Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Infections with the hepatitis B, C or D virus can all lead to chronic hepatitis. Serological and molecular methods are essential for diagnosis and for differentiation between the different forms of chronic virus hepatitis. In adults between 5 and 10% of all infections with the hepatitis B virus become chronic while the rate is as high as 80% with the hepatitis C virus. All forms of chronic hepatitis are frequently asymptomatic for a long period of time. Complications are liver cirrhosis and hepatocellular carcinoma. During chronic hepatitis B infection in around 1% of the patients per year the virus is eliminated spontaneously while virus elimination occurs rarely in patients with chronic hepatitis C infection. In patients with chronic hepatitis C infection over a period of 30 years around 3% of the patients die due to chronic hepatitis C infection. As soon as chronic virus hepatitis is diagnosed treatment should be considered. Standard therapy for all forms of chronic viral hepatitis is interferon alpha. Additionally recent results indicate that nucleoside analogous are effective for chronic hepatitis B and C virus infection. For chronic hepatitis B infection studies with famciclovir and lamivudine show that viral replication can be effectively blocked. For chronic hepatitis C infection a combination therapy with interferon and ribavirin has been shown to reach higher elimination rates compared to interferon mono-therapy. The last treatment option for all forms of viral hepatitis is liver transplantation.
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PMID:[Chronic viral hepatitis--diagnosis, therapy and prognosis]. 1020 Jun 10

The National Institutes of Health Consensus Development Conference on the management of hepatitis C, which took place in March 1997 and was published in September 1997, established guidelines for the diagnosis and management of chronic hepatitis C. The recommended treatment of chronic hepatitis C virus (HCV) infection is interferon alpha (or equivalent) 3 MIU three times per week for 12 months, in patients showing response to therapy after 3 months. Patients with the greatest risk for progression to cirrhosis (i.e. persistently elevated alanine aminotransferase levels, detectable serum HCV-RNA and liver biopsy showing portal or bridging fibrosis and at least moderate inflammation and necrosis) are recommended as candidates for therapy. The indication for therapy is less obvious in patients with milder histological changes, compensated cirrhosis and age less than 18 years or older than 60 years. Treatment is not indicated for patients with persistently normal aminotransferases or decompensated cirrhosis. This review outlines the background studies that led to the recommendations of the National Institutes of Health for the treatment of chronic hepatitis C and reviews newer evolving treatment strategies over the past year. In particular, the results of studies exploring treatment options for relapsers and non-responders to prior interferon therapy and the reported results to date on the safety and efficacy of combination therapy with interferon plus ribavirin are highlighted. Although aggressive suppression of HCV-RNA with induction therapy (daily and/or higher doses) or long-acting pegylated interferon preparations may improve the current results of therapy, few data are yet available. Finally, the treatment of chronic hepatitis C with protease inhibitors holds promise but has yet to reach the stage of clinical trials.
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PMID:Treatment strategies for chronic hepatitis C: update since the 1997 National Institutes of Health Consensus Development Conference. 1038 32

The clinical features and treatment of chronic hepatitis C in Chinese patients are the same as in Caucasian patients except that 27% of Chinese chronic hepatitis C patients have hepatitis C virus (HCV) genotype 6a. In contrast, Chinese patients with chronic hepatitis B (CHB) differ from Caucasian patients because the Chinese patients are immunologically tolerant to hepatitis B virus (HBV), having acquired hepatitis B infection perinatally or in early childhood. In the treatment of CHB, the short-term aims of loss of hepatitis B virus early antigen (HBeAg) and HBV-DNA need to be reassessed. In 1296 Chinese CHB patients, 67.7% of those who developed complications of cirrhosis or hepatocellular carcinoma, were HBeAg-antibody positive. Longer follow up of patients is, therefore, required to assess the time efficacy of a treatment regimen. After long-term follow up (median 90 months) of 206 Chinese CHB patients treated with interferon alpha (IFN alpha) compared with 203 untreated subjects, IFN alpha conferred no benefit in cumulative HBeAg seroconversion or in HBV-DNA negativity as determined by polymerase chain reaction assays or in decreasing long-term complications of cirrhosis and hepatocellular carcinoma. Lamivudine is a novel nucleoside analogue. In a recent 1 year study in 358 Chinese CHB patients, lamivudine treatment was associated with substantial histological improvement (including a reduction in fibrosis), with HBV-DNA suppression and normalization of alanine aminotransferase levels. However, lamivudine may have to be given on a long-term basis, as withdrawal of lamivudine results in rebound of HBV-DNA to pretreatment levels. The long-term effects of lamivudine are currently being assessed.
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PMID:Antiviral therapy for hepatitis B and C in Asians. 1038 33

