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Sarcopenia has been associated with poor outcomes in patients with cirrhosis and solid tumours.Analyse the influence of sarcopenia on survival and treatment duration in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib.We conducted a multicentre, retrospective study on 96 patients with advanced HCC treated with sorafenib, all with available abdominal computed tomography (CT) scan within 30 days from treatment start. Anthropometric, laboratory, treatment and follow-up data were collected. Sarcopenia was defined by reduced skeletal muscle index calculated from an L3 section CT image.Sarcopenia was present in 49% of patients. Patients were divided into two groups according to sarcopenia: age was significantly higher in the sarcopenic group (SG) (66 years (31-87) versus 72 years (30-84),Sarcopenia is present in almost half of patients with advanced HCC, and is associated with reduced survival and reduced duration of oral chemotherapy.

Annual dermatologic examination is required in all transplant recipients because of the high risk of skin cancers. Nevertheless, if the transplant recipient is merely advised to have a dermatologic consultation, the adherence usually appears to be poor. We analyzed our population of liver transplant recipients in 2 periods: in 2014 (group 1) and in 2016 (group 2), when we had organized the presence of a dermatologist at scheduled intervals to annually examine the entire liver transplant population we actively follow-up. The adherence to dermatologic screening during period 1 was significantly lower (50/179; 28% of patients) than during period 2 (198/200; 99% of patients) (P In group 1 and 2, respectively, we found cutaneous lesions in 3 of 50 (6%) and in 13 of 198 (7%) examined patients and in 3 of 179 (1.7%) and in 13 of 200 (6.5%) of the whole groups of patients in follow-up (P = .02). The type of neoplastic lesions found at dermatologic visits were similar in group 1 (1 squamous cell carcinoma, 1 basal cell carcinoma) and group 2 (2 squamous cell carcinoma, 3 basal cell carcinoma) (P = .45), but with this intensive protocol of surveillance we discovered more preneoplastic lesions (1 leukoplakia in group 1 vs 7 actinic keratosis and 1 dysplastic nevus in group 2; P = .03). These results suggest that the planned presence of a dermatologist is mandatory among the many aspects of a well-organized transplant follow-up team.

The recurrence of the hepatitis C virus (HCV) in the liver graft has been so far the main cause of morbidity and mortality in post-transplantation patients. The treatment has significantly committed the resources of transplant hepatologists despite the poor results obtained with the past standard treatment with the use of interferon plus ribavirin. The new direct-acting antivirals (DAAs) are safe and effective even in the transplant setting, and our purpose was to check whether the eradication of HCV can make predominant other clinical problems that require different skills from those classic to hepatology. Prevalence of different items, such as metabolic syndrome, chronic renal insufficiency, and post-transplantation neoplasms, analyzed in the pre-DAA and post-DAA periods within a homogeneous population of all-cause and HCV transplant patients referred to our local hepatology service resulted in an increase in the post-DAA period after the substantial eradication of HCV. The suggestion that the main active issue has become extrahepatic sets the stage for the diversification of resources to be committed in the follow-up of liver transplantation.

Rituximab is a chimeric anti-CD20 monoclonal antibody that is a widely used for the treatment of B cells non-Hodgkin lymphoma. The use of chemotherapy regimens containing rituximab in HCV-positive patients with non-Hodgkin lymphoma has been associated with liver dysfunction, but no cases of cholestatic hepatitis C were described. To our knowledge, this is the first case of cholestatic hepatitis C in an HCV-positive patient with diffuse large B-cell lymphoma describes in the literature. We discuss the pathogenetic mechanisms underlying this severe form of hepatitis and describe its evolution after antiviral treatment.

Aims of the study are to investigate, in a cohort of patients affected by HCV chronic hepatitis with genotypes 1 and 4, the prevalence of interleukin 28B (IL28B) genotypes, the possible association between IL28B polymorphism and severity of liver damage, the role of IL28B CC as a predictor of outcome. 365 patients with HCV infection were observed between 2013 and 2014. Demographic, virological, biochemical, and genetic characteristics of each patient were investigated. Liver fibrosis was assessed by transient elastometry. Mean age of the patients (72.9 % males, 27.1 % females) is 50 years. 91.5 % % of patients are Caucasian, 8.5 % African. In the patients with HCV1 and HCV4 a higher frequency of IL28B CT is observed with a prevalence of 52.1 and 61.8 % respectively. As regards ethnic group, African people have a prevalence of 35.5 % for CC, while Caucasians have a prevalence of 23.8 % for CC. In our cohort, IL28B polymorphism does not show significant differences among ethnic groups and in HCV1 and HCV4 genotypes. As described in literature, IL28B CC genotype is confirmed as predictor of sustained virological response in both Caucasians and Africans. A significant correlation between liver fibrosis and IL28B polymorphism emerges.

