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Objective There still is little attention about both nutritional/metabolic consequences and multi-organ involvement after intestinal surgery. Our multidisciplinary team aimed to an integrated approach to short bowel syndrome (SBS). Research Methods & Procedures A 37-years-old man affected by Gardner Syndrome, who previously underwent colectomy and several small bowel resections elsewhere without receiving appropriate nutritional prescriptions, was admitted into our hospital to be evaluated for intestinal transplant: biochemistry showed acute renal failure and multiple critical dysionias and the patient referred habitual copious liquid output, also containing undigested food, from ileostomy; he had lost 30 kg (-40% usual body weight, BW) in the last month. He promptly underwent nutritional assessment and, consequently, nutritional treatment: firstly we corrected dysionias and immediately started thiamin supplementation, thereafter we prescribed a personalized semielemental low-fiber diet per os, parceled out on 5-6 meals, and we started a personalized admixture parenteral nutrition support (PN). Regardless of appropriate evidences, the patient finally refused to give his consent to intestinal transplant, he was then discharged in PN and personalized diet per os. Results Despite severe dehydration and malnutrition, we early achieved and maintained hydro-electrolytic balance, thus recovering renal enhancement; besides, Refeeding Syndrome was adequately prevented and, beyond rehydration, the patient also started regaining BW. Conclusions SBS can result in both intestinal and renal failure. It needs a multidisciplinary approach, including early and appropriate nutritional assessment and treatment. When intestinal transplant is not possible, even if recommended, PN remains the main therapeutic strategy.

The arrival of potent directly acting antivirals (DAAs) for the treatment of chronic Hepatitis C virus (HCV) infection was a challenge for the regional health system of the Lombardia Region. Lombardia represents roughly 8% of the Italian territory but includes nearly 16% of the Italian population. In 2014, nearly 37,600 HCV patients were routinely followed-up in liver centers across the region; nearly 16,000 were classified as having advanced fibrosis or cirrhosis (Metavir F3-F4). The creation of a regional network was necessary to ensure uniformity in treatment access and treatment management. The first database analysis of the Lombardia Hepatitis Network was conducted in January 2016, and included data on 2432 patients who had received treatment from December 2014 to December 2015. The most prevalent HCV genotypes were HCV-1 found in 63% and HCV-3 found in 17%. Overall 90.4% patients achieved an SVR, SVR rates were 92.9% in HCV-1, 89.3% in HCV-2, 81.1% in HCV-3 and 88.9% in HCV-4.

Background: To generate a robust predictive model of Early (3 months) Graft Loss after liver transplantation, we used a Bayesian approach to combine evidence from a prospective European cohort (Liver-Match) and the United Network for Organ Sharing registry. Methods: Liver-Match included 1480 consecutive primary liver transplants performed from 2007 to 2009 and the United Network for Organ Sharing a time-matched series of 9740 transplants. There were 173 and 706 Early Graft Loss, respectively. Multivariate analysis identified as significant predictors of Early Graft Loss: donor age, donation after cardiac death, cold ischaemia time, donor body mass index and height, recipient creatinine, bilirubin, disease aetiology, prior upper abdominal surgery and portal thrombosis. Results: A Bayesian Cox model was fitted to Liver-Match data using the United Network for Organ Sharing findings as prior information, allowing to generate an Early Graft Loss-Donor Risk Index and an Early Graft Loss-Recipient Risk Index. A Donor-Recipient Allocation Model, obtained by adding Early Graft Loss-Donor Risk Index to Early Graft Loss-Recipient Risk Index, was then validated in a distinct United Network for Organ Sharing (year 2010) cohort including 2964 transplants. Donor-Recipient Allocation Model updating using the independent Turin Transplant Centre dataset, allowed to predict Early Graft Loss with good accuracy (c-statistic: 0.76). Conclusion: Donor-Recipient Allocation Model allows a reliable donor and recipient-based Early Graft Loss prediction. The Bayesian approach permits to adapt the original Donor-Recipient Allocation Model by incorporating evidence from other cohorts, resulting in significantly improved predictive capability. © 2013 Editrice Gastroenterologica Italiana S.r.l.

