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BACKGROUND Spontaneous HDV-RNA fluctuations, assessed by nonstandardised in-house assays, have been reported during the course of chronic hepatitis delta (CHD). AIMS To evaluate changes in serum HDV-RNA concentrations in untreated CHD patients and correlate these changes with other HBV markers. METHODS A total of 323 consecutive serum samples from 56 CHD patients (detectable HDV-RNA) followed for >3 years were retested for HDV-RNA levels by a sensitive technique using the first WHO international HDV-RNA standard. Quantitative HBsAg, HBV-DNA, and HBV-RNA were also determined. RESULTS Most participants were male, middle-aged, white European, and HBeAg-negative (82%). Almost half had liver cirrhosis and 64% were receiving nucleos(t)ide analogues. At inclusion, median-HDV-RNA was 5.3 (4.2-6.5) log10 IU/mL, HBsAg 4.0 (3.5-4.3) log10 IU/mL, and HBV-DNA 1.6 (1.0-2.6) log10 IU/mL; ALT values were normal in 13 (23%). During a mean follow-up of 5.6 (3-16) years, 14 (25%) showed ≥2log10 HDV-RNA decline, including 11 (20%) who spontaneously achieved undetectable HDV-RNA. Four patients (7%) lost HBsAg, with undetectable HDV-RNA. The remaining 42 (75%) had persistently detectable HDV-RNA. During follow-up, patients with a ≥2log10 HDV-RNA decline showed a greater HBsAg drop (-0.7 ± 1.1 vs -0.09 ± 0.9 log IU/mL; P = 0.039) than those with a

BACKGROUND & AIMS The epidemiology of hepatitis B virus (HBV) infection differs between Asians and non-Asians, but little is known regarding the effect of ethnicity on outcomes of HBV-related hepatocellular carcinoma (HCC). We aim to characterize the presentation and survival outcomes in Asian and non-Asian patients with HBV-related HCC. METHODS We analyzed the baseline characteristics and long-term survival of 613 Asian and 410 non-Asian patients with HBV-related HCC from three US and one Spanish centre. RESULTS Overall, non-Asian patients were more likely to have HIV or hepatitis C co-infection, cirrhosis, decompensated liver disease and advanced BCLC stage (all P ≤ .04). Compared with Asians, non-Asians were more likely to be listed for transplantation (P

The value of noninvasive tools in the diagnosis of autoimmune hepatitis (AIH)-related cirrhosis and the prediction of clinical outcomes is largely unknown. We sought to evaluate (1) the utility of liver stiffness measurement (LSM) in the diagnosis of cirrhosis and (2) the performance of the Sixth Baveno Consensus on Portal Hypertension (Baveno VI), expanded Baveno VI, and the ANTICIPATE models in predicting the absence of varices needing treatment (VNT). A multicenter cohort of 132 patients with AIH-related cirrhosis was retrospectively analyzed. LSM and endoscopies performed at the time of cirrhosis diagnosis were recorded. Most of the patients were female (66%), with a median age of 54 years. Only 33%-49% of patients had a LSM above the cutoff points described for the diagnosis of AIH-related cirrhosis (12.5, 14, and 16 kPa). Patients with portal hypertension (PHT) had significantly higher LSM than those without PHT (15.7 vs. 11.7 kPa; P = 0.001), but 39%-52% of patients with PHT still had LSM below these limits. The time since AIH diagnosis negatively correlated with LSM, with longer time being significantly associated with a lower proportion of patients with LSM above these cutoffs. VNT was present in 12 endoscopies. The use of the Baveno VI, expanded Baveno VI criteria, and the ANTICIPATE model would have saved 46%-63% of endoscopies, but the latter underpredicted the risk of VNT. Conclusions: LSM cutoff points do not have a good discriminative capacity for the diagnosis of AIH-related cirrhosis, especially long-term after treatment initiation. Noninvasive tools are helpful to triage patients for endoscopy.

Background Chronic hepatitis delta is a severe liver disease with rapid progression to cirrhosis. The impact of hepatitis delta virus (HDV)-RNA on disease progression and interferon treatment in a real-world cohort has been barely explored. Aim To assess the development of clinical events in a cohort of chronic hepatitis delta patients according to the presence or absence of HDV-RNA METHODS: Multicentre study at four academic hospitals in Spain included anti-HDV-positive patients with compensated liver disease with a follow-up ≥12 months. Results Among 2888 HBsAg-positive subjects, 151 (5.2%) tested positive for anti-HDV, and 118 were included (58% men; median age, 49 years; 73% detectable HDV-RNA and 30% cirrhosis, most often in subjects with HDV-RNA). After a median follow-up of 8 years, subjects with initially detectable HDV-RNA were more prone to developing cirrhosis (31% vs 0%, P = .002) and/or liver decompensation (28% vs 3%, P = .019). Mortality rate was 0.44 per 1000 person-months. The probability of a clinical event was 6%, 25%, and 80% according to initial baseline-event-anticipation score. HDV-RNA became undetectable in 21 (24%) subjects either due to interferon or spontaneously (48% vs 52%, P = .29). Liver decompensation was reduced in interferon-treated patients (13% vs 38%, P = .026). Conclusions Subjects with persistently positive HDV-RNA had a worse prognosis in terms of clinical events. Baseline-event-anticipation score is useful in predicting the risk of developing liver decompensation and hepatocellular carcinoma. Interferon was beneficial in reducing liver decompensation, even in the absence of virological response.

