Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression.

Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual's level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values=0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention.

Use of transient elastography (FibroScan®) for the noninvasive assessment of portal hypertension in HIV/HCV-coinfected patients.

The hepatic venous pressure gradient (HVPG) is the gold standard for assessing portal pressure and correlates with the occurrence of portal hypertension (PH)-related complications. Transient elastography (TE) is a new, highly accurate noninvasive technique, which enables us to evaluate hepatic fibrosis to detect advanced fibrosis and cirrhosis. We performed a hepatic haemodynamic study and TE in 38 HIV/HCV-coinfected patients. The association between HVPG and liver stiffness was assessed by linear regression. The diagnostic value of TE was assessed by receiver operating characteristic (ROC) curves. We considered clinically significant PH as an HVPG ≥ 10 mmHg and severe PH as an HVPG ≥ 12 mmHg. A total of 38 HIV/HCV-coinfected patients were included. Twenty-eight patients (73.7%) had clinically significant PH (HVPG ≥ 10 mmHg), and 23 (60.5%) of these had severe PH (HVPG ≥ 12 mmHg). We found a statistically significant association between liver stiffness (kPa) and HVPG (r(2) = 0.46, P < 0.001, straight line equation HVPG=7.4 + 0.204*TE). The areas under the ROC curves were 0.80 [95% confidence interval (CI), 0.64-0.97] and 0.80 (95% CI, 0.66-0.94) for the prediction of HVPG ≥ 10 and ≥ 12 mmHg, respectively. Our data suggest that TE can predict the presence of clinically significant and severe PH in HIV/HCV-coinfected patients.

The impact of insulin resistance, serum adipocytokines and visceral obesity on steatosis and fibrosis in patients with chronic hepatitis C.

AIMS: To assess whether host metabolic factors influence the degree of hepatic steatosis and fibrosis in patients infected with hepatitis C virus, and to evaluate the impact of anti-viral therapy on insulin resistance and serum levels of adipocytokines. METHODS: Clinical and biochemical features, anthropometrical characteristics, and levels of fasting insulin, leptin, adiponectin and resistin were measured in 'naïve' patients with chronic hepatitis C, before, during and after therapy with Peg-Interferon-alpha 2a plus Ribavirin. RESULTS: Forty-eight patients were included (M/F 28/20; mean age 50.0 +/- 12.6 years; 62.5% genotype-1). Body mass index was 26.4 +/- 4.0 kg/m(2), and visceral obesity was present in 24 patients. At multivariate analysis (RR; 95% CI), steatosis was associated to older age (1.08; 1-1.18), necroinflammatory activity (17.67; 1.6-194.46), and raised insulin levels (1.39; 1.1-1.77). Fibrosis was related to necroinflammatory activity (25.73; 2.54-261.11), and steatosis (6.47; 1.09-38.29). Sustained viral response was achieved by 62.5% of patients and was associated with younger age (0.92; 0.85-0.99), genotype non-1 (10.61; 1.52-73.76) and absence of visceral obesity (13.78; 2.36-80.29). At the end of follow-up, insulin and the homeostasis model assessment for insulin resistance were reduced and adiponectin increased when compared with baseline, all unrelated to the outcome of treatment. CONCLUSIONS: Visceral obesity correlates with the degree of steatosis and fibrosis, and it negatively affects treatment response. Significant changes of insulin resistance and adipocytokines occur under treatment, irrespective of virological outcome.

Prognostic value of hepatic venous pressure gradient for in-hospital mortality of patients with severe acute alcoholic hepatitis.

BACKGROUND: Hepatic venous pressure gradient (HVPG) has prognostic value in complications and survival of patients with liver cirrhosis. However, the relationship between HVPG and the outcome of acute alcoholic hepatitis (AAH), as well as the specific features of portal hypertension syndrome in this setting, have not been defined. AIMS: To evaluate the prognostic value of HVPG and to analyse the degree of portal hypertension and hyperdynamic circulation in patients with severe AAH. METHODS: Early measurements of HVPG were performed in 60 patients with severe AAH, and compared with the haemodynamic findings of 37 and 29 liver transplantation candidates with alcoholic or viral end-stage cirrhosis respectively. RESULTS: Twenty-three patients (38%) died during hospitalization. Portal hypertension and hyperdynamic circulation were more severe in AAH patients. HVPG was greater in non-survivors [26.9 (7.4) vs. 19.4 (5.2) mmHg, P < 0.001]. Only 4/31 (13%) patients with HVPG 22 (P < 0.001). Encephalopathy (OR 9.4; CI 1.4-64.8), Model for End-Stage Liver Disease (MELD) score > 25 (OR 7.4; CI 1.4-39.9) and HVPG > 22 mmHg (OR 6.7; CI 1.1-39.9) were independently associated to in-hospital mortality. CONCLUSIONS: Early measurement of HVPG provides important prognostic information on the short-term outcome of patients with severe AAH. In addition, MELD score also seems to be a strong prognostic factor in these patients.

