Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) An estimated 15% to 25% of patients with chronic hepatitis B die of complications of the disease, such as cirrhosis and liver cancer. (2) In 2000, interferon monotherapy was the first-line treatment for chronic hepatitis B. This article examines the results of trials of peginterferon and nucleoside/nucleotide analogues (adefovir, entecavir, lamivudine), through a systematic review of the literature based on standardised Prescrire methodology. (3) We found no significant new data on interferon alfa administered subcutaneously three times a week: this treatment leads to sustained eradication of HBe antigen (reflecting a lack of viral replication) in 20% to 40% of patients. Adverse effects include a flu-like syndrome, potentially severe psychiatric disorders, and haematological and thyroid problems. (4) A trial comparing peginterferon alfa-2a once a week with interferon alfa-2a three times a week in about 300 patients showed that peginterferon alfa was at least as effective as interferon alfa-2a but that it increased the risk of neutropenia. (5) Three randomised controlled trials show that adding lamivudine to peginterferon does not increase the effect on viral load. Two trials show that peginterferon alfa-2a monotherapy is more effective than lamivudine monotherapy at 48 weeks. (6) In a randomised placebo-controlled trial in more than 600 cirrhotic patients, lamivudine (100 mg/day) reduced the risk of clinical progression in 10% of patients after three years of treatment. (7) The adverse effects of lamivudine are generally mild. Viral resistance occurs frequently and can limit its use. (8) Randomised controlled trials of adefovir dipivoxil show that it is effective after lamivudine failure, and that viral resistance tends to occur later than with lamivudine. When used as first-line treatment, adefovir dipivoxil is virologically effective for at least two years in about 25% of patients. Fewer follow-up data are available for adefovir dipivoxil than for lamivudine. Adefovir dipivoxil is nephrotoxic, meaning that blood creatinine levels must be monitored. (9) Entecavir was more effective than lamivudine on viral load and histological inflammation in three comparative trials lasting 96 weeks. However, entecavir may be carcinogenic. (10) In short, the treatment options for patients with chronic hepatitis B improved significantly between 2000 and 2007. Peginterferon alfa is now the first choice treatment, followed by adefovir dipivoxil or lamivudine as second-line treatment and by entecavir as a last resort. Other antivirals are under development.
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PMID:Chronic hepatitis B: a wider range of therapeutic options. 1772 44

Historical sources for the use of Glycyrrhiza species include ancient manuscripts from China, India and Greece. They all mention its use for symptoms of viral respiratory tract infections and hepatitis. Randomized controlled trials confirmed that the Glycyrrhiza glabra derived compound glycyrrhizin and its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In hepatitis C virus-induced cirrhosis the risk of hepatocellular carcinoma was reduced. Animal studies demonstrated a reduction of mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia. In vitro studies revealed antiviral activity against HIV-1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus. Mechanisms for antiviral activity of Glycyrrhiza spp. include reduced transport to the membrane and sialylation of hepatitis B virus surface antigen, reduction of membrane fluidity leading to inhibition of fusion of the viral membrane of HIV-1 with the cell, induction of interferon gamma in T-cells, inhibition of phosphorylating enzymes in vesicular stomatitis virus infection and reduction of viral latency. Future research needs to explore the potency of compounds derived from licorice in prevention and treatment of influenza A virus pneumonia and as an adjuvant treatment in patients infected with HIV resistant to antiretroviral drugs.
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PMID:Antiviral effects of Glycyrrhiza species. 1788 24

Patients with chronic liver diseases and specially with cirrhosis have an impaired immune system and are vulnerable to viral (co-) infections. Vaccination against hepatitis A and B virus (HAV, HBV) is recommended for all patients with chronic liver diseases. However, the efficacy of vaccinations in patients with end-stage liver diseases and transplant recipients is disappointing. As soon as a chronic liver disease is diagnosed patients should be immunized with the common vaccines (flu and pneumoccocci). Due to reduced seroconversion rates, antibody levels should be tested after a booster vaccination.
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PMID:[Immunization guidelines in patients with chronic liver diseases]. 1791 90

