vitamin-b-12 and Hepatitis-C--Chronic

A 62-year-old man with chronic hepatitis C underwent interferon (IFN)-β therapy. After treatment for a period comprising 29 months and 2 weeks, hematological results showed a decrease in white blood cell, hemoglobin, and platelet counts (WBC 2,300/µl, Hb 7.2 g/dl, PLT 4.7×10(4)/µl), and IFN therapy was stopped. Despite therapy discontinuation, the pancytopenia continued to progress with elevation of LDH (LDH 4,898 IU/l), and the patient was admitted to our hospital with suspected hematological disease. The patient underwent clinical screening, and pernicious anemia caused by vitamin B12 deficiency was diagnosed. The anemia rapidly improved with vitamin B12 treatment. Interferon is the mainstay of treatment for patients with viral hepatitis. While the adverse effects of interferon therapy are widely recognized, only a few reports have documented pernicious anemia developing during IFN-therapy. We recommend that particular attention be paid to such clinical and laboratory conditions as megaloblastic anemia when administering IFN. We also recommend checking the vitamin B12 level, as a deficiency of this vitamin may lead to the development of megaloblastic anemia.

Topics: Anemia, Pernicious; Diagnosis, Differential; Hepatitis C, Chronic; Humans; Interferon-beta; Male; Middle Aged; Treatment Outcome; Vitamin B 12

In vitro, vitamin B12 acts as a natural inhibitor of hepatitis C virus (HCV) replication.. To assess the effect of vitamin B12 on virological response in patients with chronic HCV hepatitis naïve to antiviral therapy.. Ninety-four patients with chronic HCV hepatitis were randomly assigned to receive pegylated interferon α plus ribavirin (standard-of-care; SOC) or SOC plus vitamin B12 (SOC+B12). Viral response-namely, undetectable serum HCV-RNA, was evaluated 4 weeks after starting treatment (rapid viral response), 12 weeks after starting treatment (complete early viral response) and 24 or 48 weeks after starting treatment (end-of-treatment viral response) and 24 weeks after completing treatment (sustained viral response (SVR)). Genotyping for the interleukin (IL)-28B polymorphism was performed a posteriori in a subset (42/64) of HCV genotype 1 carriers.. Overall, rapid viral response did not differ between the two groups, whereas the rates of complete early viral response (p=0.03), end-of-treatment viral response (p=0.03) and SVR (p=0.001) were significantly higher in SOC+B12 patients than in SOC patients. In SOC+B12 patients, the SVR rate was also significantly higher in carriers of a difficult-to-treat genotype (p=0.002) and in patients with a high baseline viral load (p=0.002). Distribution of genotype IL-28B did not differ between the two groups. At multivariate analysis, only easy-to-treat HCV genotypes (OR=9.00; 95% CI 2.5 to 37.5; p=0.001) and vitamin B12 supplementation (OR=6.9; 95% CI 2.0 to 23.6; p=0.002) were independently associated with SVR.. Vitamin B12 supplementation significantly improves SVR rates in HCV-infected patients naïve to antiviral therapy.

Topics: Adult; Algorithms; Antiviral Agents; Female; Follow-Up Studies; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon-alpha; Male; Middle Aged; Multivariate Analysis; Polyethylene Glycols; Prospective Studies; Treatment Outcome; Viral Load; Vitamin B 12; Vitamin B Complex

Topics: Anemia, Aplastic; Anti-Bacterial Agents; Antiviral Agents; Blood Component Transfusion; Drug Therapy, Combination; Filgrastim; Folic Acid; Hepatitis C, Chronic; Humans; Interferons; Male; Middle Aged; Oligopeptides; Polyethylene Glycols; Prednisone; Ribavirin; Viremia; Vitamin B 12

Chronic hepatitis C (CHC) is a global health challenge. New therapeutic agents with excellent sustained virological response (SVR) rates are available mainly in developed countries, while the majority of CHC patients live in countries with low health budget. Predictors of therapeutic response are therefore necessary. Vitamin B12 appears to be involved in hepatitis C virus replication.. We therefore studied retrospectively the relationship between baseline serum vitamin B12 levels and clinical features in 116 CHC genotype 1 infected patients. Logistic regression models with univariate and multivariate analysis were used in the statistical analysis.. Baseline serum vitamin B12 levels were found to be positively associated with serum transaminase activities (AST, p = 0.002, ALT, p = 0.04), baseline viral load (p < 0.0001), stage of fibrosis (p = 0.0001) and favorable interferon-λ3/4 (IFNL3/IFNL4) rs12979860 genotypes (p = 0.04), and inversely with SVR (p < 0.001) as well as with rapid virological response (p = 0.001). Patients with baseline serum vitamin B12 levels below a cut-off value of 570 ng/L achieved a SVR rate of 59% with an odds ratio (OR) of 13.4 [confidence interval (CI) 4.3-41.9, p < 0.0001] compared to patients above the cut-off value. By combining serum vitamin B12 levels and IFNL3/IFNL4 rs12979860 genotypes, patients with baseline serum vitamin B12 levels below the cut-off value of 570 ng/L and IFNL3/IFNL4 rs12979860 CC genotype achieved a SVR rate of even 80% with an OR of 54 (CI 9.9-293, p < 0.0001) compared to patients above the cut-off value and non-CC-genotypes.. Our data suggest baseline serum vitamin B12 levels as useful noninvasive marker for characterizing CHC patients. They might further help to identify responders to a standard treatment.

