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There is a lack of knowledge regarding the effect of peginterferon ( PEG- IFN) on the expression of intrahepatic hepatitis B core and surface antigen ( HBc Ag and HBs Ag) in chronic hepatitis B ( CHB) and its relation with response to therapy. Fifty-two HBe Ag-positive and 67 HBe Ag-negative CHB patients with paired liver biopsies taken at baseline and after 1 year of PEG- IFN therapy were studied. After PEG- IFN therapy, HBe Ag-negative patients showed a significant reduction in both intrahepatic HBc Ag ( P = 0.04) and HBs Ag expression ( P < 0.001). In contrast, a reduction in intrahepatic HBc Ag expression was not observed in HBe Ag-positive patients, while a trend in reduction of intrahepatic HBs Ag staining was found ( P = 0.09). Post-treatment, 7 (13%) HBe Ag-positive and 9 (14%) HBe Ag-negative patients had no expression of intrahepatic HBs Ag. Patients without any intrahepatic HBs Ag expression post-treatment were more likely to achieve a combined response ( HBe Ag loss with hepatitis B virus ( HBV) DNA <2000 IU/mL for HBe Ag -positive and HBV DNA <2000 IU/mL and normal alanine aminotransferase for HBe Ag-negative CHB): 71% vs 5% for HBe Ag-positive ( P < 0.001) and 60% vs 16% for HBe Ag-negative patients ( P = 0.004), respectively. Moreover, a more profound decline of serum HBs Ag was observed in patients with absence of intrahepatic HBs Ag staining (3.1 vs 0.4 log IU/mL, P < 0.001 and 1.7 vs 0.4 log IU/mL, P = 0.005 for HBe Ag-positive and HBe Ag-negative CHB, respectively). In conclusion, PEG- IFN reduces expression of intrahepatic HBs Ag. Loss of HBs Ag as assessed by immunohistochemistry from the liver predicts a sustained response and is reflected in a pronounced serum HBs Ag decline. [ABSTRACT FROM AUTHOR]

: Treatment with interferon-alpha has beenshown to be effective in one-third of hepatitis B e antigen-positive chronic hepatitis B patients, but is clinically associated with relevant adverse events.: To investigate the safety of pegylated interferon alpha-2b in 300 hepatitis B e antigen-positive patients with compensated liver disease.: Patients were treated with pegylated interferon alpha-2b for 52 weeks combined with either lamivudine 100 mg/day or placebo. Pegylated interferon alpha-2b was administered for 100 μg once a week for 32 weeks; thereafter, the dose was reduced to 50 μg once a week. Adverse events and their effect on study medication were reported at monthly visits in a standardized way.: The most frequently reported side-effects were flu-like syndrome (68%), headache (40%), fatigue (39%), myalgia (29%) and local reaction at the injection site (29%). These symptoms typically occurred within the first month of therapy and subsided during the course of therapy. Neutropenia and thrombocytopenia induced by pegylated interferon alpha-2b increased the risk of infections and bleeding complications, but these complications were rare and mild. The frequency of all side-effects was not different between patients treated with pegylated interferon alpha-2b combined with lamivudine or placebo. In 69 (22%) patients the dose of pegylated interferon alpha-2b was reduced prematurely. Of these dose reductions, 36 (52%) were because of neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent reasons for early discontinuation were psychiatric side-effects (depression, psychosis) and flu-like symptoms. Multivariate Cox regression analysis showed that low neutrophil count at baseline and cirrhosis were independent predictors of dose reduction or therapy discontinuation.: We conclude that in patients with chronic hepatitis B and compensated liver disease prolonged pegylated interferon alpha-2b therapy is safe, and that pre-existent cirrhosis and neutropenia are the most important predictors of dose reduction or early treatment discontinuation. [ABSTRACT FROM AUTHOR]