BACKGROUND: The Liver Match is an observational cohort study that prospectively enrolled liver transplantations performed at 20 out of 21 Italian Transplant Centres between June 2007 and May 2009. Aim of the study is to investigate the impact of donor/recipient matching on outcomes. In this report we describe the study methodology and provide a cross-sectional description of donor and recipient characteristics and of graft allocation. METHODS: Adult primary transplants performed with deceased heart-beating donors were included. Relevant information on donors and recipients, organ procurement and allocation were prospectively entered in an ad hoc database within the National Transplant Centre web-based Network. Data were blindly analysed by an independent Biostatistical Board. RESULTS: The study enrolled 1530 donor/recipient matches. Median donor age was 56 years. Female donors (n = 681, median 58, range 12-92 years) were older than males (n = 849, median 53, range 2-97 years, p < 0.0001). Donors older than 60 years were 42.2%, including 4.2% octogenarians. Brain death was due to non-traumatic causes in 1126 (73.6%) cases. Half of the donor population was overweight, 10.1% was obese and 7.6% diabetic. Hepatitis B core antibody (HBcAb) was present in 245 (16.0%) donors. The median Donor Risk Index (DRI) was 1.57 (>1.7 in 35.8%). The median cold ischaemia time was 7.3h (≥ 10 in 10.6%). Median age of recipients was 54 years, and 77.7% were males. Hepatocellular carcinoma (HCC) was the most frequent indication overall (44.4%), being a coindication in roughly 1/3 of cases, followed by viral cirrhosis without HCC (28.2%) and alcoholic cirrhosis without HCC (10.2%). Hepatitis C virus infection (with or without HCC) was the most frequent etiologic factor (45.9% of the whole population and 71.4% of viral-related cirrhosis), yet hepatitis B virus infection accounted for 28.6% of viral-related cirrhosis, and HBcAb positivity was found in 49.7% of recipients. The median Model for End Stage Liver Disease (MELD) at transplant was 12 in patients with HCC and 18 in those without. Multivariate analysis showed a slight but significant inverse association between DRI and MELD at transplant. CONCLUSIONS: The deceased donor population in Italy has a high-risk profile compared to other countries, mainly due to older donor age. Almost half of the grafts are transplanted in recipients with HCC. Higher risk donors tend to be preferentially allocated to recipients with HCC, who are usually less ill and older. No other relevant allocation strategy is currently adopted at national level.

Background and aim. Earlier diagnosis and more effective treatments are improving the survival of patients with HCC. Moreover, the natural history of HCC patients is different from that patients with non-neoplastic indications for liver transplantation. This issue becomes critical to provide an equitable allocation policy to patients listed for transplantation. UNOS adopted a MELD-based policy that assigns the native MELD for patients with stage I HCC and 22 points for patients stage II HCC listed for Liver Transplant (LT), with an additional three points added every 3 months of waiting time in list for the latter. Organs are then assigned on the basis of the MELD score, irrespective of the indication. In countries outside the UNOS area, allocation for HCC patients still misses uniformity. Aim. The aim of the study was to generate an updated prognostic model for HCC applicable to organ allocation. Material and methods. We analysed disease progression (death or progression of HCC beyond T2 stage) in a cohort of 177 consecutive patients that presented with HCC inside the Milan criteria. Patients were treated according to the BCLC algorithm and prospectively followed by imaging every 3 months; 76 patients (43%) were listed for transplantation according to AISF/CNT guidelines. Transplanted patients were censored at the time of transplantation. Results. Median follow-up was 16 months. HCC progressed beyond T2 stage in 75 cases; 8 patients died while in T2 stage and 68 were transplanted. To verify the ability of the UNOS policy to predict HCC progression rate (PR), we compared the expected PR according to the UNOS policy with the observed PR for the respective population at risk. The current policy resulted in a large overestimation of PR in T2 patients. Two sensitivity analyses were conducted to identify risk factor (RF) for progression using the log-rank method: in the first one, transplanted patients were considered as disease progression; in the second one, only non-transplanted patients were analysed. RF significant in any analysis was considered for multivariable analysis. RF with the strongest relationship to progression included tumor persistence after local therapy or recurrence inside Milan criteria (HR 2.52–3.16; p < 0.0001). Using strongest RF for progression and the patient's natural MELD, an adjusted model applicable to organ allocation was generated, which decreased the discrepancy between expected and observed PR. Conclusions. Tumor persistence/recurrence inside Milan criteria after treatment strongly predicted the risk of tumor progression beyond Milan criteria. The current MELD exception largely overestimates progression in T2 patients treated according to BCLC. An adjusted model that begins with the patient's natural MELD, and stratifies progressive risk according to the response to local treatment, better captures the PR of T2 HCC

