Review article: management of chronic hepatitis C in patients with contraindications to anti-viral therapy.

BACKGROUND: There are patients with chronic hepatitis C who are not eligible for the current interferon-based therapies or refuse to be treated due to secondary effects. AIM: To provide information on alternative treatments for the management of these patients. METHODS: A PubMed search was performed to identify relevant literature. Search terms included hepatitis C virus, anti-inflammatory treatment, antioxidant, natural products and alternative treatment, alone or in combination. Additional publications were identified using the references cited by primary and review articles. RESULTS: Several approaches, such as iron depletion (phlebotomy), treatment with ursodeoxycholic acid or glycyrrhizin, have anti-inflammatory and/or anti-fibrotic effects. Life interventions like weight loss, exercise and coffee consumption are associated with a biochemical improvement. Other alternatives (ribavirin monotherapy, amantadine, silibinin, vitamin supplementation, etc.) do not have any beneficial effect or need to be tested in larger clinical studies. CONCLUSION: There are therapeutic strategies and lifestyle interventions that can be used to improve liver damage in patients with chronic hepatitis C who cannot receive or refuse interferon-based treatments.

Registro electrónico de enfermería en la valoración de las heridas / Electronic records for wound assessment for nurses

El registro de la valoración de una herida es la documentación escrita y fotográfica de su evolución y conlleva un proceso de observación, recolección de datos y evaluación. Con el avance de la informática, se han implementado diversos sistemas de registro electrónico en el área del cuidado de las heridas. La presente revisión de literatura tiene por objetivo describir la utilidad de los registros electrónicos como herramienta de apoyo en el área de la valoración de las heridas. Se realizó una exhaustiva revisión de literatura, de las bases de datos COCHRANE LIBRARY MEDLINE, PUBMED, PROQUEST NURSING & ALLIED HEALTH SOURCE. Se incluyeron artículos publicados desde el año 1998 hasta el 2010. Dentro de los principales resultados se desprende que el contar con una óptima documentación de valoración de las heridas es fundamental debido a razones clínicas, legales, de investigación, de docencia, de administración de recursos materiales y humanos y de comunicación con los diferentes miembros del equipo de salud. Existen variados beneficios en la utilización del uso del sistema de registro electrónico (SRE), sin embargo, no existe consenso si el SRE o el sistema de registro manual es la mejor manera de registrar las actividades de enfermería. Se recomienda la creación de un formato electrónico amigable, contando con la participación de profesionales relacionados al área de la informática, junto a profesionales de enfermería, para definir en forma exacta lo que debe registrarse en la valoración de las heridas (AU)

The wound assessment record, is the written and photographic documentation of their development and involves a process of observation, data collection and evaluation. With the advance of computer technology, have implemented various electronic record systems in the area of wound care. This literature review aims to describe the usefulness of electronic records as a support tool in the assessment area of the wounds. We conducted a thorough review of literature, the COCHRANE LIBRARY databases MEDLINE, PUBMED, Proquest NURSING & ALLIED HEALTH SOURCE. Articles published from 1998 to 2010. Among the main results suggest that having an excellent documentation of assessment of injury, is essential due to medical reasons, legal, research, teaching, administration and human resources and communication with different members of health team. There are many benefits in using the use of electronic registration system (ERS), but there is no consensus whether the ERS or the manual registration system is the best way to record the activities of nursing. We recommend creating a user-friendly electronic format, with the participation of professionals working in the area of information technology, along with nursing professionals to define exactly what should be recorded in the assessment of injuries (AU)

Presence of HCV-RNA after ultracentrifugation of serum samples during the follow-up of chronic hepatitis C patients with a sustained virological response may predict reactivation of hepatitis C virus infection.

