Chiara Masi

Factors Associated With Response to Therapy and Outcome of Patients With Primary Biliary Cirrhosis With Features of Autoimmune Hepatitis

BACKGROUND & AIMS For patients with primary biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH), treatment with ursodeoxycholic acid (UDCA) alone or in combination with immunosuppression is controversial. Little is known about the factors associated with initial response to therapy or outcome. We performed a retrospective analysis of treatment strategies and factors associated with outcomes of patients with PBC-AIH. METHODS We analyzed data from 88 patients who were diagnosed with PBC-AIH according to Paris criteria, from 7 centers in 5 countries. First-line therapies included UDCA alone (n = 30) or a combination of UDCA and immunosuppression (n = 58). RESULTS Of patients who received UDCA alone as the first-line therapy, 37% did not respond to treatment. Severe interface hepatitis was independently associated with lack of response to treatment (P = .024; odds ratio, 0.05; 95% confidence interval, 0.004-0.68). The combination of UDCA and immunosuppression was effective in 73% of patients who had not been previously treated or had not responded to UDCA. The presence of advanced fibrosis was associated with lack of response to the combination of UDCA and immunosuppression (P = .003; odds ratio, 0.13; 95% confidence interval, 0.03-0.48). Second-line immunosuppressive agents (cyclosporine, tacrolimus, and mycophenolate mofetil) led to biochemical remission in 54% of patients who did not respond to initial immunosuppression. Liver transplants were given to 4 patients with PBC-AIH. Five patients died during follow-up (3 from liver-related causes). CONCLUSIONS In a retrospective study of a large cohort of patients with PBC-AIH, UDCA alone did not produce a biochemical response in most patients with severe interface hepatitis; these patients require additional therapy with immunosuppression. Second-line immunosuppressive agents are effective in controlling disease activity in patients who do not respond to conventional immunosuppression.

Fatigue and pruritus at onset identify a more aggressive subset of primary biliary cirrhosis

In recent years, primary biliary cirrhosis is mostly diagnosed in patients who are asymptomatic; however, a proportion of cases still present with typical complaints such as fatigue and/or pruritus. We compared biochemical, histological and immunological features of patients with or without fatigue and/or pruritus at onset to see whether the different clinical presentation may eventually impact on disease progression.

Clinical and diagnostic aspects of gluten related disorders

Gluten is one of the most abundant and widely distributed components of food in many areas. It can be included in wheat, barley, rye, and grains such as oats, barley, spelt, kamut, and triticale. Gluten-containing grains are widely consumed; in particular, wheat is one of the worlds primary sources of food, providing up to 50% of the caloric intake in both industrialized and developing countries. Until two decades ago, celiac disease (CD) and other gluten-related disorders were believed to be exceedingly rare outside of Europe and were relatively ignored by health professionals and the global media. In recent years, however, the discovery of important diagnostic and pathogenic milestones led CD from obscurity to global prominence. In addition, interestingly, people feeding themselves with gluten-free products greatly outnumber patients affected by CD, fuelling a global consumption of gluten-free foods with approximately

Sequential presentation of primary biliary cirrhosis and autoimmune hepatitis.

2.5 billion in United States sales each year. The acknowledgment of other medical conditions related to gluten that has arisen as health problems, providing a wide spectrum of gluten-related disorders. In February 2011, a new nomenclature for gluten-related disorders was created at a consensus conference in London. In this review, we analyse innovations in the field of research that emerged after the creation of the new classification, with particular attention to the new European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for CD and the most recent research about non-celiac gluten sensitivity.

Anti-ribosomal P protein antibody: an autoreactivity devoid of prognostic value in patients with autoimmune hepatitis.

Background Primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome is used to describe the coexistence of both diseases, with either a sequential or a simultaneous presentation in the same patient. Available studies have focused on the simultaneous form, whereas there is limited information on sequential PBC-AIH. We carried out a retrospective study of patients who sequentially developed PBC-AIH overlap syndrome. Methods The medical data of 1065 patients diagnosed with PBC (n=483) and AIH (n=582) were retrospectively analyzed. Results A sequential development of PBC-AIH was observed in 19 (1.8%) patients after a mean of 6.5 (1–14) years of follow-up. AIH developed in 12 (2.5%) PBC patients, whereas PBC occurred in seven (1.2%) patients with AIH. The baseline serologic and histological findings of patients who developed PBC-AIH were similar to those of patients with typical PBC or AIH. Eighteen patients were treated with a combination of ursodeoxycholic acid (UDCA) and immunosuppression after the diagnosis of PBC-AIH was established. One patient showed a spontaneous resolution of hepatitic flare under UDCA therapy. Biochemical remission was achieved in 16 patients, whereas three progressed to decompensated cirrhosis and required liver transplantation. Conclusion The sequential overlap of PBC-AIH can occur during the follow-up of patients with pure PBC or AIH. In our cohort, we could not identify any factors that predicted the development of this rare condition. The combination of UDCA and immunosuppression seems to be an appropriate therapy in the setting of PBC-AIH.