A novel DNA virus (TTV) was identified recently in Japanese patients with posttransfusion hepatitis non-A-E and has been implicated as a cause of acute and chronic liver diseases of unknown etiology in some patients. The frequency of TTV infections was investigated in 284 blood donors, 105 patients with different liver disorders before and after liver transplantation (OLT), as well as in 64 patients with chronic hepatitis C who received antiviral therapy. TTV infections were found more frequently by nested-PCR in patients with liver disorders (15%) as compared to blood donors (7%). TTV occurred independently of the aetiology of the liver disease (e.g., cryptogenic cirrhosis [12.5%], alcoholic cirrhosis [16%], fulminant hepatic failure non-A-E [35%], and chronic hepatitis C [12.5%]; p=n.s.). After OLT, a high rate of TTV de novo infections (44%) was observed. However, TTV viremia after OLT (in 56 out of the 105 patients) was not associated with graft hepatitis. Analysis of patients with chronic hepatitis C coinfected with TTV who have been treated with interferon alpha alone or in combination with ribavirin revealed that TTV is an interferon-sensitive virus. Phylogenetic analysis of TTV sequences suggest that at least four different genotypes and several subtypes exist in Germany. In conclusion, the high prevalence of TTV infections observed in patients with parenteral risk factors is an argument in favour of transmission of the virus via blood and blood products. A relevant hepatitis-inducing capacity of TTV, however, seems unlikely, considering the observation that in the majority of patients, TTV infection after OLT was not accompanied by graft hepatitis.
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PMID:Occurrence of a novel DNA virus (TTV) infection in patients with liver diseases and its frequency in blood donors. 1044 Aug 18

A 46-year-old woman with common variable immune deficiency acquired acute non-A, non-B hepatitis from contaminated intravenous gamma globulin in 1983. For 6 years she had fluctuating elevations of her serum aminotransferase levels. In 1990 her serum was documented to be hepatitis C virusribonucleic acid positive by polymerase chain reaction, and her liver biopsy revealed chronic hepatitis with early cirrhosis (Knodell score, 15 points). Hepatitis C virus genotyping indicated that she had been infected with the type 3 genotype. She subsequently underwent treatment with interferon alpha (IFN-alpha) for 1 year and experienced biochemical, virologic, and histologic (Knodell score, 9) suppression. She was continued on maintenance therapy for an additional 7 years, with sustained biochemical and virologic suppression. During the sixth year of therapy, complications of portal hypertension were noted with mild ascites and eventually bleeding esophageal varices. This case report documents a favorable biochemical, virologic, and histologic response to IFN-alpha therapy in this setting; supports the notion that the natural progression of hepatitis C virus infection may be more aggressive in patients with common variable immune deficiency; and, although complications of portal hypertension eventually occurred, the suppressive maintenance IFN therapy may have delayed their onset. The future establishment of the long-term effects of IFN therapy on important clinical outcomes is necessary to understand better its therapeutic benefit in chronic hepatitis C infection.
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PMID:Long-term interferon alpha maintenance therapy for chronic hepatitis C infection in a patient with common variable immune deficiency. 1047 89

Hepatitis C is the commonest form of chronic viral hepatitis in most western countries. A significant proportion of patients develop cirrhosis, hepatic failure and hepatocellular carcinoma. The results of controlled trials have shown that interferon alpha is an effective treatment for hepatitis C. Treatment results in normalization of elevated transaminase levels in up to 50% of patients, although only 15-25% of patients have a sustained response. Recent studies have shown that iron influences the response of chronic hepatitis C to treatment and the natural history of hepatitis C. The mechanisms responsible for the effects of iron are not clear but emerging data suggest that the cellular location of iron within the liver lobule and the subsequent effects on immune function are likely to be critical determinants for these effects. It is likely that therapies for chronic hepatitis C which either remove iron or interfere with the action of iron at the cellular level may not only prove useful clinically but may also elucidate further the mechanisms of cellular injury in this disease.
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PMID:Hepatitis C and iron. 1053 73

