Prevalence and Risk Factors of Elevated Alanine Aminotransferase (ALT) in 2382 Treatment-naïve HBV/HDV Co-Infected Patients.

Chronic Hepatitis C in Patients With Persistently Normal Alanine Transaminase Levels

Chronic hepatitis D associated with worse patient-reported outcomes than chronic hepatitis B

Long-term Therapy With Adefovir Dipivoxil for HBeAg-Negative Chronic Hepatitis B for up to 5 Years

Management of hepatitis virus infections

Objective. To study the efficacy and safety of bulevirtide, an entry inhibitor of the hepatitis D/B viruses (HDV/HBV), in patients with chronic hepatitis D (CHD) in real-world clinical practice. Patients and methods. The study group consisted of 63 patients with CHD, predominantly with liver cirrhosis (67%) and high HDV RNA load (median 6.8 log10 copies/mL), including 19 patients with HIV co-infection. Treatment outcomes were analyzed in 48 patients: 29 received monotherapy, and 19 received combination therapy with pegylated interferon α (including 3 who switched to monotherapy). Results. After 96 weeks of treatment, the median HDV RNA level decreased from 6.8 log10 to undetectable levels (median reduction –5.9 log10), with an increase in the rate of virologic response (VR) during treatment to 88%, and complete virologic response (cVR) to 63%. The high rate of early partial virologic response (pVR) (29% at week 12) subsequently decreased due to the conversion of pVR to VR. Combination therapy was associated with higher rates of VR and cVR in the first year of treatment compared to monotherapy, and later normalization of alanine aminotransferase (ALT) activity (at 48 weeks, due to the cytolytic effect of interferon). With monotherapy, early normalization of ALT activity (at 12 weeks) was observed, and VR and cVR rates reached levels comparable to combination therapy by the end of the second year of treatment. All patients with HIV co-infection and available follow-up of HDV RNA levels achieved VR (including cVR) or pVR; the dynamics of biochemical response were consistent with those in the overall group. Treatment was characterized by good tolerability, with no serious adverse reactions, no cases of treatment discontinuation, and no deterioration of liver function in patients with cirrhosis. Conclusion. High virologic and biochemical efficacy, safety, and good tolerability of bulevirtide in the treatment of CHD in realworld practice, including in HIV co-infected patients, were demonstrated. The obtained data support the choice of combination therapy as a first-line treatment and emphasize the importance of treatment duration for increasing its effectiveness. Further accumulation of real-world experience with antiviral therapy is necessary to develop an optimal treatment algorithm aimed at disease cure. Key words: bulevirtide, HIV co-infection, monotherapy, combination therapy, pegylated interferon, chronic hepatitis D

Reply to: “Is transient elastography inaccurate in chronic hepatitis B and non-alcoholic fatty liver disease?”

Chronic Hepatitis B: A Critical Appraisal of Current Approaches to Therapy

Objective. To analyse the results of using bulevirtide, HBV/HDV entry inhibitor, in patients with chronic hepatitis D (CHD) at the stage of decompensated cirrhosis. Patients and methods. Bulevirtide monotherapy was performed in 3 patients with decompensated cirrhosis Child-Pugh B and C on the liver transplant waiting list, as well as in 1 patient with decompensation during treatment due to the progressive course of a cholangiocarcinoma. The observation period was 24 and 36 weeks, respectively. Results. All patients with decompensated cirrhosis achieved virological response at week 24 (including 1 patient with early virological response at week 12) with HDV RNA decline by 1.8-3.1 log10 from baseline; alanine aminotransferase (ALT) level normalisation, including 2 patients at week 12; non-invasive fibrosis markers (APRI, FIB-4) decrease; improvement in Child-Pugh and MELD score, hepatic encephalopathy (2 patients), ascites (2), bilirubin (2) and albumin (1) level. In 1 patient with decompensation due to the progressive course of stage IV cholangiocarcinoma, early response (virological, ALT normalisation, APRI score decrease) was achieved at week 12, with further HDV RNA and ALT increase to the initial level against the background of immuno- and chemotherapy of cholangiocarcinoma and bulevirtide dose reduction to 2 mg 2 times a week for 24 weeks (adaptation of immuno- and chemotherapy) followed by ALT decrease and liver function improvement from Child-Pugh B to A, Child-Pugh score decrease from 8 to 6, MELD index decrease from 10 to 8, improvement of ascites, bilirubin level normalisation. Treatment with bulevirtide was characterized by good tolerability, no severe or serious adverse reactions or treatment discontinuation were reported. Conclusion. Our analysis of the results of bulevirtide use in patients with severe liver dysfunction demonstrated efficacy (virological, biochemical response, reduction of fibrosis markers), safety and good tolerability of treatment for 24–36 weeks, as well as improvement of liver function during the waiting period for transplantation. The obtained data allow us to recommend the use of bulevirtide in patients with liver dysfunction. Further treatment experience accumulation in this category of patients is necessary to clarify the treatment algorithm and improve the prognosis. Key words: bulevirtide, decompensated cirrhosis, monotherapy, combination therapy, cholangiocarcinoma, chronic hepatitis D, liver cirrhosis