It has been recently suggested that the risk of graft loss after liver transplantation (LT) may increase in female HCV patients. The aim of the study was to examine gender differences in HCV therapy tolerance and outcome in LT patients treated for HCV recurrence. A retrospective study was conducted on liver recipients with HCV recurrence, who were given antiviral therapy from 2001 to 2009 in 12 transplant centers in Italy. Sustained virological response (SVR), adherence-to-therapy, and side effects were evaluated. A multivariate logistic regression model was used after adjusting for possible confounders. The data regarding 342 treated patients were analyzed. SVR was reported in 38.8% of patients. At baseline, male and female did not differ in HCV viral load, histology, or rate of diabetes. SVR was lower in females than in males (29.5% vs. 42.1%; P=0.03). Adherence-to-therapy was also lower in females than in males 43.4% vs. 23.8%; P=0.001); anemia was the main reason for lower adherence. In a multivariate analysis in patients Genotype1, female gender (P

Background: It is unclear whether and to which extent respiratory function abnormalities may complicate the earliest stages of chronic liver disease (CLD). Aim of this study was to compare pulmonary capillary volumes and gas exchange efficiency of CLD patients with and without cirrhosis. Methods: Sixty-seven participants (mean age 56.5 years; women 22.4%) were divided into three groups (matched by age, sex, smoking) according to the baseline CLD stage as follows: (a) healthy controls (Group A, n=20); (b) non-cirrhotic CLD patients (Group B; n=23); (c) cirrhotic CLD patients (Group C; n=24). All participants underwent clinical assessment, respiratory function tests, gas exchange estimation by the alveolar diffusion of carbon monoxide (TLCO) measurement and 6-min walking test. Groups were compared by chi-square and one-way anova tests. Results: Chronic liver disease patients had significantly lower levels of TLCO (Group B=17.7 ml/min mmHg, and Group C=14.2 ml/min mmHg) compared with healthy controls (Group A=24.4 ml/min mmHg). Consistent results were obtained when analyses were performed using TLCO expressed as percentage of the predicted value. TLCO adjusted for the alveolar volume was lower in cirrhotic patients compared with both controls and non-cirrhotic CLD patients (P

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.

Objective Infection with hepatotropic viruses is associated with a variable degree of liver disease, and there is evidence that more severe lesions are related to the association with another viral infection. The aim of this investigation is to establish the relationship between different viral infections occurring in the same individual and the presence and progression of liver disease. Design The study population comprises 754 intravenous (IV) drug abusers exposed to hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or cytomegalovirus (CMV). All individuals were followed for an average of 2 years. Liver disease was assessed by liver function tests, 99m-technetium ( 99m Tc) liver scintigraphy, and also by liver biopsy in a subset (n 136) of patients. The different viral patterns and presence of disease were analysed by logistic regression, and the risk factors were calculated. Contingency tables of patients with single or associated infections were drawn up to evaluate progression of liver disease. Results Association of HIV with at least one other viral infection was constant. Surface antigens of HBV (HBsAg) were always associated with HIV (n 19); in this group, 18 patients had signs of liver disease. A past infection with HBV, as revealed by the presence of at least antibodies against the surface antigen (HBsAb) and antibodies against the core antigen of HBV (HBcAb), was detected in 463 patients (61.4%). The overall prevalence of HCV antibodies was 63.91% (n 482). In 96.8% of the 406 patients tested, HCV-RNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The majority of patients with high alanine transaminase (ALT) had anti-HBV antibodies in the presence of HCV (56.1%). At the end of follow-up, all of these patients showed signs of active liver disease, and scoring was significantly worse than in patients with either HBV or HCV alone. An infection/reactivation of CMV was found in patients previously exposed to HBV and with increased ALT values. Conclusions Data emerging from this study reveal the association of HCV or CMV, or both, with a previous HBV infection, as demonstrated by HBsAb and HBcAb, and rapid progression of the disease in this group of patients. A previous HBV infection therefore appears to be an important risk factor for subsequent viral-related liver disease. Eur J Gastroenterol Hepatol 13:1347‐1354 & 2001 Lippincott Williams & Wilkins