BACKGROUND: Concentration of viral particles by ultracentrifugation of serum prior to PCR allows detection of hepatitis C virus (HCV) RNA in patients with undetectable viral RNA by conventional PCR assays. AIM: To analyse if HCV-RNA is detected after serum ultracentrifugation in chronic hepatitis C patients with a sustained virological response to antiviral therapy (defined as serum HCV-RNA negativity by conventional assays 6 months after the end of therapy). METHODS: HCV-RNA was tested using real-time PCR in ultracentrifuged sera collected during the post-treatment follow-up (mean: 42 +/- 27 months) in 57 sustained virological responders (SVR). RESULTS: After serum ultracentrifugation, HCV-RNA was detected on at least one occasion during the follow-up in 29/57 (51%) SVR. Thirteen (23%) of these 57 SVR suffered a reactivation 18 +/- 8 months after the end of therapy (reappearance of serum HCV-RNA detectable by conventional assays). Among reactivated patients, 11/13 (85%) had HCV-RNA in ultracentrifuged serum samples (detectable 10 +/- 5 months before reactivation), while HCV-RNA was positive after ultracentrifugation in 18/44 (41%) long-term SVR (P = 0.01). Persistence of detectable HCV-RNA after serum ultracentrifugation was associated with reactivation (P = 0.001). CONCLUSIONS: Serum ultracentrifugation prior to PCR allows detection of HCV-RNA in SVR and its persistence may predict late reactivation.

The role of genomic and antigenomic HCV-RNA strands as predictive factors of response to pegylated interferon plus ribavirin therapy.

BACKGROUND: Hepatitis C virus replicates by the synthesis of an antigenomic HCV-RNA. As the end point of anti-viral therapy is to decrease viral replication, the amount of antigenomic HCV-RNA could influence the response. AIM: To study if amounts of genomic and antigenomic HCV-RNA in the baseline liver biopsy are predictive factors of response to anti-viral therapy. METHODS: Eighty-eight patients with chronic HCV infection (anti-HIV-negative) treated with pegyltaed-interferon-alpha2b plus ribavirin for 12 months were included. Intrahepatic genomic and antigenomic HCV-RNA concentrations were determined by real-time polymerase chain reaction and percentage of infected hepatocytes by in situ hybridization. RESULTS: Of the 88 patients, 31% were responders while 69% were not. Median of antigenomic HCV-RNA in liver of responders and non-responders was 120 000 copies/microg RNA (range: 10,000-775,000) vs. 150,000 copies/microg RNA (range: 100-3,200,000; P = 0.38). Median of genomic HCV-RNA in liver of responders was 1,250,000 copies/microg RNA (range: 5000-9,000,000) and in non-responders 3,180,000 copies/microg RNA (range: 4600-18,000,000; P = 0.0191). Predictive factors of response in the logistic regression were: intrahepatic amount of genomic HCV-RNA, percentage of infected hepatocytes and previous therapy. CONCLUSION: Response to 12 months of therapy with pegylated interferon-alpha2b plus ribavirin depends on the amount of genomic HCV-RNA in the pre-treatment liver biopsy.

Comparative study between occult hepatitis C virus infection and chronic hepatitis C.

We have recently described the presence of occult hepatitis C virus (HCV) infection (HCV-RNA in liver in the absence of anti-HCV and serum HCV-RNA) in patients with persistently abnormal liver function tests of unknown aetiology. The aim of this study was to compare the characteristics of patients with occult HCV infection vs those of patients with chronic hepatitis C. We compared clinical features of 68 patients with occult HCV infection and 69 untreated chronic HCV patients (anti-HCV and serum HCV-RNA positive), matched for age, gender, duration of abnormal liver function tests and body mass index. Aspartate aminotransferase and alanine aminotransferase were higher (P < 0.001) in chronic HCV, but cholesterol and triglycerides were significantly higher in patients with occult HCV infection (P < 0.001 and P = 0.002). Chronic HCV patients had higher gamma-globulin (P = 0.005), alpha-foetoprotein (P < 0.001) and iron (P < 0.001) levels. Percentage of patients with necroinflammatory activity and fibrosis was higher (P < 0.001) in chronic HCV than in occult HCV infection. Mean percentage of infected hepatocytes was higher (P = 0.001) in chronic HCV (10.1%) than in occult HCV infection (5.3%). This occult HCV infection is a milder disease than chronic HCV, and this could be related to the significantly lower number of infected hepatocytes observed in occult HCV.

