F. Ferrara

Clinical Course and Outcome of Autoimmune Hepatitis/Primary Sclerosing Cholangitis Overlap Syndrome

Autoimmune hepatitis/primary sclerosing cholangitis (AIH/PSC) overlap syndrome is a relatively uncommon variant of PSC.AIM:To evaluate the natural history of AIH/PSC overlap syndrome compared to a group of “classical” PSC.METHODS:Forty-one consecutive PSC patients, with a regular follow-up of at least 2 years, were prospectively included in the study. Among these, 7 fulfilled the criteria for AIH/PSC overlap syndrome.RESULTS:The AIH/PSC overlap group significantly differed from the “classical” PSC group in the following parameters: mean age at presentation (21.4 ± 5.0 vs 32.3 ± 10 years, p < 0.01), AST 191.0 ± 14.8 vs 48.9 ± 34.5 U/L, p < 0.005), ALT (357.0 ± 26.5 vs 83.7 ± 60.7 U/L, p < 0.005) and serum IgG (25.6 ± 4.7 vs 12.9 ± 6.0 mg/dl, p < 0.0001). The mean follow-up was similar in the 2 groups (93.3 ± 65.9 vs 98.1 ± 65.9 months respectively). Treatment included immunosuppression + ursodeoxycholic acid (UDCA) in the AIH/PSC overlap patients, and UDCA in the “classical” PSC group. Deaths were recorded only in the classical PSC group. The median survival in the latter group was 207 months (95% C.I. 87.6-326.4). The major events during the follow-up included: OLTx (1/7 vs 6/34), and neoplasms (only in the group of “classical” PSC). The new Mayo score prognostic index only increased significantly during follow-up in the “classical” PSC group (r2 0.8117, p < 0.01)CONCLUSION:Patients with AIH/PSC overlap syndrome seem to benefit from immunosuppression + UDCA therapy, survival is apparently better than in “classical” PSC condition.

Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study

Background  Many reports of autoimmune hepatitis (AIH) were written in the ‘pre‐Hepatitis C era’ and data on the natural history are still incomplete.

Are elderly patients poor candidates for pegylated interferon plus ribavirin in the treatment of chronic hepatitis C

