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
Query: UMLS:C0023890 (
cirrhosis
)
42,195
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cirrhosis
occurs in 20-50% of patients with hepatitis C and is thought to be irreversible. We describe two patients with
cirrhosis
secondary to hepatitis C in whom the extensive fibrosis and
cirrhosis
appeared to regress in response to treatment with
interferon-alpha
(IFN-alpha). Both patients were in the early stages of
cirrhosis
, class A in the Child-Pugh classification, total score 5 for each patient. Both responded fully to IFN-alpha and had normalization of all liver function tests and disappearance of hepatitis C viral RNA. Liver biopsies, performed before and after treatment, were coded unpaired by patient, combined with 21 liver biopsies from eight other patients with chronic hepatitis, and read independently by two pathologists using the Knodell scoring system. Knodell scores decreased from 14 to 3.5 and from 13.5 to 4 in these two patients.
Cirrhosis
and extensive fibrosis, present at baseline, were not present on follow-up liver biopsies, which were of sufficient size to reduce the likelihood of sampling error. We conclude that hepatic fibrosis and clinically early
cirrhosis
may be reversible in some patients with hepatitis C who respond to treatment with IFN-alpha.
...
PMID:Regression of hepatic fibrosis in hepatitis C with long-term interferon treatment. 988 84
We investigated the efficacy and tolerability of three different types of
interferon-alpha
, administered with the same schedule to naive patients with chronic hepatitis C. One hundred and seven patients with histologically proven chronic hepatitis C were enrolled during a period of three years and randomly divided into three groups, to receive (a) leukocyte-
interferon-alpha
, 6 MU three times a week for 4 months, followed by 3 MU three times a week for 8 months (Group I); (b) recombinant-IFN-alpha-2a, with the same schedule (Group II); and (c) lymphoblastoid-IFN-alpha-N1, with the same schedule (Group III). All patients were followed-up for 6 months to evaluate the long-term response. The 'Complete Response' rates at the end of treatment were: 50%, 46.1% and 41.6%, in Groups I, II and III, respectively; most patients relapsed after the end of therapy, so that the 'sustained responders' were, after 6 months of follow-up, 18.7%, 23.1% and 19.4%, respectively. Analysis of pre-treatment variables showed that age, ALT and gamma GT serum levels, as well as the prevalence of
liver cirrhosis
, were lower in the 'sustained responder' group. Four patients were eliminated from the study because of severe adverse events: 1, 2 and 1, in Groups I, II and III, respectively. Our results indicate a similar response rate with the three different types of
interferon-alpha
, although at baseline, age, serum levels of gamma globulins and the number of patients with
cirrhosis
-possible negative-risk factors, were higher in Group I.
...
PMID:Comparative responses to three different types of interferon-alpha in patients with chronic hepatitis C. 989 Nov 96
The pathogenic potential of the newly discovered TT virus (TTV) is currently a matter of conjecture. Its presence was investigated in the serum of 660 patients, by polymerase chain reaction. TTV was detected in 50% of 221 patients with unselected pathologies, and no significant differences related to age, sex, or organ disease were noted. TTV was present at a significantly higher rate in hemophiliacs (73%) and at lower rates in patients with
cirrhosis
(30%) and rheumatoid arthritis (28%). Patients with other liver diseases, systemic lupus erythematosus, or psoriasis or receiving hemodialysis had rates of infection similar to those in unselected patients. TTV-positive patients treated with
interferon-alpha
for underlying type C hepatitis showed no appreciable changes of TTV viremia levels. Type 1b was by far the most frequent viral genotype (92%), followed by types 2c (5%) and 1a (3%).
...
PMID:High prevalence of TT virus viremia in italian patients, regardless of age, clinical diagnosis, and previous interferon treatment. 1066 84
The present study assessed the clinical significance of hepatitis C virus (HCV) genotypes and their influence on response to long term recombinant-
interferon-alpha
(r-IFN-alpha) therapy in Brazilian patients. One hundred and thirty samples from patients previously genotyped for the HCV and with histologically confirmed chronic hepatitis C (CH-C) were evaluated for clinical and epidemiological parameters (sex, age, time of HCV infection and transmission routes). No difference in disease activity, sex, age or mode and time of transmission were seen among patients infected with HCV types 1, 2 or 3. One hundred and thirteen of them were treated with 3 million units of r-IFN-alpha, 3 times a week for 12 months. Initial response (IR) was significantly better in patients with genotype 2 (100%) and 3 (46%) infections than in patients with genotype 1 (29%) (p < 0. 005). Among subtypes, difference in IR was observed between 1b and 2 (p < 0.005), and between 1b and 3a (p < 0.05). Sustained response (SR) was observed in 12% for (sub)type 1a, 13% for 1b, 19% for 3a, and 40% for type 2; significant differences were found between 1b and 2 (p < 0.001), and between 1b and 3a (p < 0.05). Moreover, presence of
cirrhosis
was significantly associated with non response and response with relapse (p < 0.05). In conclusion, non-1 HCV genotype and lack of histological diagnosis of
cirrhosis
were the only baseline features associated with sustained response to treatment. These data indicate that HCV genotyping may have prognostic relevance in the responsiveness to r-IFN-alpha therapy in Brazilian patients with chronic HCV infection, as seen in other reports worldwide.