This article presents the laboratory tests used to diagnose hepatitis C, to evaluate the severity of the chronic fibrosing disease, and to monitor the efficacy of treatment. Histological examination of liver biopsies is of the utmost importance for evaluating the development of fibrosis. Factors that precipitate fibrosis are reviewed. The annual rate of fibrosis progression can be assessed based on the estimated duration of hepatitis C virus contamination and on the fibrosis score established using the METAVIR classification. This allows to distinguish slow, fast, and intermediate fibrosis and to estimate the mean time to cirrhosis development. Combined use of interferon alpha (3 million units three times a week) and of Ribavirine (1000-1200 mg per day orally according to body weight) for 6 to 12 months is currently the standard treatment for hepatitis C. Treatment efficacy varies with a number of virus-related factors (genotype, viral burden) and patient-related factor (hepatic fibrosis, age, sex). In nonresponders, the value of treatment should not be assessed in terms of efficacy but in terms of slowing of fibrosis progression.
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PMID:[Hepatitis C: natural history, biology, treatment monitoring]. 1060 71

Hepatitis B virus (HBV) infection is a worldwide public health problem. In France, 150,000 individuals are infected with the HBV. Although many are asymptomatic carriers, about 30% have chronic hepatitis, a condition associated with a risk of cirrhosis and hepatocellular carcinoma. Antiviral treatments, most notably interferon alpha, probably modify the natural history of hepatitis B, decreasing the risk of hepatocellular carcinoma and increasing survival. Nucleoside analogs, particularly lamivudine, have also demonstrated potent antiviral activity, which should however be weighed against the increasing risk over time of mutation development in the YMDD region of the DNA polymerase reverse transcriptase. Antiviral therapy monitoring should include clinical safety evaluations and periodic laboratory tests including blood cell counts, transaminase activities, and serum DNA levels. The improving results provided by antiviral drugs should not deflect attention away from the importance of large-scale hepatitis B immunization of neonates, which has been shown to decrease the incidence of hepatocellular carcinoma in areas with high levels of hepatitis B endemicity.
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PMID:[Hepatitis B: epidemiology, natural history, biology, treatment monitoring]. 1060 72

Treatment of chronic hepatitis C virus (HCV) infection in naive patients with interferon alpha alone or in combination with ribavirin is reviewed. Two placebo-controlled randomised studies including 150 patients have shown that ribavirin as single therapy at standard dosage (15 mg/kg bodyweight in two divided doses daily) only reduces ALT levels transiently during therapy, whereas HCV RNA levels are not substantially reduced. Interferon alpha (IFN) alone at standard dosage (3 MU t.i.w.) given for 12 months results in sustained virological response (SR) rates of some 15-25% depending on the genotype and baseline HCV RNA levels. Ribavirin in combination with alpha interferon, in standard doses for 6-12 months significantly improves the sustained biochemical and virological response rates 2-3 times compared with IFN alone for 12 months. In the future, combination therapy will become standard therapy for most naive patients, at least those with unfavourable viral parameters such as a high baseline viral load (>2-3 million gE/ml serum) and genotype 1a+1b. In patients with favourable baseline viral characteristics (genotypes 2 and 3, irrespective of viral load) 6 months of combination therapy is likely to be sufficient, whereas those with unfavourable viral baseline characteristics will need longer combination treatment. Both genotype and baseline viral load need to be assessed to optimise the choice of therapy. Many questions must still be answered, such as the optimal dose of ribavirin and IFN in combination regimens, and the optimal treatment length. Furthermore, should induction treatment be used in combination regimens? What regimen should be used for patients with more advanced disease such as those with cirrhosis and decompensation?
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PMID:Treatment of naive patients with chronic hepatitis C. 1062 81

In the great majority of patients, hepatitis C virus (HCV) infection is not self-limiting. Approximately 70% to 85% of patients exposed to HCV will go on to develop chronic hepatitis. Among those who undergo treatment with interferon alpha, only 15% to 20% can be expected to respond to a 12- to 18-month course of therapy. With the addition of ribavirin to interferon monotherapy, the likelihood of sustained response (defined as normal alanine aminotransferase levels and negative HCV RNA persisting 6 months after the end of therapy) increases to approximately 40%. The fact remains, however, that there is still a substantial proportion of patients who will fail to respond to treatment. Without viral eradication, cirrhosis and hepatocellular carcinoma persist as long-term risks. Several options are available for the treatment of patients who fail to respond to interferon monotherapy. These include interferon dose escalation, whether by administering higher doses or administering them more frequently; changing to a different form of interferon; retreatment with a combination of interferon and ribavirin; adjunctive therapies, of which the best studied is phlebotomy to decrease hepatic iron stores; use of long-term, low-dose "maintenance"-type therapy; and watchful waiting with frequent follow-up. In the absence of long-term, large-scale clinical trials to support these modalities, physicians must exercise their best clinical judgment and individualize treatment to suit the patient's condition, needs, and preferences.
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PMID:Available options for treatment of interferon nonresponders. 1065 61


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