitric oxide (NO) production and supersensitivity and increased and maintained production of sensory neuropeptides. The present study supports the above pathogenic mechanisms demonstrating a significant increase in glutamate and nitrite levels in the CSF of CDH patients, without a significant difference between patients without and those with analgesic overuse headache (P < 0.0001 and P < 0.002). The increase in CSF nitrites was accompanied by a significant rise in the CSF values of cyclic guanosine monophosphate (cGMP) in patients in comparison with controls (P < 0.0001). A statistically significant correlation emerged between visual analogic scale (VAS) values and glutamate, nitrites and cGMP. Although substance P (SP) and calcitonin gene-related peptide (CGRP), and to a lesser extent neurokinin A, were significantly increased in CSF compared with control subjects, their values did not correlate with glutamate, nitrites and cGMP levels in CSF in the patient group. The present study confirms the involvement of glutamate-NO-cGMP-mediated events underlying chronic head pain that could be the target of a new therapeutic approach which should be investigated.

Adult↗

Characteristics of migraine in an out-patient population over 60 years of age.

One hundred and sixty-three consecutive patients (129 females and 34 males) over 60 years of age attending the Headache Centre of the University of Perugia in the period January 2000-December 2001 were included in the study. One hundred and fifty-two (93.3%) were affected by a primary headache disorder. According to the 1988 IHS Criteria, their prevailing attacks could be diagnosed as migraine without aura (MwoA) in 57.2% of cases (n = 87) and as migraine with aura (MwA) in 11.8% of cases (n = 18). Attacks both in MwoA and MwA were unilateral and of severe-to-moderate intensity in 45% and 50% of cases. Head pain was referred as pulsating by 56% and 38.9% of MwoA patients MwA patients, respectively. Aggravation with routine daily activities was present in 72.4% and 61.1% in MwoA and MwA patient groups. The most frequent accompanying symptoms were photophobia and phonophobia. Headache attacks were of shorter duration in MwA patients, but in 3.4% of MwoA patients attacks lasted between 2 and 4 h. Of patients affected by MwA, 55% referred, together with the typical attacks, symptoms of aura not followed by headache. A worsening of headache in the last 5 years was reported by 67.8% and 44.4% of MwoA and MwA patients, respectively. Of the patients with MwoA, 86.2% (n = 75), and 83.3% (n = 15) of those with MwA used symptomatic drugs for their attacks. In the majority of cases they took more than one analgesic or non steroidal anti-inflammatory drug. A total of 51.7% of patients with MwoA and 55.5% of patients with MwA were under prophylactic treatment. Preventive drugs included antidepressants, beta-blockers, calcium channel antagonists and antiepileptic drugs. The choice of symptomatic or prophylactic drugs was made, in the majority of cases, on the basis of concomitant diseases.

Aged↗

Ten year incidence of HCV infection in northern Italy and frequency of spontaneous viral clearance.

BACKGROUND: Little is known of the incidence of hepatitis C virus (HCV) infection, and the frequency of spontaneous viral clearance in the general population is unknown. We conducted an epidemiological study in two Apennine towns in northern Italy. METHODS: Anti-HCV (ELISA and RIBA third generation) and HCV-RNA by polymerase chain reaction were tested in thawed sera from an adult general population of Loiano-Monghidoro in 1986 and 1996, obtained in the context of the MICOL (Multicenter Italian Study on Cholelithiasis). In 1999, anti-HCV positive subjects and sex and age matched controls were recalled in order to identify risk factors for acquiring HCV infection and to assess the family composition of anti-HCV+ subjects. RESULTS: For 1646 subjects, sera were available from both 1986 and 1996 (mean age in 1986 43 (0.39) years). In 1986, 57 (3.46%) subjects were HCV antibody positive (HCV-Ab+). Eight new cases were recorded in 1996: adult incidence was 50.3 cases/100 000 inhabitants/year. Fifty three of 63 (84.1%) HCV-Ab+ sera were also HCV-RNA+. Genotype 2a/2c accounted for 44% and 1b for 47.0% of cases. HCV-Ab+ subjects had higher serum levels of alanine aminotransferase with respect to controls (p<0.005), as did subjects infected with genotype 1 with respect to those with genotype 2 (p<0.05). Eleven of 65 (16.9%) HCV-Ab+ subjects spontaneously cleared HCV-Ab; 7/11 also lost HCV-RNA- in both serum and leucocytes. Sixteen anti-HCV+ subjects belonged to families containing more than one infected member. Married couples accounted for 10 of these 16 subjects. In four of these five married couples, HCV genotype was identical in the two spouses. CONCLUSIONS: In rural northern Italy, the adult incidence of HCV is approximately 50 cases/100 000 inhabitants/year. Our findings suggest that as many as 17% of infected subjects may spontaneously clear HCV-Ab. Interfamilial transmission seems to have a role in the spread of infection.

