Occurrence Of Liver Dysfunction Research Articles

Weekly split-dose regimen for oral methotrexate reduced polyglutamation in red blood cells in patients with rheumatoid arthritis compared with single-dose regimen: Results from a multicentered randomized control trial.

We compared the incidence of adverse events between single and divided-dose regimens of methotrexate (MTX) by using a multicenter randomized controlled trial. Eighty-nine patients with insufficient control on MTX 8mg/wk were randomly assigned into single-dose (39 patients) or triple dose (39 patients) groups. The MTX dose for all patients was gradually increased to 16mg/wk. The primary endpoint was the occurrence of liver dysfunction during the observation period (20weeks). There were no differences in baseline data and MTX dose at Week 20 between groups. There was no significant difference in the incidence of liver dysfunction between groups (single dose, 3 [7.7%] patients vs. triple dose, 5 [13.2%] patients; P=.455). The incidence of adverse event increased in triple dose (single dose, 12 [30.8%] patients vs. triple dose, 20 [51.3%]), but the difference was not significant (P=.066). There was no significant difference in disease activity between groups, although MTX-triglutamate (PG3), MTX-PG4, and MTX-PG5 were significantly higher in the single dose group. Weekly split dosing reduced the polyglutamation of MTX. There was no significant difference in efficacy and safety between the 2 groups.

Statins May Increase the Risk of Liver Dysfunction in Patients Treated With Steroids for Active Graves' Orbitopathy

Intravenous glucocorticoids (IVGC) administered at high doses for the treatment of active moderate-severe Graves' orbitopathy (GO) may induce liver toxicity. Cumulative doses should not exceed 8 g and strict monitoring of liver function is recommended to avoid potentially life-threatening side effects. The 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitors, also known as statins, are employed to prevent major cardiovascular events. Patients with active GO, requiring immunosuppression with IVGC, are often treated with statins also. We studied a 64-year-old man and a 58-year-old woman who developed significant liver toxicity after moderate doses of IVGC (methylprednisolone 2.3 g and 5 g in patients 1 and 2, respectively) and concomitant administration of statins. Liver function tests were monitored every two weeks. Hepatitis virus markers and serology for autoimmune hepatitis were negative. At the occurrence of liver dysfunction (5-fold increase of serum aspartate aminotransferase/alanine aminotransferase concentrations), in patient 1 we stopped simvastatin indefinitely and discontinued IVGC for 2 weeks, whereas in patient 2, ongoing treatment with rosuvastatin was discontinued 3 weeks after IVGC therapy. In patient 1, off simvastatin, liver function remained normal after resuming IVGC. In patient 2, a further increase of the aminotransferase values was observed 3 weeks after IVGC discontinuation, with a progressive normalization only after statin withdrawal. Our study shows that statins, when concomitantly employed with methylprednisolone, may be a cause of liver dysfunction during IVGC in active GO. An accurate pharmacological history of all patients who are candidates for IVGC treatment is suggested to identify subjects at risk for hepatotoxicity.

Monitoring serum hepatitis C virus (HCV) RNA in patients with HCV‐infected CD20‐positive B‐cell lymphoma undergoing rituximab combination chemotherapy

Several studies have shown that the frequency of hepatitis C virus (HCV) infection is high in patients with B-cell non-Hodgkin's lymphoma (NHL). In these studies, liver dysfunction during chemotherapy has been demonstrated, but changes in HCV ribonucleic acid (RNA) levels during chemotherapy have not been well documented. In this study, we monitored serum HCV RNA levels and liver function in five HCV-infected patients with B-cell NHL undergoing treatment with rituximab-combination chemotherapy. Increased HCV RNA levels during or after the chemotherapy were observed in all five patients, and a significant increase in transaminases was seen in one case. In this case, serum HCV RNA level dramatically decreased at the time of the increase of transaminases, and this suggested that the cause of liver damage was an immune reaction against hepatocytes with HCV and not any anticancer drug induced liver toxicity. Monitoring of serum HCV RNA levels and transaminases may be helpful to understand the cause of liver dysfunction in patients receiving chemotherapy. However, increases of HCV viral load were not associated with the occurrence of liver dysfunction in this study. Further studies will be necessary to investigate more fully the relationship between changes in HCV viral load and liver function during chemotherapy for HCV-infected patients.

