Liver toxicity and risk of discontinuation in HIV/hepatitis C virus-coinfected patients receiving an etravirine-containing antiretroviral regimen: influence of liver fibrosis.

OBJECTIVES: The aim of the study was to establish the risk of liver toxicity in HIV/hepatitis C virus (HCV)-coinfected patients receiving etravirine, according to the degree of liver fibrosis. METHODS: A prospective cohort study of 211 HIV-infected patients initiating an etravirine-containing regimen was carried out. HCV coinfection was defined as a positive HCV RNA test, and baseline liver fibrosis was assessed by transient elastography. Hepatotoxicity was defined as clinical symptoms, or an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value > 5-fold higher than the upper limit of normal if baseline values were normal, or 3.5-fold higher if values were altered at baseline. RESULTS: Overall, 145 patients (69%) were HCV coinfected, with a lower nadir (165 versus 220 cells/µL, respectively; p = 0.03) and baseline (374 versus 498 cells/µL, respectively; p = 0.04) CD4 count than monoinfected patients. Etravirine was mainly used with two nucleoside reverse transcriptase inhibitors (129; 61%) or with a boosted protease inhibitor (PI) (28%), with no significant differences according to HCV serostatus. Transient elastography in 117 patients (81%) showed a median (range) stiffness value of 8.25 (3.5-69) kPa, with fibrosis stage 1 in 43 patients (37%) and fibrosis stage 4 in 28 patients (24%). During an accumulated follow-up time of 449.3 patient-years (median 548 days), only one patient with advanced fibrosis (50.8 kPa) had grade 3-4 liver toxicity (0.7%). Transaminases changed slightly, with no significant differences compared with baseline fibrosis, and nine and six patients had grade 1 and 2 transaminase increases, respectively. Also, HCV coinfection was not associated with a higher risk of discontinuation (25% discontinued versus 21% of monoinfected patients; p = 0.39, log-rank test) or virological failure (8% versus 12%, respectively; p = 0.4). CONCLUSIONS: Our data suggest that etravirine is a safe option for HIV/HCV-coinfected patients, including those with significant liver fibrosis.

Trends on epidemiological, virological, and clinical features among newly diagnosed HIV-1 persons in Northwest Spain over the last 10 years.

To describe temporal trend and characteristics of newly HIV-diagnosed patients in a medical care area in Northwest Spain over the last 10 years. All newly diagnosed patients for HIV-infection from 2004 to 2013 at a reference medical care area in Northwest of Spain were identified. Epidemiological, virological, immunological, and clinical data, as well as HIV genotype and drug resistance information were recorded. A total of 565 newly HIV-diagnosed patients were identified. The number of new cases increased in the last 5 years (66 cases/year). Overall, 53.1% had a median CD4 counts < 350 cells/µl and 33.6% had an AIDS defining criteria. Non-B variants were found in 34.4% of patients being subtype F (25.8%) the most common non-B subtype. The rate of transmitted drug resistance (TDR) over the study period was 3.7%, but a decreased to 2.6% was observed in the last 5 years. The most prevalent TDR mutations were: T215 revertants (1.5%), K219QENR (1.2%), for NRTIs; K103N (1.9%), for NNRTIs; L90M (0.3%), for PIs. Overall, 73.2% of patients started antiretroviral treatment and 9.9% of patients died during follow-up. The number of newly HIV diagnosed patients increased since year 2009. There is a high prevalence of late diagnosis (53%) and 33% had an AIDS defining criteria. Interestingly, the most prevalent non-B subtype in our population was F (25.8%). These findings support the need to facilitate the access for HIV testing to reduce the rate of late HIV diagnosis, improve the clinical outcome and prevent HIV transmission.

Long-term acute infections during a bovine viral diarrhea virus (BVDV) outbreak in dairy farm from Galicia (NW Spain).