Liver disease can develop in chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT) who seldom undergo liver biopsy. We aimed to determine histologic characteristics of a large cohort of Chinese CHB patients undergoing liver biopsy and to evaluate the utility of ALT and HBV DNA values at the time of biopsy in predicting liver disease in this population. This prospective study enrolled 230 treatment-naïve patients with persistently normal or mildly elevated ALT. All patients had a liver biopsy. ALT, aspartate aminotransferase (AST), and HBV DNA levels were some of the other parameters measured. Using Scheuer's classification, significant histology was defined as stage ≧2 fibrosis and/or stage 1 fibrosis plus≧ grade 2 inflammation. Liver disease was observed in 34.4% and 61.8% of patients with normal ALT and mildly elevated ALT, respectively. Patients with mildly elevated ALT levels had significantly more events, including liver disease, elevated AST, and moderate to severe inflammation and liver fibrosis, than patients with normal ALT (all P≤0.005). A total of 107 patients (46.5%) had liver disease and 123 (53.5%) did not. PLT and ALT were significantly associated with liver disease (both P<0.001). Patients with elevated ALT, lower platelet count and HBV DNA < 7 log10copies/mL may have histologically significant changes associated with liver disease. Multivariate analysis showed that PLT and HBV DNA levels were significantly associated with liver disease in patients with normal ALT while gender and HBV DNA levels were significantly associated with liver disease in patients with mildly elevated ALT. Assessing liver damage via biopsy in patients with normal or mildly elevated ALT may help to identify those who would benefit from antiviral therapy.

BackgroundBulevirtide (BLV) is approved in Europe for the treatment of chronic hepatitis D (CHD). Optimal BLV monotherapy duration for CHD is unknown). This analysis evaluated BLV monotherapy in pts without...

Aim: to evaluate the significance of a positive polymerase chain reaction result for hepatitis D virus RNA (HDV RNA) in liver biopsy specimens of patients with chronic hepatitis D (CHD) after completion of antiviral therapy (AVT) as a predictor of infection relapse.Materials and methods. The study included 21 patients with CHD who received combined AVT with peginterferon alpha and bulevirtide for 48 weeks, followed by bulevirtide monotherapy for 48–96 weeks, making the total duration of antiviral therapy 96–144 weeks. In all patients HDV RNA became undetectable in serum 24–96 weeks from the start of treatment, with aviremia maintained for at least 48 weeks until the end of AVT. At the end of treatment, all patients underwent liver biopsy to detect HDV RNA in liver tissue.Results. Out of 21 patients with sustained complete virological response (negative polymerase chain reaction result for HDV RNA in serum), 8 (38 %) had HDV RNA detected in liver tissue, indicating that a tissue virological response was not achieved. All 8 patients experienced a relapse of CHD within 24 weeks after discontinuing AVT.Conclusions. In patients with chronic hepatitis D who have achieved a complete virological response in serum, the absence of a virological response in liver tissue (detection of HDV RNA in liver biopsy) is a predictor of relapse, providing a rationale for the continuation of antiviral therapy.

BackgroundBulevirtide (BLV) is conditionally approved in the EU for the treatment of chronic hepatitis D (CHD) based on surrogate endpoint results. Virologic responders (VR) to HDV therapy are defined as...

Pre-S Deletion and Complex Mutations of Hepatitis B Virus Related to Advanced Liver Disease in HBeAg-Negative Patients

miRNAs circulating in whole serum and HBsAg-particles are differentially expressed in chronic hepatitis B (CHB) and HBeAg-negative-HBV infection (ENI); their profiles are unknown in chronic hepatitis D (CHD). Serum- and HBsAg-associated miRNAs were analyzed in 75 subjects of 3 well-characterized groups (CHB 25, CHD 25, ENI 25) using next-generation sequencing (NGS). Overall miRNA profiles were consonant in serum and HBsAg-particles but significantly different according to the presence of hepatitis independently of Hepatitis D Virus (HDV)-co-infection. Stringent (Bonferroni Correction < 0.001) differential expression analysis showed 39 miRNAs upregulated in CHB vs. ENI and 31 of them also in CHD vs. ENI. miRNA profiles were coincident in CHB and CHD with only miR-200a-3p upregulated in CHB. Three miRNAs (miR-625-3p, miR-142-5p, and miR-223-3p) involved in immune response were upregulated in ENI. All 3 hepatocellular miRNAs of MiR-B-Index (miR-122-5p, miR-99a-5p, miR-192-5p) were overexpressed in both CHB and CHD patients. In conclusion, CHD and CHB patients showed highly similar serum miRNA profiling that was significantly different from that of individuals with HBeAg-negative infection and without liver disease.

BackgroundBulevirtide (BLV) is a first-in-class entry inhibitor for chronic hepatitis D (CHD) which was conditionally approved in the EU. Results from the Week 48 primary endpoint analysis for MYR301, a...