Effect of anti-viral therapy for occult hepatitis C virus infection.

BACKGROUND: Occult hepatitis C virus infection is defined by the presence of hepatitis C virus-RNA in liver but with undetectable anti-hepatitis C virus and serum viral RNA. AIM: To study the response to anti-viral therapy in occult hepatitis C virus infection to assess the pathogenic effect of occult hepatitis C virus. METHODS: Ten patients with occult hepatitis C virus infection were treated with pegylated-interferon plus ribavirin for 24 weeks and were followed-up 24 weeks after therapy. All patients had abnormal alanine aminotransferase, hepatitis C virus-RNA positive in peripheral blood mononuclear cells and liver necroinflammation. RESULTS: At the end of treatment and follow-up, the percentage of patients with normal alanine aminotransferase was 80% (95% CI: 48-96%) and 60% (95% CI: 31-84%) respectively, and hepatitis C virus-RNA in peripheral blood mononuclear cells was negative in 80% (95% CI: 48-96%) and 70% (95% CI: 40-90%) cases. At the end of follow-up sustained response was observed in 30% (95% CI: 11-61%) of cases. Five patients underwent a second liver biopsy. In all cases, liver hepatitis C virus-RNA persisted, although hepatitis C virus-RNA load was significantly lower (3.2 x 10(4) +/- 5.1 x 10(4) copies/microg RNA) than in the basal biopsy (2.4 x 10(5) +/- 3.8 x 10(5) copies/microg RNA); (P = 0.043). Necroinflammation and fibrosis decreased in three cases. CONCLUSION: The biochemical, virological and histological response to therapy achieved in patients with occult hepatitis C virus infection demonstrates the pathologic effects of occult hepatitis C virus.

Hepatitis C virus (HCV) and hepatitis B virus (HBV) can coinfect the same hepatocyte in the liver of patients with chronic HCV and occult HBV infection.

In this work, we have shown that hepatitis C virus (HCV) and hepatitis B virus (HBV) can coexist in the same hepatocyte using double fluorescent in situ hybridization in liver biopsy samples from patients with chronic HCV infection with occult HBV infection. Digital image analysis of hybridization signals showed that the HBV DNA levels in coinfected hepatocytes were lower than those in cells infected only with HBV. This finding supports the hypothesis of inhibition of HBV replication by HCV. Furthermore, HCV RNA levels were lower in coinfected cells than in cells infected only with HCV, suggesting that HBV may also inhibit HCV replication.

Hepatitis C virus replicates in peripheral blood mononuclear cells of patients with occult hepatitis C virus infection.

BACKGROUND: Occult hepatitis C virus (HCV) infection is characterised by the presence of HCV-RNA in the liver in the absence of anti-HCV, and serum viral RNA. Up to 70% of these patients also have HCV-RNA in peripheral blood mononuclear cells (PBMC) but it is not known if HCV is replicating in these cells. AIM: We studied possible HCV replication in PBMC of 18 patients with an occult HCV infection who were selected on the basis of HCV-RNA positivity in PBMC. METHODS: Detection of HCV-RNA positive and negative strands in PBMC was done by strand specific reverse transcriptase-polymerase chain reaction (RT-PCR) and by in situ hybridisation. RESULTS: The presence of HCV-RNA positive strand in PBMC was confirmed in all patients by strand specific RT-PCR and by in situ hybridisation. Mean percentage of PBMC which had the HCV-RNA positive strand was 3.3% (95% confidence interval (CI) 2.1-4.4) The HCV-RNA negative strand was found in the PBMC of 11/18 (61%) patients by strand specific RT-PCR and confirmed by in situ hybridisation, and the percentage of PBMC harbouring the HCV-RNA negative strand was 3.1% (95% CI 0.8-5.5). There was a significant correlation (p = 0.001, r = 0.84) between the percentage of PBMC with the HCV-RNA positive strand and that of PBMC with the HCV-RNA negative strand. CONCLUSION: HCV replicates in the PBMC of patients with occult HCV infection and thus, although these patients do not have serum HCV-RNA, they could be potentially infectious.