An observational study describes an outbreak of bovine viral diarrhea virus (BVDV) in a dairy herd in Spain. The herd was subjected to a voluntary control program. In a sampling carried out in June 2020, bulk tank milk antibody levels increased compared to the previous sampling. Additionally, serum samples from 4 young heifers also tested positive for antibodies. Since the results were consistent with a recent infection, we proceeded to detect possible persistently infected (PI) animals using antigen ELISA (on serum/ear-notch samples), following the program guidelines. From this moment on, 42 animals tested positive for BVDV antigen, of which 17 were under typical acute infection (AI), 13 were deemed as PI, and eight died early on the farm before having information to determine their status. The remaining 4 showed intriguing test results consistent with a long-term AI since they tested BVDV positive in at least two antigen tests more than 3 weeks apart. Thus, one animal was positive until 80 days of age in serum, and others even for longer periods in ear-notch samples, until they finally tested negative for BVDV. Based on these results, longer follow-up may be necessary in BVDV positive animals to accurately confirm persistent infection.

Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study.

Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV-infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients was lower than in HCV-monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.

Long-term prognosis of HIV-infected patients with Kaposi sarcoma treated with pegylated liposomal doxorubicin.

INTRODUCTION: Incidence of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected persons has dramatically decreased in the highly active antiretroviral therapy era. However, this tumor still represents the most common cancer in this population. OBJECTIVES: The objectives of this study were to evaluate long-term prognosis of HIV-infected patients with KS who had received pegylated liposomal doxorubicin (PLD) and, more specifically, to assess tumor relapse rate, mortality, and cause of death in these subjects. DESIGN: This study was a retrospective review of all patients with KS who had received PLD in centers belonging to the Caelyx/KS Spanish Group. Kaplan-Meier analysis and univariate and multivariate Cox-regression analysis were used to assess the rate of and factors associated with relapse and death through January 2006. RESULTS: A total of 98 patients received PLD from September 1997 through June 2002. Median follow-up after initiation of treatment was 28.7 months (interquartile range, 6.6-73.2 months); during follow-up, 29 patients died (a mortality rate of 14.6% per year). In 9 patients (31%), the cause of death was related to the appearance of other tumors (including 7 lymphomas, 1 gastrointestinal adenocarcinoma, and 1 tongue epidermoid cancer). Death caused by progression of KS occurred in 3 cases. Death risk was inversely related to CD4(+) cell counts at the end of follow-up (hazard ratio for every increase in CD4(+) cell count of 100 cells/microL, 0.7; 95% confidence interval, 0.5-0.9). A relapse study was performed for 61 patients who had complete or partial response to PLD and who attended a control visit after treatment completion. After a median follow-up of 50 months (interquartile range, 17.2-76 months), 8 patients (13%) had experienced relapse; 5 of these patient experienced relapse within the first year after stopping PLD. The only factor that was independently related to risk of relapse was having a CD4(+) cell count >200 cells/microL at baseline (hazard ratio, 6.2; 95% confidence interval, 1.2-30). Lower CD4(+) cell count at the end of follow-up was marginally associated with relapse (hazard ratio for every increase in CD4(+) cell count of 100 cells/microL, 0.7; 95% confidence interval, 0.6-1.01). CONCLUSIONS: Treatment of KS with PLD in HIV-infected patients is followed by a low relapse rate, with most relapses occurring during the first year after stopping chemotherapy. However, the mortality rate in this population was high, in part because of an unexpectedly high incidence of other tumors, mainly lymphomas.

Field evaluation for anthelmintic-resistant ovine gastrointestinal nematodes by in vitro and in vivo assays.

