M. Milana

Complete hepatitis B virus prophylaxis withdrawal in hepatitis B surface antigen-positive liver transplant recipients after longterm minimal immunosuppression.

Tailored approaches have been attempted to prevent hepatitis B virus (HBV) reinfection in antibodies against hepatitis B surface antigen (HBsAg)–positive liver transplantation (LT) recipients in order to minimize the use of hepatitis B immune globulin (HBIG) and nucleoside analogues (NAs). We report the results of complete HBV prophylaxis withdrawal after a follow‐up of at least 6 years in LT recipients with undetectable serum HBV DNA and intrahepatic total HBV DNA and covalently closed circular DNA at LT. We included 30 HBsAg positive, hepatitis B e antigen–negative recipients, 6 with hepatitis C virus and 7 with hepatitis D virus coinfection, who had received HBIG plus NA for at least 5 years after LT. Stepwise HBIG and NA withdrawal was performed in two 6‐month periods under strict monitoring of HBV virology. All patients underwent a clinical, biochemical, and virological follow‐up at 3‐6 month intervals. HBV recurrence (HBsAg seroreversion ± detectable HBV DNA) occurred in 6 patients: in 1 patient after HBIG interruption and in 5 after both HBIG and NA cessation. Only 3 patients required reinstitution of HBV prophylaxis because of persistent HBV replication, and all achieved optimal control of HBV infection and did not experience clinical events. The other who recurred showed only short‐lasting HBsAg positivity, with undetectable HBV DNA, followed by spontaneous anti‐HBs seroconversion. An additional 15 patients mounted an anti‐HBs titer, without previous serum HBsAg detectability. At the end of follow‐up, 90% of patients were still prophylaxis‐free, 93.3% were HBsAg negative, and 100% were HBV DNA negative; 60% had anti‐HBs titers >10 IU/L (median, 143; range, 13‐1000). This small series shows that complete prophylaxis withdrawal is safe in patients transplanted for HBV‐related disease at low risk of recurrence and is often followed by spontaneous anti‐HBs seroconversion. Further studies are needed to confirm this finding. Liver Transplantation 22 1205–1213 2016 AASLD

Crusted scabies in a liver transplant patient mimicking rupioid psoriasis.

Crusted scabies is a rare, highly contagious infection caused by massive infestation of Sarcoptes scabiei var. hominis. Patients with a weakened immune system are particularly affected by crusted scabies, as an inadequate host response and subsequent unrestrained growth of parasitic mites play a key pathogenetic role. Clinical presentation of crusted scabies typically features psoriasiform, warty skin plaques. We hereby report the case of a liver transplant patient with a peculiar presentation of [...]

Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post-transplant hepatitis C recurrence and severe fibrosis and cirrhosis: A prospective study

In 2012, an Italian Named Patient Program began for hepatitis C virus (HCV)‐infected liver transplant (LT) recipients with advanced fibrosis, before approval of direct antiviral agents (DAA), to benefit severely ill patients. The aim of this “real‐life” study was to assess treatment efficacy and safety with an extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without ribavirin (RBV).