[Liver damage and celiac disease]. / Daño hepático y enfermedad celíaca.

Celiac disease (CD) is an important cause of serum aminotransferase elevation: between 5 and 10% of patients with persistent and cryptogenetic transaminase elevation may have CD. In fact, a wide spectrum of liver injuries in children and adults may be related to CD, particularly: a) mild parenchymal damage characterized by absence of any clinical signs or symptoms suggesting chronic liver disease, and by non-specific histological changes reversible on a gluten-free diet; b) chronic liver damage with autoimmune etiology, including autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis, which may be associated with CD but are generally unaffected by gluten withdrawal; and c) severe liver failure and decompensated cryptogenetic liver cirrhosis, potentially treatable with a gluten-free diet. Such different types of liver injuries may represent one same disorder where individual factors, such as genetic predisposition, precocity, and duration of exposure to gluten may influence reversibility of liver damage. A rigorous cross-checking for asymptomatic liver damage in CD individuals and, conversely, for CD in any cryptogenic liver disorder, including end-stage liver failure, is recommended.

Soluble adhesion molecules correlate with liver inflammation and fibrosis in chronic hepatitis C treated with interferon-alpha.

BACKGROUND: In chronic hepatitis C the relation of circulating adhesion molecules to disease features before, during and after therapy has not been completely established. AIM: To analyse the basal levels of circulating adhesins and the changes induced by interferon in these patients. METHODS: We studied, using ELISA assays, the serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in 52 patients with chronic hepatitis C on entry, prior to finalizing a 6-month course of interferon-alpha therapy and at the end of the follow-up. Correlations with clinical, virological and histological features, including inflammation and fibrosis, were calculated by Pearson's r-test. RESULTS: Liver necroinflammation was more closely related to sICAM-1 (r = 0.54, P = 0.0000) than to sVCAM-1 (r = 0.32, P = 0.02). Fibrosis, both as serum pIIIP and histological scoring, was, however, clearly related to sVCAM-1 (1071+/-291 in patients who scored 0-2 vs. 1870+/-458 in patients who scored 3-4; P = 0.0000). Severe fibrosis was never found below a sVCAM-1 cut-off threshold of 1300 ng/mL. Levels of both adhesins did not correlate with viraemia and were comparable among 1b and non-1b genotypes. Sustained response to interferon was significantly related to low viraemia (P = 0.03), non-lb type (P = 0.04) and low sICAM-1 (P = 0.04), but not to sVCAM-1. On finalizing therapy, patients with normal transaminases had reduced sICAM-1 (P = 0.0005), but not sVCAM-1 levels. CONCLUSIONS: In chronic hepatitis C, sICAM-1 was a marker of liver necroinflammation while sVCAM-1 reflected fibrosis. Both low sVCAM-1 and pIIIP serum concentrations were strictly linked, suggesting that measuring sVCAM-1 could give information on the degree of liver fibroplasia.

Increased circulating and intrahepatic T-cell-specific chemokines in chronic hepatitis C: relationship with the type of virological response to peginterferon plus ribavirin combination therapy.