Adolescent↗

Localized (1)H magnetic resonance spectroscopy in mainly cortical gray matter of patients with multiple sclerosis.

The brain water fraction (R), the brain water transverse relaxation time (T2), the atrophy index (alpha) and the absolute concentration of the principal brain metabolites (NAA, Cho and Cr) were measured by localized proton magnetic resonance spectroscopy in the occipito-parietal cortex (mainly gray matter) of 15 relapsing-remitting (R-R) multiple sclerosis (MS) patients, 15 secondary progressive (SP) MS patients and 8 healthy subjects. Significantly lower values of N-acetylaspartate (NAA), creatine (Cr) and the NAA/Cr ratio in the occipito-parietal cortex were detected in SP MS patients than in R-R MS and control subjects (p < 0.01). Moreover, MS patients showed shorter T2 water relaxation times and reduced brain water fraction compared with controls. Higher atrophy indices were also detected in the mainly occipito-parietal gray matter of MS patients, particularly in those with the progressive form. These findings suggest that the pathological process in MS is not limited to either white matter lesions or normal-appearing white matter but extends into the cortical gray matter (occipito-parietal), particularly in the progressive form of the disease. This can involve changes in neural metabolism or neural shrinkage and neuron loss. The significant increase in atrophy indices could be the expression of the relatively higher cerebrospinal fluid signal from the occipito-parietal cortex, even in the absence of obvious cortical atrophy.

Adult↗

Surfactant apoprotein A modulates interleukin-8 and monocyte chemotactic peptide-1 production.

Previous studies have shown that surfactant apoprotein A (SP-A) and natural or synthetic surfactant can modulate the release of pro-inflammatory cytokines from alveolar mononuclear phagocytes. The aim of this study was to assess whether SP-A or Surfactant (Surf) from patients with pulmonary alveolar proteinosis (PAP) can affect the release of two chemokines (interleukin (IL)-8 and monocyte chemtactic peptide (MCP)-1) from human monocytes and rat lung type-II cells. In addition IL-8 and MCP-1 levels were assessed in the brochoalveolar lavage fluid (BALF) of seven patients with PAP and compared with those in a group of control subjects (n=5). SP-A, tested over a wide range of concentrations, significantly increased IL-8 and MCP-1 release from monocytes. SP-A retained its activity after collagenase digestion, but was not active after heat treatment. The release of IL-8 by monocytes was also stimulated by Surf. Finally, median BALF IL-8 and MCP-1 levels in PAP patients were significantly higher than in controls (9.50 and 9.51 pg x mL(-1) in controls versus 151.95 and 563.70 pg x mL(-1) in PAP, respectively) and significantly correlated with SP-A concentrations in BALF. Overall the results of this study support the view that the high content of alveolar surfactant apoprotein A may contribute to the upregulation of chemokine release in pulmonary alveolar proteinosis, thus contributing to airway inflammation.

Adult↗

A 385 insertion in the hypervariable region 1 of hepatitis C virus E2 envelope protein is found in some patients with mixed cryoglobulinemia type 2.