Objective The objective of this study was to quantify incidence rates (IR) and risks of de novo tumors (except nonmelanoma skin cancers) in patients who underwent orthotopic liver transplantation (OLT) in central and southern Italy. Methods Data were collected on 1675 patients (75.5% males) who underwent OLT in six Italian transplantation centers in central and southern Italy (1990–2008). The time at risk of cancer (person years [PY]) was computed from OLT to the date of cancer diagnosis, death, or last follow-up, whichever occurred first. The number of observed cancer cases were compared with the expected one using data from population-based cancer registries. We computed gender- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Results During 10,104.3 PYs (median follow-up, 5.2 years), 98 patients (5.9% of the total) were diagnosed with a de novo malignancy (for a total of 100 diagnoses). Twenty-two of these cancers were post-transplantation lymphoproliferative disorders (PTLD; 18 non-Hodgkin lymphoma [NHL] and 2 Hodgkin's lymphoma [HL]), 6 were Kaposi's sarcoma (KS), and 72 were solid tumors (19 head and neck [H&N], 13 lung, 11 colon-rectum, 6 bladder, and 4 melanoma). The overall incidence was 9.9 cases/103 PYs, with a 1.4-fold significantly increased SIR (95% CI, l.2–1.7). Significantly increased SIRs were observed for KS (37.3), PTLD (3.9), larynx (5.7), melanoma (3.1), tongue (7.1), and H&N (4.5) cancers. Conclusions These results confirmed that OLT patients are at greater risk for cancer, mainly malignancies either virus-associated or related to pre-existent factors (eg, alcohols). These observations point to the need to improve cancer surveillance after OLT. The on-going enrollment of patients in the present cohort study will help to elucidate the burden of cancer after OLT and better identify risk factors associated with its development.

Introduction. Hepatitis C virus genotype 4 is predominant in the Middle East and Northern Africa, even if it has recently spread to Southern Europe. Data about the treatment of post-liver transplantation (LT) genotype 4 hepatitis C recurrence are scarce. We report a retrospective analysis of post-LT genotype 4 hepatitis C treatment in 9 Italian transplant centres, focusing on the overall survival rates and treatment outcome. Results. Among 452 recipients, we identified 17 HCV genotype 4 patients (16 males, 1 female) transplanted between 1998 and 2007. All patients received combined antiviral treatment with conventional doses of interferon (recombinant or pegylated) and ribavirin after histological diagnosis of hepatitis C recurrence. The observed overall survival after LT was 100% at 1 year and 83.3% at 5 years. More than 1/3 (35.3%) of patients achieved a sustained virological response (SVR) and 40% (data available in 15 subjects) an early virological response (EVR), which was significantly associated with the achievement of SVR (overall accuracy: 85.7%; predictive values of EVR absence/presence 80/88.8%; chi-square p < 0.05). Conclusion. In conclusion, in post-LT genotype 4 hepatitis C treatment, SVR rates are similar to genotype 1. Patients who don't show an EVR are not likely to achieve a SVR.

Background & Aims: The appropriate allocation of grafts from HBcAb positive donors in liver transplantation is crucial, yet a consensus is still lacking. Methods: We evaluated this issue within Liver Match, a prospective observational Italian study. Data from 1437 consecutive, first transplants performed in 2007-2009 using grafts from deceased heart beating donors were analyzed (median follow-up: 1040 days). Of these, 219 (15.2%) were HBcAb positive. Sixty-six HBcAb positive grafts were allocated to HBsAg positive and 153 to HBsAg negative recipients. Results: 329 graft losses occurred (22.9%): 66 (30.1%) among 219 recipients of HBcAb positive grafts, and 263 (21.6%) among 1218 recipients of HBcAb negative grafts. Graft survival was lower in recipients of HBcAb positive compared to HBcAb negative donors, with unadjusted 3-year graft survival of 0.69 (s.e. 0.032) and 0.77 (0.013), respectively (log-rank, p = 0.0047). After stratifying for recipient HBsAg status, this difference was only observed among HBsAg negative recipients (log rank, p = 0.0007), 3-year graft survival being excellent (0.88, s.e. 0.020) among HBsAg positive recipients, regardless of the HBcAb donor status (log rank, p = 0.4478). Graft loss due to de novo HBV hepatitis occurred only in one patient. At Cox regression, hazard ratios for graft loss were: MELD (1.30 per 10 units, p = 0.0002), donor HBcAb positivity (1.56, p = 0.0015), recipient HBsAg positivity (0.43, p