A coprological survey to analyze the presence of flock resistance to benzimidazoles (BZ) and macrocyclic lactones (ML) was performed in sheep under field conditions. Fecal samples were collected from 2,625 sheep in 72 commercial farms from Galicia (NW Spain). The in vitro (FECRT, fecal egg count reduction test) and in vivo (EHA, egg hatch assay, and LFIA, larval feeding inhibition assay) tests were used to assess the efficacy of these anthelmintics. Coprocultures were also developed to obtain knowledge on the main genera of trichostrongylid nematoda prior to, and after, the administration of the anthelmintics. By using the FECRT, BZ resistance was observed in 13 (18%) flocks, whereas ML resistance was only detected in 2 (3%) farms. The number of resistant flocks to BZ was 21 (29%) by using the EHA and 7 (10%) by means of the LFIA. None of the flocks used in this study showed simultaneous resistance to both employed anthelmintics. The results from the in vitro and in vivo tests revealed that 92% of the flocks FECRT resistant to BZ were also resistant with the EHA. The LFIA confirmed all the farms resistant to ML by using the in vivo test. After the administration of BZ, nematode larvae belonging to Teladorsagia circumcincta (32.2%), Trichostrongylus spp. (29%), Nematodirus spp. (6.5%), and Chabertia ovis (3.2%) were identified. In the flocks receiving ML, only T. circumcincta was identified (57%). We recommend the use of in vitro tests because they are more efficient. As the use of macrocyclic lactones is increasing in this region, further investigation is needed for detecting resistance to the anthelmintic family compounds by the LFIA.

Immunodiagnosis of current fasciolosis in sheep naturally exposed to Fasciola hepatica by using a 2.9 kDa recombinant protein.

A 2.9 kDa recombinant-Fasciola hepatica protein (FhrAPS) was employed to estimate the prevalence of fasciolosis in sheep maintained under field conditions. For this purpose, 340 samples with known status in relation to fasciolosis by using a direct-ELISA and the coprological sedimentation were used. These samples were analysed by using an indirect-ELISA (iELISA) and the FhrAPS recombinant protein and excretory/secretory antigens (FhES) of this trematode. Current fasciolosis (CF) was named when results were positive to antigenemia and/or coprology. Out of 198 sheep with current fasciolosis, 68% were positive to the FhrAPS-ELISA test and 53% to the FhES. We observed 14% of the CF-neg sheep were positive to the FhrAPS, whereas this percentage was 52% with the FhES. A significant correlation between FhrAPS and current fasciolosis was obtained (r2=0.513, p=0.001). We concluded that the FhrAPS provides a more suitable antigen than FhES for developing field trials to know the prevalence of early and current fasciolosis.

Assessment of climatic and orographic conditions on the infection by Calicophoron daubneyi and Dicrocoelium dendriticum in grazing beef cattle (NW Spain).

From February 2003 to March 2004, 1148 faecal samples from autochthonous Rubia Gallega cattle breed were collected in 170 farms from Lugo (NW Spain), in order to find out the prevalence and intensity of egg-excretion by Calicophoron daubneyi and Dicrocoelium dendriticum, and the possible influence of external factors as annual mean temperature and rainfall, altitude and mean slope. Twenty-six percent (95% CI 19%, 33%) and the 18% (12, 24) of the farms were infected with rumen and lancet flukes. C. daubneyi egg-output (Me=24) was found in 13% (11, 15) of the individual samples. Six percent (5, 7) of the animals in the study had low D. dendriticum eggs (Me=8). By estimating the odds ratio values it was shown that the highest probability of infection by C. daubneyi was in pastures with a mean slope of less than 13% (OR=1.9) and situated under 600 m (OR=1.6). Annual mean rainfall and temperature were not identified as risk factors for the infection with rumen flukes. Mountainous pastures with a mean slope of higher than 25% (OR=5.8) and situated over 600 m (OR=24.6) where precipitation was high (>1000 mm; OR=7) and temperature low (<11 degrees C; 2.8) had involved the highest risk of infection by D. dendriticum. Because of the prevalences found in this study, employment of suitable management practices with strategic treatments with efficacious anthelmintics are needed to reduce the presence of both trematodes and to increase the health status of grazing beef cattle.

A 2.9 kDa Fasciola hepatica-recombinant protein based ELISA test for the detection of current-ovine fasciolosis trickle infected.

