Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease.

AIM: To evaluate the safety and feasibility of bone marrow cell (BMC) transplantation in patients with chronic liver disease on the waiting list for liver transplantation. METHODS: Ten patients (eight males) with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as Child-Pugh B and three as Child-Pugh C. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. RESULTS: The median age of the patients was 52 years (range 24-70 years). All patients were discharged 48 h after BMC infusion. Two patients complained of mild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 (2.19 +/- 0.9) and 4 mo (2.10 +/- 1.0) after cell transplantation that baseline levels (2.78 +/- 1.2). Albumin levels 4 mo after BMC infusion (3.73 +/- 0.5) were higher than baseline levels (3.47 +/- 0.5). International normalized ratio (INR) decreased from 1.48 (SD = 0.23) to 1.43 (SD = 0.23) one month after cell transplantation. CONCLUSION: BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease.

Clinical and epidemiological features of patients with chronic hepatitis C co-infected with HIV.

UNLABELLED: Co-infection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is increasingly common and affects the clinical course of chronic hepatitis C. Highly active antiretroviral therapy has improved the life expectancy of HIV infected patients, but, by extending survival, it permits the development of HCV cirrhosis. This study tried to evaluate clinical and epidemiological features of patients with chronic hepatitis C co-infected with HIV. We evaluated 134 HCV-infected patients: i) group A-- 65 co-infected HCV/HIV patients, ii) group B-- 69 mono-infected HCV patients. The impact of HIV infection on HCV liver disease was analyzed using Child's score, ultrasound findings and liver histology. Patients were subjected to HCV genotyping and anti-HBs dosage. Patients mean age was 42.4 years (+/-9.1) and 97 (72.4%) were males. Injected drug use and homo/bisexual practice were more frequently encountered in the co-infected group: 68.3% and 78.0%, respectively. Antibodies against hepatitis B virus (anti-HBs) were found in only 38.1% of the patients (66.7% group A x 33.3% group B). Ten out of 14 individuals (71.4%) who had liver disease (Child B or C) and 25 out of 34 (73.5%) who showed ultrasound evidence of chronic liver disease were in the co-infection group. HCV genotype-2/3 was more frequently encountered in co-infected patients (36.9% group A vs. 21.8% group B). CONCLUSIONS: a) HIV infection seems to adversely affect the clinical course of chronic hepatitis C, b) injected drug use, bi/homosexual practice and genotype-2/3 were more frequently encountered in co-infected patients, c) immunization against HBV should be encouraged in these patients.

Daily interferon induction regimen using different manufactured interferons (alpha-2A or alpha-2B) in combination with ribavirin for treatment of chronic hepatitis C: a prospective randomized study.

BACKGROUND: [corrected] Studies on hepatitis C virus kinetics showed that serum levels of interferon fall 48 h after drug administration, when viral load is increasing again. Previously to the availability of pegylated interferon, daily induction therapy with standard interferon was under evaluation. AIMS: To evaluate the safety and efficacy of interferon alpha daily induction regimen in combination with ribavirin. PATIENTS AND METHODS: A randomized trial including 93 patients with chronic hepatitis C was carried out. On satisfying all eligibility criteria, patients were randomly allocated to two different treatment groups: 44 individuals in treatment arm A: IFN 3 MU thrice weekly + ribavirin 1.0-1.2 g daily for 48 weeks (IFN TIW) and 49 individuals in treatment arm B: IFN 3 MU daily + ribavirin 1.0-1.2 g daily for 12 weeks followed by IFN 3 MU thrice weekly + ribavirin 1.0-1.2 g daily, until completion of 48 weeks of therapy (IFN QD). HCV genotyping was obtained in 85 subjects. A negative HCV-RNA 6 months after cessation of therapy was considered a sustained virological response RESULTS: Eighty three patients completed treatment, five dropped out (one from IFN TIW and four from IFN QD) and in five patients therapy was discontinued due to medical request (two from IFN TIW and three from IFN QD). There was no statistically significant difference between groups with respect to therapy interruption. The frequency of cirrhosis was 29%, similar in both groups. In the "intention to treat" analysis the overall sustained virological response was 39.8%. There was no significant difference in sustained virological response rate between both treatment strategies (36.4% IFN TIW vs 42.9% IFN QD). In the 83 patients who finished the trial, sustained virological response was 44.6%. Among subjects with HCV genotype-1, the sustained virological response was 42% (40.9% IFN TIW vs 42.9% IFN QD) and among patients with HCV genotype 2 or 3, the sustained virological response was 55.6% (50% IFN TIW vs 63.6% IFN QD) CONCLUSIONS: Combination therapy had an overall sustained virological response rate of 39.8% ("intention to treat analysis"). There was no difference with respect to sustained virological response rates between patients who used daily induction schedule compared to standard regimen. Adverse events, even more frequent in the daily induction group, did not interfere with the treatment strategies.

