UMLS:C0023890 - FACTA Search

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Query: UMLS:C0023890 (cirrhosis)
42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic hepatitis C is a major health care problem throughout the world. The disease may progress to cirrhosis, with complications such as hepatocellular carcinoma. The usual primary goal of therapy is viral eradication, as patients with long-term remission are generally regarded as unlikely to develop cirrhosis or hepatocellular carcinoma. Another primary goal should be the reduction in liver fibrosis progression. Interferon-alpha (IFN-alpha) is the only drug approved for the treatment of hepatitis C in Europe and North America. Its effectiveness appears to be related to dose and duration of therapy. The best efficacy/risk ratio seems to be in favour of 3 million units (MU) IFN-alpha three times per week on a 12-month schedule. With this regimen, a sustained alanine aminotransferase (ALT) response is achieved in nearly 35% of patients. Ribavirin has emerged as potentially the second most effective drug. While it appears unsatisfactory when given alone, it seems much more effective in combination with IFN. Combining them seems to exert a synergistic effect between the two drugs and sustained remission might be achieved in nearly 50% of patients with combination therapy. Controversy persists concerning the long-term benefit of therapy in transient responders and non-responders. It is possible that IFN therapy, in comparison to natural history, might reduce liver fibrosis progression and prevent hepatocellular carcinoma, even in non-responders, and have greater efficacy if used in long-term treatment. Whatever the treatment schedule, prolonged viral eradication may not be achieved in all patients and new drugs should be sought to improve the results of therapy.
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PMID:Management of hepatitis C. 957 31

Antiphospholipid antibodies have been demonstrated in chronic hepatitis C, but their clinical and pathogenetic significance remains elusive. We prospectively studied 115 patients (85 men, mean age 36.9 years) with chronic hepatitis C without cirrhosis and treated by alpha-interferon (alpha-IFN). Antiphospholipid determinations comprised anticardiolipin (ACA), anti-beta2-glycoprotein I and anti-prothrombin antibodies of the IgG and IgM classes. At entry, 24 patients (21%) were found to possess low to moderate ACA levels (18 IgG, two IgM and four both isotypes) compared with only 4/115 age- and sex-matched control subjects (3.5% P=0.001). ACA positivity rate increased to 31% (P=0.01) after a 6-month course of alpha-IFN treatment. In contrast, the prevalence of anti-beta2-glycoprotein I and anti-prothrombin antibodies was not significantly different from controls at either time point. The presence of ACA correlated with that of antinuclear antibodies (P=0.0002), but was not associated with parameters such as histological activity, viral burden and response to alpha-IFN, nor with a history of thrombosis or pregnancy loss. However, a non-significant trend of higher incidence of mild thrombocytopenia among ACA-positive patients was observed. We conclude that low-titre ACA positivity is a common finding in patients with chronic hepatitis C, especially following alpha-IFN treatment, but does not select a category with different clinical features. These data are in keeping with the absence of associated anti-beta2GPI and anti-prothrombin antibodies, and do not support a role for HCV infection in the pathogenesis of the antiphospholipid syndrome.
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PMID:Prevalence and significance of anticardiolipin, anti-beta2 glycoprotein I and anti-prothrombin antibodies in chronic hepatitis C. 963 88

An estimated 3.5 million people in the United States have chronic hepatitis C. Each year, 8,000 to 10,000 of these chronically infected patients die of a liver-related complication of their infection. The introduction of effective blood screening assays has resulted in a remarkable decrease in the incidence of post-transfusion HCV infection. Nonetheless, hepatitis C remains an important clinical problem. Some important new treatment programs can help prevent the development and progression of compensated cirrhosis to either decompensated cirrhosis or HCC. Patients who present to the health care system with advanced chronic active hepatitis or cirrhosis have been treated with interferon. Of those studied, only IFN therapy has been shown to induce remissions of the hepatic inflammatory process and to eliminate viral infection in most treated cases. However, it is widely held assumption that cirrhotic individuals do not respond to IFN therapy and that the treatment of decompensated cirrhotic individuals with HCV infection is dangerous. We believe that this assumption is false. In many studies, cirrhotic patients with chronic hepatitis C have been shown to respond to IFN therapy. However, they do so at a rate of half that reported for individuals with non-cirrhotic chronic active hepatitis. There have been no reports of hepatic decompensation as a consequence of IFN treatment of cirrhotic individuals with chronic hepatitis C. The use of IFN for cirrhotic patients is reviewed.
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PMID:Interferon treatment of HCV positive cirrhotic patients. 963 3