Pegylated interferon-alpha2a kinetics during experimental haemodialysis: impact of permeability and pore size of dialysers.

BACKGROUND: Therapeutics in end-stage renal disease (ESRD) patients undergoing haemodialysis (HD) has to consider potential drug clearance during the dialysis procedure. Pegylated interferon-alpha (PEG-IFN-alpha), a middle-size protein drug active against viral hepatitis, allows convenient once-weekly dosing due to prolonged plasma half-life. AIM: To investigate the impact of permeability and dialyser pore size on PEG-IFN-alpha blood levels during experimental HD. METHODS: Polymethylmetacrylate (PMMA) membrane 1.6 m2 dialysers with three different permeabilities/pore sizes were selected. RESULTS: A 40 kDa PEG-IFN-alpha2a (PEGASYS) was not cleared (< 5%) through low-flux/small pore size (25 A;B3A) and high-flux/middle-large pore size (60 A;BKP) dialysers, and was partially (approximately 15%) through intermediate permeability/large pore size (100 A;BKF) dialysers. In contrast, unmodified 17 kDa IFN-alpha2a(Roferon-A) was removed (65%-95%) through BKP or BKF, but not B3A, PMMA dialysers. Moreover, 12 kDa PEG-IFN-alpha2b(PegIntron) was cleared (40%-80%) through PMMA dialysers with pore sizes > or = 60 angstroms. When B3A or BKP were replaced every hour PEG-IFN-alpha2a plasma levels remained constant throughout three experimental-HD-sessions, but PEG-IFN-alpha2b was cleared partially every BKP replacement. Porosity differ among high-flux dialysers. Neither PEG-IFN-alpha2a nor PEG-IFN-alpha2b were removed after three HD sessions through (27/31/33 A) pore size polysulphone dialysers. Although PEG-IFN-alpha2a was not cleared through middle pore-size (43 A/AN69ST) polyacrylonitrile dialyser, PEG-IFN-alpha2b was partially removed. CONCLUSIONS: The pharmacokinetics of Peg-IFN-alpha may vary in a patient on dialysis.

[Guidelines on hemodialysis-associated viral infections]. / Guías sobre enfermedades víricas en hemodiálisis (HD).

The viric infections influence morbi-mortality in Chronic kidney Disease patients in hemodialysis therapy and can affect to the Staff of the Units. The guides considered the most relevant virus at the present moment: C Virus, B Virus and HIV. To prevent horizontal nosocomial transmission is necessary the observance always the universal precautions in the HD units, although sometimes can appeared seroconversions and epidemic bud when exist a break of these. Is analyzed different situations with special focus in units for acute patients. The following steps under the suspicious of the epidemic bud appeared in one of the annexes together with legislation according to this case. Respect to the staff in every one of the virus is shown prevention patterns, serologic markers to perform when an accident with infected blood occur, also is considered when treatment is indicated. The guides considered too the conditions necessary for include these patients on waiting list for kidney transplantation.

Guías sobre enfermedades víricas en hemodiálisis (HD) / Guidelines on hemodiaglysis-associated viral infections

Las infecciones víricas influyen en la morbi-mortalidad de los pacientes con Enfermedad renal crónica (ERC) en Hemodiálisis y pueden afectar al personal de las unidades han considerado los virus con mas relevancia en el momento actual: Virus B, Virus C y VIH. Las guías se han desarrollado con los mínimos exigibles, dejando abierta la posibilidad de actuación hacia mayores logros en el diagnóstico sexológico, ,tratamiento (cuando, como y cuanto tiempo), y prevención de infecciones víricas (vacuna en VHB) así como políticas de aislamiento según las características de los virus. Para prevenir la vía de transmisión nosocomial horizontal deben cumplirse las Precauciones Universales siempre, no obstante se considera la posibilidad de que en ocasiones puedan no cumplirse y por ello pueda aparecer la seroconversión e incluso el brote epidémico. Se analizan situaciones diferentes con eSpecial interés en unidades de agudos. Los pasos a seguir bajo la sospecha de aparición de un brote epidémico quedan reflejados en uno de los anexos así como la legislación vigente a este respecto. Con respecto al personal en cada uno de los virus se habla de criterios de prevención, marcadores a realizar ante un accidente con sangre infectada y cuando tratar. También se considera las indicaciones de inclusión en lista de trasplante renal para los pacientes infectados en los 3 virus. The Guides have developed with the minimun required, living open the possibilities of actuation the best adquiries in the serologic diagnose, treatment (when, how and how long) and prevention of the viric infections (HBV vaccination) as isolation politics according virus characteristics (AU)