Infusion of autologous bone marrow mononuclear cells through hepatic artery results in a short-term improvement of liver function in patients with chronic liver disease: a pilot randomized controlled study.

AIM: This randomized controlled study evaluated the effect of autologous infusion of bone marrow cells (BMC) in patients with hepatic cirrhosis. METHODS: Thirty patients on the liver transplant waiting list were randomly assigned to receive BMC therapy or no treatment. They were followed up for 1 year. The study was nonblinded. Autologous mononuclear-enriched BMC were infused into the hepatic artery; liver function scores/tests were chosen as endpoints to assess efficacy. Statistical analysis calculated mean relative changes (RC) from baseline and fitted a random-effects model. RESULTS: Mean age, baseline model for end-stage liver disease, and Child-Pugh score were similar in both groups. Child-Pugh score improved in the first 90 days in the cell therapy group compared with controls (P = 0.017, BMC group RC = -8%, controls RC = +5%). The model for end-stage liver disease score remained stable in the treated patients (RC -2 to +6%), whereas it increased during follow-up in the control group (RC +6 to +18%). Albumin levels improved in the treatment arm, whereas they remained stable among controls in the first 90 days (P = 0.034; BMC group RC = +16%, control group RC = +2%). Bilirubin levels increased among controls, whereas they decreased in the therapy arm during the first 60 days; INR RC differences between groups reached up to 10%. The changes observed did not persist beyond 90 days. CONCLUSION: Transplantation of autologous BMC into the hepatic artery improved liver function in patients with advanced cirrhosis in the first 90 days. However, larger studies are necessary to define the role of BMC therapy in cirrhotic patients. Repeated autologous BMC infusions or combination therapy with granulocyte-colony-stimulating factor might improve or sustain the treatment response.

Distribution of hepatitis B virus genotypes among patients with chronic infection.

UNLABELLED: Hepatitis B virus (HBV) can be classified into at least eight genotypes, A-H. We evaluated the distribution HBV genotypes among patients with chronic infection. METHODS: We consecutively evaluated adult patients with chronic HBV infection from Salvador, Brazil. Patients were classified according to HBV infection chronic phases based on HBV-DNA levels and presence of serum HBV markers. HBV-DNA was qualitatively and quantitatively detected in serum by polymerised chain reaction (PCR). Isolates were genotyped by comparison of amino acid mutations and phylogenetic analysis. RESULTS: One-hundred and fourteen patients were evaluated. HBV-DNA was positive in 96 samples. HBV genotype was done in 76. Mean age was 36 +/- 11.3. In 61 of 76 cases subjects were classified as inactive HBsAg carriers. Their mean HBV serum level was 1760 copies/ml and 53 of 61 were infected with HBV genotype A, seven with HBV genotype F and one with genotype B. Twelve of the 76 patients had detectable hepatitis B e-antigen (HBeAg) in serum. Ten were infected with HBV genotype A and two with genotype F; most had increased alanine aminotransferase and high HBV-DNA levels. Three patients were in the immunotolerant phase, two were infected with HBV genotype A and one with genotype F. HBV subtyping showed subtypes adw2 and adw4. CONCLUSIONS: HBV genotype A adw2 and genotype F adw4 were the most prevalent isolates found. We could not find differences in genotype distribution according to HBV clinical phases and DNA levels. We did not detect HBV genotype D in contrast to a previous study in our center with acute hepatitis B. All inactive HBsAg carriers had low HBV-DNA levels.

Daily interferon induction regimen using different manufactured interferons (alpha-2a or alpha-2b) in combination with ribavirin for treatment of chronic hepatitis C: a prospective randomized study