Chronic hepatitis C virus (HCV) infection has been associated with development of mixed cryoglobulinemia type 2 (MC2), a lymphoproliferative disorder characterized by B cell monoclonal expansion and immunoglobulin M/k cryoprecipitable immunoglobulin production. A short sequence (codons 384-410) of the HCV E2 protein, which has the potential to promote B cell proliferation, was investigated in 21 patients with HCV-related MC2 and in a control group of 20 HCV carriers without MC2. In 6 of the 21 (29%) patients with MC2, all the clones isolated from plasma, peripheral blood mononuclear cells, and liver showed sequence length variation compared with the hypervariable region 1 (HVR1) consensus sequence; 5 patients had an insertion at codon 385, and 1 patient had a deletion at codon 384. Inserted residues at position 385 were different within and between patients. No such mutations were observed in any of the HVR1 clones from control patients without MC2, and the difference between the 2 groups was statistically significant (P =.02). Analysis of 1345 HVR1 sequences obtained from GenBank strongly supported the conclusion that the observed insertions and deletion represent a rare event in HCV-infected patients, suggesting that they are significantly associated with MC2. The physical and chemical profiles of the 385 inserted residues detected in the MC2 patients were consistent with the possibility that these mutations, which occurred in a region containing immunodominant epitopes for neutralizing antibodies and binding sites for B lymphocytes, may be selected by functional constraints for interaction with host cells.

Adult↗

Levels of nerve growth factor in cerebrospinal fluid of chronic daily headache patients.

Nerve growth factor (NGF) levels were determined in the CSF of patients with chronic daily headache (CDH) and correlated with levels of sensory neuropeptides. Patients with CDH showed higher NGF levels in the CSF compared with control subjects (p < 0.0001). Higher CSF levels of substance P (SP) (p < 0.002) and calcitonin-gene-related peptide (CGRP) (p < 0.0001) were also found. There was a significant positive correlation between NGF and both SP and CGRP values. These findings suggest that NGF is involved in the long-lasting sensitization and sustained activation of the trigeminal system in CDH.

Adult↗

Cloning and expression of a novel hepatitis B virus-binding protein from HepG2 cells.

A direct involvement of the hepatitis B virus (HBV) preS1-(21-47) sequence in virus attachment to cell membrane receptor(s) and the presence on the plasma membranes of HepG2 cells of protein(s) with receptor activity for HBV have been suggested by many previous experiments. In this study, by using a tetravalent derivative of the preS1-(21-47) sequence, we have isolated by affinity chromatography from detergent-solubilized HepG2 plasma membranes a 44-kDa protein (HBV-binding protein; HBV-BP), which was found to closely correspond to the human squamous cell carcinoma antigen 1 (SCCA1), a member of the ovalbumin family of serine protease inhibitors. Comparison of SCCA1 sequence with the sequence of the corresponding HBV-BP cDNA, cloned by polymerase chain reaction starting from RNA poly(A)(+) fractions extracted from HepG2 cells, indicated the presence of only four nucleotide substitutions in the coding region, leading to three amino acid changes. Intact recombinant HBV-BP lacked inhibitory activity for serine proteases such as alpha-chymotrypsin and trypsin but inhibited with high potency cysteine proteases such as papain and cathepsin L. Direct binding experiments confirmed the interaction of recombinant HBV-BP with the HBV preS1 domain. HepG2 cells overexpressing HBV-BP after transfection of corresponding cDNA showed a virus binding capacity increased by 2 orders of magnitude compared with untransfected cells, while Chinese hamster ovary cells, which normally do not bind to HBV, acquired susceptibility to HBV binding after transfection. Native HBV particle entry was enhanced in transfected cells. Both recombinant HBV-BP and antibodies to recombinant HBV-BP blocked virus binding and internalization in transfected cells as well as in primary human hepatocytes in a dose-dependent manner. Our findings suggest that this protein plays a major role in HBV infection.

Amino Acid Sequence↗

Patterns of hepatocellular carcinoma development in hepatitis B virus and hepatitis C virus related cirrhosis.