The viric infections influence morbi-mortality in Chronic kidney Disease patients in hemodialysis therapy and can affect to the Staff of the Units. The guides considered the most relevant virus at the present moment: C Virus, B Virus and HIV. To prevent horizontal nosocomial transmission is necessary the observance always the universal precautions in the HD units, althought sometimes can appeared seroconversions and epidemic bud when exist a break of these. Is analyzed different situations with special foccus in units for acute patients. The following steps under the suspicius of the epidemic bud appeared in one of the annexes together with legislation according to this case Respect to the staff in every one of the virus is shown prevention paterns, serologic markers to perform when an accident with infected blood occur, also is considered when treatment is indicated. The guides considered too the conditions necessary for include these patients on waiting list for kidney transplantation (AU)

Replicación del virus de la hepatitis C en lesiones cutáneas de liquen plano / Hepatitis C virus replication in lichen planus lesions

El liquen plano (LP) es una enfermedad dermatológica cuya etiología es desconocida. En la última década se ha constatado en estudios epidemiológicos una asociación estadísticamente significativa entre dicha enfermedad y la infección crónica por virus de la hepatitis C (VHC). El objetivo de este estudio es investigar si el VHC está presente en las lesiones de LP para así obtener datos que apoyen un papel etiopatogénico del VHC en la inducción de lesiones de LP. Con este fin se ha analizado mediante hibridación in situ la presencia de VHC-RNA genómico y antigenómico en biopsias cutáneas procedentes de 32 pacientes con hepatitis crónica C (26 pacientes en los que la biopsia procedía de piel sana de tronco y 6 pacientes en los que era de piel sana facial), 24 pacientes con LP (5 con y 19 sin infección por VHC) y 6 pacientes sanos.Se detectó VHC-RNA en los queratinocitos del 69,2 por ciento y del 100 por ciento de los pacientes con hepatitis crónica C y piel sana, de tronco y facial respectivamente; en el 100 por ciento de los pacientes con hepatitis crónica C y LP y en ninguno de los pacientes sin hepatitis crónica C pero con LP. El porcentaje de queratinocitos que mostraban VHC-RNA genómico o antigenómico fue estadísticamente menor (p < 0,01) en la piel sana de tronco (5,7 ñ 3,5 por ciento y 2,7 ñ 3,1 por ciento de los queratinocitos con VHC-RNA genómico o antigenómico, respectivamente) que en las lesiones de LP (31,7 ñ 7,9 por ciento y 18,8 ñ 7,4 por ciento) o la piel adyacente no afecta (24,8 ñ 6,9 por ciento y 14,3 ñ 3,8 por ciento). Como conclusión, en este estudio se ha demostrado que el VHC infecta y replica en los queratinocitos de la piel de pacientes con hepatitis crónica C, independientemente de que presenten o no lesiones de LP. El hecho de que el porcentaje de queratinocitos infectados por VHC fuese significativamente mayor en las lesiones de LP que en las pieles dermatológicamente sanas, sugiere que la infección de los queratinocitos por VHC podría ser el agente etiopatogénico del desarrollo de las lesiones de LP cutáneo en estos pacientes, debiéndose aclarar esta cuestión en trabajos futuros (AU)

Ribozymes as antiviral agents.

Ribozymes are RNA molecules with cleavage activity that can be engineered to specifically target a given RNA molecule. The hammerhead, hairpin and hepatitis delta virus ribozymes have been widely studied for their use as therapeutical agents. This review discusses the structure and properties of these ribozymes, along with the advances made in the development of these molecules for their application in the treatment of hepatitis B, hepatitis C and human immunodeficiency virus infections.