The aim of this study was to evaluate the efficacy and safety of interferon-alpha (IFN-alpha) therapy of chronic hepatitis B, C and D (HBV, HCV and HDV, respectively) in renal transplant recipients. A group of 42 patients (30 males, 12 females, mean age 38 years) with documented viraemia and chronic active hepatitis (CAH) were studied, of whom 1 had HBV infection alone, 11 had HCV infection alone, 3 had HBV and HDV infection concomitantly, 12 had HBV and HCV infection concomitantly, and 2 had HBV, HCV and HDV infection concomitantly. Patients received 3 MU IFN-alpha three times weekly for 6 months. After IFN-alpha therapy, 18 patients (43%) achieved normal alanine aminotransferase (ALT) activity and a partial response was observed in 12 (29%) patients. Two patients relapsed (one with HCV and one with HBV + HCV infection) immediately after the cessation of IFN-alpha therapy. Repeated liver biopsy was performed in 16 patients after 6-24 months of therapy and revealed progression to cirrhosis in five patients, remission in two and stable disease in nine. None of the patients cleared HCV RNA, four patients cleared HBeAg (two also HDV), and one both HBV and HCV. Five patients died during IFN-alpha therapy (one as a consequence of liver failure), and four died during the 6 months after therapy (two as a consequence of liver failure). During IFN-alpha therapy renal allograft function remained stable in 31 patients and acute rejection episodes occurred in 7, of whom 5 lost their graft and all had experienced rejection episodes before. In 16 patients normalization of ALT continued during long-term follow-up (median 22 months, range 0-84 months). IFN-alpha seemed to be moderately effective in the treatment of chronic HBV or HCV infections, but cannot be recommended for recipients infected with both HBV and HCV.
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PMID:Long-term results of treatment of chronic hepatitis B, C and D with interferon-alpha in renal allograft recipients. 966 63

Medical guidelines for interferon-alpha2a or -alpha2b (IFN-alpha) treatment of chronic hepatitis C virus (HCV) infection depend upon baseline liver histology. A better long-term response to IFN-alpha therapy correlates with less inflammation and absence of cirrhosis. It has been suggested that the presence of cirrhosis in patients with chronic hepatitis C virus infection may be predicted based on an AST/ALT ratio > or = 1. This study was designed to determine if the presence of cirrhosis can be predicted in patients with chronic HCV infection by such a ratio. Seventy-seven patients, including 23 cirrhotics, with chronic HCV infection were studied. Serum ALT, AST, and HCV-RNA levels and hepatic activity index (HAI), reflecting histologic inflammation in all liver biopsies, were assessed. AST/ALT ratios and mean ALT, AST, and HCV-RNA were determined for both cirrhotic and noncirrhotic patients. HAI was correlated with ALT, AST, and HCV-RNA levels, the latter determined by quantitative RT-PCR. The likelihood ratio (LR) and positive predictive value of an AST/ALT ratio > or = 1 for cirrhosis was 7.3 and only 77%, respectively. In cirrhotics vs noncirrhotics, there were no significant differences between mean serum ALT (149 +/- 28 vs 176 +/- 17 units/liter), AST (139 +/- 28 vs 102 +/- 8 units/liter), or HCV-RNA levels (589,160 +/- 147,053 vs 543,915 +/- 75,497 copies/ml), respectively. There was a significant, but clinically weak, correlation between serum ALT and HAI (r = 0.234), and none between HAI and either serum AST or HCV-RNA levels. Our results support the need for a liver biopsy prior to treatment of chronic HCV infection, since the AST/ALT ratio fails to predict accurately the presence of cirrhosis.
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PMID:AST/ALT ratio > or = 1 is not diagnostic of cirrhosis in patients with chronic hepatitis C. 975 86