Variability in the health of human populations is greater in economically vulnerable areas. We tested whether this variability reflects and can be explained by: (1) underlying vulnerabilities and capacities of populations and/or (2) differences in the distribution of individual socioeconomic status between populations. Health outcomes were rates of mortality from 12 causes (cardiovascular disease, malignant neoplasms, accidents, chronic lower respiratory disease, cerebrovascular disease, pneumonia and influenza, diseases of the nervous system, suicide, chronic liver disease and cirrhosis, diabetes, homicide, HIV/AIDS) for 59 New York City neighborhoods in 2000. Negative binomial regression models were fit with a measure of socioeconomic vulnerability, median income, predicting each mortality rate. Overdispersion of each model was used to assess whether variability in mortality rates increased with increasing neighborhood socioeconomic vulnerability. To assess the two hypotheses, we examined changes in the variability of mortality rates (as indicated by changes in overdispersion of the models) for outcomes with significant non-constant variability after accounting for (1) vulnerabilities and capacities (social control, quality of local schools, unemployment, low education), and (2) the distribution of individual socioeconomic status (low income, poverty, socioeconomic distribution, high income). Some variability in all mortality rates was explained by accounting for a range of potential vulnerabilities and capacities, supporting the first explanation. However, variability in some causes of mortality was also explained in part by accounting for the distribution of individual resources, supporting the second explanation. The results are consistent with a theory of underlying socioeconomic vulnerabilities of human populations. In areas with lower levels of income, other characteristics of those neighborhoods exacerbate or temper the economic vulnerability, leading to more or less healthy conditions. Understanding the vulnerabilities and capacities that characterize populations may help us better understand the production of population health, and may inform efforts aimed at improving population health.
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PMID:Population vulnerabilities and capacities related to health: a test of a model. 1802 2

Chronic hepatitis B in children is mainly asymptomatic, but they are at life long risk for severe complications. Treatment is considered to suppress the virus and to prolong the survival by preventing the progression to cirrhosis and HCC. Therapeutic options for children are interferon-alpha (IFN-alpha) with antiviral, antiproliferative and immuno-modulatory effects and lamivudine (LAM) which inhibits HBV replication and increases cellular immune response. IFN-alpha, 5 MU/m(2), thrice weekly for 6 months is used in patients with high ALT levels which is associated with virologic response rate of 30-40%. Predictors of response are high ALT levels, low HBVDNA levels and high histological activity index. The response is sustained in 85%-90% of responders. Adverse events include flu-like syndrome, bone marrow suppression, hair loss, and psychiatric side effects, induction of autoimmunity and temporarily suppression of weight gain and growth velocity. LAM, a nucleoside anolog, leads to a virologic response rate of 20-30% when used for 12 months. High ALT levels, low HBVDNA levels and high histological activity index predict better response. Maintenance of HBeAg seroconversion is 56-80%. Longer courses of treatment with LAM increases the seroconversion rate but with high mutation rate and viral resistance. Except for causing mutations, LAM doesn't have serious adverse events. Different timing and durations of combination treatment with IFN and LAM were also evaluated without any significant superiority over monotherapy. In conclusion, the best approach for treatment of chronic HBV infection in children haven't been determined yet. Future developments concerning new drugs and different treatment strategies are needed.
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PMID:Treatment of chronic hepatitis B in children. 1822 Nov 87

We report about a 42-year-old farmer with leucocytosis, elevation of transaminases and liver cirrhosis as an underlying condition. The diagnosis of Q fever hepatitis was made through liver biopsy and serology. Under therapy with doxycycline, transaminases initially increased again; after switching to ciprofloxacin, the patient could be discharged 3 weeks after admission. Q fever is caused by Coxiella burnetii. The most frequent acute manifestation is a self-limiting flu-like illness. Chronic Q fever mostly presents as endocarditis. The diagnosis is made through histology ("doughnut" granulomas), PCR, serology (acute: anti-phase II antibodies, chronic: anti-phase I antibodies) and culture. Standard therapy is doxycycline.
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PMID:[A 42-year-old farmer with nonspecific leucocytosis and elevated transaminases. Acute septic reaction in Coxiella burnetii infection]. 1830 71

Viral hepatitis has long been under-diagnosed. Hepatitis A is an acute disease, while patients infected by hepatitis B and hepatitis C viruses are likely to develop chronical infections and severe complications (cancer, cirrhosis). The current treatment of hepatitis B and C consists in alpha interferon (preferably under its pegylated form), in combination with ribavirin for hepatitis C. The frequent and severe adverse effects of interferon-based therapy constitute, however, a major limiting factor (reactions at the injection site, flu-like syndrome, neurological disorders, ...). For hepatitis B, two alternatives are available so far, namely lamivudine and adefovir (used as a prodrug with highe oral bioavailability).
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PMID:[The ABC of viral hepatitis]. 1847 77