Yttrium-90 microspheres radioembolization has shown to be an effective modality of treatment in patients with primary or metastatic liver tumours [1-4]. It is usually offered to patients with advanced liver cancers. However, surgical experience after radioembolization is very limited to anecdotal cases mainly related to hepatocellular carcinoma. We have treated patients with hepatocellular carcinoma or liver metastasis mainly from colon, breast, melanoma and neuroendocrine tumours. In our experience after such treatment we were able to downstage the tumour to surgery only in the case of hepatocellular carcinoma. Five patients had liver transplantation and 1 had right hepatic resection after Yttrium-90 microspheres radioembolization. Of note 2 patients had neoplastic infiltration of a portal vein branch which resolved after treatment with Yttrium-90 microspheres radioembolization. The extra-hepatic spread was ruled out and later they were both transplanted. Here we report our initial single center experience with Yttrium-90 microspheres radioembolization as downstaging and bridging method for hepatocellular carcinoma prior liver surgery, resection or liver transplantation.

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.

The level of CD81 cell surface expression, a cellular co-receptor for hepatitis C virus (HCV), is critical for productive HCV infection of host cells. In addition, the cross-linking of HCV-E2 protein to CD81 can alter the function of T and B lymphocytes as well as that of NK cells by interfering with the activation signalling pathway. The down-regulation of CD81 expression on peripheral blood lymphocytes (PBL) has been associated to effective therapy of HCV infection. The aim of the present study is to quantitatively assess the levels of CD81 expression in PBL from HCV-infected patients compared to subjects at high risk for HCV infection such as HIV-infected individuals or patients with Porphyria Cutanea Tarda (PCT). The expression of CD81 was quantified by flow-cytometry using Phycoerythrin-labelled standard beads. Determination of CD81 was performed on CD3+ and CD19+ lymphocytes from 34 healthy controls, 51 patients with HCV infection and different clinical outcomes [these included HCV-RNA-negative subjects (8), patients with chronic active hepatitis (16), recipients of liver transplantation under immunosuppressive therapy (12), a subgroup with concomitant HIV infection (9) or concomitant PCT (6)]. In addition, 60 HIV-infected subjects and 4 patients with PCT were studied. The putative role of inflammatory cytokines in modulating CD81 was explored in vitro by assessing the effect of IL-6 or IFN-gamma on cultured human hepatocytes. A significant increase of the CD81 expression was found on CD19+ lymphocytes in association with either HIV or HCV infection, as compared to the control group. Immunosuppressive therapy with FK506, subsequent to liver transplantation, restored CD81 expression at normal levels. Data gathered in vitro using the WRL 68 hepatocytic cell line confirmed that inflammatory cytokines can up-regulate CD81 expression in liver cell inclusion. Our data suggest that CD81 up-regulation can increase the risk of HCV infection, particularly in HIV-infected subjects. In addition, the results strongly suggest that the cytokines released by activated lymphocytes at sites of inflammation may play a part in up-regulating CD81 expression.