...
PMID:Chronic hepatitis C virus infections in brazilian patients: association with genotypes, clinical parameters and response to long term alpha interferon therapy 1052 39
Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis,
liver cirrhosis
, and hepatocellular carcinoma worldwide. Therapeutic options for hepatitis C are limited. Standard monotherapy with
interferon-alpha
leads to a sustained response in only 10-20% of patients. Recent studies have shown improved sustained response rates for the combination of
interferon-alpha
and ribavirin. Despite these improvements, more effective therapies are needed. A variety of alternative agents are currently being evaluated in clinical trials. Recent advances in the molecular virology of hepatitis C have identified specific antiviral targets such as the viral NS3 serine protease, the RNA helicase, and the RNA-dependent RNA polymerase. In addition, gene therapeutic strategies aimed at inhibiting HCV gene expression and replication as well as immunotherapeutic concepts aimed at enhancing the cellular immune response against HCV are being explored in various experimental systems. These and other novel antiviral strategies may complement the existing therapeutic modalities in the future.
...
PMID:Current and evolving therapies for hepatitis C. 1056 26
Little is known about treatment of hepatitis C virus (HCV) infection in "other groups" than the general population, namely patients with hematologic or renal disorders and patients with human immune deficiency (HIV) co-infection. The aim was to better define HCV therapies in these groups. We analyzed the medical literature focusing on treatment of HCV infection in other populations to suggest conclusions about indications based on tolerance and efficacy. As in the general population, the decision to treat should be based mainly on liver pathology, and to a lesser extent on virologic profiles (genotype, quantitative viremia). Hemophilia does not modify therapeutic strategies which combine
interferon-alpha
and ribavirin. Similar combinations should be discussed in patients with inherited hemoglobin disorders but iron overload (secondary hemochromatosis) associated with multiple transfusions may decrease the potential efficacy of
interferon-alpha
and chronic anemia may limit the use of ribavirin. In hemodialyzed patients, therapy by
interferon-alpha
is feasible with 3 MU subcutaneously after each hemodialysis three times weekly for 6-12 months. Virologic results are at least similar to those obtained in the general population with frequent pathological improvement. Combinations are not possible because ribavirin is contraindicated for pharmacokinetic reasons. In kidney recipients,
interferon-alpha
is deleterious and inefficient; ribavirin monotherapy has a potential interest which remains to be evaluated. In HIV co-infected patients, treatment is mandatory given the high rate of
cirrhosis
and the improved survival related to multiple anti-HIV therapies (which have no clear efficacy for quantitative HCV viremia). Due to the limited efficacy of
interferon-alpha
monotherapy, the combination of
interferon-alpha
and ribavirin appears to be the logical treatment. An important point is the in vitro inhibition of phosphorylation by ribavirin of HIV reverse transcriptase inhibitors which has to be analyzed in vivo before the combination can be recommended. On the basis of the results of liver biopsy, antiviral treatments may be proposed for HCV-infected patients with hematologic or renal disorders as well as for HIV co-infected patients. The choice of therapy (monotherapy or combined therapies) should be based on the clinical situation (contraindicated with chronic anemia or renal failure, for example) and its duration on the virologic factors of response as in the general population.
...
PMID:Treatment of chronic hepatitis C in special groups. 1062 89
The prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection ranges from nearly 30% to over 50%, depending on the population. Shared modes of transmission and the success of current antiretroviral regimens have contributed to the emergence of HCV as a significant pathogen in the HIV-positive population. HIV coinfection appears to worsen HCV infection, with studies showing more severe fibrosis, a higher frequency of
cirrhosis
, and increased deaths from liver disease. HIV coinfection may also increase the rate of maternal-fetal transmission of HCV. Similarly, studies suggest a more rapid progression to AIDS or death for HCV genotypes 1a and 1b than for other genotypes in HIV-infected patients with hemophilia. Highly active antiretroviral therapy (HAART), such as HIV protease inhibitors, has no effect on HCV infection and may transiently increase ALT, AST, and hepatitis C viral load. Hepatotoxicity associated with HAART may or may not be related to the presence of HCV and may depend on the specific agents used. Data suggest that treating chronic hepatitis C in HIV-co-infected patients can decrease fibrosis, increase T-cell responsiveness to HCV antigens, and decrease the rate of fatal hepatomas. Interferon alpha may provide sustained biochemical or virologic responses in HIV/HCV-coinfected patients. The combination of
interferon-alpha
and ribavirin may also be a treatment option but is more complex, and additional research is needed. Treating HCV infection in HIV/HCV-coinfected individuals may help lower the hepatitis C viral load and permit treatment with protease inhibitors.