The main problem of children with HBeAg positive hepatitis B and associated hepatitis D is progression to liver cirrhosis with decompensation of liver function and need for liver replacement therapy within 15-20 years after infection. To determine whether interferon-alpha (IFN-alpha) therapy has a positive effect on HBV replication and inflammatory activity, we evaluated clinical and serological data of 8 children treated with IFN-alpha and 6 historic control patients without treatment. 4 of the nontreated patients seroconverted from HBeAg to anti-HBe between 7 to 17 years after initial diagnosis and showed decreased inflammatory activity in the liver. In the treatment group, the rate of seroconversion to anti-HBe (3 early, 2 late seroconverters) corresponded well to former trial results obtained in patients exclusively infected by HBV. Serum aminotransferase levels decreased or normalized in seroconverted children. In chronic HBV infection with associated hepatitis D (HDV) infection--compared to the spontaneous course of the disease--IFN-alpha therapy reduced inflammatory activity by earlier seroconversion to anti-HBe in responding patients. Moreover, viral replication and infectivity of hepatitis B was markedly reduced, but no effect on replication of HDV could be documented. Although long-term effects cannot be exactly estimated, at present IFN-alpha remains the only available treatment for HBeAg and anti-HDV positive children and seems to be of benefit for responding patients.
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PMID:Alpha-interferon treatment in HBeAg positive children with chronic hepatitis B and associated hepatitis D. 978 81

Thrombocytopenia is common in advanced-stage liver disease and is partly caused by inadequate thrombopoietin (TPO) production in the failing liver. Treatment of chronic hepatitis C with interferon alfa (IFN-) often induces thrombocytopenia, sometimes even leading to discontinuation of treatment. TPO regulation in response to IFN--induced thrombocytopenia was studied in patients with chronic hepatitis C with and without cirrhosis (Child A). An in vitro culture system with HepG2 cells was used to demonstrate any direct effects of IFN- on TPO mRNA expression, TPO synthesis, or TPO secretion from liver cells. Thrombocyte count was lower (U test: P < .05) in patients with hepatitis C cirrhosis compared with patients with chronic hepatitis C without cirrhosis before IFN therapy, and decreased in both patient groups (Wilcoxon matched-pairs test: P < . 05) on IFN therapy, the median decrease in both groups being comparable (noncirrhotic patients, 35%; cirrhotic patients, 32%; U test: P = .57). TPO levels rose in noncirrhotic patients (Wilcoxon matched-pairs test: P < .05), but not in patients with cirrhosis (noncirrhotic patients' median increase: 43% vs. cirrhotic patients' median decrease: 5%; U test: P < .001). Even in patients without cirrhosis, the increase in TPO levels was relatively small for the decrease in platelet count. No effect of IFN- could be demonstrated on TPO mRNA expression in vitro, but TPO secretion from liver cells was significantly reduced. Lower platelet counts but similar TPO levels in patients with chronic hepatitis C and cirrhosis compared with noncirrhotic patients and a moderate increase in TPO levels in noncirrhotic patients with a missing increase in cirrhotic patients during IFN--induced thrombocytopenia provide further evidence for an impairment of TPO production in patients with cirrhosis and during IFN therapy. Recombinant human TPO could be of value in patients developing severe thrombocytopenia under IFN- therapy.
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PMID:Blunted thrombopoietin response to interferon alfa-induced thrombocytopenia during treatment for hepatitis C. 979 32