The suitability of an enzyme linked immunosorbent assay (ELISA) test with a 2.9 kDa Fasciola hepatica-recombinant protein (FhrAPS) for diagnosing early and current-ovine fasciolosis was analyzed, and compared to that obtained by using a direct ELISA for detecting F. hepatica-circulating FhES antigens and to the coprological sedimentation for fluke egg quantitation. Fourteen Gallega autochthonous breed sheep were experimentally infected with metacercariae by a trickle system (small repetitive infections) and divided into two groups: G-I represented a primary infection for 34 weeks; G-R, animals with primary infection and reinfected 18 w.a.p.i. Seven sheep were left uninfected as the control group (G-C). Serum IgG antibody values against the FhrAPS rose rapidly by 1st w.a.p.i. in all infected sheep. Antibody levels in those with primary infection (G-I, G-C) peaked at 10 weeks, diminishing slightly and levelling from 16 to 34 weeks. Those with primary infection reinfected at 18 weeks had a rebound effect with the highest values observed. Circulating F. hepatica-ES antigens were detected by the 1st w.a.p.i. in all infected groups peaking at 6 weeks, decreasing rapidly to uninfected control values by 10 weeks of infection. Faecal egg-output started 11 weeks after primary infection. An increase in the IgG antibody as well as antigen responses to the FhrAPS and to anti-FhES from the 18 w.a.p.i. was recorded in G-T and G-R after the challenge infection. Antibody levels remained high whereas antigenemia values diminished after 6 weeks. A positive significant correlation between the IgG response against the FhrAPS and the F. hepatica circulating antigens (r2 = 0.428, p = 0.001) was obtained. In conclusion, our standardized diagnostic ELISA for fasciolosis based on the detection of IgG responses to the FhrAPS would be a valuable tool to diagnosis early and current F. hepatica-infections in sheep.

Analysis of the IgG antibody response against Paramphistomidae trematoda in naturally infected cattle. Application to serological surveys.

The IgG antibody response to Calicophoron daubneyi (Digenea: Paramphistomidae) excretory/secretory antigens was evaluated in naturally infected cattle from Lugo (Galicia, NW Spain) by using an ELISA procedure. Two studies were conducted, first a survey in 524 cattle separated into three groups according to age, G-1 (0-2 years old), G-2 (3-5 years old) and G-3 (> 6 years old). In the second study, three groups of cattle were employed: G-I, naturally infected; G-T, naturally infected and treated with oxyclozanide plus levamisole (Nilzan Plus); G-C, cattle maintained in a farm where C. daubneyi has never diagnosed. Variations on egg-output and haematic parameters (erythrocytes, haematocrite, leukocytes and lymphocytes) were also analyzed. The ELISA procedure showed that 61.2% of the cattle in the first study had been exposed to the trematode, but only 10.1% passed eggs in the feces. Age-association with egg-output was shown but not with the IgG values. In the second experiment, the administration of the anthelmintic reduced significantly the IgG kinetic levels and the C. daubneyi-egg-output was suppressed during 12 weeks in the G-T group. The values of red cells, haematocrite, leukocytes and lymphocytes increased significantly in the treated cattle 5 weeks after chemotherapy; however, new reduction after week 5 was recorded, as results of the challenge of these cattle. This is the first investigation in which evaluation of the IgG humoral response against C. daubneyi in cattle has been carried out. We proved that a notable IgG response in naturally infected cattle is induced, and can be detected by using an ELISA procedure. The IgG antibodies did not increase after challenge infection. Our results proved an important percentage of cattle were exposed to this trematode in the area of study and suitable measures for preventing this relationship must be considered.

Prevalences of gastrointestinal parasites in sheep and parasite-control practices in NW Spain.