To the Editor: The National Institutes of Health consensus conference on hepatitis C defines elderly patients with chronic hepatitis C as a difficult group to treat, and no standard guidelines have been published so far for this particular age group. Only three uncontrolled trials with interferon (IFN) monotherapy in older people have been reported, and the sample size in each study was small, ranging from 21 to 25 subjects. In all these trials, the authors found no difference in the prevalence of adverse effects between older and younger patients. Only one of the studies evaluated the sustained response, which was much the same in subjects younger than 60 as in subjects aged 60 and older (26% vs 33%). There are no reports on the treatment of older people with pegylated IFN and ribavirin (RBV). Thirty-three naı̈ve patients with chronic hepatitis C (25 women, 8 men) with a mean age standard deviation of 70.2 1.2 were consecutively enrolled to receive pegylated IFN a-2b at a dose of 1.5mg/kg weekly plus a RBV dose of at least 10.6 mg/kg per day for 6 (genotype 2 or 3) or 12 (genotype 1 or 4) months. Tolerance and efficacy were compared with those observed in a 1:2 adult group (66 subjects, aged 45.2 8.9) matched for sex, genotype, viral load, and grading/staging parameters. All subjects gave their informed consent, and the local ethical committee approved the study. All subjects were treated for at least 24 weeks and, in the event of negativization of hepatitis C virus ribonucleic acid (HCVRNA), for 52 weeks. Early virological response (EVR) was defined as the absence of detectable HCV-RNA using PCR after the 4th week of treatment. Sustained virological response (SVR) was defined as the absence of detectable HCV-RNA 24 weeks after completing the treatment. Patients who failed to achieve a HCV-RNA reduction of at least 2 logs after the first 12 weeks of treatment were defined as nonresponders. The likelihood of SVR for each patient was determined using intention-to-treat analysis. Differences in baseline characteristics between the groups were compared using the chi-square test for dichotomous variables and the two-sided t test for continuous variables. Response rates were compared using chi-square analysis. The proportion of side effects leading to discontinuation of therapy was higher in elderly patients (24.2%) than in younger adults (12.2%), although the difference lacked statistical significance. All adverse effects except depression disappeared spontaneously within 2 to 3 weeks of discontinuing the treatment; the younger adult patients recovered completely from depression within 2 months, whereas the elderly patients required pharmacological therapy with trazodone (50 mg twice a day) for 3 months. The proportion of patients who reached EVR was significantly higher for the younger adults than for the elderly patients (80.3% vs 54.5%, Po.002) (Table 1). Similarly, the proportion of patients reaching a virological response at the end of treatment was significantly higher in younger adults than in older people (83.3% vs 54.5%, P o .002), and SVR was 69.7% in younger adults and 45.5% in elderly patients (P o .02). The percentage of relapsers did not differ statistically between the two groups. The problem of whether to offer antiviral treatment to a wide range of patients has arisen over the last 7 to 8 years, since the reduction in the risk of hepato-cellular carcinoma was analyzed. It is generally agreed in the literature that patients responding to IFN therapy have a lower risk of hepato-cellular carcinoma, so in terms of cost/benefit, every patient with chronic hepatitis C should be considered as a potential candidate for antiviral therapy. A 45% rate of SVR in elderly patients should be considered a good result, even though it is significantly lower than in younger adults. This is the same rate as the one reported by a previous study in 20 patients aged 65 and older treated with IFN and RBV. The most important decision-making matter is the high rate of side effects in elderly patients. We failed to demonstrate a significantly higher percentage of adverse effects in older people than in younger adults, but this is probably because of our careful patient selection; an accurate monitoring of symptoms and biochemical parameters (including the hematological profile) is recommended. In conclusion, elderly patients with chronic hepatitis C receiving combined treatment with IFN and RBV have a higher likelihood of side effects and a significantly lower rate of virological response at the end of the treatment and 6 months afterward than younger adults. Cost-benefit anal-

Plasma Adiponectin Levels in Primary Biliary Cirrhosis: A Novel Perspective for Link Between Hypercholesterolemia and Protection Against Atherosclerosis

INTRODUCTION:Hypercholesterolemia is a common finding in primary biliary cirrhosis (PBC), but the risk of cardiovascular events in PBC patients is not increased in respect to the general population. High serum adiponectin levels appear to play a protective role in the development of either metabolic syndrome or cardiovascular disease.AIM:To investigate factors potentially preventing atherosclerosis in PBC patients.METHODS:Circulating levels of adiponectin, resistin, leptin, and tumor necrosis factor-alpha (TNF-α) were measured in 137 consecutive PBC patients (125 women, 12 men; mean age 61.6 ± 12.3 yr), 137 sex- and age-matched healthy controls, and 30 female patients with nonalcoholic steatohepatitis (NASH) and associated metabolic syndrome.RESULTS:The body mass index (BMI) was comparable in the three groups, whereas total cholesterol was significantly higher in both PBC and NASH cases than in controls (221.6 ± 50.5 mg/dL in PBC vs 221.7 ± 39.7 mg/dL in NASH vs 209.8 ± 39.2 mg/dL in controls, P < 0.05). Serum concentrations of adiponectin, resistin, and leptin were significantly higher in PBC patients than in either NASH cases or controls (P < 0.05). Among the PBC patients, only adiponectin correlated positively with histological progression of the disease (P= 0.001) and negatively with BMI (P= 0.01). Logistic regression analysis revealed that adiponectin correlated independently with age, BMI, Mayo score, and gamma-glutamyl transpeptidase.CONCLUSIONS:The high adiponectin concentrations observed in PBC patients should be regarded as a possible protective factor against atherogenesis. The search for further protective factors should be encouraged.