An unusual duodenal polyp causing anemia in a liver-transplanted patient

A 62-year-old man, liver-transplanted three years earlier for HBV-related cirrhosis complicated by hepatocellular carcinoma (HCC) within the Milan criteria, presented to our outpatient clinic with a three-week history of progressively worsening fatigue. Bloodwork revealed severe microcytic anemia (Hb 7 g/dL) and a positive fecal occult blood test. Other laboratory tests were unremarkable. At duodenoscopy a 25-millimeter pedunculated polyp with a congested and ulcerated mucosa was found in the first duodenal portion (Fig. 1), which did not have the typical macroscopic appearance of an adenoma or adenocarcinoma. A contrast-enhanced computed tomography confirmed the presence of a duodenal lesion showing a slight contrastenhancement in the arterial phase, and no other relevant findings. After stalk infiltration with adrenalin 1/1000 in saline, endoscopic polypectomy with a diathermic loop was performed and the duodenal polyp was entirely removed (Fig. 2) and harvested for histological examination. Histological examination supported the diagnosis of a moderately differentiated (G2) HCC. Hepatocyte specific antigen (HAS), cytokeratin pan antibody (PanCK) and vimentin (VIM) staining resulted positive. Pseudoacinar architecture with no prominent cytological atypia and typical vascular invasion are shown in Fig. 3 (hematoxylin and eosin, magnification ×20 and ×40, respectively). The polyp stalk was free of tumor infiltration. A strict endoscopic and radiological surveillance program was undertaken, based on upper endoscopy and contrast-enhanced CT scan performed at month 3 and 6 after polypectomy. No evidence of recurrent HCC was reported after one year, including also a positive emission computed tomography. Fatigue and anemia progressively improved after endoscopic polyp resection, with return to normal hemoglobin levels within six months. HCC extension to small bowel is considered anecdotal and generally restricted to patients with diffuse neoplastic involvement of the liver [1, 2]. To our knowledge, only one case has been described of a single duodenal isolated recurrence of HCC [2]. However, this patient was not a liver transplant recipient and had fibrolamellar HCC. HCC recurrence nowadays is reported at a rate lower than 20% after liver transplantation, according to a retrospective radiologic Fig. 1 Duodenoscopy showing a 25-mm pedunculated polyp with a congested and ulcerated mucosa in the first duodenal portion, which did not have the typical macroscopic appearance of an adenoma or adenocarcinoma

Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1–4 in Italy

Natural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mainly due to 80K presence in GT1a (17%). Almost all GTs showed high prevalence of NS5A-RASs (range: 10.2–45.4%), and especially of 93H (5.1%). NS5A-RASs with fold-change >100x were detected in 6.8% GT1a (30H/R-31M-93C/H), 10.3% GT1b (31V-93H), 28.4% GT2c (28C-31M-93H), 8.5% GT3a (30K-93H), 45.5% GT4a (28M-30R-93H) and 3.8% GT4d (28V-30S-93H). Sofosbuvir RAS 282T was never detected, while the 159F and 316N RASs were found in GT1b (13.4–19.1%, respectively). Natural RASs are common in Italian patients infected with HCV-GTs 1–4. High prevalence of clinically-relevant RASs (such as Y93H) supports the appropriateness of HCV resistance-test to properly guide DAA-based therapy.

Pitfalls in the reporting of upper endoscopy features in cirrhotic patients

BACKGROUND Upper endoscopy is the main tool for the accurate assessment of the risk of bleeding in cirrhotic patients. AIM To evaluate the diagnostic accuracy of upper endoscopy, in cirrhotic subjects, during common clinical practice. METHODS 120 endoscopic reports produced in different hospitals in our region were retrospectively and randomly selected. After a general evaluation, aimed at assessing the description of various endoscopic features, reports were evaluated by four expert endoscopists and four expert hepatologists. Experts were asked to fill in a questionnaire for each single endoscopic procedure, regarding the diagnostic accuracy of the report. RESULTS Endoscopic reports lacked descriptions of the size of esophageal varices and red signs in 14% and 29% of cases respectively. Presence (or absence) of gastric varices or portal hypertensive gastropathy were not reported in 62% and 34% of cases respectively. According to expert endoscopists 41% of the reports were incomplete, while, according to hepatologists, reports were incomplete and inadequate for clinical purposes in 36% of cases. CONCLUSION Our study clearly evidenced a significant lack of information in reports on upper endoscopy in cirrhotic patients, and supports the prompt adoption of corrective strategies.

