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 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of alpha-interferon (IFNalpha) alone to the combination of IFNalpha plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNbeta represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNbeta treatment in HCV-related chronic hepatitis. The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNbeta are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNbeta treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported. A more recent study, performed to compare IFNbeta alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have been observed in subpopulations such as patients with genotype-1b HCV hepatitis unresponsive to IFNalpha treatment or with HCV-related cirrhosis and patients with acute viral hepatitis. If further studies will confirm the efficacy of combined IFNbeta and ribavirin treatment, this regimen could represent a safe and alternative therapeutic option in selected patients.
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PMID:Safety of interferon beta treatment for chronic HCV hepatitis. 1469 60

Chronic hepatitis C virus infection is a common and serious disease. Although an estimated 2.7 million persons in the United States have this disease, most have not yet been diagnosed. Recent advances in treatment provide successful cure in 50 to 80 percent of cases. Current drug therapy consists of a combination of pegylated interferon and ribavirin. Although all patients with chronic hepatitis C virus infection are potential candidates for treatment, pharmacologic therapy has a number of contraindications. Evaluation of suitability for treatment includes a thorough search for comorbid medical and psychiatric conditions that can be contraindications. Initial testing involves anti-hepatitis C virus antibodies, but definitive diagnosis of active disease requires detection of viral RNA. Most patients require a liver biopsy to determine the amount of hepatic fibrosis and ongoing hepatocellular inflammation. Viral genotype also should be determined: type 1 requires 12 months of treatment and does not respond as well as types 2 and 3, which require only six months of treatment. Common side effects of drug therapy include anemia, anorexia, depression, fatigue, fever, headache, myalgia, nausea, and erythema at the injection site.
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PMID:Management of hepatitis C: evaluating suitability for drug therapy. 1586 91

We report a case of fatal liver failure due to reactivation of lamivudine-resistant HBV. A 53-year-old man was followed since 1998 for HBV-related chronic hepatitis. Serum HBV-DNA was 150 MEq/mL (branched DNA signal amplification assay) and ALT levels fluctuated between 50-200 IU/L with no clinical signs of liver cirrhosis. Lamivudine (100 mg/d) was started in May 2001 and serum HBV-DNA subsequently decreased below undetectable levels. In May 2002, serum HBV-DNA had increased to 410 MEq/mL, along with ALT flare (226 IU/L). The YMDD motif in the DNA polymerase gene had been replaced by YIDD. Lamivudine was continued and ALT spontaneously decreased to the former levels. On Oct 3 the patient presenting with general fatigue, nausea and jaundice was admitted to our hospital. The laboratory data revealed HBV reactivation and liver failure (ALT: 1828 IU/L, total bilirubin: 10 mg/dL, and prothrombin INR: 3.24). For religious reasons, the patient and his family refused blood transfusion, plasma exchange and liver transplantation. The patient died 10 d after admission. The autopsy revealed remarkable liver atrophy.
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PMID:Fatal liver failure due to reactivation of lamivudine-resistant HBV mutant. 1516 53

We report the case of an ABO-incompatible kidney transplant recipient who died suddenly following a good transplant course of 12 years. For 10 years after transplantation, the graft function had been stable (s-Cr: 1.0-1.5 mg/dL), although chronic hepatitis C had developed, with elevation of transaminase. In the 11th year, he was admitted into the hospital with low-grade fever and general fatigue. Jaundice and anaemia progressed, and he died 2 months after admission. The autopsy diagnosis was: (1) post-renal transplantation state, (2) phlegmonous enterocolitis with septic infarction, (3) cellulitis and necrotic myositis, and (4) sepsis. The transplanted kidney graft showed well-preserved glomeruli and tubules, corresponding to chronic allograft nephropathy (CAN) grade Iota (ci1, ct1, cv1), according to the Banff classification. The pathological changes observed in this long-surviving ABO-incompatible kidney graft were similar to those of an ABO-compatible graft, although its degree was milder.
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PMID:An autopsy case of bacterial septic shock 12 years following ABO-incompatible renal transplantation. 1519 73

Neuropsychiatric side effects are common with interferon-based therapy for chronic hepatitis C, and their prompt recognition and management is essential to effective patient care. Depression induced by interferon has been a significant cause of early treatment discontinuation in clinical trials. The need to monitor for and treat interferon-induced depression is well established, but whether to use antidepressants prophylactically remains controversial. Nonetheless, clinicians should maintain a low threshold for antidepressant therapy. Other significant neuropsychiatric side effects include anxiety, hypomania or mania, fatigue, and cognitive dysfunction. These can be additional sources of patient distress during interferon therapy and require appropriate intervention through patient education, psychotropic medications, support, and behavioral techniques.
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PMID:Managing the neuropsychiatric side effects of interferon-based therapy for hepatitis C. 1546 15

Fatigue is common and can be profound in patients with chronic liver diseases, such as primary biliary cirrhosis (PBC) and chronic hepatitis C. The pathogenesis of fatigue in such patients is unknown; it may be related to infection with the hepatitis C virus or the pathophysiology of cholestasis in PBC, to a psychological reaction to knowledge of the diagnosis, or to the presence of chronic liver disease. A major problem in evaluating a treatment for fatigue in a randomized controlled trial is the inherent subjectivity of fatigue and the lack of a satisfactory objective quantitative primary efficacy endpoint. Experimental studies in rats and male athletes have implicated the serotonin neurotransmitter system in fatigue of central origin. Administration of the 5-HT3 serotonin receptor subtype antagonist, ondansetron, has been associated with substantial sustained clinical ameliorations of profound fatigue in at least some patients with chronic liver disease.
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PMID:Fatigue complicating chronic liver disease. 1555 32

