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Obeticholic acid (OCA) was recently approved as the only on-label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials.To assess the effectiveness and safety of OCA in a real-world cohort of patients with non-effective UDCA therapy.Open-label, prospective, real-world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK-PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA . Liver fibrosis was evaluated by FIB-4 and AST to platelet ratio index (APRI).One hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0-13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy-eight patients completed at least 1 year of OCA. The Globe-PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK-PBC score decreased to 0.81 (95% CI -0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB-4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus).This study supports data from phase III trials with significant improvement of PBC-Globe continuous prognostic marker score among OCA-treated patients with good tolerability.

Background & Aims The addition of protease inhibitors (PIs) changed the hepatitis C virus (HCV) treatment standards and improved sustained viral response (SVR) rates in patients with genotype 1 HCV infection. Methods Prospective, multicentre, national registry that includes naive and treatment-experienced patients with HCV genotype 1 infection, who had bridging fibrosis or cirrhosis and were treated with triple therapy (peginterferon alfa-2a or alfa-2b, ribavirin and boceprevir) as compassionate use, and in accordance with the Summary of Product Characteristics. Results Most of the patients (68.2%) were male, with a mean age of 53 years, 75% (n = 128) had HCV 1b genotype and baseline viral load of 6.2 log. According to prior treatment, 20% of patients were treatment-naive and 80% had received prior treatment. Approximately 36.5% of patients (n = 62) reported at least one serious adverse events (SAEs) (total SAEs = 103). The most common SAEs were neutropenia (57.6%), anaemia (47.6%) and grade 3 thrombopenia (25.9%). Patients with albumin 2 mg/dl had an increased relative risk (greater than one-fold) for SAEs, including infections and hepatic decompensation. In the intent-to-treat analysis (n = 170), the overall percentage of patients with SVRw12 was 46.5%. In patients with 1 log decrease at week 4 (lead-in phase), the overall SVRw12 rate was 67.0%. In the patients initiating triple therapy with boceprevir (n = 139), the global response rate was 56.4%. In a multivariate analysis, an increased probability of achieving SVR was associated with response to prior treatment (relapsers), >1 log decrease in viral load in the lead-in phase and baseline albumin >3.5 g/dl. Conclusions Triple therapy in patients with severe fibrosis/cirrhosis is associated with a higher rate of SAE and a lower rate in comparison with patients with mild disease. However, for patients with intact liver function, it could be considered as a treatment option, when other alternatives would not be available.

Objectives The aim of this study was to evaluate the efficacy and safety of entecavir monotherapy in nucleos(t) ide-naive chronic hepatitis B patients and to analyse the influence of the comorbidity burden on therapy outcome. Methods We retrospectively analysed data from 237 nucleos(t) ide-naive chronic hepatitis B white patients treated with entecavir (0.5 mg/day) at 23 Spanish centres. For the efficacy and safety analyses, patients were grouped according to their baseline comorbidities. Results The mean age of the cohort was 43 years (range: 19-82 years); 73% were male, 83% were white, and 33% were hepatitis B e antigen (HBeAg) positive. At baseline, the median hepatitis B virus DNA level was 6.20 log10 IU/ml. Of the patients, 18% had cirrhosis, 9.7% had diabetes, 16.3% had hypertension, and 15.7% had obesity; 13.4% of patients had more than one comorbid condition. Virological and biochemical responses at month 36 were obtained independently of the patients' baseline comorbid condition. Of 10 HBeAg-positive patients who discontinued treatment after HBeAg seroconversion, those who had not also cleared HBsAg (six) experienced virological recurrence in a median 5.6 months. There were no treatment discontinuations due to adverse events. Three patients were diagnosed with hepatocellular carcinoma at months 12, 30 and 54, and six experienced hepatic decompensation during follow-up. The median serum creatinine levels did not increase after 36 months of treatment, even in patients with comorbidities. Conclusion Entecavir is safe, well tolerated, and highly effective, even in patients with comorbid condition(s). Discontinuation of treatment in patients who have not been cleared of HBsAg may lead to virological recurrence. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Summary. Background: Hepatitis C virus (HCV) translation is initiated in a cap-independent manner by an internal ribosome entry site (IRES) located within the 5′ untranslated region (5′UTR). Sequence changes in this region could affect translation efficiency and presumably viral replication. Aim: To determine translation efficiency of 5′UTR variants developing during post-transfusion hepatitis C in two immunocompetent subjects and in two immunosuppressed liver recipients with recurrent HCV. Methods: Sequential samples were screened for 5′UTR changes by single-strand conformation polymorphism followed by cloning and sequencing whenever band pattern suggested sequence changes. 5′UTR variants were tested for IRES activity using a bicistronic dual luciferase expression plasmid transfected into HepG2 and Huh7 cell-lines. Results: In the transfused patients, translation efficiency of 5′UTR variants from early post-transfusion samples was 5.1- to 13.7-fold higher than that of predominant variants found in late follow-up samples. Post-transplant variants in the other two patients had 2.6- to 5.9-fold higher translation efficiency than those present only in pretransplant samples. Conclusion: In the immunocompetent host there may be selection of low translation efficiency HCV variants over the course of infection. However, in immunosuppressed subjects the opposite seems to be true as low translation efficiency variants are superseded by high translation efficiency variants.