Trans-splenic Embolization Plus Partial Splenic Embolization for Management of Variceal Bleeding Due to Left-Sided Portal Hypertension

Bleeding from gastric fundal varices (GFVs) is generally less frequent but more severe than bleeding from esophageal varices [1], and currently a gold standard treatment does not yet exist. The presence of GFVs without esophageal varices could be a sign of splenic vein occlusion because blood drainage is diverted by the coronary vein into the portal system within a framework of so-called left-sided portal hypertension (LSPH) [2]. Often LSPH may be due to iatrogenic splenic vein injury or ligation [3]. The importance of differentiating between left-sided and generalized portal hypertension lies in the distinct therapeutic management of each disease process. In the patient described here, since it proved impossible to achieve a safe and effective embolization throughout a previously placed TIPS that did not allow gastric veins (GVs) decompression, a percutaneous trans-splenic embolization (PTSE) of GFVs and two partial splenic embolizations (PSEs) were performed with the aim to reduce the splenic venous outflow. Case Report

Evidence of Spontaneous Post-transplant HCV Eradication in Two Failed DAA Treatments Awaiting Liver Transplantation

Recurrence of HCV infection (rHCV) in patients with detectable HCV-RNA at the time of liver transplantation (LT) is almost universal and is associated with a rapidly progressing course, leading to chronic hepatitis and cirrhosis [1]. Transplant recipients with high levels of HCVRNA prior to LT are more likely to experience fibrosis progression and poor outcome [1]. It is therefore essential to consider early antiviral therapy in the transplant setting, since achievement of sustained virological response (SVR) improves clinical outcomes and survival rates in LT recipients [2]. The recent introduction of direct-acting antivirals (DAAs) has revolutionized the management of HCV therapy [3]. The use of new DAAs has resulted in high SVR rates, with short treatment courses and excellent safety profiles. Yet, the optimal timing of antiviral therapy in the liver transplant setting is still under discussion. We report here two cases of LT in patients with endstage HCV-related cirrhosis recently performed at our centre, which presented unusual features, which we believe deserve attention.

Physical examination of the liver: does it make sense in the third millennium?

To the Editor: A 1995 report suggests that physical examination is inadequate in evaluating liver volume in comparison with the ultrasonographic approach, even though the possibility that it could be used to assess organ consistency was suggested (1). We reassessed this issue to evaluate the possible correlation between assessment of organ consistency by physical examination and liver stiffness measurement using transient elastography (FibroScan , Echosens, Paris, France). Fifty consecutive patients (M/F 30/20, mean age 47 ± 18) referred to our outpatient liver clinic for chronic HCV, HBV or alcoholic liver disease and ten healthy subjects (M/F 6/4, mean age 43 ± 21) gave their written informed consent for enrolment in this study, which was approved by our local ethical committee. The patients underwent a physical examination of the liver carried out by three different hepatologists (>4 years training in hepatology) with the assessment of organ consistency, and were subsequently submitted to FibroScan examination by another operator. The hepatologists and operator were completely unaware of the clinical condition of the patients before examination. Physical examination of liver consistency was carried out in the morning after an overnight fast. Patients were visited in a supine position and scored according to a four-step scale as follows: 0 = normal liver; 1 = slight increase in stiffness; 2 = marked increase in stiffness; 3 = cirrhosis. When results of the physical examination were in disagreement, a consensus was achieved by the three specialists after consulting. Results are depicted in Fig. 1. Transient elastography was performed immediately after physical assessment and carried out using a model 502 FibroScan equipped with an M probe (Echosens). There was a linear positive correlation between transient elastography and liver palpation data (r = 0.76, P < 0.001). Statistical differences in stiffness among the different classes, stratified according to the

166 HCV DIVERSITY AND FIBROSIS PROGRESSION: NS5A AND CORE VARIANTS CORRELATE WITH SEVERITY OF HCV RECURRENCE AFTER LIVER TRANSPLANTATION

Results: The overall 1-, 5and 10-year posttransplant survival rates, stratified by the composite risk score are presented in table 1. More than half (53.6%) of patients had at least one of the risk factors (obesity, renal dysfunction or advanced age). Patients with two or more risk factors (score ≥2) experienced a significantly higher covariate-adjusted risk of death compared to patients with zero (HR: 5.9, 95%CI: 2.3–14.3; p < 0.001) or one (HR: 2.6, 95%CI: 1.3–5.6; p = 0.009) risk factor.