Quantification by magnetic resonance imaging and liver consequences of post-transfusional iron overload alone in long-term survivors after allogeneic hematopoietic stem cell transplantation

We quantified and studied the impact of post transfusional iron overload alone in post allogeneic HSCT. Median number of RBCs was 18. Ferritin was 532 mg/L. Liver iron content (LIC) was 117 mmoles/gdw. Correlation RBCs and ferritin was (r=0.81); RBCs and LIC was (r=0.84). The high ferritin group differed from normal ferritin group in terms of RBCs transfused (p<10(-3)), ALT (p<0.009). But occurrence of liver dysfunction was not significant. Magnitude of iron overload correlates closely to the number of RBCs and is quantified by MRI. Impact on liver dysfunction is moderate in absence of co-morbidity.

Alterações hepáticas na doença celíaca

O envolvimento do fígado tem sido freqüentemente descrito em pacientes celíacos. Condições como hipertransaminasemia, que retorna a valores normais após a dieta isenta de glúten, doenças hepáticas de origem auto-imune e outras doenças crônicas do fígado, sobretudo a hepatite crônica pelo vírus C, estão associadas com a doença celíaca. O objetivo deste artigo é discutir as relações recentemente evidenciadas na literatura entre essa enteropatia glúten-sensível e os tipos de alterações hepáticas.&lt;br /&gt;

Human parvovirus B19 infection in patients with chronic hepatitis B or hepatitis C infection

Parvovirus B19 has been reported to be detected in the sera of patients with acute or chronic hepatitis. The prevalence and clinical significance of B19 DNA in serum samples from patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were investigated. Serum samples from 54 patients with HBV infection, 51 with HCV infection and 53 normal controls were examined for anti-B19 antibodies and B19 DNA by enzyme-linked immunosorbent assay (ELISA), the nested polymerase chain reaction (PCR), Southern blotting and direct nucleotide sequencing, respectively. Anti-B19 IgM and IgG antibodies were detected in 19 (35.2%) and 46 (85.2%) of 54 serum samples from patients with HBV infection, and eight (15.7%) and 36 (70.6%) of 51 serum samples from patients with HCV infection. B19 DNA was detected in serum samples of 20 (37%) of 54 patients with HBV infection and 12 (23.5%) of 51 patients with HCV infection, but not in 53 serum samples from normal controls. The occurrence of liver dysfunction was not affected by B19 infection in patients with HBV and HCV infection (P > 0.05). All of the 20 serum samples with B19 DNA from patients with chronic HBV infection and all of the 12 serum samples with B19 DNA from patients with chronic HCV infection exhibited TW-3 subtype and TW-9 subtype, respectively. The variant subtypes of B19 were found to be distinctive in patients with HBV or HCV infection. These data revealed that human parvovirus B19 infection was frequently found in patients with chronic HBV or HCV infection. The variant genotypes were present in patients with different chronic hepatitis. The coinfection of B19 with HBV or HCV did not increase the frequency of liver dysfunction in patients with chronic hepatitis. Long-term longitudinal studies are required to determine the natural course of parvovirus B19 infection and whether its coinfection affects the natural history of chronic hepatitis B or hepatitis C.

Long-term outcome of renal transplantation in hepatitis B surface antigen-positive patients in cyclosporin era.

The impact of hepatitis B virus (HBV) infection on the outcome of renal transplantation (Tx) has been controversial. To determine the indication of renal Tx in patients infected by HBV, we investigated the long-term outcome of renal transplant patients with hepatitis B surface antigen (HBsAg). We analyzed 980 patients, including 18 HBsAg carriers, who underwent renal Tx and were immunosuppressed with cyclosporin in our institute. Fourteen out of 18 patients (77.8%) showed hepatic dysfunction after an average period of 17.8 months (range 1-65) after Tx. Four out of 14 patients (28.5%) with hepatic dysfunction died of liver failure due to fulminant hepatitis with functioning grafts between 15 and 71 months after Tx. The remaining 10 patients with hepatic dysfunction are alive up to the time of last follow-up; however, 5 of them lost their grafts because of rejection between 44 and 92 months after Tx. Their liver function improved after withdrawal of cyclosporin. Only 4 patients did not develop chronic liver disease and have had functioning grafts for between 44 and 147 months. One patient died of subarachnoid hemorrhage 22 months after Tx. HBe antigen, antibody and HCV antibody status were not related to the occurrence of liver dysfunction after Tx. Four HBV-DNA-positive patients showed deteriorated liver function. Three patients with chronic active hepatitis confirmed by the biopsy were treated with interferon. Interferon improved liver function in 2 patients, however, 1 patient died of liver failure despite interferon therapy. Our data suggested that the presence of HBsAg is often associated with chronic liver disease leading to liver failure regardless of HBe and HCV status after Tx. The indication of renal Tx in patients with HBsAg should be determined carefully giving consideration to these results.