Given the high prevalence of infection with human herpesvirus type 8, Italy is an area of utmost interest for studying Kaposi sarcoma (KS). We investigated the risk of KS in transplant recipients compared with the general population. A longitudinal study was performed from 1970 to 2006 in 4767 kidney, heart, liver, and lung transplant recipients from 7 Italian transplantation centers. The sample included 72.3% male patients with an overall patient median age of 48 years. Patient-years (PYs) at risk for KS were computed from 30 days posttransplantation to the date of KS, death, last follow-up, or study closure (December 31, 2007). Standardized incidence ratios (SIRs) and 95% confidence intervals were computed to quantify the risk of KS in transplant recipients compared with the general Italian population. Incidence rate ratios were computed to identify risk factors using adjusted Poisson regression. Based on 33,621 PYs, KS was diagnosed in 73 patients (62 men): 31 in kidney recipients, 27 in heart recipients, 8 in liver recipients, and 7 in lung recipients. The overall incidence was 217 cases per 10(5) PYs, with a significantly increased SIR of 125. SIR was particularly high in women (n = 34) and lung recipients (n = 428) but decreased significantly with time posttransplantation. The primary predictors of increased risk of KS were male sex, older age, and lung transplantation. A 5-fold reduction was observed after 18 months posttransplantation. After adjustment, patients born in southern Italy compared with northern Italy demonstrated a significant 2.2-fold increased risk. Our findings confirm that in the early posttransplantation period, Italian patients who have undergone solid-organ transplantation, particularly those from southern Italy and those who are lung recipients, are at greater risk of KS compared with the general population. These findings underscore the need for appropriate models for monitoring transplant recipients for KS, especially those at greater risk and, in particular, in the early postoperative period.

The outflow venovenous anastomosis represent a crucial aspect during orthotopic liver transplantation (OLT) with inferior vena cava (IVC) preservation. The modified Belghiti liver hanging maneuver applied to the last phase of hepatectomy, lifting the liver, provides a better exposure of the suprahepatic region and allows easier orthogonal clamping of the three suprahepatic veins with a minimal portion of IVC occlusion. The outflow anastomosis constructed with a common cloacae of the three native suprahepatic veins is associated with a lower incidence of graft related venous outflow complications. The procedure planned in 120 consecutive OLT was achieved in 118 (99%). The outflow anastomosis was constructed on the common cloaca of the three hepatic veins in 111/120 cases (92.5%). No major complications were observed (bleeding during tunnel creation, graft outflow dysfunction, etc) except in one patient with acute Budd-Chiari, who successfully underwent retransplantation.

s / Digestive and Liver Disease 47S (2015) e43–e66 e63 driving the synthesis of abnormal peptides, possibly leading to virion assembly defects and to the intracytoplasmatic accumulation of HBsAg. Conclusions Selective pressure by the immune system selects variants in theprecore region that arenotproportionally detectable in the periphery, possibly due to the abnormal release of defective virions. This may also have clinical implications for hepatic pathology (steatosis) andmay lead to the underestimation of viral load. A better comprehensionof the relationshipbetween intrahepatic and peripheral (virological and clinical) markers may confer to these a higher diagnostic power. http://dx.doi.org/10.1016/j.dld.2015.01.136

P0367 SARCOPENIA IS ASSOCIATED WITH A REDUCED SURVIVAL IN PATIENTS WITH HEPATOCARCINOMA UNDERGOING SORAFENIB TREATMENT E. Gigante, G. Antonelli, P. Begini, F. Carbonetti, E. Iannicelli, P. Marchetti, A. Pellicelli, L. Miglioresi, G. Delle Fave, M. Marignani. Digestive and Liver Diseases unit, Radiology unit, Oncology unit, St. Andrea Hospital, Faculty of Medicine and Psychology, University ’Sapienza’, Liver Unit, San Camillo Forlanini Hospital, Rome, Italy E-mail: elia.gigante@hotmail.it

The amount of copies of HCV-RNA and count of CD8(+) lymphocytes was retrospectively evaluated in 326 patients: sampling was performed in basal condition, during treatment with alpha-IFN (n=232) and post-treatment follow-up, and at the same time points in untreated patients (n=94). In the treated group the difference between CD8(+) lymphocytes in the patients successfully treated (n=65) and those with an unfavourable outcome (n=176) is statistically significant (898+/-172 vs., 440+/-176 CD8(+) lymphocytes per mm(3) P0.005 ANOVA). Also, in the untreated patients the average count of CD8(+) cells is statistically higher in patients with a favourable outcome (P0.01 ANOVA). The present data show that the count of CD8(+) lymphocyte is of clinical value in order to predict the outcome of HCV infection and may be used together with the viral load and genotype, already established predictors.