Hematologic side effects (anemia, neutropenia, and thrombocytopenia) of combination therapy with pegylated (PEG)-interferon alfa and ribavirin are commonly encountered during antiviral therapy for chronic hepatitis C (HCV). An important consequence of these side effects is dose modification of PEG-interferon alfa, ribavirin, or both. Dose modification (including discontinuation) diminishes the efficacy of optimal treatment regimen for HCV and may have a negative impact on sustained virologic response. Additionally, fatigue associated with anemia may impair patients' quality of life. The clinical implications of neutropenia or thrombocytopenia are less clear than for anemia; nevertheless, severe infection and bleeding are uncommon. Dose adjustments effectively treat these hematologic side effects, but the resulting suboptimal dosing and potential impact on virologic response are major concerns. Recent attempts to maximize adherence to the optimal treatment regimen have used hematopoietic growth factors rather than dose adjustment to treat side effects. Research on growth factor support has focused on anemia and neutropenia. Epoetin alfa and darbepoetin alfa are erythropoietic growth factors that effectively increase hemoglobin while maintaining the optimal ribavirin dose and improving patients' quality of life. Preliminary work suggests that filgrastim, granulocyte colony stimulating factors, may be an effective treatment of interferon-induced neutropenia. Although this early work shows tremendous promise for managing hematologic side effects of combination therapy for HCV, and potentially enhancing adherence, further research is needed to clarify the efficacy, safety, and cost-effectiveness of growth factors in the management of patients with chronic HCV.
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PMID:The use of growth factors to manage the hematologic side effects of PEG-interferon alfa and ribavirin. 1559 26

Since the discovery of hepatitis C virus (HCV) in 1989, significant advances have been made in our understanding of this important viral pathogen. Children at risk for HCV infection include recipients of potentially contaminated blood products and organ transplants, and infants born to HCV-infected mothers. Chronic HCV infection is usually asymptomatic in children but active hepatitis, cirrhosis and hepatocellular carcinoma can occur. The development of treatment strategies for chronic hepatitis C in children has directly evolved from clinical trials in adults. Sustained virologic response, defined by undetectable HCV RNA in serum 24 wk after completion of treatment, occurs in approximately 36% of children treated with conventional interferon alone and in about 50% of those given conventional interferon in combination with ribavirin. Pegylated interferon-based treatment regimens are better than those based on conventional interferon in adults but little is known about pegylated interferon in children. Factors associated with a favorable response to antiviral therapy in children are similar to those in adults and include infection with HCV genotype 2 or 3 and low pretreatment serum HCV RNA levels. Treatment related adverse events in children include 'flu-like' syndrome, fatigue, anorexia, weight loss, depression, anemia, leukopenia and thrombocytopenia.
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PMID:Treatment of chronic hepatitis C in children. 1559 40

Trichloroethylene (TCE) is an organic solvent used in a variety of industries for more than 60 years. Several adverse events following acute or chronic exposure to trichloroethylene have been reported. However, TCE-induced hepatitis is very rare. We present the case of a 55-year old male who was presented with anorexia, fatigue and upper abdominal discomfort. Routine laboratory examination revealed marked elevation of liver enzyme values. All possible causes of hepatitis were ruled out. The patient has been working as a shoemaker, in a small room of a basement, with insufficient air-exchange; during the last 5 years he used daily a glue containing 1,1,1 trichloroethylene. The diagnosis of hepatitis was confirmed by liver biopsy. The offending agent was withdrawn. Three months later, he was "feeling well" and liver enzyme values had returned to normal. Six months after the initial biopsy, a second liver biopsy was performed and histology was markedly improved. Workers exposed to hazardous chemicals, such as trichloroethylene, must have periodic follow-up examinations. Good work practices are very important when using toxic substances. In patients whose initial diagnostic workout is negative for common causes of acute or chronic hepatitis, toxic causes should be considered, with emphasis on patient's job and working conditions.
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PMID:Hepatitis caused by occupational chronic exposure to trichloroethylene. 1572 81

Neurocognitive morbidity has been reported in individuals with chronic hepatitis C virus (HCV) infection, but the magnitude of such dysfunction in the absence of disease-correlated factors known to affect the central nervous system (e.g., substance abuse, cirrhosis, depression, interferon treatment) and the impact of any such change on functioning is unclear. We investigated a cohort of individuals with HCV, all of whom were carefully screened to exclude relevant comorbidities, to elucidate virus-related changes in the brain using neuropsychological tests and magnetic resonance spectroscopy (MRS). A cohort of 37 patients with chronic HCV infection was culled from 300 consecutive patients presenting to a tertiary care liver clinic. A comparison group of healthy controls (n = 46) was also assessed. Of 10 neurocognitive measures evaluated, the HCV group showed marginally poorer learning efficiency compared with controls; only 13% of patients demonstrated a clinical level of impairment on this test (defined as 1.5 SD below the normative standard). Although patients reported greater levels of fatigue and symptoms of depression, these factors did not correlate with the degree of learning inefficiency. With respect to MRS, the HCV group demonstrated increased choline and reduced N-acetyl aspartate relative to controls in the central white matter. Indicators of liver disease severity did not correlate with either memory or MRS abnormalities. In conclusion, while our findings support an association between hepatitis C and indicators of central nervous system involvement in a cohort of patients carefully screened to eliminate other factors influencing neurocognitive integrity, the clinical significance of these effects is limited.
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PMID:Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors. 1579 53


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