A coprological survey to know the presence of gastro-intestinal nematode parasites infecting sheep was done in Galicia (NW Spain), an area with Atlantic climate where sheep production is replacing cattle due to the Agricultural Community Politics of the European Union. From September 2001 to November 2002, 1710 faecal samples were randomly collected from 49 sheep farms and examined by using the flotation technique to determine the prevalence of gastro-intestinal nematode parasites. The sheep-level prevalence was 100%, and the genera identified were Chabertia, Cooperia, Haemonchus, Nematodirus, Oesophagostomum, Teladorsagia, Trichostrongylus and Trichuris spp. A questionnaire was distributed to the farmers (at the same time as sampling) about parasite-control practices during the year before sampling (2000). Ninety percent (95% CI 81%, 98%) of the farmers said they used antiparasitic drugs occasionally, but none of them asked for a coprological analysis prior to the treatment and the efficacy of the drugs was never evaluated. A higher median EPG was observed in the treated sheep (163) than in the untreated ones (26). Chemotherapy was the only parasite-control practice. Flocks that treated according to the farmer's previous experience had higher median EPG (236) than other flocks (185 following the prescription of their veterinary clinician and 232 based on the commercial agent's counsel). Typically, one benzimidazole-treatment per year was applied in autumn and non-veterinary counsel was used. Sheep treated with imidotiazoles had lower EPG (144) than other drugs (164 for the benzimidazoles and 166 for the macrocyclic lactones). We found a higher median EPG in the sheep receiving two treatments/year (175) than in those treated only once per year (156). These results suggest lack of knowledge about worm-control strategies and anthelmintic use or unwillingness to apply such knowledge.

Analysis of the humoral immune response to Oestrus ovis in ovine.

Antibody responses (IgG, IgM and IgA) against Oestrus ovis were analyzed in sheep and in first year grazing lambs from Sardinia (Italy) by an indirect-enzyme-linked immunoassay test and L2 O. ovis excretory/secretory antigens. Serum samples from 208 sheep were obtained prior to be slaughtered, and then heads were removed and cut open along their longitudinal axis to collect the parasites from the nasal cavities, turbinates and sinus. Besides this, blood samples were monthly collected from the lambs of G-1 (maintained under field conditions) and the lambs of G-2 (kept housed since birth to avoid Oestrus infestations) throughout a year. In the sheep, a positive significant correlation was observed between the number of first instar O. ovis larvae and the values of IgM, and between the second instar larvae and the IgG optical densities. In the lambs, all classes of antibodies increased significantly from July in G-1. The highest values of IgG were reached in September (IgG) and decreased in November-December. The IgM response peaked in November, and very low values of IgA were observed during the study. Matching these data with chronobiology of O. ovis in this region, we conclude that the first infection occurs on May, stimulating the production of humoral antibodies. The reduction of the IgG antibody levels starting from October means the beginning of the diapause while the IgM response seems to be associated to the presence of L1 in the nasal cavities. The data obtained led us to forecast an early treatment of the ovine on June-July, which should keep away from the maturation of O. ovis L1 larvae, avoiding the development of clinical lesions and interrupting the life cycle of this parasite.

Early pleural effusion in histiocytosis X.

Two cases of histiocytosis X, one of the disseminated form and the other localized to the lung, are reported, in which pleural effusion, probably due to pleural involvement as assessed by biopsy, was one of the initial manifestations of the disease.

Drug resistance in patients experiencing early virological failure under a triple combination including indinavir.

OBJECTIVE: To assess the pattern of drug resistance mutations selected in HIV-1-infected patients failing a first line triple combination therapy including indinavir. PATIENTS AND METHODS: Plasma samples from 87 patients collected at the time of the first virological rebound (> 50 HIV-RNA copies/ml) were examined for the presence of drug-resistant genotypes. RESULTS: The mean level of plasma viraemia at rebound was 7824 HIV-1 RNA copies/ml in 73 subjects with good compliance, whereas it was 359,460 HIV-1 RNA copies/ml in 14 patients who admitted to poor adherence. Genetic sequence analysis yielded results for 51 (70%) of the patients having good adherence. More than half of them (26/51, 51%) carried primary mutations associated with resistance to nucleoside analogues. In contrast, primary protease inhibitor resistance mutations were recognized less frequently (14/51, 27%; P < 0.05). Moreover, in 23 (45%) patients there was no evidence of drug-resistant viruses at all. The most frequent drug-resistant genotypes in the reverse transcriptase gene were at codons 184 (n = 19), 215 (n = 14) and 41 (n = 8), whereas for the protease they were at codons 46 (n = 10), 82 (n = 9) and 90 (n = 7). No resistance genotypes were found among non-compliant patients. CONCLUSION: The overall rate of drug-resistant HIV genotypes was 38% (28/73) in patients with good adherence and who were experiencing a first virological failure under a triple combination regimen including indinavir; resistance to nucleoside analogues was more frequent than resistance to indinavir. Therefore, treatment intensification in those patients without resistance, or a selective substitution of nucleosides in those with resistance limited to these compounds, might be justified.