Nineteen patients with chronic hepatitis C who were virological non-responders (seven responder/relapse and 12 no response) to an initial 24-week course of interferon-alpha 2b (IFN-alpha 2b) at a dose of 3 million units (MU) thrice weekly were retreated for an additional 48 weeks at the same dosing schedule and followed-up for another 24 weeks post-therapy. At the end of follow-up (week 72), six (32%) of the 19 patients were hepatitis C virus (HCV) RNA negative and were virological complete responders to retreatment. The viral genotypes in these six patients included two each with 1b and 3a, one with 2b, and another with 2a/2b; five of the six virological responder patients had cirrhosis. Significant predictors for successful retreatment included lower baseline HCV RNA concentrations prior to the first course of therapy, 2 log10 reductions in serum HCV RNA during the initial treatment and classification into the virological 'responder/relapse' category after the first course of IFN (P < 0.01 for all observations). When the above factors were used to construct a predictive model to determine response to retreatment, it was found that the absence of a 2 log10 drop in HCV RNA concentrations during the first course of IFN therapy was the most reliable indicator of non-response to retreatment (likelihood ratio = 10, P = 0.0014). In addition, the presence of HCV RNA at week 12 of retreatment was 100% predictive of virological non-response to the 48-week course of therapy. Our findings indicate that an additional 48-week course of IFN-alpha 2b therapy at 3 MU thrice weekly will achieve a virological complete response in 60% of patients who had a 2 log10 drop in HCV RNA during their first course of treatment, and measurement of week-12 HCV RNA during retreatment to identify non-responders is beneficial to patients as well as being cost-effective. Thus, a second course of IFN remains a viable option in a subgroup of non-responder patients, regardless of genotype or the presence of compensated cirrhosis.
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PMID:Long-term retreatment in chronic hepatitis C patients who were non-responders to an initial course of interferon-alpha 2b. 979 16

This study was performed to evaluate the long-term effects of interferon-alpha 2a (IFN-alpha 2a) vs no treatment in patients with chronic hepatitis B and to determine whether viral clearance, following therapy or occurring spontaneously, was sustained. Patients originating from three previously published multicentre, randomized, controlled trials were analysed. Information about survival and response during long-term follow-up was available in 340 (73%) and 308 (66%) of 469 randomized patients respectively. Response to therapy (viral clearance) was defined as: loss of hepatitis B virus (HBV) DNA and loss of hepatitis B e antigen (HBeAg) and improvement in alanine aminotransferase level. Scheduled treatment-free follow-up was 12 months in all studies. Median long-term follow-up time after inclusion in the individual studies was 4.7 years (range: 0.2-7.5 years). Viral clearance after IFN-alpha 2a, or occurring spontaneously, was sustained in 70 out of 80 evaluable patients (88%) who were responders at the end of the original trials and 21 (30%) lost hepatitis B surface antigen (HBsAg). A total of 80 patients received (re)treatment during the long-term follow-up period and 33% of them responded, irrespective of previous treatment category. Overall response rate was not significantly affected by gender, sexual inclination or ethnic origin. Durability of response did not depend upon ethnic origin or presence of cirrhosis. At the end of the original trial periods, 253 patients were histologically evaluated and 22 (9%) had histologically confirmed progression to cirrhosis. During long-term follow-up an additional five patients developed cirrhosis. Hepatocellular carcinoma developed in three patients (1%): in one patient during the follow-up period of the original trial and in two patients (one untreated) during the long-term follow-up period. Ten of 25 deaths were liver-related (hepatocellular carcinoma in three, gastrointestinal bleeding in two and liver failure in five). The distribution of clinical events (progression to cirrhosis, hepatocellular carcinoma and liver-related deaths) was unrelated to original treatment category and response to treatment. Hence, 90% of responding patients will, irrespective of treatment category, have a sustained response. At least 30% of responding patients will eventually lose HBsAg. For a number of reasons, the present patient population and observation period are insufficient to establish a presumed beneficial effect of IFN-alpha 2a on disease progression and survival.
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PMID:The long-term effect of treatment with interferon-alpha 2a in chronic hepatitis B. The Long-Term Follow-up Investigator Group. The European Study Group on Viral Hepatitis (EUROHEP). Executive Team on Anti-Viral Treatment. 985 48

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.
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PMID:Regression of hepatic fibrosis in hepatitis C with long-term interferon treatment. 988 84

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