Interferon α (IFN) is the only agent currently approved by the FDA for the treatment of chronic viral hepatitis due to hepatitis C (HCV). Unfortunately, less than half the patients with HCV treated with IFN respond. Worse yet, half or more of those who do respond relapse when the agent is withdrawn. Materials and Methods: In this prospective randomized study, 30 individuals who failed to respond to a standard course of IFN therapy consisting of 3 MU IFN administered 3 x weeks for 6 months were randomized to receive a second 6 month course of either 5 MU IFN daily or 5 MU IFN plus regular phlebotomies at weekly intervals to achieve a hemoglobin level of between 10-11 g/dl. The response rates defined as HCV-RNA negativity after 6 months of therapy and after 6 months of follow-up without IFN were determined. Results: Both groups experienced a significant reduction in their serum ALT levels (p < 0.01) and Knodell scores with treatment. A greater number of responders were found in the phlebotomy plus IFN group than in the IFN alone group whether the response was defined by the serum ALT level or presence or absence of HCV-RNA in serum at the end of treatment and follow-up. Conclusions: The results of this study suggest that both an increased IFN dose coupled with more frequent dosing of IFN alone and combined with phlebotomy treatment are effective at obtaining a response to IFN in individuals with HCV disease who previously have failed to respond to a standard treatment regimen.

A total of 41 patients with chronic hepatitis C virus (HCV) defined as abnormal liver injury test results for 6 months or more and HCV RNA positivity in plasma were studied to determine if the liver might not be the only focus of HCV infection in individuals treated with interferon alfa (IFN-α). All patients were examined for the presence of confounding liver disease and tested negatively for such findings. All tested positively for HCV RNA and had an abnormal hepatic histology. All were treated with IFN for 6 months at a dosage of 5 million units daily. After 6 months of therapy, 29 (71%) had normal alanine transaminase (ALT) values, and 25 (61%) tested negatively for HCV RNA. After 6 months of follow-up, without IFN therapy, 17 (41%) still had normal ALT values, and 16 (39%) still tested negatively for HCV RNA in serum. Patients who continued to test negatively for HCV RNA in serum after 6 months of follow-up also tested negatively for HCV RNA in the liver at the end of IFN therapy. Only 2 subjects who tested negatively for HCV RNA in the liver at the end of treatment relapsed after discontinuing IFN therapy. In contrast, patients who tested positively for HCV RNA in the liver after 6 months of therapy relapsed and tested positively for HCV RNA in serum during the 6 months of follow-up. These results suggest that (1) a nonhepatic site of HCV infection may exist; (2) this putative extrahepatic site appears to be less responsive to IFN therapy than in the liver and (3) this unknown extrahepatic site of infection may be the source of HCV reactivation in cases that relapse during IFN follow-up periods.

Objective: To determine whether individuals with concurrent active psychiatric disease and chronic hepatitis C virus (HCV) can be treated safely and effectively with interferon-alpha. Design: Prospective, open label study. Setting: Tertiary referral hospital. Patients: Thirty-one consecutive patients with co-existent chronic HCV and a psychiatric illness. Interventions: Interferon-alpha was administered at doses of either 5 MU three times per week for 6 months (n = 17) or 5 MU daily for 6 months (n = 14). Methods: HCV-RNA in serum was measured using reverse transcriptase polymerase chain reaction. Serum alanine aminotransferase levels were assessed and liver biopsy was performed before and after 6 months of treatment and again after 6 months of follow-up. Results: Twenty-nine of the 31 patients completed 6 months of therapy. Two patients discontinued therapy after 2 and 3 months of treatment. Serum alanine aminotransferase levels returned to normal in 22 (71%) patients. Fifteen (48%) of the 31 patients cleared HCV-RNA from their serum. Only four patients experienced a worsening of their psychiatric illness during treatment. Interferon therapy was discontinued in two of these patients. Conclusions: Patients with a co-existent psychiatric illness and chronic HCV can be treated successfully with interferon-alpha with the active participation of a psychiatrist and the maintenance of psychotropic drug therapy during interferon treatment.

Background/Aims: We performed a prospective non-randomized clinical trial to demonstrate that Interferon (IFN) treatment of individuals with chronic hepatitis C virus (HCV) positive hepatitis (CH-C) and serologic and/or histologic evidence of autoimmune dysregulation is feasible and whether the benefits of successfully treating CH-C are outweighed by the risk of exacerbating Autoimmune Chronic Active Hepatitis (ACAH). Patients and Methods: 23 patients with positive autoimmune dysregulation markers underwent a 6 month course of IFN treatment for chronic HCV hepatitis and were followed for a total of 12 months. Patients were treated with 5 MU of α2b IFN administered subcutaneously 7 days a week for 6 months. Complete blood counts and a panel of liver enzymes were monitored weekly for 4 weeks and then monthly for an additional 11 months (6 months of therapy and 6 months of follow-up). Serum auto-antibodies titers were determined prior to treatment, at the end of the treatment and again after 6 months of follow-up. A liver biopsy was performed prior to, and at the end of treatment and again at 12 months. Results: Using the standard ALT criteria for defining a response to IFN therapy, 14 (61%) patients experienced a full response and 3 (13%) experienced a partial response. Forty-three percent of the full responders and 33% of the partial responders experienced a relapse during the follow-up. The titer of each of the previously positive autoantibodies either remained unchanged or increased by 1 or 2 dilutions. No clinical exacerbations of a co-existent ACAH were observed. Conclusions: Individuals with combined CH-C and one or more markers of autoimmune dysregulation can be treated successfully with IFN. Such treatment does not necessarily increase or exacerbate co-existent ACAH and elevate the serum ALT level. In those who clear HCV-RNA as a result of IFN, the liver histology shifts from one consistant with CH-C to resembling ACAH.