AIMS: To determine the serum and intrahepatic levels of T-helper-1-associated chemokines in patients with chronic hepatitis C before, during and after peginterferon plus ribavirin combination therapy and to search for correlations with baseline characteristics of hepatitis C virus-related chronic liver disease and type of therapeutic response. METHODS: Serum chemokine levels were determined by enzyme-linked immunosorbent assays and intrahepatic chemokine messenger RNA and protein levels were tested by ribonuclease protection assay and immunohistochemistry. RESULTS: Serum and intrahepatic chemokine levels were elevated in all patients with chronic hepatitis C and showed a marked decrease in patients who obtained a virological response vs. non-responders. Increased serum interferon-gamma-inducible protein-10 levels at baseline in genotype 1-infected patients were significantly associated with greater degrees of intrahepatic inflammation and fibrosis (P = 0.0046 and P = 0.02, respectively) and with virological non-response (P = 0.01). In patients with genotype 1, basal serum interferon-gamma-inducible protein-10 levels greater than 299 pg/mL identified 80% of non-responders and lower than 299 pg/mL identified 63% of responders. CONCLUSIONS: Circulating and intrahepatic T-helper-1-associated chemokines are abnormally elevated in patients with chronic hepatitis C. Increased baseline serum interferon-gamma-inducible protein-10 levels in genotype 1-infected patients are associated with virological non-response to peginterferon plus ribavirin combination therapy.

Interferon alfa-2b plus ribavirin for chronic hepatitis C patients who have not responded to interferon monotherapy.

BACKGROUND: The role of combination therapy is poorly defined in chronic hepatitis C patients who are non-responders to interferon. AIM: To assess the efficacy, safety and tolerance of interferon alfa-2b plus ribavirin in chronic hepatitis C patients who do not respond to interferon monotherapy. METHODS: A total of 127 non-responder patients with chronic hepatitis C received 3 mU t.i.w. of interferon alfa-2b plus 1000-1200 mg ribavirin daily for 48 weeks. Effects of therapy were evaluated by serum aminotransferases and hepatitis C virus (HCV) RNA levels. RESULTS: Twenty-nine (23%) patients had an end-of-treatment response. Six months after treatment, 20 (16%) patients were sustained responders. Early loss of HCV RNA was the strongest predictor of a sustained response (P < 0.0001). Remission was also more frequent in patients with genotype 1b (P < 0.02), elevated alanine aminotransferase (P < 0.03) and low gamma glutamiltranspeptidase (P < 0.002). Treatment was discontinued in 21 (17%) patients: in 14 for intolerance and in seven due to side-effects. CONCLUSIONS: Combination therapy with interferon plus ribavirin produced a sustained response in 16% of chronic hepatitis C patients who were non-responders to interferon. This combination was safe and well tolerated.

Hepatitis C virus infection in Spanish volunteer blood donors: HCV RNA analysis and liver disease.

OBJECTIVE: To evaluate in a large group of volunteer blood donors the prevalence of antibodies to hepatitis C virus (anti-HCV) and the relation of transaminase (ALT) levels and viraemia to liver damage. DESIGN: A prospective study. SETTING: Transfusion Centre of the Autonomous Community of Madrid and the Liver Unit of the Princesa University Hospital. PATIENTS: From a population of 55,587 volunteer blood donors, 160 seropositive cases were further evaluated for virological and histological assessment. METHODS: Anti-HCV was tested by ELISA-2 and RIBA-2 assays. HCV RNA was analysed by nested PCR. Liver biopsies were obtained in 35 volunteer blood donors with abnormal ALT levels. RESULTS: The prevalence of anti-HCV detected by ELISA-2 was 0.93%. Serum ALT was abnormal in 61 of the 160 volunteers (38.1%). Of these, RIBA-2 was positive in 96.7% and HCV RNA was detectable in 96.1%. Serum ALT was normal in the remaining 99, 70.7% being RIBA-2 negative and 98.3% HCV RNA negative. The majority of biopsies (85.6%) showed chronic hepatitis. CONCLUSION: This study demonstrates that in blood donors screening for anti-HCV, a positive ELISA-2 test, when associated with abnormal ALT levels, is effective in recognizing subjects with active infection detected by HCV RNA and liver disease. Concerning ELISA-2 positive volunteer blood donors with normal ALT, long-term studies are warranted to elucidate whether they are really infected by HCV.

Heterogeneity of HVR-1 quasispecies is predictive of early but not sustained virological response in genotype 1b-infected patients undergoing combined treatment with PEG- or STD-IFN plus RBV.