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that manifests as pulmonary emphysema, liver cirrhosis and, rarely, as the skin disease panniculitis, and is characterized by low serum levels of AAT, the main protease inhibitor (PI) in human serum. The prevalence in Western Europe and in the USA is estimated at approximately 1 in 2,500 and 1 : 5,000 newborns, and is highly dependent on the Scandinavian descent within the population. The most common deficiency alleles in North Europe are PI Z and PI S, and the majority of individuals with severe AATD are PI type ZZ. The clinical manifestations may widely vary between patients, ranging from asymptomatic in some to fatal liver or lung disease in others. Type ZZ and SZ AATD are risk factors for the development of respiratory symptoms (dyspnoea, coughing), early onset emphysema, and airflow obstruction early in adult life. Environmental factors such as cigarette smoking, and dust exposure are additional risk factors and have been linked to an accelerated progression of this condition. Type ZZ AATD may also lead to the development of acute or chronic liver disease in childhood or adulthood: prolonged jaundice after birth with conjugated hyperbilirubinemia and abnormal liver enzymes are characteristic clinical signs. Cirrhotic liver failure may occur around age 50. In very rare cases, necrotizing panniculitis and secondary vasculitis may occur. AATD is caused by mutations in the SERPINA1 gene encoding AAT, and is inherited as an autosomal recessive trait. The diagnosis can be established by detection of low serum levels of AAT and isoelectric focusing. Differential diagnoses should exclude bleeding disorders or jaundice, viral infection, hemochromatosis, Wilson's disease and autoimmune hepatitis. For treatment of lung disease, intravenous alpha-1-antitrypsin augmentation therapy, annual flu vaccination and a pneumococcal vaccine every 5 years are recommended. Relief of breathlessness may be obtained with long-acting bronchodilators and inhaled corticosteroids. The end-stage liver and lung disease can be treated by organ transplantation. In AATD patients with cirrhosis, prognosis is generally grave.
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PMID:Hereditary alpha-1-antitrypsin deficiency and its clinical consequences. 1856 11

Chronic hepatitis C is associated with substantial morbidity and mortality and poses a considerable socioeconomic burden. Improved treatment regimens, including the standard of care pegylated interferon alfa and ribavirin, have increased sustained virologic response rates; however, treatment has a long duration and is often associated with adverse events that may affect adherence. The goal of therapy is viral eradication and reduced disease-related complications such as fibrosis, cirrhosis, and hepatocellular carcinoma. The clinical outcome of hepatitis C virus infection is altered with antiviral treatment, which can be influenced by host (e.g., weight, ethnicity, health) and viral (e.g., genotype, baseline viremia) factors. Overall, sustained virologic response was attained by 54-63% of patients in clinical trials treated with pegylated interferon alfa-2a or -2b and ribavirin. However, this benefit is not without risk. Interferon-induced adverse events include flu-like symptoms, bone marrow suppression, and emotional or cognitive effects, whereas hemolytic anemia accounts for most ribavirin dosage reductions. These adverse events may be ameliorated with dosage adjustments, symptom therapy, and judicious use of preventive strategies (e.g., antidepressants, hematopoietic growth factors). Appropriate management of adverse events can increase treatment adherence, thereby enhancing outcomes and improving quality of life. Pharmacists are in an ideal position to improve the treatment of patients with chronic hepatitis C by providing education about the disease and its treatments and associated adverse events and by emphasizing the importance of treatment adherence for successful outcomes.
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PMID:Treatment options for patients with hepatitis C: role of pharmacists in optimizing treatment response and managing adverse events. 1875 86

Hepatitis C virus (HCV) is a major cause of chronic liver disease, with about 170 million people infected worldwide. Up to 70% of patients will have persistent infection after inoculation, making this disease a significant cause of morbidity and mortality. The severity of disease varies widely, from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma. Since the discovery of HCV, the treatment of hepatitis C has considerably improved. Recently, combination of pegylated interferons with ribavirin gives a response rate of about 55%. Treatment is indicated in patients with moderate or severe fibrosis. The tolerability of combination treatment is relatively poor, with a frequent flu-like syndrome and an impaired quality of life. In addition to viral and environmental behavioural factors, host genetic diversity is believed to contribute to the spectrum of clinical outcomes in HCV infection. The sequencing of the human genome, together with the development of high-throughput technologies that measure the function of the genome, have afforded unique opportunities to develop profiles that can distinguish, identify and classify discrete subsets of disease, predict the disease outcome or predict the response to treatment. This paper reviews the published literature on gene expression associated with HCV infection (HCV infection, fibrosis progression), and also according to response to treatment.
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PMID:Gene expression and hepatitis C virus infection. 1907 78


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