Interferon alpha (IFN) is the only Food and Drug Administration (FDA)-approved therapy available for the treatment of chronic hepatitis C. The ideal dose and frequency of IFN administration that produces the greatest number of patient responders with the least number of relapses following drug withdrawal remains unclear. METHODS. One hundred seventeen patients recruited over a five-year period with chronic hepatitis C were divided into four groups and treated with progressively larger doses. The rate of clinical responses defined as a loss of detectable hepatitis C virus-ribonucleic acid (HCV-RNA) in serum by polymerase chain reaction (PCR) and normalization of the serum ALT (abnormal alanine aminotransferase) for each group was calculated. RESULTS. As the dose of IFN administration increased, the response rate defined by the absence of HCV-RNA in the patient's serum after six months of follow-up increased from 7.7% to 26.6%. If the end point utilized was HCV-RNA negativity after six months of treatment, the response rate varied from 19.2% to 30%. Using the less difficult end point of a normal ALT level, the response rates varied from 32.1% to 63.3% after six months of therapy and from 10.7% to 26.7% after six months of follow-up. CONCLUSIONS. This experience demonstrates that both the response rate at the end of therapy and after six months of follow-up improves with an increase in dose of IFN administered over a six-month period.

Backgound/Aims: This study was performed to identify response predictors for Interferon therapy given to patients with chronic hepatitis C. Materials and Methods: The biochemical measures of liver injury that characterize viral hepatitis due to hepatitis C were followed prospectively in 84 individuals treated with α-Interferon. In addition, the liver histology and the hepatic iron content of these same individuals, prior to the initiation of Interferon therapy, were determined. Results: Patients not responding to the interferon therapy showed an increase in liver iron content from an average of 337 ug/g wet weight. In responder to a value of 1075 μg/g wet weight in non responders. γ-glutamyl transpeptidase levels in responders were significantly lower than in partial or non-responders. Conclusions: Both the hepatic iron content of the liver and the γ-glutamyl transpeptidase value prior to treatment were able to predict a clinical response to Interferon therapy. More importantly, the γ-glutamyl transpeptidase level measured in serum could be used to monitor the IFN response during treatment and was found to predict clinical exacerbations of hepatitis following withdrawal of interferon therapy.

Background/Aims: Interferon (IFN) is the only therapy currently approved for chronic hepatitis C treatment. Unfortunately, not all patients respond to IFN therapy with a disease remission. Some people consider advanced histologic disease to be either a contraindication for treatment or a predictor of a poor reponse to treatment. To assess the validity of the two preceding widely held views, a total of 30 consecutive patients with advanced histologic disease associated with hepatitis C were studied. Materials and methods: Patients were treated with 5 million units of IFN administered SQ daily either alone or in combination with G-CSF (300 μg SQ on Mondays and Thursdays). Results: Both groups responded to the IFN therapy with 53 and 60% respectively being HCV-RNA negative after 6 months of therapy and 40 and 53% respectively continuing as HCV-RNA negative after 6 months of follow-up after IFN. The mean white blood cell (WBC) count and peak WBC counts of those receiving G-CSF were greater than those not receiving G-CSF therapy. The nadir values for both groups, however, were similar. Conclusions: Based upon this study, utilizing daily high dose IFN (5 MU) therapy, it can be concluded that individuals with advanced histologic disease can be treated successfully with IFN and obtain a prolonged remission. The addition of G-CSF during IFN therapy of patients with histologically advanced disease increases the mean WBC and peak WBC count levels achieved during the course of IFN therapy rate defined as clearance of HCV-RNA at the end of treatment and follow-up.

This paper is an attempt to present some of the unusual indications for OLTx that are occasionally seen at transplant centers. It is not an all-encompassing treatise but rather an attempt to present the more usual of the unusual indications for OLTx. As such, it is a framework to which readers could add any we do not mention as and when they are encountered in their own practice.