ISDR mutation pattern and HVR-1 quasispecies were analyzed in HCV genotype 1b-infected patients treated with either PEG- or STD-IFN plus ribavirin, in order to find virological correlates of therapy outcome. ISDR region analysis, performed at baseline (T0) and at 4 weeks of therapy (T1), indicated that ISDR mutation pattern was not predictive of response to treatment. Moreover, no selection of putative resistant strains in the first month of therapy was observed. Viral load was not correlated with any parameter of HVR-1 heterogeneity. Among the HVR-1 heterogeneity parameters considered, complexity was inversely correlated to viral load decline at T1. In univariate analysis, complexity, proportion of non synonymous substitutions (NS) and NS/S ratio were lower in patients showing virological response at 6 months of treatment. Complexity was the only parameter independently associated with both decline of viral load at T1 and virological response after 6 months, even after adjustment for confounding variables. At the end of treatment or later, these correlations were lost. Evolution pattern of the HVR-1 quasispecies indicated a strong selective pressure in sustained responders, with complete substitution of pre-existing quasispecies, while minor changes occured in non responders. In relapsers both patterns were present at a similar rate. In conclusion, this study shows that HVR-1 heterogeneity may be involved in the early response to combined IFN-RBV therapy. The loss of correlation between viral heterogeneity and therapy outcome at 6 months of therapy, or later, suggests that other factors may play a role in maintaining sustained response to treatment.

Epidemiological risk factors and clinico-pathological presentation in chronic hepatitis C.

BACKGROUND/AIMS: To analyze the epidemiological risk factors related to clinical and pathological patterns on presentation in patients with chronic hepatitis C (CHC) without cirrhosis. METHODOLOGY: This prospective study, carried out in the Liver Unit of the Princesa University Hospital, includes a population of 253 patients with CHC without clinical features of cirrhosis evaluated for clinical, virological and histological assessment. A standardized questionnaire was used to identify the presence of risk factors for hepatitis C virus (HCV) infection. Anti-HCV was tested by ELISA-2 and RIBA-2 assays. HCV RNA was analyzed by nested PCR. Liver biopsies were obtained percutaneously or in some cases by laparoscopy. RESULTS: The mean age of patients was 43+/-15 years and 154 were males, being significantly younger than females (39+/-13 versus 50+/-14 years). A source of infection was ascertained in 204 (80.6%) patients and only 37 (14.6%) referred a history of acute hepatitis. Anti-HCV was ELISA-2 positive in all 253, and 133 were tested by RIBA-2 (131 positive, 1 negative, 1 indeterminate) and by nested PCR to detect HCV RNA, with positivity in all except 3, including both the RIBA-2 negative and indeterminate. No differences appeared in the histological activity index according to routes of infection, but in comparing sexes, females had a significantly higher total score as well as the inflammatory/hepatitic index and fibrosis. CONCLUSIONS: In CHC no epidemiological, clinical or biochemical patterns are indicative of pathological features. The more severe disease in females could be attributed to the fact that they were older and it could be assumed that viral infection progressed longer. This slow progression calls for a therapeutical option over many years.

[Mesenteric fibromatosis as the cause of a single abdominal mass]. / Fibromatosis mesentérica como causa de masa abdominal única.

We present a mesenteric desmoid tumor in a man without associated diseases. Characteristics of this tumor are reviewed and the need to perform total exeresis of the mass for diagnosis is emphasized. Although surgery is the treatment of choice, alternative treatments are recommended when surgery cannot be performed, has been incomplete, or in cases of repeated recurrence.

Impaired autophagic flux is associated with increased endoplasmic reticulum stress during the development of NAFLD.

The pathogenic mechanisms underlying the progression of non-alcoholic fatty liver disease (NAFLD) are not fully understood. In this study, we aimed to assess the relationship between endoplasmic reticulum (ER) stress and autophagy in human and mouse hepatocytes during NAFLD. ER stress and autophagy markers were analyzed in livers from patients with biopsy-proven non-alcoholic steatosis (NAS) or non-alcoholic steatohepatitis (NASH) compared with livers from subjects with histologically normal liver, in livers from mice fed with chow diet (CHD) compared with mice fed with high fat diet (HFD) or methionine-choline-deficient (MCD) diet and in primary and Huh7 human hepatocytes loaded with palmitic acid (PA). In NASH patients, significant increases in hepatic messenger RNA levels of markers of ER stress (activating transcription factor 4 (ATF4), glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP)) and autophagy (BCN1) were found compared with NAS patients. Likewise, protein levels of GRP78, CHOP and p62/SQSTM1 (p62) autophagic substrate were significantly elevated in NASH compared with NAS patients. In livers from mice fed with HFD or MCD, ER stress-mediated signaling was parallel to the blockade of the autophagic flux assessed by increases in p62, microtubule-associated protein 2 light chain 3 (LC3-II)/LC3-I ratio and accumulation of autophagosomes compared with CHD fed mice. In Huh7 hepatic cells, treatment with PA for 8 h triggered activation of both unfolding protein response and the autophagic flux. Conversely, prolonged treatment with PA (24 h) induced ER stress and cell death together with a blockade of the autophagic flux. Under these conditions, cotreatment with rapamycin or CHOP silencing ameliorated these effects and decreased apoptosis. Our results demonstrated that the autophagic flux is impaired in the liver from both NAFLD patients and murine models of NAFLD, as well as in lipid-overloaded human hepatocytes, and it could be due to elevated ER stress leading to apoptosis. Consequently, therapies aimed to restore the autophagic flux might attenuate or prevent the progression of NAFLD.

