[Twenty-four weeks therapy with peginterferon alfa-2a could be similar to 48 weeks therapy in patients with HBeAg positive chronic hepatitis B and good predictors of response: results of a pilot study]. / El tratamiento de 24 semanas con PEG interferón alfa 2a podría ser similar al de 48 semanas en pacientes con hepatitis B crónica HBeAg positivo y buenos predictores de respuesta: resultados de un estudio piloto.

BACKGROUND: 48 week therapy with peginterferon alfa-2a has demonstrated to be effective in about one third of patients with HBeAg-positive chronic hepatitis B. Although the recommended treatment duration for these patients is 48 weeks, there are no enough data supporting 48 weeks of therapy over 24 weeks of therapy. Treatment might be shortened particularly in patients with good predictors of response. AIM: To compare the efficacy of 48 weeks vs 24 weeks of therapy with peginterferon alfa-2a, in patients with chronic hepatitis B who had good predictors of response. PATIENTS AND METHODS: Nineteen patients with high baseline ALT levels (> 3 ULN) and low viral load (HBV DNA < 10(9) copies/ml) were treated with peginterferon alfa-2a 180 mcg/week, during 48 weeks. Virological, biochemical and serological responses were compared with those obtained in 16 patients with similar baseline characteristics treated with peginterferon alfa-2a for 24 weeks. All patients had a followup period of 24 weeks after the end of therapy. RESULTS: At end of follow-up, HBeAg seroconversion was observed in 7/19 (36.8%) of patients treated for 48 weeks and in 6/16 (37.5%) of patients treated for 24 weeks (NS). Patients treated for 48 weeks evidenced a significantly higher decrease in HBV DNA at the end of therapy than patients treated for 24 weeks (-4.8 logs vs -3.6 logs respectively, p < 0.05). However, the percentage of patients with HBV DNA < 100.000 copies/ml was similar in both groups at the end of follow up (42.1% vs 43.7%, NS). No significant differences between both groups were observed regarding ALT normalization, HBsAg loss or seroconversion. The incidence of aderse events was similar in both groups. CONCLUSION: The results from this pilot study indicate that 24 weeks of therapy with peginterferon alfa-2a could be similar to 48 weeks therapy in patients with HBeAg positive chronic hepatitis B who have good predictors of response.

Successful interferon treatment in a patient chronically infected with hepatitis B virus carrying unusual S- (and P-) mutants in the presence of anti-HBs antibodies.

BACKGROUND: Hepatitis B virus (HBV) immune escape mutants with point mutations within the S gene may arise during the natural course of HBV infection, due to a positive selection pressure exerted by the host immune response. Mutations within the immunodominant B and T cell epitopes of hepatitis B surface antigen (HBsAg) allow the resulting S-mutants to propagate even in the presence of neutralizing anti-HBs antibodies and the HBV-specific T-cell immune response. AIM: To study the antiviral effect of Pegylated-interferon (Peg-IFN) in a patient with chronic hepatitis B carrying unusual S-(and P-) mutants in the presence of anti-HBs antibodies. PATIENTS, METHODS AND RESULTS: We report on a 43-year-old male chronically infected with a genotype A HBV strain, with cocirculation of both HBsAg and anti-HBs antibodies, who received treatment with 120 mug of Peg-IFN for 24 weeks. HBeAg seroconversion and clearance of both HBV DNA by polymerase chain reaction and HBsAg were successfully achieved. Improved histology was observed in a biopsy performed 44 weeks after Peg-IFN therapy was completed. It seems plausible that the ascribed genotype A could have contributed to the effective response to Peg-IFN, even though the treatment was provided only throughout a 24-week period. CONCLUSION: To our knowledge, this is the first report regarding the successful result obtained by using Peg-IFN as a treatment for a chronically HBV-infected patient carrying HBsAg immune escape mutants.

Unusual naturally occurring humoral and cellular mutated epitopes of hepatitis B virus in a chronically infected argentine patient with anti-HBs antibodies.