Multicenter randomized, controlled study of intramuscular administration of interferon-beta for the treatment of chronic hepatitis C.

The intramuscular administration of interferon-beta (IFN-beta) at a dosage of 6 million units three times per week for 6 months has been evaluated in 90 patients included in a multicenter, randomized, controlled trial for the treatment of chronic hepatitis C. Transaminase levels were significantly reduced in IFN-beta-treated patients (p = 0.015) and were significantly lower with respect to those of the untreated controls (p = 0.040 at 6 months). Four treated (8%) and one untreated (2.5%) patients had normal transaminase values after 6 months. At study end (12 months), three quarters of the IFN-beta-treated patients had sustained transaminase normalization, whereas the untreated case had relapsed. Hepatitis C viremia was cleared in 6 (12%) treated patients but in none of the untreated controls (p = 0.058). Side effects of IFN-beta were infrequent (a mild flu-like syndrome in < 10%, asthenia in 16%, anorexia in 8%, headaches and weight loss in 8%, and hair loss in 4%). Leukocyte and platelet counts decreased during IFN-beta treatment, but no dose modifications were necessary. Such decreases were not statistically significant when compared with the levels in the untreated controls. Intramuscular IFN-beta at the dosage used has little efficacy in the treatment of chronic hepatitis C. Because of IFN-beta tolerance, higher doses and alternate routes of injection might prove beneficial for the treatment of this disease.

Interferon-alpha plus ribavirin for 12 months increases the sustained response rates in chronic hepatitis C relapsers.

BACKGROUND: The effectiveness and tolerability of combination therapy for 12 months have not been evaluated sufficiently in chronic hepatitis C relapsers to interferon. AIMS: To evaluate the sustained response to interferon plus ribavirin for 12 months in chronic hepatitis C relapsers. METHODS: We included 55 chronic hepatitis C relapsers in a 12-month treatment protocol with interferon (3 MU thrice weekly) plus ribavirin (1-1.2 g/day). The effectiveness was evaluated using serum aminotransferase and hepatitis C virus RNA levels, alanine aminotransferase normalization and viraemia clearance after 12 months, defining the end-of-treatment response, and 6 months after completion of therapy, defining the sustained response. Adverse effects were recorded. RESULTS: End-of-treatment response and sustained response were achieved in 47 (85%) and 37 (67%) patients, respectively; there were 10 (21%) relapsers after combination therapy. Predictive factors of sustained response included the genotype (non-1 95% vs. 1 48%; P < 0.001), lower viraemia (503 917 +/- 553 230 vs. 901 393 +/- 548 267 copies/mL; P < 0.005), higher alanine aminotransferase levels (137 +/- 75 vs. 103 +/- 41 IU/L; P < 0.05) and a lower gamma-glutamyl transpeptidase/alanine aminotransferase ratio (0.30 +/- 0.23 vs. 0.49 +/- 0.39; P < 0.05). Tolerance to therapy was good, with no withdrawals. CONCLUSIONS: Interferon plus ribavirin treatment for 12 months in chronic hepatitis C relapsers yields high sustained response rates and is well tolerated. The sustained response is related to a non-1 genotype, lower baseline viraemia, higher alanine aminotransferase level and a lower gamma-glutamyl transpeptidase/alanine aminotransferase ratio.

Interferon alfa-2b plus ribavirin for chronic hepatitis C patients who have not responded to interferon monotherapy.