Ultrasound changes in abdominal echinococcosis treated with albendazole.

Fifty patients with 81 abdominal hydatid cysts were followed with ultrasound during and after treatment with albendazole. In 61 cysts (75%), regressive changes were observed after treatment. Detachment of the membrane and change to a solid pattern in anechoic cysts were observed. Disappearance of septa or change to a solid pattern in anechoic cysts with intracystic septation were also found. There was an increase of hyperechoic structures in cysts with a mixed pattern. Follow-up ultrasound examination showed disappearance of 7 cysts, while anechoic structures reappeared in five cases. In anechoic cysts, regressive changes due to albendazole seem to be permanent, but in cysts with a mixed pattern recurrences are sometimes observed.

Transfusion-associated chronic hepatitis C: alpha-n1 interferon for 6 vs. 12 months.

AIMS: To compare the long-term effects of brief and prolonged therapy with alpha-n1 interferon for transfusion-associated chronic hepatitis C. METHODS: One hundred and sixteen subjects (male/female 48/68, mean age 46.9 years) were studied. Sixty patients were randomised to brief treatment (group 1: interferon 5 Mu/msq. t.i.w. for 2 months, then 3 Mu/msq. t.i.w. for 4 months), and 56 to prolonged treatment (group 2: interferon 5 Mu/msq. t.i.w. for 2 months, then 3 Mu/msq. t.i.w. for 10 months). All were followed for 12 months after stopping interferon. RESULTS: The early response rate was 47.4% (Group 1 [45%], Group 2[50%]. No "breakthrough" reactivations were observed. The early response rate was 19% in patients with and 63% in patients without cirrhosis. Twenty-three (19.8%) subjects stopped therapy. Among 54 evaluable early responders, 21 had a sustained response. The rate of sustained response was comparable in group 1 (18.3%) and group 2 (18.2%). All sustained response subjects and some non-responders were HCV-RNA negative at the end of follow-up. Histological improvement was seen only after sustained response. Cirrhosis developed in 20% of non-responders. Overall, interferon induced a long-lasting remission of chronic hepatitis C in about one of every five patients. CONCLUSIONS: In a population predominantly infected by hepatitis C virus type 1, 12 months of therapy with high doses of interferon does not confer any additional benefit on the early response or sustained response rates as compared to a 6-month course.

Interferon-alpha for chronic hepatitis C: an analysis of pretreatment clinical predictors of response.

To identify predictors of short-term and sustained ALT normalization after interferon treatment in adult patients with chronic hepatitis C, we performed a meta-analysis of individual patients' data, with construction and cross-validation of a prediction rule, in 361 patients from two randomized trials. In one trial, 116 subjects with transfusion-related chronic hepatitis C were treated with lymphoblastoid interferon (5 MU/m2 three times a week for 2 mo, then 3 MU/m2 three times a week for 4 or 10 mo). In the other study, 245 patients with community-acquired chronic hepatitis C received recombinant interferon-alpha 2b (10 MU three times a week for 2 mo, then 5 MU three times a week for 4 mo; then random allocation of subjects with normal aminotransferase levels to stop or continue interferon for a further 6 mo). Overall, 164 subjects (45%; 95% confidence interval, 40% to 50%) had short-term responses; 61 (18%; 95% confidence interval, 14% to 22%) maintained sustained responses. Sixty patients (17%; 95% confidence interval, 13% to 21%) withdrew from treatment because of side effects or subjective intolerance. Logistic regression analysis showed that short-term and sustained response were independently predicted by lobular structure on pretreatment liver biopsy (p < 0.0001) and by short disease duration, defined as the time elapsed since transfusion in posttransfusion cases or since the first observation of abnormal aminotransferase levels in cryptogenic disease (p < 0.01). Rules to predict short-term and sustained response to interferon were derived from these items, showing a discriminatory ability of 0.73 and 0.70.(ABSTRACT TRUNCATED AT 250 WORDS)

alpha-Interferon treatment of chronic hepatitis C in young patients with homozygous beta-thalassemia.