Chronic hepatitis C virus (HCV) infection is generally a slowly progressive disease. A minority of infected patients, however, eventually will develop cirrhosis and its life-threatening complications.Recent development of combination interferon (IFN) and ribavirin(RBV) antiviral therapy has changed the approach to patients infected with the virus. Once cirrhosis develops, treatment is a difficult task and should be done with close monitoring because of numerous adverse effects. In patients with compensated cirrhosis,combination therapy is the most efficient approach and offers the highest sustained virological response. Although data are limited,no significant differences have been reported between the use of pegylated interferon (PEG-IFN) and standard IFN in combination with RBV. Moreover, PEG-IFN has a higher risk of hematological complications, and this should be considered when using in advanced disease. Antiviral therapy for patients with decompensated cirrhosis should be used only in a clinical trial setting because of reported severe adverse effects. After liver transplantation, combination therapy may be an alternative for a limited number of patients. Although definitive recommendations cannot be made because of limited studies, there is a group of very well compensated patients with HCV and cirrhosis who benefited from treatment by clinicians well versed in the use of combination therapy.

The present organ donor crisis has led to accepted use of organs from donors infected with hepatitis C virus (HCV) and hepatitis B virus (HBV). Although capable of transmitting disease, these grafts offer opportunities to expand the donor pool for certain populations. Anti-HBc positive grafts can be used if care is taken to provide prophylaxis. Good quality grafts from HCV+ donors may be used in recipients who are themselves HCV+ with good outcomes.

Patients with liver disease frequently experience changes in their nutritional status.To determine changes in vitamin B12 and folic acid plasma levels in patients with chronic cirrhosis and to assess whether these parameters may be useful in the etiologic diagnosis of this disease.Thirty-nine patients admitted for decompensated cirrhosis (29 with alcoholic etiology and 10 with non-alcoholic etiology) and 35 controls were prospectively studied. Plasma levels of vitamin B(12), folate acid, mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyltransferase (GGT), among other parameters, were measured.Vitamin B(12) levels were 1151+/-568pg/ml in patients with decompensated cirrhosis and 440+/-133pg/ml in controls (p0.05). Plasma folate levels were 8.57+/-3.8ng/ml in controls and 6.68+/-2.74ng/ml in patients with cirrhosis (p0.05). Folate levels were lower in patients with alcoholic cirrhosis (mean value, 5.7+/-2.1) than in those with non-alcoholic cirrhosis (9.3+/-2.6; p0.0005). The vitamin B(12)/folate ratio discriminated alcoholic etiology better than other parameters such as AST, ALT, MCV, AST/ALT ratio and GGT.Plasma levels of vitamin B12 in patients with decompensated chronic liver disease are high, whereas plasma folate levels are low. The ratio between vitamin B12 and folic acid may be useful in the differential diagnosis of the etiology of chronic liver disease.

1. Liver grafts from hepatitis C virus (HCV)-infected deceased donors can be used safely in HCV-infected recipients. 2. Histological assessment of the graft before orthotopic liver transplantation (OLT) is advised. 3. Recipients of these grafts should give consent accordingly. 4. The course of HCV disease after OLT parallels that in patients who received noninfected organs.

Background. The dynamics of hepatitis C virus (HCV) quasi species in the E2 region may correlate with the course of infection after orthotopic liver transplantation (OLT).Methods. Thirty-four patients who underwent transplantation for HCV-related cirrhosis were studied. Serum and liver samples were available before OLT and at 1 week, 4 months, and 1 year after OLT. Patients were divided into group 1 (Knodell/Ishak fibrosis stage [FS] at 1 year

Background: Wilson's disease, heralded by severe hepatic insufficiency, is a rare disorder for which emergency liver transplantation is considered to be the only effective therapy. Aims: To report the features of Wilson's disease with severe hepatic insufficiency in a series of 17 patients and, during the second period of the study, to assess the efficacy of a policy consisting of early administration of D-penicillamine. Patients: Seventeen consecutive patients with Wilson's disease were studied. During the first period of the study (up to 1979), none of the patients received D-penicillamine. During the second period (after 1979), all patients without encephalopathy at admission received D-penicillamine. Results: The four patients observed during the first period who did not have encephalopathy at admission and did not receive D-penicillamine progressed to encephalopathy and died. Among the 13 consecutive patients observed during the second period, two patients with encephalopathy at admission did not receive D-penicillamine and were transplanted. The 11 remaining patients all received D-penicillamine. Ten of these patients survived without the need for transplantation and returned to compensated liver disease without liver insufficiency. In one patient, liver insufficiency progressed and transplantation had to be performed. Conclusions: In most patients with Wilson's disease heralded by severe hepatic insufficiency and without encephalopathy at admission, early administration of D-penicillamine was associated with survival without transplantation. These results suggest the importance of early diagnosis of this form of Wilson's disease before the onset of encephalopathy, and favour early administration of D-penicillamine which could avoid the need for transplantation in most cases.

Nowadays, the number of cases in which malignant colorectal polyps are removed is increasing due to colorectal cancer screening programmes. Cancerous polyps are classified into non-invasive high grade neoplasia (NHGN), when the cancer has not reached the muscularis mucosa, and malignant polyps, classed as T1, when they have invaded the submucosa. NHGN is considered cured with polypectomy, while the prognosis for malignant polyps depends on various morphological and histological factors. The prognostic factors include, sessile or pedunculated morphology of the polyp, whether partial or en bloc resection is carried out, the degree of differentiation of the carcinoma, vascular or lymphatic involvement, and whether the polypectomy resection margin is tumor free. A malignant polyp at T1 is considered cured with polypectomy if it is a pedunculated polyp (Ip of the Paris classification), it has been completely resected, it is not poorly differentiated, the resection edge is not affected by the tumor and there is no vascular or lymphatic involvement. The sessile malignant polyp (Is of the Paris classification) at T1 is considered not cured with polypectomy. Only in some cases (e.g. older people with high surgical risk) local excision (polypectomy or endoscopic submucosal dissection or conventional endoscopic mucosal resection) is considered the definitive treatment.