To compare incidence, risk factors and morphologic pattern of hepatocellular carcinoma (HCC) development in hepatitis B virus (HBV) and hepatitis C virus (HCV) related cirrhosis, 401 patients were followed prospectively by periodic ultrasound examination for 14-189 months (mean: 84.8+/-36.7). During follow-up, 77 (19.2%) patients developed HCC, with 5 and 10 year cumulative incidence of 10 and 27.5%, respectively. The risk of HCC was significantly higher in HBV and HCV co-infected patients (P=0.014) compared to those with single HBsAg or anti-HCV (antibodies to hepatitis C virus) positivity. In anti-HCV positive cases the annual risk of HCC increased from 2% in the first 5 year period to 4% in the third 5 year period, while it decreased from 2 to 0% in the same time periods in the HBsAg positive group. By Cox's regression, age above 59 years (P=0.001), male sex (P=0.09), longer duration (P=0.04) and more advanced stage (P=0.01) of cirrhosis, lower platelets count (P=0.001) and higher ALT levels were significant risk factors for HCC in anti-HCV positive patients, while only high alpha-fetoprotein (AFP) levels during follow-up (P=0.04) was a significant risk factor for HCC in HBsAg positive cases. The pattern of HCC was nodular in 63 (81.8%) patients and infiltrating in 14 (18.2%), and the former type was associated with older age (P=0.0001), longer duration (P=0.002) and more advanced stage (P=0.0001) of cirrhosis but not with the viral etiology of disease. In contrast, development of infiltrating HCC was unrelated to age and disease duration and stage, and was associated with male sex (P=0.01), HBV infection (P=0.06) and HBV and HCV co-infection (P=0.0001). Our results indicate different incidence profile, risk factors and patterns of morphogenesis of HCC development in HBV and HCV associated cirrhosis, suggesting different mechanisms of carcinogenesis.

Analysis of Variance↗

High levels of soluble tumor necrosis factor superfamily receptors in patients with hepatitis C virus infection and lymphoproliferative disorders.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with a variety of extrahepatic disorders that may relate to direct or indirect effects of virus infection. Increased levels of soluble forms of tumor necrosis factor (TNF) receptors I and II, found in lymphoproliferative and infectious diseases, can interfere with TNF induced apoptotic cell death. The aim of the present study was to evaluate soluble TNF family receptors levels in lymphoproliferative disorders associated with HCV infection. METHODS: One hundred and forty-nine subjects were studied, including 120 anti-HCV positive patients (60 without lymphoproliferative manifestations, 47 with type II cryoglobulinemia and 13 with low-grade B-cell non-Hodgkin's lymphoma (B-NHL)) and 29 anti-HCV negative subjects (19 with low-grade B-NHLs and ten normal controls). RESULTS: Soluble forms of TNF receptor I, TNF receptor II and Fas were significantly higher in HCV positive patients compared with normal controls. The highest levels were found in patients affected by type II cryoglobulinemia or HCV positive lymphoplasmacytoid lymphomas (LP-NHLs), while HCV positive patients without type II cryoglobulinemia or with other B-NHLs had lower values (P < 0.01). CONCLUSIONS: Among HCV infected individuals, very high levels of soluble TNF receptors are significantly associated with type II cryoglobulinemia and LP-NHLs, suggesting that they may be involved in these proliferative disorders.

Adult↗

Human leucocyte interferon-alpha in the treatment of chronic hepatitis C.

AIM: To assess the efficacy of different schedules of human leucocyte interferon alpha in chronic hepatitis C. PATIENTS AND METHODS: A total of 213 naive patients with chronic hepatitis C were treated with 4 different schedules of human leucocyte interferon alpha. Sustained response was defined as persistently normal alanine amino transferase values with negative serum hepatitis C virus-RNA up to 12 months after therapy withdrawal. RESULTS: Rates of sustained response were 16% with 3 MU tiw for 6 months, 33% with 6 MU tiw for 5 months after a priming dose of 9 MU tiw for a month, 32% with 3 MU tiw for 12 months and 20% with 3 MU daily for 6 months. The major factors affecting the response rate were age and the hepatitis C virus genotype, as a sustained response was significantly higher in patients under 45 years and infected by hepatitis C virus types other than hepatitis C virus-1. Treatment was well tolerated and side-effects and drop-out events were similar to those described with other types of alpha-interferons. CONCLUSIONS: Human leucocyte interferon alpha appears to be equivalent to recombinant interferon-alpha in the treatment of chronic hepatitis C.

Alanine Transaminase↗