...
PMID:Hepatitis C virus and human immunodeficiency virus: clinical issues in coinfection. 1065 64
The hepatitis C virus (HCV) infects some 170 million people worldwide and is responsible for approximately 20% of cases of acute hepatitis and 70% of cases of chronic hepatitis. Acute hepatitis is icteric in only 20% of patients and is rarely severe. Eighty five per cent of the infected patients develop chronic infection which is generally asymptomatic. Among the HCV chronic carriers, 25% have persistently normal serum alanine aminotransferase (ALT) levels despite having detectable HCV-ribonucleic acid in serum, 75% have elevated ALT levels. While the majority of patients with mild chronic hepatitis have a slowly progressive liver disease, the patients with moderate or severe chronic hepatitis may develop
cirrhosis
within a few years. In patients with HCV-related
cirrhosis
, the incidence of hepatocellular carcinoma is 2-5% per year. HCV-related end-stage
cirrhosis
is currently the first cause of liver transplantation. Treatment with the combination of
interferon-alpha
and ribavirin induces a sustained virological response in roughly 40% of the patients. The virological response is associated with a biochemical response and histological improvement. It is believed that the decrease of necroinflammatory liver lesions induced by anti-viral therapy in responders, is associated with a decreased risk of development of
cirrhosis
and hepatocellular carcinoma
...
PMID:Natural history of hepatitis C and the impact of anti-viral therapy. 1071 54
No consistently effective therapy is yet available for the treatment of chronic HBsAg, anti-HBe, HBV-DNA-positive hepatitis. A multicenter trial has shown that the response rates are not significantly different when patients with anti-HBe-positive hepatitis are treated with six-month course of thymosin-alpha1 or of
interferon-alpha
. However, since among these patients, interferon's real efficacy is still debated, with sustained biochemical response achieved in only a few of the treated patients, we conducted this controlled study to investigate the safety and efficacy of thymosin-alpha1 as compared with no treatment. Forty-four chronic hepatitis B virus (HBV) carriers, who were anti-HBe- and HBV-DNA-positive, were randomized, with stratification for the presence of
cirrhosis
at baseline liver biopsy, to receive either thymosin-alpha1 at a dose of 900 microg/m2 twice a week for six months or no treatment. At entry, both groups of patients were comparable for sex, age, liver histology, ALT, IgM anti-HBc, and HBV-DNA levels. Forty-two patients were followed-up for 20 months (median; range 12-32 months) after completion of therapy: one dropped out, and one developed hepatocellular carcinoma at six months. Thymosin-alpha1 treatment had no side effects. Six months after the end of the therapy, HBV-DNA was negative and ALT had normalized in 14% of treated cases and in 4.5% of control group, while IgM anti-HBc was negative (<0.200) in 14% of the treated patients and in 4.5% of the controls. Among the treated patients, the median ALT levels stayed significantly lower compared to the pretreatment values during the treatment period and six months of follow-up. During the first year, there were six flares of hepatitis in the control group and five among the treated patients (P = NS), yielding a per year average of 0.3 and 0.23 flares per patient, respectively. Among the treated patients, median IgM anti-HBc levels were low with respect to baseline values 4-10 months after treatment started. None became HBsAg negative. In conclusion, these results indicate that, in anti-HBe, HBV-DNA-positive chronic hepatitis B, thymosin-alpha1 therapy alone does not increase the response rate, but may contribute to reduce the immune-mediated liver cell necrosis as indirectly assessed by ALT and IgM anti-HBc levels.
...
PMID:A randomized, controlled study of thymosin-alpha1 therapy in patients with anti-HBe, HBV-DNA-positive chronic hepatitis B. 1075 36
Acute hepatitis can be caused by the enterically spread hepatitis A and E viruses and the parenterally spread hepatitis B, C or D viruses. The clinical features of acute viral hepatitis are similar among the five viruses and include non-specific symptoms and icterus. In general, a specific therapy is not necessary, but patients with fulminant hepatitis may require liver transplantation. For acute hepatitis C, the effect of
interferon-alpha
on the risk of chronicity is evaluated in clinical trials. Chronic hepatitis is defined as inflammatory reaction in the liver that continues without improvement for at least 6 months after infection with hepatitis B, C or D viruses. Hepatitis B resolves in more than 90% of the patients, but chronic infection can lead to
liver cirrhosis
and hepatocellular carcinoma. Chronic hepatitis C is an insidious disease, because early diagnosis is missed easily due to asymptomatic presentation and about 70% of infected patients develop chronic hepatitis. The benefits of
interferon-alpha
and/or nucleoside analogues have been proven in recent clinical trials that show sustained responses in more than a third of all patients with chronic viral hepatitis. The future treatment of chronic viral hepatitis will likely include immunomodulation and gene therapy.
...
PMID:[Clinical aspects and therapy of viral hepatitis]. 1084 Jun 5
<< Previous
1
2
3
4
5
6
7
8
9
10
Next >>