BACKGROUND: Chronic infection with the hepatitis C virus (HCV) and iron overload are the main causes of chronic liver disease in subjects with homozygous beta-thalassemia (HBT). Iron overload can be counteracted by intensive chelation. alpha-interferon reduces viremia and necroinflammation in patients with chronic HCV hepatitis. METHODS: To assess the effectiveness and safety of alpha 2b-Interferon (IFN), we enrolled in an open pilot trial of treatment 12 patients with HBT and biopsy-proven anti-HCV positive chronic hepatitis. IFN was given at a dose of 5 MU/m2 thrice weekly for 8 weeks, then 3 MU/m2 thrice weekly for 18 weeks. Patients were followed up to 24 months after stopping treatment when a second liver biopsy was performed in subjects with sustained response (normal ALT during follow-up). RESULTS: Two patients discontinued IFN at 7 weeks because of haemolytic anemia and one after 8 weeks due to persistent fever. Among 9 subjects completing the protocol, 5 normalized ALT while on treatment and a further 2 within two months after stopping IFN. A sustained response was obtained altogether in 5 patients, since ALT relapsed in 2 responders. None of the 3 subjects who discontinued IFN and of the 2 patients who did not respond to treatment normalized ALT over a 24 months follow-up. Post-treatment liver histology in long-term responders showed a reduction of portal, periportal and lobular necroinflammation, while siderosis was essentially unchanged. CONCLUSIONS: Although the pattern of response to IFN in HCV-infected subjects with HBT might differ from that of non-thalassemics, due to peculiar side effects and delayed response, the drug appears to be effective and deserves further investigation.

Alpha interferon treatment of chronic hepatitis C in beta-thalassaemia.

In this open, pilot study, interferon (IFN) alpha-2b seemed effective in the treatment of hepatitis C virus (HCV) infection in patients with beta-thalassaemia. In seven of nine patients who completed the study alanine aminotransferase activities returned to normal, and a completely stable response 24 months after treatment was seen in five. Liver biopsy specimen showed a clear reduction in portal, periportal, and lobular necroinflammation in all five cases. Three patients stopped treatment early because of side effects.

Long-term efficacy of alpha-interferon in beta-thalassemics with chronic hepatitis C.

Hepatitis C virus (HCV) infection is a common cause of liver disease among polytransfused thalassemics. We treated a cohort of subjects with beta-thalassemia major and chronic hepatitis C with alpha-interferon. The aims of the study were to assess the long-term biochemical and virologic efficacy of alpha-interferon and to evaluate the influence of HCV type and liver siderosis on the outcome of therapy. Seventy subjects (mean age, 14.1 years) with chronic HCV infection and abnormal aminotransferases received recombinant alpha-interferon for 12 months and were observed after therapy for at least 24 months. Sixty-three subjects (90%) were HCV-RNA positive at the start of therapy. HCV type 1b was found in 41 subjects (65.1%), non-1b types in 13 (20.6%), and mixed HCV types in 9 (14.3%). Liver biopsy showed cirrhosis in 11 subjects (15.7%) and siderosis grade 3-4 in 24 patients (34.2%). Three patients stopped therapy due to adverse events. Twenty-eight subjects (40%) had normal aminotransferases and had cleared HCV-RNA when last observed (mean follow-up, 36.5 months; range, 25 to 49 months). Of 41 patients who did not normalize aminotransferases, 9 had become HCV-RNA negative at the end of follow-up. The absence of cirrhosis, low liver iron content, and infection with non-1b HCV type were independently associated to complete sustained response upon multivariable analysis. In conclusion, alpha-interferon may induce a sustained virologic and biochemical remission of hepatitis in beta-thalassemic patients with chronic HCV infection and nonadvanced liver disease.