Background: Treatment of hepatitis C virus (HCV) infection with interferon (IFN) in older patients may not be feasible on account of side effects: we, therefore, attempted combined treatment with amantadine hydrochloride (AH) in order to improve not only the flu-like symptoms associated with IFN but also the anti-viral effect. Methods: Patients over 65 years of age, (n=165), who had failed to eradicate HCV infection after previous treatment with IFN were randomized into three groups and treated for 12 months, group A received AH 100 mg twice per day; group B received IFNalpha-n(3) 6 M units every other day for 3 months followed by 3 MU and group C the same dose of IFNalpha-n(3), as in B, and AH 200 mg per day. Results: Group A, 42 patients agreed to undergo treatment (genotype 1b n=39); at the end of treatment 21 patients (50%) had normal ALT and seven (17%) negative polymerase chain reaction (PCR). HCV-RNA was not detectable in seven patients at the sixth month follow-up and in six (14%) after 23plus minus2 months. Group B, 39 patients accepted the treatment (genotype 1b n=31); at the end of treatment, 17 patients (44%) had normal ALT and 13 negative PCR (13%). HCV-RNA was not detectable in nine patients (23%) at the sixth month of follow-up and in eight (21%) after 22plus minus4 months. Group C, 38 patients accepted the treatment (genotype 1b n=32); at the end of treatment, 20 (53%) patients had normal ALT and 15 negative PCR (39%). HCV-RNA was not detectable in 15 patients at the sixth month follow-up and in 11 after 21plus minus4 months (29%). Forty-six patients did not accept the scheme of treatment and 26 of them had a follow-up of 20plus minus3 months. HCV-RNA copies and prevalence of genotype 1b were comparable to the treated groups: HCV-RNA was fluctuating or unchanged during the entire follow-up. Conclusions: AH associated with IFN was able to improve the negativization of HCV-RNA and sustained response to IFN and decreased the malaise associated with IFN; an increase in viral copies was observed under AH in about 40%.

The natural history of primary sclerosing cholangitis (PSC) is, to say the least, puzzling in its variability, in terms of age of onset, symptoms and prognosis.[1–2] As a matter of fact there are several, unfortunately independent areas of observation: the Doctor following a patient with Ulcerative Colitis (UC) or Crohn’s Disease (CD), who sees quite a benign increase of serum alkaline phosphatase (sALP) and is not worried about it, the Hepatologist who is quite happy to have found a rare disease, or the Endoscopist willing to perform exploration and diagnosis, but little interested in the radiologic aspect.

Finding one major hepatotropic virus may not be enough to identify the aetiology of liver disease when risk factors are present, particularly in patients with past or present infection with other viral agents, or chronic liver disease. The pathogenic process in these cases is often complex. In the five cases we report, acute hepatitis (initiated by halothane, cytomegalovirus or Epstein-Barr virus) preceded the reactivation of hepatitis B infection, and these events occurred in patients with chronic hepatitis C infection. Each case demonstrates how several viruses can be implicated in the development of hepatitis, either as single agents or via cross-activation of T cells. The nosography of hepatitis, therefore, and the optimum therapeutic choices, can puzzle the clinical team.

Background/Aims. The aim of this study was to estabilish the ‘true’ therapeutical gain of a combined therapy interferon — ribavirin versus interferon monotherapy in hepatitis C virus infection. Methods . A systematic review of published trials comparing combined treatment (interferon+ribavirin) vs interferon monotherapy, was performed on articles printed from 1991 to 1999. Results. The meta-analysis of retrieved trials showed that ribavirin significantly enhances the sustained response rate to interferon therapy in all types of patients. The results of almost all studies were homogeneous: combined therapy approximately doubles response rates compared to interferon monotherapy. At the end of the treatment, ribavirin increased the rate of viral clearance approximately 22% and the biochemical response of about 31%. The net gain was about 24% for both viral and biochemical response rate after 24 weeks of follow-up. Conclusion . Combined therapy showed a significantly higher efficacy in terms of sustained negativity of viral genome in all classes of patients (naives, relapsers, non-responders) becoming the therapy of choice. Nevertheless, more than about 50% of patients infected by hepatitis C virus show no sustained response to treatment. The whole weight of final data is beared by the major trials all with similar results.