In vitro infection of human peripheral blood mononuclear cells by a defective hepatitis B virus with a deletion in the PreS1 region of the viral genome.

Previously, we identified a defective hepatitis B virus (HBV) which contains a 183 nucleotide deletion in the PreS1 region of the viral genome affecting the S gene promoter in sera from hepatitis B surface antigen (HBsAg)-negative patients with serum HBV-DNA. The aim of this study was to analyse the infectivity of this mutant. Peripheral blood mononuclear cells (PBMC) from a healthy donor were incubated with serum samples from 2 HBsAg-negative patients with serum HBV-DNA (infected with wild-type and deletion mutant HBV), from an HBsAg carrier (infected with wild-type HBV) and from a healthy donor. After 1 week, HBV-DNA was detected by polymerase chain reaction (PCR) in all supernatants and cells incubated with the HBV-DNA-positive inocula. DNase and trypsin pretreatment confirmed intracellular localization of HBV-DNA in cells. HBV-RNA and covalently closed circular HBV-DNA were also detected in PBMC, indicating that the viral DNA infecting these cells was transcriptionally active. Deletion mutant and wild-type HBV were detected in the supernatants and cells infected with the two HBsAg-negative sera, while only wild-type HBV was detected in the supernatant and cells incubated with the serum from the HBsAg-carrier. In conclusion, this HBV deletion mutant can infect, replicate and release viral particles in in vitro infected PBMC.

Present treatment expectations and risks of chronic hepatitis C.

During recent years, the treatment of chronic hepatitis C has increased in efficacy. Initially, the only approved treatment for this disease was interferon-alpha (IFN-alpha) monotherapy, achieving a 15% rate of sustained response. Subsequently, a combination of IFN-alpha plus ribavirin showed a greater efficacy: up to 40% success with 3 MU of IFN-alpha three times weekly and 1000-1200 mg of ribavirin daily in naive patients and in those who had relapsed after a course of IFN-alpha therapy. Pegylated interferon (PEG-IFN), due to its better efficacy and tolerance, has displaced the use of recombinant IFN. Nevertheless, the sustained response rate mainly depends on HCV RNA load and HCV genotype. Presumably, in future, new strategies based on gene therapy will play an important role in the treatment of chronic hepatitis C.

Detección del virus C de la hepatitis en lesiones cutáneas de liquen plano / Detection of hepatitis C virus in lichen planus lesions

Objetivos: Estudios epidemiológicos han demostrado una correlación entre el liquen plano y la hepatitis crónica por virus C. Para el conocimiento del papel que pueda desempeñar el VCH en el desarrollo de las lesiones de liquen plano, es necesario obtener evidencias morfológicas de la presencia del VCH en esta afección cutánea. Pacientes y métodos: Se ha analizado por hibridación in situ la presencia de VCH-RNA en biopsias de piel de 23 pacientes divididos en tres grupos: 1) once pacientes con liquen plano (cinco con VCH-RNA en suero); 2) seis pacientes sin liquen plano y con VCH-RNA en suero, y 3) seis sin liquen plano ni hepatopatía por VCH. Resultados: El VCH-RNA se detectaba en los queratinocitos de la piel de los pacientes con RNA del virus en suero independientemente de si tenían liquen plano o no y en ninguno de los casos VCH negativos. El porcentaje de células infectadas oscilaba desde un 13,1 per cent a un 44,26 per cent. Conclusión: Se ha demostrado que el VCH infecta los queratinocitos de la piel de los pacientes con hepatitis crónica C tanto en lesiones de liquen plano como de piel sana. Se necesitan investigaciones en esta línea para esclarecer las consecuencias patológicas de este hallazgo (AU)

Extended follow-up of anti-HBe-positive patients with chronic hepatitis B retreated with ribavirin and interferon-alpha.