BACKGROUND: The role of combination therapy is poorly defined in chronic hepatitis C patients who are non-responders to interferon. AIM: To assess the efficacy, safety and tolerance of interferon alfa-2b plus ribavirin in chronic hepatitis C patients who do not respond to interferon monotherapy. METHODS: A total of 127 non-responder patients with chronic hepatitis C received 3 mU t.i.w. of interferon alfa-2b plus 1000-1200 mg ribavirin daily for 48 weeks. Effects of therapy were evaluated by serum aminotransferases and hepatitis C virus (HCV) RNA levels. RESULTS: Twenty-nine (23%) patients had an end-of-treatment response. Six months after treatment, 20 (16%) patients were sustained responders. Early loss of HCV RNA was the strongest predictor of a sustained response (P < 0.0001). Remission was also more frequent in patients with genotype 1b (P < 0.02), elevated alanine aminotransferase (P < 0.03) and low gamma glutamiltranspeptidase (P < 0.002). Treatment was discontinued in 21 (17%) patients: in 14 for intolerance and in seven due to side-effects. CONCLUSIONS: Combination therapy with interferon plus ribavirin produced a sustained response in 16% of chronic hepatitis C patients who were non-responders to interferon. This combination was safe and well tolerated.

[The antigenic e system in carriers of the surface antigen of viral hepatitis B (author's transl)]. / El sistema antigénico e en los portadores de antígeno de superficie de la hepatitis por virus B.

In 1972, Magnius and Espmark on confronting different sera containing the surface antigen of hepatitis B with each other, demonstrated a new antigenic item which they called e. In later works the presence of this new antigenic specificity was associated with a greater rate of incidence of chronic hepatic lesion and a greater contagiousness of B virus. In the present study the e system was determined in a group of HBsAG positive blood donors and in a group of patients carrying HBeAG who had been admitted to the hospital for different reasons. The results showed an elevated rate of anti-e antibodies in the asymptomatic donors, and this could be correlated with clinical and biochemical indemnity of the liver function. HBsAg carriers mainly presented renal insufficiency or hematologic disorders, probably related to a deficient immune response. Determination of the e system shows its usefulness in enabling HBsAg positive carriers to be classified according to whether they present or not present hepatic lesion. The presence of HBeAg could be correlated with hepatic lesion, while HBeAc seems to determine some type of protection on those patients who have it in their sera.

[Treatment of acute brucellosis with cotrimoxazole, doxicyclin and streptomycin. A comparative study (author's transl)]. / Tratamiento de la brucelosis agunda con cotrimoxazol, doxiciclina y estreptomicina. Estudio comparativo.

Human brucellosis can be managed with different therapeutic measures. The present study compares the therapeutic efficacy of the classical treatment with streptomycin, doxicyclin and cotrimoxazole, every one of the treatment regimes being applied to 19 patients with acute brucellosis. The results do not demonstrate an advantage of the new association over the classical treatment. Relapses, time elapsed until the patient was afebrile and drug tolerance were similar for both treatments. The classical treatment has a lower cost but the new association implies more patient comfort because the number of pills to be ingested daily is reduced to less than half, a fact that could make it the treatment of choice.

[Clinical study of gastric lymphomas and pseudolymphomas (author's transl)]. / Linfomas y seudolinfomas gástricos. Estudio clínico.

The differentiation between gastric lymphomas and pseudolymphomas represents a clinical, surgical, and pathologic problem affecting both prognosis and therapy. Twenty patients were diagnosed for gastric lymphomas or gastric pseudolymphomas. Only those in stages IE or IIE were included in the first group (13 patients). Pseudolymphomas were diagnosed in seven patients on the basis of histopathologic criteria; all seven had peptic ulcers. Survival among the 13 patients diagnosed for lymphomas was low; six of them died within the first year. The seven cases diagnosed as pseudolymphoma progressed favorably over periods between 2 months and 5 years. The histologic parameters on which the differentiation of the two conditions was based included: a) cell type; b) distribution and limits of infiltration; c) presence of peptic ulcers in pseudolymphomas; and c) characteristics of the regional lymph nodes. The various possible mechanisms of pseudolymphomatous reaction are discussed. It is suggested that the relatively good prognosis reported in some series of gastric lymphomas may be due to the inclusion of pseudolymphomas. There is obvious justification for distinguishing between this two conditions.