Regulatory T cell defects in adult autoimmune hepatitis

To the Editor: We read with great interest the paper ‘Antiribosomal P protein: a novel antibody in autoimmune hepatitis’ by et al. Calich et al. (1), which suggests a relevant prognostic value for such a reactivity in patients with autoimmune hepatitis (AIH). In particular, the Authors state that ‘this antibody appears to predict the patients with worse AIH prognoses’. Nevertheless, this assertion is not substantiated by the data presented. Of the 93 AIH patients studied, 9 (9.7%) were positive for IgG anti-C22 ribosomal P peptide; of these 9 AIH patients with anti-ribosomal P protein antibody, 4 (44.4%) were already cirrhotic at the time of AIH diagnosis, whereas among the remaining 84 AIH patients without anti-ribosomal P protein reactivity, 24 (28.5%) had cirrhosis at diagnosis, according to Table 1. The Authors state that ‘the evaluation of the outcomes revealed a significantly higher frequency of cirrhosis in the anti-rib P-positive group compared with those patients without this antibody (100 vs. 60.0%, respectively, P = 0.04)’ and conclude that ‘the observed predictive value of this antibody for AIH severity appears to be a promising tool for the management of these patients’. Unexpectedly, this claim is in contrast with the reported results, as the data provided in Table 1 and in the text do not fit with the numbers shown in Table 2. In Table 1 (and in the text), 4 of 9 anti-rib P-positive patients are reported as already having cirrhosis at diagnosis; therefore, it is logical to assume that cirrhosis could newly develop in no more than the remaining 5 anti-rib P-positive patients, whereas in Table 2, inexplicably, 7 of 7 (100%) anti-rib P-positive patients are reported to have developed cirrhosis as an outcome of their liver disease. No mention of patients lost during follow-up is made. As far as the anti-rib P-negative AIH patients are concerned, among the 84 patients reported in Table 1, twenty-four were cirrhotic at diagnosis; therefore, it is logical to assume that cirrhosis could be an outcome only in the remaining 60 patients. According to Table 2, cirrhosis developed in 48 of 80 patients, whereas the correct number of non-cirrhotic AIH patients without anti-rib P antibody at diagnosis should be 60. Again, no mention of patients lost during follow-up is made. Overall, cirrhosis appears to have developed in 5 of 5 (100%) anti-rib P-positive AIH patients and in 48 (80%) of 60 anti-rib P-negative AIH patients (P = 0.5746, Fisher’s exact test). If the extrapolation of these data is correct, the anti-ribosomal P protein antibody is a novel autoreactivity, which, however, fails to bear any prognostic value in patients with AIH.

Nailfold capillaroscopy in primary biliary cirrhosis: a useful tool for the early diagnosis of scleroderma.

tors of the metabolic syndrome, including waist circumference, systolic blood pressure, diastolic blood pressure, triglyceride, HDL cholesterol and fasting plasma glucose, the adjusted hazard ratio (95% CI) was 2.21 (1.42–3.44). These results indicated that subclinical hypothyroidism is an independent factor that predicts the development of NAFLD. A limitation of this study is that ultrasound examination is not sensitive enough to detect mild steatosis. However, ultrasonography is the most commonly used in epidemiological surveys of NAFLD. Ultrasonography has the advantage of being non-invasive, safe, widely available, and sensitivity for detecting hepatic steatosis is acceptable. Another limitation is that the causal relationship between subclinical hypothyroidism and development of NAFLD could not been drawn by this study. Further evidence is needed to clarify this issue. Taken together, our prospective case-control study provided evidence that subclinical hypothyroidism is a significant factor associated with NAFLD development. This finding may have important clinical implications for disease therapy and prevention.