BACKGROUD: Studies on hepatitis C virus kinetics showed that serum levels of interferon fall 48 h after drug administration, when viral load is increasing again. Previously to the availability of pegylated interferon, daily induction therapy with standard interferon was under evaluation. AIMS: To evaluate the safety and efficacy of interferon alpha daily induction regimen in combination with ribavirin. PATIENTS AND METHODS: A randomized trial including 93 patients with chronic hepatitis C was carried out. On satisfying all eligibility criteria, patients were randomly allocated to two different treatment groups: 44 individuals in treatment arm A: IFN 3 MU thrice weekly + ribavirin 1.0-1.2 g daily for 48 weeks (IFN TIW) and 49 individuals in treatment arm B: IFN 3 MU daily + ribavirin 1.0-1.2 g daily for 12 weeks followed by IFN 3 MU thrice weekly + ribavirin 1.0-1.2 g daily, until completion of 48 weeks of therapy (IFN QD). HCV genotyping was obtained in 85 subjects. A negative HCV-RNA 6 months after cessation of therapy was considered a sustained virological response RESULTS: Eighty three patients completed treatment, five dropped out (one from IFN TIW and four from IFN QD) and in five patients therapy was discontinued due to medical request (two from IFN TIW and three from IFN QD). There was no statistically significant difference between groups with respect to therapy interruption. The frequency of cirrhosis was 29 percent, similar in both groups. In the "intention to treat" analysis the overall sustained virological response was 39.8 percent. There was no significant difference in sustained virological response rate between both treatment strategies (36.4 percent IFN TIW vs 42.9 percent IFN QD). In the 83 patients who finished the trial, sustained virological response was 44.6 percent. Among subjects with HCV genotype-1, the sustained virological response was 42 percent (40.9 percent IFN TIW vs 42.9 percent IFN QD) and among patients...

RACIONAL: Estudos em cinética viral na hepatite C demonstraram que há uma queda dos níveis séricos de interferon 48 h após a sua administração, quando a carga viral do vírus C volta a se elevar. Antes da disponibilidade do interferon peguilado, diversos ensaios clínicos investigaram a terapia de indução com interferon standard OBJETIVOS: Avaliar a segurança e eficácia do esquema de indução diário com interferon alfa associado à ribavirina. PACIENTES E MÉTODOS: Noventa e três pacientes com hepatite crônica C foram incluídos. Através de randomização, foram alocados em um de dois braços terapêuticos: 44 indivíduos no grupo A: IFN 3MU três vezes por semana + ribavirina 1,0-1,2 g diariamente por 48 semanas e 49 indivíduos no grupo B: IFN 3MU diariamente por 12 semanas, seguindo-se por IFN 3MU três vezes por semana até completar 48 semanas + ribavirina 1,0-1,2 g diariamente por 48 semanas. A genotipagem do vírus C foi realizada em 85 indivíduos. Considerou-se resposta virológica sustentada a persistência do HCV-RNA negativo 6 meses após o término da terapia RESULTADOS: Oitenta e três pacientes completaram o tratamento. Houve cinco abandonos (um do grupo A e quatro do grupo B) e em cinco pacientes a terapia foi retirada devido a efeitos adversos (dois do grupo A e três do grupo B). Não houve diferença estatisticamente significante entre os grupos quanto à interrupção do tratamento. A freqüência de cirrose foi 29 por cento, semelhante entre os grupos. Na análise "intention to treat" a resposta virológica sustentada foi 39,8 por cento. Não houve diferença estatística na taxa de resposta virológica sustentada entre ambas as estratégias terapêuticas (36,4 por cento grupo A vs 42,9 por cento grupo B). Nos 83 pacientes que finalizaram o estudo, a resposta virológica sustentada foi 44,6 por cento. Entre os pacientes com genótipo 1, a resposta virológica sustentada foi 42 por cento (40,9 por cento grupo A vs 42,9 por cento grupo B) e entre os pacientes...

Clinical and epidemiological features of patients with chronic hepatitis C co-infected with HIV

Co-infection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is increasingly common and affects the clinical course of chronic hepatitis C. Highly active antiretroviral therapy has improved the life expectancy of HIV infected patients, but, by extending survival, it permits the development of HCV cirrhosis. This study tried to evaluate clinical and epidemiological features of patients with chronic hepatitis C co-infected with HIV. We evaluated 134 HCV-infected patients: i) group A - 65 co-infected HCV/HIV patients, ii) group B - 69 mono-infected HCV patients. The impact of HIV infection on HCV liver disease was analyzed using Child's score, ultrasound findings and liver histology. Patients were subjected to HCV genotyping and anti-HBs dosage. Patients mean age was 42.4 years (±9.1) and 97 (72.4 percent) were males. Injected drug use and homo/bisexual practice were more frequently encountered in the co-infected group: 68.3 percent and 78.0 percent, respectively. Antibodies against hepatitis B virus (anti-HBs) were found in only 38.1 percent of the patients (66.7 percent group A x 33.3 percent group B). Ten out of 14 individuals (71.4 percent) who had liver disease (Child B or C) and 25 out of 34 (73.5 percent) who showed ultrasound evidence of chronic liver disease were in the co-infection group. HCV genotype-2/3 was more frequently encountered in co-infected patients (36.9 percent group A vs. 21.8 percent group B). Conclusions: a) HIV infection seems to adversely affect the clinical course of chronic hepatitis C, b) injected drug use, bi/homosexual practice and genotype-2/3 were more frequently encountered in co-infected patients, c) immunization against HBV should be encouraged in these patients.