Topics: Adult; Aged; Aged, 80 and over; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged; Retrospective Studies; Vitamin B 12; Young Adult

Vitamin B12 is stored in hepatocytes and inhibits hepatitis C virus (HCV) RNA translation. The implication of B12 in the setting of antiviral treatment is unknown. This study aims to retrospectively evaluate the discriminative efficacy of pretreatment B12 serum levels (s-B12) on end-of-treatment response (ETR) in patients with chronic HCV. Ninety-nine treatment naïve HCV patients, treated with interferon and ribavirin were studied. Serum B12 (s-B12) was analysed in samples collected before treatment start. Pretreatment s-B12 levels were correlated to ETR using univariate analysis. S-B12 and clinical data were evaluated in a multivariate logistic regression model. Mean pretreatment s-B12 was 331 pm in ETR and 260 pm in nonresponders (NR) (P = 0.012). In patients with s-B12 levels ≤ 360 pm, 23 (31.5%) were NR and 50 (68.5%) had ETR. In patients with s-B12 > 360 pm, one (3.8%) was NR and 25 (96.2%) had ETR (P = 0.0034). The results of the multivariate analysis were as follows: Pretreatment s-B12 > 360 vs ≤ 360 pm: OR 28.6 CI 2.31-354, P = 0.008. Fibrosis stage 3-4 vs 0-2: OR 0.29 CI 0.074-1.12, P = 0.068. Genotype 2/3 vs 1/4/5: OR 15.5 CI 2.87-83.9, P = 0.0012. Dose reduction vs no dose reduction: OR 0.21, CI 0.048-0.91 P = 0.034. Standard interferon vs pegylated-interferon: OR 0.079, CI 0.0091-0.68 P = 0.019. Age and gender were not correlated to ETR. S-B12 > 360 pm is independently correlated to ETR in HCV patients treated with interferon and ribavirin. This suggests that B12 is involved in suppression of viral replication during anti-HCV treatment.

Topics: Adult; Aged; Aged, 80 and over; Antiviral Agents; Female; Hepatitis C, Chronic; Humans; Interferons; Liver Cirrhosis; Male; Middle Aged; Prognosis; Retrospective Studies; Ribavirin; Serum; Severity of Illness Index; Treatment Outcome; Vitamin B 12

Chronic hepatitis C affects about 3% of the world's population. Pegylated interferon (IFN) alpha plus ribavirin is the gold standard treatment. Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in the metabolism of homocysteine. MTHFR gene polymorphisms and high levels of homocysteine are associated with a high degree of steatosis and fibrosis, conditions associated with a low sustained virological response (SVR) rate.. To evaluate whether MTHFR polymorphisms and homocysteine levels are predictors of the outcome of treatment in 102 prospectively enrolled patients with chronic hepatitis C naive to treatment.. Patients were treated with pegylated interferon alpha-2b plus ribavirin. All patients underwent blood tests, assessment of homocysteine, vitamin B(12), folate, hepatitis C virus (HCV)-RNA levels, screening for MTHFR gene polymorphisms and liver ultrasound examination.. Homocysteine levels were deranged (>16 micromol/L) in 10.5% of MTHFR wild-type patients vs 40.3% of non-wild-type patients (P=0.015). Homocysteine levels were 14.4 micromol/L in SVR patients and 15.5 micromol/L in non-SVR patients (P=0.049). The SVR rate was 40.0% in MTHFR wild-type patients, 52.0% in heterozygote mutants and 39.3% in homozygote mutants (P=0.467). At logistic regression analysis, genotypes 2 and 3 (odds ratio: 12.328, 95% confidence interval: 3.390-44.837, P=0.0001), homocysteine <16 micromol/L (odds ratio: 3.397, 95% confidence interval: 1.033-11.177, P=0.044) and aspartate aminotransferase (AST) levels <48 U/L (odds ratio: 3.262, 95% confidence interval: 1.125-9.458, P=0.029) were independent predictors of SVR.. In patients with chronic hepatitis C, homocysteine levels are associated with the outcome of pegylated-IFNalpha plus ribavirin treatment, while polymorphisms of MTHFR are not.

Topics: Antiviral Agents; Folic Acid; Hepacivirus; Hepatitis C, Chronic; Homocysteine; Humans; Interferon alpha-2; Interferon-alpha; Italy; Methylenetetrahydrofolate Dehydrogenase (NADP); Polyethylene Glycols; Polymorphism, Genetic; Prospective Studies; Recombinant Proteins; Ribavirin; RNA, Viral; ROC Curve; Vitamin B 12

Some latent diseases, such as immune disorders, can appear during interferon-alpha (IFN-alpha) therapy. These disorders are difficult to predict because of their low prevalence in the general population. We describe a case of pernicious anemia (PA) in a patient affected by chronic hepatitis C and macrocytosis during IFN-alpha therapy. Hemoglobin (Hb) concentration reached 7.3 g/dl. Anti-intrinsic factor (IF) antibodies were present, but not antiparietal cell antibodies (APCA). Suspension of IFN-alpha and administration of vitamin B(12) resulted in normal Hb concentrations. This case is the first instance of early PA (at the second month of IFN therapy) in a patient affected by chronic hepatitis C. The only other case of PA in a patient affected by hepatitis C virus (HCV) infection occurred during the second year of maintenance IFN therapy. We recommend that particular attention be paid to such clinical and laboratory conditions as macrocytosis in administering IFN-alpha therapy for chronic hepatitis C.

Topics: Anemia, Pernicious; Antiviral Agents; Erythrocyte Indices; Erythrocytes; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Recombinant Proteins; Vitamin B 12