Serum hepatitis B virus (HBV) DNA was extracted from a chronically infected patient with cocirculation of hepatitis B surface antigen (HBsAg) and anti-HBs antibodies. Direct PCR and clone-derived sequences of the S and overlapped P genes were obtained. DNA sequences and phylogenetic analysis ascribed this isolate to genotype A (serotype adw2). Five of six HBV DNA clones exhibited point mutations inside and outside the major hydrophilic region, while the sixth clone exhibited a genotype A "wild-type" amino acid sequence. Observed replacements included both humoral and/or cellular (major histocompatibility complex class I [MHC-I] and MHC-II) HBV mutated epitopes, such as S45A, P46H, L49H, C107R, T125A, M133K, I152F, P153T, T161S, G185E, A194T, G202R, and I213L. None of these mutants were individually present within a given clone. The I213L replacement was the only one observed in the five clones carrying nonsynonymous mutations in the S gene. Some of the amino acid substitutions are reportedly known to be responsible for the emergence of immune escape mutants. C107R replacement prevents disulfide bonding, thus disrupting the first loop of the HBsAg. Circulation of some of these mutants may represent a potential risk for the community, since neither current hepatitis B vaccines nor hyperimmune hepatitis B immune globulin are effectively prevent the liver disease thereto associated. Moreover, some of the recorded HBsAg variants may influence the accuracy of the results obtained with currently used diagnostic tests.

[Development of porphyria cutanea tarda in a chronic hepatitis C patient with indetectable viremia under treatment with peg-interferon plus ribavirin]. / Aparición de porfiria cutánea tarda durante el tratamiento con peg-interferón más ribavirina en un paciente con hepatitis C crónica con viremia indetectable.

Porphyria cutanea tarda (PCT) is considered an extra-hepatic manifestation of HCV infection. The frequency of this association varies according to different authors and the mechanism by which the virus can trigger this disease is not yet clear. We present a 47-year-old-man with chronic hepatitis C genotype 1b who, during the treatment with peg-interferón alfa 2b plus ribavirina, with no detectable viremia at weeks 12th, 24th, and 48th, developed dermatological photosensitive lesions at week 44th. With a presumptive diagnosis of PCT a cutaneous/skin biopsy was performed as well as a porphyrin dosage with urine porphyirins of 4185 microg/24 hs (nv<250). The chromatographic analysis revealed the typical PCT pattern thus confirming the diagnosis. The hemochromatosis HFE gen evaluation showed heterozigotus character mutations (H63D and C282Y) a frequent association in patients with iron overload and PCT. The antiviral treatment of the HCV infection can improve the clinical-humoral manifestations of PCT. The novo occurrence of PCT was recently reported during chronic hepatitis C treatment with interferón and ribavirin, but no cases of late appearance of PCT in patients with no detectable viremia were reported. The mutation of the gen HFE in our patient and the hemolysis caused by ribavirin can be related to the development of the disease, but the iron overload because of ribavirin use is also controversial. This is another example of the complexity of this association.

Aparición de porfiria cutánea tarda durante el tratamiento con peg-interferón más ribavirina en un paciente con hepatitis C crónica con viremia indetectable / Development of porphyria cutanea tarda in a chronic hepatitis C patient with indetectable viremia under treatment with peg-interferon plus ribavirin

La porfiria cutánea tarda (PCT) es considerada una manifestación extrahepática de la infección por el virusde la hepatitis C (HCV). La frecuencia de esta asociación es variable y no es claro el mecanismo por el cual el virus la desencadena. Se presenta un hombre de 47 años con hepatitis C, genotipo-1b, que durante el tratamiento con peg-interferón alfa-2b más ribavirinasin viremia detectable en las semanas 12, 24 y 48, en la semana 44 consulta por presentar lesiones dermatológicasfotosensibles. Con el diagnóstico presuntivo de PCT se realizó biopsia cutánea y el dosaje de porfirinasurinarias fue 4185 ug/24hs (vn: < 250). El análisis cromatográfico reveló el típico patrón de PCT, confirmando el diagnóstico. El gen HFE de la hemocromatosis mostró mutaciones de carácter heterocigoto (H63D y C282Y), asociación frecuente en los pacientescon sobrecarga de hierro y PCT. El tratamiento antiviral de la infección por HCV puede mejorar las manifestacionesde la PCT. La ocurrencia de novo de éstafue reportada recientemente durante el tratamiento de la hepatitis C crónica con interferón y ribavirina pero no hay casos relatados de aparición tardía de PCT enpacientes HCV con viremia no detectable. La presencia de la mutación del gen HFE y la posibilidad de unaumento de oferta de hierro por la acción hemolítica de la ribavirina podrían explicar un exceso de hierrocapaz de desencadenar la crisis de PCT. Tampoco sonconcluyentes los estudios con respecto al aumento o no de la concentración de hierro en hígado en pacientes con anemia que reciben ribavirina.