BACKGROUND Primary biliary cholangitis is a rare, chronic cholestatic liver disease characterized by the destruction of interlobular bile ducts, leading to cholestasis and liver fibrosis. Whether elafibranor, an oral, dual peroxisome proliferator-activated receptor (PPAR) α and δ agonist, may have benefit as a treatment for primary biliary cholangitis is unknown. METHODS In this multinational, phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 2:1 ratio) patients with primary biliary cholangitis who had had an inadequate response to or unacceptable side effects with ursodeoxycholic acid to receive once-daily elafibranor, at a dose of 80 mg, or placebo. The primary end point was a biochemical response (defined as an alkaline phosphatase level of <1.67 times the upper limit of the normal range, with a reduction of ≥15% from baseline, and normal total bilirubin levels) at week 52. Key secondary end points were normalization of the alkaline phosphatase level at week 52 and a change in pruritus intensity from baseline through week 52 and through week 24, as measured on the Worst Itch Numeric Rating Scale (WI-NRS; scores range from 0 [no itch] to 10 [worst itch imaginable]). RESULTS A total of 161 patients underwent randomization. A biochemical response (the primary end point) was observed in 51% of the patients (55 of 108) who received elafibranor and in 4% (2 of 53) who received placebo, for a difference of 47 percentage points (95% confidence interval [CI], 32 to 57; P<0.001). The alkaline phosphatase level normalized in 15% of the patients in the elafibranor group and in none of the patients in the placebo group at week 52 (difference, 15 percentage points; 95% CI, 6 to 23; P=0.002). Among patients who had moderate-to-severe pruritus (44 patients in the elafibranor group and 22 in the placebo group), the least-squares mean change from baseline through week 52 on the WI-NRS did not differ significantly between the groups (-1.93 vs. -1.15; difference, -0.78; 95% CI, -1.99 to 0.42; P=0.20). Adverse events that occurred more frequently with elafibranor than with placebo included abdominal pain, diarrhea, nausea, and vomiting. CONCLUSIONS Treatment with elafibranor resulted in significantly greater improvements in relevant biochemical indicators of cholestasis than placebo. (Funded by GENFIT and Ipsen; ELATIVE ClinicalTrials.gov number, NCT04526665.) [ABSTRACT FROM AUTHOR]

Introduction In Phase III studies evaluating treatment of chronic hepatitis B (CHB), entecavir demonstrated superior efficacy compared to lamivudine and a comparable safety and tolerability profile. Long-term safety data from the rollover study ETV-901 are reviewed, focussing on adverse events (AEs) with a potential nucleos(t)ide association. Method Long-term cumulative safety and tolerability results are based on investigator-reported AEs, regardless of causal relationship. Results Median exposure to entecavir in ETV-901 was 168 weeks. Of the 1045 treated patients, 402 (38%) had received entecavir for =5 years at the time of analysis. Also, 488 (47%) patients had additional prior entecavir exposure from Phase II or III participation. Baseline characteristics were: mean age 41 years; 804 (77%) male, 539 (52%) Asian, and 480 (46%) Caucasian. The most common AEs (=10%) were upper respiratory tract infection, headache and nasopharyngitis. On-treatment alanine aminotransferase (ALT) flares were reported in 3% of patients. The cumulative rate of serious AEs was 15%. Discontinuations due to AEs were 1% (n=13), and generally (n=11) occurred during the first 2 years of ETV-901. Selected AEs with a potential nucleos(t)ide association are described below. Conclusion Entecavir is a safe and well-tolerated treatment for patients with CHB and compensated liver disease. Long-term administration of entecavir was associated with low rates of serious AEs, discontinuations due to AEs and ALT flares. Spontaneous reports of AEs potentially associated with nucleos(t)ide use occurred at low rates. Results Multiple adverse events per individual patient are possible. No prospective testing for laboratory parameter (reactive only). [ABSTRACT FROM PUBLISHER]

The article describes the case of a 63-year-old man who suffered massive upper gastrointestinal bleeding caused by Dieulafoy's lesion within a giant midesophageal diverticulum.

