hello 2024
The years do not live, and the seasons flow.
In the blink of an eye, 2023 has come to a gorgeous end.
This year, I am grateful to the readers and colleagues for their love to accompany us through spring and summer
This makes us feel rewarded at the same time
The steps towards the New Year are also more determined.
Summing up the past 2023,
What are the major events in the hepatology community?
This journal specially invites all domestic liver disease experts
It has carefully concocted an annual important ...... of progress in various fields of liver disease for a wide range of readers
Editor's note
Chronic hepatitis D (CHD) is a serious form of viral hepatitis that is estimated to be infected with hepatitis D virus (HDV) in about 12 million people worldwide, accounting for about 45%[1]。Compared with patients with hepatitis B virus (HBV) infection alone, patients with superinfection with HDV have significantly higher incidence of liver cirrhosis and hepatocellular carcinoma (HCC), and their progression to cirrhosis or HCC is also earlier, which should be paid sufficient attention clinically. In the past, international guidelines only recommended a 48-week regimen of peginterferon (PEG-IFN) for patients with chronic HDV infection**; However, the response rate to chronic HDV infection with PEG-IFN* is low, the adverse effects are high [2], and some patients with a virologic response at the end of the day will still have HDV RNA after many years of follow-up [3]. In recent years, there has been a lot of progress in the development and screening of anti-HDV drugs. To this end, this journal invitesProfessor Niu Junqi from the First Hospital of Jilin UniversityTogether with the majority of readers, we will take stock of the major events and important developments in the field of hepatitis D in 2023.
Keywords: new drugs
Bulevirtide progression
Bulevirtide (BLV) is an NTCP-targeting drug that blocks the binding of HBsAg envelope particles to NTCP receptors, thereby blocking the entry of HDV into hepatocytes and stopping the spread of the virus in the liver. In recent years, several studies have evaluated the efficacy and safety of BLV in chronic HDV infection. In July 2020, based on the results of the Phase II clinical trial, BLV was conditionally approved by the European Medicines Agency for the treatment of compensated patients with chronic HDV infection, and the marketing application in the United States is also underway.
The 2023 European Society of Hepatology Annual Meeting (EASL 2023) presented some of the results of the ongoing phase III clinical trial [4]. In this multicenter, open-label, randomized trial designed to evaluate the long-term efficacy and safety of bulevirtide in 150 patients with chronic HDV, eligible patients were assigned 1:1:1 to 2 mg bulevirtide, 10 mg bulevirtide, or no antiviral** (delayed**), with the first two groups receiving BLV subcutaneously** at 2 mg or 10 mg per day; The delayed** group did not receive antiviral ** for the first 48 weeks and received BLV subcutaneous injection** of 10 mg daily after 48 weeks for a total of 96 weeks. All patients were observed for 144 weeks. Key efficacy and safety data were assessed at 48 weeks. The primary endpoint was undetectable HDV RNA at week 48 or a decrease in HDV RNA levels of at least 2 log10 IU mL from baseline (virologic response) and a return to normal ALT levels (biochemical response). The results showed that 24 50 patients (48%) of 22 49 patients in the 2 mg group met the primary endpoint of combined response, and 1 out of 51 patients (2%) in the control group met the primary endpoint of combined response. The proportion of patients with combined response in the 2 mg group was significantly higher than that in the control group, and the proportion of patients in the 10 mg group was also significantly higher than that in the control group. In terms of safety, major adverse effects included mild to moderate headache, itching, fatigue, eosinophilia, injection site reactions, epigastric pain, arthralgia, and wheezing. In addition, there was a dose-dependent increase in total bile acid levels in the 2 mg and 10 mg groups, and the increase in total bile acid levels did not lead to discontinuation in any patient. Participants in the different doses of bulevirtide achieved a similar combined response at week 96, i.e., ALT normalization and virologic response. At the same time, the combined response rate of virology and biochemistry continued to increase at week 96 compared to week 48. Response rates were 55% and 56% in the 2 mg and 10 mg groups, respectively. The results of this Phase III clinical trial increase confidence in the clinical use of BLV and provide more solid evidence-based evidence for the full launch of BLV.
In addition, EASL 2023 also published the results of several studies on BLV, which add to and enrich the information on BLV in CHD**.
New anti-HDV drugs in China
The clinical trials related to China's original new drug Hepratide and the humanized monoclonal antibody HH-003** targeting the Pres1 region for hepatitis D have been approved by the Center for Drug Evaluation (CDE) of the National Medical Products Administration, and the relevant clinical trials are actively underway.