Porphyria cutanea tarda (PCT) is considered an extra-hepatic manifestation of HCV infection. The frequency of this association varies according to different authors and the mechanism by which the virus can trigger this disease is not yet clear. We present a 47-year-old-man with chronic hepatitis C genotype 1b who, during the treatment with peg-interferón alfa 2b plus ribavirina, with no detectable viremia at weeks 12th, 24th, and 48th, developed dermatological photosensitive lesions at week 44th. With a presumptive diagnosis of PCT a cutaneous/skin biopsy was performed as well as a porphyrin dosage with urine porphyirins of 4185 microg/24 hs (nv<250). The chromatographic analysis revealed the typical PCT pattern thus confirming the diagnosis. The hemochromatosis HFE gen evaluation showed heterozigotus character mutations (H63D and C282Y) a frequent association in patients with iron overload and PCT. The antiviral treatment of the HCV infection can improve the clinical-humoral manifestations of PCT. The novo occurrence of PCT was recently reported during chronic hepatitis C treatment with interferón and ribavirin, but no cases of late appearance of PCT in patients with no detectable viremia were reported. The mutation of the gen HFE in our patient and the hemolysis caused by ribavirin can be related to the development of the disease, but the iron overload because of ribavirin use is also controversial. This is another example of the complexity of this association.

Aparición de porfiria cutánea tarda durante el tratamiento con peg-interferón más ribavirina en un paciente con hepatitis C crónica con viremia indetectable / Development of porphyria cutanea tarda in a chronic hepatitis C patient with indetectable viremia under treatment with peg-interferon plus ribavirin

La porfiria cutánea tarda (PCT) es considerada una manifestación extrahepática de la infección por el virusde la hepatitis C (HCV). La frecuencia de esta asociación es variable y no es claro el mecanismo por el cual el virus la desencadena. Se presenta un hombre de 47 años con hepatitis C, genotipo-1b, que durante el tratamiento con peg-interferón alfa-2b más ribavirinasin viremia detectable en las semanas 12, 24 y 48, en la semana 44 consulta por presentar lesiones dermatológicasfotosensibles. Con el diagnóstico presuntivo de PCT se realizó biopsia cutánea y el dosaje de porfirinasurinarias fue 4185 ug/24hs (vn: < 250). El análisis cromatográfico reveló el típico patrón de PCT, confirmando el diagnóstico. El gen HFE de la hemocromatosis mostró mutaciones de carácter heterocigoto (H63D y C282Y), asociación frecuente en los pacientescon sobrecarga de hierro y PCT. El tratamiento antiviral de la infección por HCV puede mejorar las manifestacionesde la PCT. La ocurrencia de novo de éstafue reportada recientemente durante el tratamiento de la hepatitis C crónica con interferón y ribavirina pero no hay casos relatados de aparición tardía de PCT enpacientes HCV con viremia no detectable. La presencia de la mutación del gen HFE y la posibilidad de unaumento de oferta de hierro por la acción hemolítica de la ribavirina podrían explicar un exceso de hierrocapaz de desencadenar la crisis de PCT. Tampoco sonconcluyentes los estudios con respecto al aumento o no de la concentración de hierro en hígado en pacientes con anemia que reciben ribavirina.(AU)

Porphyria cutanea tarda (PCT) is considered an extra-hepatic manifestation of HCV infection. The frequency of this association varies according to different authors and the mechanism by which the virus can trigger this disease is not yet clear. We present a 47-year-old-man with chronic hepatitis C genotype 1b who, during the treatment with peg-interferón alfa 2b plus ribavirina, with no detectable viremia at weeks 12th, 24th, and 48th, developed dermatological photosensitive lesions at week 44th. With a presumptive diagnosis of PCT a cutaneous/skin biopsy was performed as well as a porphyrin dosage with urine porphyirins of 4185 microg/24 hs (nv<250). The chromatographic analysis revealed the typical PCT pattern thus confirming the diagnosis. The hemochromatosis HFE gen evaluation showed heterozigotus character mutations (H63D and C282Y) a frequent association in patients with iron overload and PCT. The antiviral treatment of the HCV infection can improve the clinical-humoral manifestations of PCT. The novo occurrence of PCT was recently reported during chronic hepatitis C treatment with interferón and ribavirin, but no cases of late appearance of PCT in patients with no detectable viremia were reported. The mutation of the gen HFE in our patient and the hemolysis caused by ribavirin can be related to the development of the disease, but the iron overload because of ribavirin use is also controversial. This is another example of the complexity of this association.(AU)

Aparición de porfiria cutánea tarda durante el tratamiento con peg-interferón más ribavirina en un paciente con hepatitis C crónica con viremia indetectable / Development of porphyria cutanea tarda in a chronic hepatitis C patient with indetectable viremia under treatment with peg-interferon plus ribavirin