Background and Aim: Liver biopsy is the gold standard method for the diagnosis and treatment of liver diseases. In this study, we aimed to evaluate the results of liver biopsies performed in a year in our clinic. In addition, we also aimed if these liver biopsies could reveal the etiology of liver disease in patients with elevations of transaminases or/and alkaline phosphatase levels or liver masses., Materials and Methods: Patients who had liver biopsies for persistently elevated transaminases or/and alkaline phosphatase levels, protocol biopsies after liver transplantation, or liver masses in our hepatology clinic between 2011 and 2012 were included in the study. Liver biopsy decisions were made by experts during the hepatology council. Liver biopsies were previously performed using classical percutaneous liver biopsy or ultrasonography-guided Sonocan ® liver biopsy sets. The pathology results of liver biopsies and clinical data of the matching patients were obtained from the liver biopsy record archives and patient files, respectively., Results: Totally, 479 liver biopsy results (male=252, 52.6%, mean age 49±14.5 years) were evaluated in the study. Of these patients, 432 (male=228) underwent percutaneous liver biopsy and 47 (male=24) underwent Sonocan ® needle biopsy. The most common histopathologic diagnoses in the percutaneous liver biopsy group were chronic hepatitis B (n=127, 29.4%), normal histopathological findings (n=50, 11.6% and 32 of them were protocol biopsies after liver transplantation), and nonalcoholic steatohepatitis (NASH, n=41, 9.5%). The most common histopathologic diagnoses in the Sonocan ® group were 25 liver metastasis out of 29 liver tumors (n=25, 53.2% of all) chronic hepatitis B (n=5, 10.6%), and NASH (n=3, 6.4%)., Conclusion: In this study, diversity in liver biopsy results indicates the importance of histopathological evaluation. The most prevalent pathology in the liver biopsies was chronic hepatitis B, which is the most common chronic liver disease in Turkey. The metastatic liver tumor was the most common among the liver masses., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare., (© Copyright 2022 by Hepatology Forum - Available online at www.hepatologyforum.org.)

Objective: In hepatitis B infection, it is difficult to make a treatment decision in patients with slightly elevated transaminases and HBV DNA level between 2000 and 20000 IU/ml, and in those with normal ALT, despite high levels of HBV DNA. Objectives: In HBeAg negative patients whose HBV DNA levels were between 2000 and 20000 IU/ml with ALT 1-2 times the upper limit of normal (ULN) and those with HBV DNA >20000 IU/ml and normal ALT, the concordance between liver fibrosis in biopsy and liver stiffness measured by transient elastography with FibroScan ® (FS) was investigated, and diagnostic value of FS to predict the liver fibrosis was tested., Methods: The patients were selected from the outpatient hepatology clinics between the dates of November 2014 and October 2016 among those who were taken liver biopsy. Transient elastography was obtained within 3 months after liver biopsy. The diagnostic value of FS in detecting advanced fibrosis or moderate to advanced (MTA) fibrosis was investigated for each group., Results: In 38 patients with HBV DNA 2000-20000 IU/ml and ALT 1-2×ULN, advanced fibrosis was detected in only one patient (2.6%) on liver biopsy, sensitivity of FS to show advanced fibrosis is 100%, specificity 78.3%, and diagnostic accuracy rate 79%. The area under curve was determined to be 0.892. In detecting MTA fibrosis, these values are 100%, 62%, 71%, and 0.810, respectively. Of 79 patients with HBV DNA >20000 IU/ml and normal ALT, five had advanced (5.5%) and 18 had MTA (23%) fibrosis. Sensitivity of FS in detecting advanced fibrosis was 100%, specificity 87.8%, and accuracy 88.6%, and these values for MTA fibrosis were 85.7%, 81%, and 82.3%, respectively., Conclusion: Because of false negativity in a few patients with HBV DNA >20000 IU/ml in detecting MTA, FS may be combined with other non-invasive techniques. Negative predictive values of FS in predicting advanced or MTA fibrosis were very high, while positive predictive values were low. However, FS may save several patients from liver biopsy., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright © by by Istanbul Provincial Directorate of Health - Available online at www.northclinist.com.)

Background and Aim: Hepatocellular carcinoma (HCC) is one of the most common and most lethal cancers worldwide. The objective of this study was to investigate the relationship between basal parameters and survival characteristics in patients with HCC., Materials and Methods: The records of 1447 HCC patients of a tertiary center during the period 2000-2017 were screened retrospectively. The demographic details; basal clinical, laboratory, and radiological characteristics; treatments; and survival time were recorded and prognostic scores were calculated., Results: A total of 788 patients with HCC (male/female: 623/165; mean age: 60.5±10.9 years) were included in the study. The median length of survival was 26.3 months (95% confidence interval [CI], 22.3-30.4 months). The 5-year survival rate was 28.1%. The number and diameter of the tumors; platelet count; platelet-to-lymphocyte ratio; level of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase; portal and hepatic vein involvement; and an alpha-fetoprotein level of <9.6 ng/mL were found to be independently related to survival., Conclusion: The positive predictive value of the prognostic index derived from independent survival-related parameters for 5- and 10-year survival or overall survival was approximately 86%. Integration of this prognostic index to the criteria used in making treatment decisions for patients with HCC should be considered., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare., (© Copyright 2022 by Hepatology Forum - Available online at www.hepatologyforum.org.)