BACKGROUND Hepatitis E virus (HEV) can be transmitted by transfusion of any type of blood component, but there are few data on the potential risk of transmitting this virus and the associated complications. We provide evidence that HEV can be transmitted by cryosupernatant plasma, and that HEV infection can act as a trigger for thrombotic thrombocytopenic purpura (TTP). STUDY DESIGN AND METHODS A patient with a history of TTP treated with plasmapheresis 2 months previously developed jaundice and a TTP exacerbation with purpura, thrombocytopenia, schistocytes, and undetectable ADAMTS-13 activity. He was diagnosed with acute hepatitis E and treated with ribavirin. TTP remitted with remission of HEV infection. RESULTS Traceback to determine the source of the infection showed that 1 cryosupernatant plasma among the 99 different blood components used for the patient's last plasmapheresis was positive for HEV RNA, with an estimated viral load of 5000 to 10,000 IU/mL. Phylogenetic analysis proved the transfusion-transmitted route of acute hepatitis E. CONCLUSION In a patient with TTP, acute HEV infection transmitted by cryosupernatant plasma may trigger exacerbation of TTP, which can be controlled on remission of HEV infection with ribavirin.

Long-term treatment of chronic hepatitis B (CHB) with nucleos(t)ide analogues is often necessary to achieve durable viral suppression. Therefore, current guidelines recommend the most potent drugs with optimal resistance profiles. Entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are the first-line monotherapies for CHB. All of these drugs are highly effective in suppressing viral replication but with slightly different safety profiles. This review provides an overview of the long-term efficacy and safety data that have become available over the 10 years since ETV and TDF were first approved for the treatment of chronic hepatitis, and recent data on TAF in patients with CHB.

BACKGROUND Acute hepatitis E in industrialized countries is usually related to intake or manipulation of undercooked or raw meat. Cases of transfusion-transmitted hepatitis E have rarely been documented in immunosuppressed patients, mainly after receiving frozen plasma. STUDY DESIGN AND METHODS A 61-year-old man was admitted to hospital for jaundice. His personal history included disseminated bacillus Calmette-Guerin infection treated with antituberculous drugs. He had received red blood cell (RBC) transfusion 2 months previously, during admission for mycotic aneurysm surgery. Since liver function tests worsened despite stopping antituberculous drugs, other causes of acute hepatitis were explored. RESULTS Acute hepatitis E was diagnosed by the presence of both immunoglobulin M and hepatitis E virus (HEV) RNA. Traceback procedure for the 8 RBC units was carried out, and one of the eight archive plasma samples tested positive for HEV RNA, with an estimated viral load of 75,000 IU/mL. Phylogenetic analysis revealed the same HEV strain Genotype 3 in one of the transfused RBC products and in the patient's serum sample. CONCLUSION Transfusion of RBCs with detectable HEV RNA is a risk factor for acute hepatitis E in immunocompetent patients in Europe.

Background Despite the reported decrease in the incidence and mortality rates of central nervous system (CNS) infections after the introduction of highly active antiretroviral therapy (HAART), few studies have focused on the global incidence and the relationship of these diseases with immune reconstitution inflammatory syndrome (IRIS) in the developed world. Methods A descriptive cohort study of all consecutive adult HIV-infected patients with CNS opportunistic infections diagnosed between 2000 and 2010 in a tertiary hospital in Spain was carried out. Demographic, clinical, laboratory, and microbiological data were recorded. Patients were followed up until death or loss to follow-up or until 30 July 2011, when the study finished. The significance of differences in the incidence rate between early and late HAART periods was determined using the Mantel–Haenszel test. Survival distribution was estimated using the Kaplan–Meier method. Results A total of 110 cases of CNS infections were diagnosed. The incidence of CNS opportunistic infections decreased from 9 cases per 1000 HIV-infected patients per year in the early HAART period to 3.8 in the late HAART period (P = 0.04). Overall, the estimated mean survival time was 58.8 months (95% confidence interval 47.1–70.6 months). Of the 110 patients, 18 (16.4%) met the criteria of IRIS, 10 (55.6%) were paradoxical and eight (44.4%) were unmasking. IRIS was not associated with a higher mortality rate. Conclusions The annual incidence of CNS infections decreased progressively during the period of study. The mortality rate associated with these diseases remains high despite HAART. The development of IRIS associated with neurological infections had no influence on prognosis.