La porfiria cutánea tarda (PCT) es considerada una manifestación extrahepática de la infección por el virusde la hepatitis C (HCV). La frecuencia de esta asociación es variable y no es claro el mecanismo por el cual el virus la desencadena. Se presenta un hombre de 47 años con hepatitis C, genotipo-1b, que durante el tratamiento con peg-interferón alfa-2b más ribavirinasin viremia detectable en las semanas 12, 24 y 48, en la semana 44 consulta por presentar lesiones dermatológicasfotosensibles. Con el diagnóstico presuntivo de PCT se realizó biopsia cutánea y el dosaje de porfirinasurinarias fue 4185 ug/24hs (vn: < 250). El análisis cromatográfico reveló el típico patrón de PCT, confirmando el diagnóstico. El gen HFE de la hemocromatosis mostró mutaciones de carácter heterocigoto (H63D y C282Y), asociación frecuente en los pacientescon sobrecarga de hierro y PCT. El tratamiento antiviral de la infección por HCV puede mejorar las manifestacionesde la PCT. La ocurrencia de novo de éstafue reportada recientemente durante el tratamiento de la hepatitis C crónica con interferón y ribavirina pero no hay casos relatados de aparición tardía de PCT enpacientes HCV con viremia no detectable. La presencia de la mutación del gen HFE y la posibilidad de unaumento de oferta de hierro por la acción hemolítica de la ribavirina podrían explicar un exceso de hierrocapaz de desencadenar la crisis de PCT. Tampoco sonconcluyentes los estudios con respecto al aumento o no de la concentración de hierro en hígado en pacientes con anemia que reciben ribavirina.(AU)

Porphyria cutanea tarda (PCT) is considered an extra-hepatic manifestation of HCV infection. The frequency of this association varies according to different authors and the mechanism by which the virus can trigger this disease is not yet clear. We present a 47-year-old-man with chronic hepatitis C genotype 1b who, during the treatment with peg-interferón alfa 2b plus ribavirina, with no detectable viremia at weeks 12th, 24th, and 48th, developed dermatological photosensitive lesions at week 44th. With a presumptive diagnosis of PCT a cutaneous/skin biopsy was performed as well as a porphyrin dosage with urine porphyirins of 4185 microg/24 hs (nv<250). The chromatographic analysis revealed the typical PCT pattern thus confirming the diagnosis. The hemochromatosis HFE gen evaluation showed heterozigotus character mutations (H63D and C282Y) a frequent association in patients with iron overload and PCT. The antiviral treatment of the HCV infection can improve the clinical-humoral manifestations of PCT. The novo occurrence of PCT was recently reported during chronic hepatitis C treatment with interferón and ribavirin, but no cases of late appearance of PCT in patients with no detectable viremia were reported. The mutation of the gen HFE in our patient and the hemolysis caused by ribavirin can be related to the development of the disease, but the iron overload because of ribavirin use is also controversial. This is another example of the complexity of this association.(AU)

Aparición de porfiria cutánea tarda durante el tratamiento con peg-interferón más ribavirina en un paciente con hepatitis C crónica con viremia indetectable. / [Development of porphyria cutanea tarda in a chronic hepatitis C patient with indetectable viremia under treatment with peg-interferon plus ribavirin]

Porphyria cutanea tarda (PCT) is considered an extra-hepatic manifestation of HCV infection. The frequency of this association varies according to different authors and the mechanism by which the virus can trigger this disease is not yet clear. We present a 47-year-old-man with chronic hepatitis C genotype 1b who, during the treatment with peg-interferón alfa 2b plus ribavirina, with no detectable viremia at weeks 12th, 24th, and 48th, developed dermatological photosensitive lesions at week 44th. With a presumptive diagnosis of PCT a cutaneous/skin biopsy was performed as well as a porphyrin dosage with urine porphyirins of 4185 microg/24 hs (nv<250). The chromatographic analysis revealed the typical PCT pattern thus confirming the diagnosis. The hemochromatosis HFE gen evaluation showed heterozigotus character mutations (H63D and C282Y) a frequent association in patients with iron overload and PCT. The antiviral treatment of the HCV infection can improve the clinical-humoral manifestations of PCT. The novo occurrence of PCT was recently reported during chronic hepatitis C treatment with interferón and ribavirin, but no cases of late appearance of PCT in patients with no detectable viremia were reported. The mutation of the gen HFE in our patient and the hemolysis caused by ribavirin can be related to the development of the disease, but the iron overload because of ribavirin use is also controversial. This is another example of the complexity of this association.