In a pilot study of combination therapy with ribavirin and IFN alpha conducted in anti-HBe-positive individuals with chronic hepatitis B, 21% of patients achieved a sustained ALT normalization and clearance of hepatitis B virus (HBV) DNA as measured by PCR. The present work has assessed whether these sustained responses are lasting long-term. In addition, IFN gamma levels were tested serially in serum as a measure of the immune system activation during treatment. By extending the post-treatment follow-up period 2 years the occurrence of delayed HBV DNA relapses was observed. A low serum level of IFN gamma was detected during and after treatment. IFN gamma demonstrated a multiphasic time-course: the amount of IFN gamma increased in parallel with reductions in HBV DNA but also with ALT flare-ups. In conclusion, the extended follow-up study of anti-HBe-positive patients after combined treatment with ribavirin and IFN alpha has shown that sustained responses are lasting in 17% patients but also that a late onset HBV DNA relapse may occur.

Interleukin-12 in the treatment of chronic hepatitis B and C.

Interleukin-12 plays a central role in mounting an effective cellular immune response directed towards elimination of intracellular pathogens. In two open label, multicenter, dose-escalation phase I/II studies tolerability, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneously administered recombinant human interleukin-12 (rHuIL-12) was assessed in the treatment of chronic hepatitis B and C. Forty-six patients with chronic hepatitis B and 60 patients with chronic hepatitis C were treated for 12 and 10 consecutive weeks, respectively. rHuIL-12 was generally well tolerated, but was associated with temporary decreases in neutrophils and lymphocyte counts, and with elevations in serum transaminases and bilirubin. Serum IL-12 levels observed were higher at 0.5 microg/kg compared with 0.25 microg/kg doses, suggesting a dose-related increase in systemic exposure of IL-12. Measurable levels of interferon-gamma were also observed at the highest dose of 0.5 microg/kg. At the end of treatment HBV DNA clearance was greater in patients treated with 0.50 microg/kg (25%) or with 0.25 microg/kg (13%) compared with those given 0.03 microg/kg. In patients with chronic hepatitis C, HCV RNA remained detectable in all patients. A more than 50% decrease in pretreatment HCV RNA levels was observed in 3/16 patients (0.03 microg/kg), in 3/14 (0.10 microg/kg), in 6/15 (0.25 microg/kg), and in 8/15 patients of the 0.5 microg/kg dose group. In conclusion, antiviral activity of rHuIL-12 in patients with chronic hepatitis B or C does not appear to be advantageous in comparison to other currently available treatments.

Multicenter randomized study comparing initial daily induction with high dose lymphoblastoid interferon vs. standard interferon treatment for chronic hepatitis C.

One hundred fifty-five chronic hepatitis C patients were assigned at random to receive natural lymphoblastoid interferon (IFN)alpha-n1, s.c., for 13 months in one of three treatment regimens: initial daily induction with 10 million units (MU) followed (group 1, n = 50) or not (group 2, n = 52) by 1 month of rest and then three times weekly 10 MU (2 months), 5 MU (2 months), and 3 MU (8 months); group 3 (n = 53) received tiw 5 MU (2 months) followed by 3 MU (11 months). By intention-to-treat analysis, ALT normalization at completion of treatment was greater in patients who received continuous IFNalpha-n1 therapy with initial daily induction (group 2: 24/52, 46%) compared with those given intermittent therapy with initial daily induction (group 1: 17/50, 34%) and those who received standard IFNalpha-n1 therapy (group 3, 18/53, 34%; P not significant). The sustained ALT response was 26%, 27% and 21% and the sustained virological response was 20%, 27%, and 19%, in groups 1, 2, and 3, respectively. A trend was observed towards a higher biochemical and virological end-of-treatment response in patients given induction therapy (17%) compared with standard therapy (6%, P = 0.053). Sustained biochemical and virological responses were 20%, 27%, and 17% in groups 1, 2, and 3, respectively. Platelet and leukocyte counts decreased following daily high-dose treatment and remained low until therapy cessation (P < 0.001). The data suggest that daily s.c. induction with 10 MU IFNalpha-n1 followed by intermittent or continuous maintenance therapy for 1 year does not improve the results achieved with the standard 1-year IFNalpha course in the treatment of chronic hepatitis C patients.