Keywords: new guidelines
Significant innovations in HDV diagnosis and ** prompted the European Society of Hepatology (EASL) to publish the first Clinical Practice Guidelines for EASL for HDV Infection in July 2023 [5]. The guidelines mainly focus on six aspects: screening, diagnosis, clinical features and influencing factors of the disease, patient monitoring and selection, methods and endpoints. The release of the EASL HCD guidelines has had a significant impact on clinical practice in Europe and around the world.
In terms of screening, the EASL guidelines recommend that all HBSAG-positive patients should be screened for anti-HDV at least once; HBSAG-positive patients with clinical manifestations (eg, elevated aminotransferases, acute decompensation in chronic liver disease) should be retested for anti-HDV; People who are at persistent risk of infection can be screened annually for anti-HDV.
In terms of testing methods, the EASL guidelines recommend that all anti-HDV-positive patients should be tested for HDV RNA using a standardized and highly sensitive reverse transcription polymerase chain reaction (RT-PCR) method to identify active HDV infection. No PCR test kit for HDV RNA has been approved in China, and we look forward to the successful development of relevant detection reagents as soon as possible for the benefit of patients."
In terms of testing for HBV markers, the EASL guidelines recommend testing for anti-HBC IgM in patients with acute hepatitis to distinguish between HBV co-infection and HDV superinfection in HBSAG-positive patients. In addition, because HBV activation can lead to worsening of hepatitis D, HBeAg anti-HBE status and HBV DNA levels should be measured.
In terms of histologic testing, EASL guidelines recommend that liver biopsy be performed when there is no evidence of cirrhosis on clinical features or imaging, and liver biopsy is helpful to the patient or to determine the extent of liver disease. Non-invasive noninvasive testing (NITS) can be used to evaluate for advanced liver disease, but the specific cut-off has not been established.
In terms of factors associated with disease progression, the EASL guidelines suggest that elevated levels of aminotransferases (ALT AST) and glutamyl transpeptidase (GGT), advanced liver disease, persistent HDV viremia, high levels of serum HBV DNA, and co-viral infection are all risk factors for liver disease progression in patients with CHD. In addition, alcoholism, obesity, diabetes, etc. are also influencing factors for chronic liver damage.
In addition, patients with advanced liver fibrosis or cirrhosis, regardless of whether they are anti-HDV**, should have abdominal ultrasound every 6 months to monitor HCC.
*In addition, the guidelines consider that despite the lack of data on the long-term efficacy, safety, and optimal duration of treatment of BLV, preliminary results from phase II trials (BLV alone or BLV+PEG-IFN- combinations), phase III trial data of BLV monotherapy, and real-world studies recommend that BLV is available as an option for CHD. Therefore, guidelines recommend that all patients with CHD and CHD-related compensated liver disease should be considered for BLV**. In patients with PEG-IFN- tolerance or no contraindications, PEG-IFN- in combination with BLV** may be considered.
Keywords: Challenge
In recent years, China has made some research achievements in the screening and detection of HDV infection, thanks to the contributions of Academician Zhuang Hui, Professor Niu Junqi and Professor Hou Jinlin. Although the incidence of hepatitis D in China is relatively low, research on HDV infection is still significant. HDV-positive people are mainly concentrated in ethnic minority areas, such as Inner Mongolia Autonomous Region and Xinjiang Uygur Autonomous Region, where the prevalence of HDV infection is high. In Han areas, the detection rate is higher mainly in patients with severe hepatitis and cirrhosis.
At present, the biggest challenge facing China is to develop its own anti-HDV virus drugs. Due to the high cost of foreign drugs, it has brought a huge financial burden to Chinese patients. Therefore, the two ongoing clinical trials of Hepratide and HH-003 in China are highly anticipated. Both drugs have shown good antiviral effects in early clinical trials. Given the obvious advantages of drug research and development in China, if these two drugs can be approved, it will not only bring good news to CHD patients in China, but also provide more economical and accessible options and more options for patients around the world.
Keywords: 2024 outlook
Talking about the planning and outlook for 2024, Professor Niu Junqi said that we are looking forward to the emergence of some important drug clinical trial results, especially the results of new hepatitis D drugs. This will provide new possibilities for the development of hepatitis D, further improving the quality of life and prognosis of patients.
In addition, two genetically engineered albumin drug trials being conducted by Professor Niu Junqi's team have also attracted much attention. These two studies aimed to develop plant-derived recombinant human serum albumin and yeast gene-expressing albumin. These two albumin drugs, once approved, are expected to change the history of albumin use. Traditional albumin** in human blood is not only produced in limited quantities, but also the raw material is mainly from the United States. The use of genetic engineering technology will provide a stable and large-scale industrial production route for albumin, while avoiding the risk of blood-borne infectious diseases.
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References: (Swipe up and down to see more).
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*: Editorial Board of International Liver Disease.