I. Carderi

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.

Intrahepatic cholestasis of pregnancy: three novel MDR3 gene mutations

The aetiology of intrahepatic cholestasis of pregnancy is unknown, but more than 10 different MDR3 gene mutations have recently been identified.

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-

Pegylated Interferon Alpha-2b Plus Ribavirin for Naive Patients With HCV-related Cirrhosis

Background Data on the efficacy of antiviral therapy in patients with HCV-related compensated cirrhosis are generally drawn from analyzing subgroups in larger trials. Aims (1) To analyze the safety and efficacy of combination therapy in naive patients with HCV-related cirrhosis; (2) to evaluate the factors influencing the sustained virologic response (SVR) in cirrhotic patients by comparison with a group of noncirrhotic patients; (3) to analyze the outcome of cirrhotic patients either acquiring SVR and nonresponders to the antiviral therapy during the posttreatment follow-up. Methods We consecutively enrolled 365 patients with biopsy-proven HCV-related chronic hepatitis meeting the inclusion criteria for pegylated interferon a-2b plus Ribavirin: 87 patients had compensated liver cirrhosis and 278 had histologic stages between 1 and 4 according to Ishaks classification. Results The 2 groups were comparable for genotype, viral load, and alanine transferase at presentation. Cirrhotic patients were significantly older and had significantly higher body mass index, serum ferritin, and gamma-glutamyl transpeptidase. The rate of side effects was similar in the 2 groups, whereas the rate of SVR was significantly lower in cirrhotic (45.9%) than in noncirrhotic patients (65.8%). Logistic regression analysis showed that genotype 1 to 4 and high viral load were independent variables correlating with nonresponse in the sample as a whole. During follow-up, hepatocellular carcinoma developed in 5/38 (13.2%) cirrhotic patients not responding or relapsing after treatment. No cases of hepatocellular carcinoma were seen among cirrhotic or noncirrhotic patients with a SVR. Conclusions Cirrhotic patients with compensated disease have a reasonably good chance of virologic response and should be offered treatment, carefully monitoring any side-effects.

A novel multidrug-resistance protein 2 gene mutation identifies a subgroup of patients with primary biliary cirrhosis and pruritus.

A single nucleotide polymorphism characterized by the substitution of valine for glutamate (V1188E) in exon 25 of the multidrug resistance protein 2 gene was found in a group of patients with primary biliary cirrhosis. This heterozygous mutation was significantly associated with the presence of pruritus. (HEPATOLOGY 2006;43:1152–1154.)

Lack of higher frequency of the chemokine receptor 5-delta32/delta32 genotype in hepatitis C.

PURPOSE An elevated frequency of the CCR5-Delta32 mutation in German patients with hepatitis C with viremia has been reported. The aim of the present study was to verify whether this mutation occurs in an Italian population with hepatitis C and whether it is an adverse host factor indicative of severity of liver disease and response to antiviral therapy. STUDY The authors amplified 189-bp (wild-type) and 157-bp (Delta32 deletion) fragments of the CCR5 gene by polymerase chain reaction in 130 patients with chronic hepatitis C. Comparisons were drawn with 110 blood donors and 135 patients with primary biliary cirrhosis. RESULTS Four (3.1%) patients with chronic hepatitis C and 1 blood donor (0.9%) were CCR5-Delta32 homozygous, whereas there was no CCR5-Delta32 homozygosity among primary biliary cirrhosis patients; the wild-type gene was present in a similar percentage in the 3 groups of patients without any significant difference (83.1% vs 90.4% vs 83.6%, respectively). Among the patients with chronic hepatitis C, no significant correlation was found between CCR5-Delta32 homozygosity and the following parameters: histologic grade/stage, hepatitis C virus genotype, viral load, serum aspartate aminotransferase, serum alanine aminotransferase, and serum gamma-glutamyltransferase. Ninety-five patients received a standard antiviral protocol with pegylated interferon (PEG Intron)+ribavirin; a sustained response was achieved in 59 patients (62.1%), and the remainder did not respond or experienced a relapse. Response to treatment was not influenced by CCR5-Delta32 deletion. CONCLUSION No greater frequency of CCR5-Delta32 homozygosity was seen in an Italian population of patients with chronic hepatitis C. This mutation does not seem to influence either the overall severity of liver disease or the response to viral therapy.

A novel multidrug-resistance protein 2 gene mutation identifies a subgroup of patients with primary biliary cirrhosis and pruritus

A single nucleotide polymorphism characterized by the substitution of valine for glutamate (V1188E) in exon 25 of the multidrug resistance protein 2 gene was found in a group of patients with primary biliary cirrhosis. This heterozygous mutation was significantly associated with the presence of pruritus.