In this randomized trial involving patients with HBeAg-positive chronic hepatitis B, entecavir was associated with better histologic, biochemical, and virologic responses than was lamivudine. Adverse ...events were similar between the groups, and viral resistance to entecavir did not develop in this 48-week study. Longer studies are needed to evaluate adverse effects and viral resistance to entecavir.
In patients with HBeAg-positive chronic hepatitis B, entecavir was associated with better histologic, biochemical, and virologic responses than was lamivudine. Viral resistance to entecavir did not develop in this 48-week study.
Chronic hepatitis B affects more than 350 million people worldwide and each year is responsible for more than 1 million deaths from cirrhosis and hepatocellular carcinoma.
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Suppression of hepatitis B virus (HBV) replication is a principal goal of long-term hepatitis B therapy.
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Studies of long-term lamivudine treatment in patients with hepatitis B e antigen (HBeAg)–positive chronic hepatitis B have found that maintenance of virologic suppression is associated with improved histologic findings in the liver.
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Liaw and coworkers have shown that lamivudine treatment delays the progression of disease among patients with chronic hepatitis B and advanced liver disease, probably . . .
Hepatitis B virus (HBV) and hepatitis D virus are leading causes of morbidity and mortality worldwide. Despite the availability of HBV vaccinations that are 98% to 100% effective, an estimated ...820,000 annual deaths were attributed to HBV in 2019, mainly related to the sequelae of cirrhosis and hepatocellular carcinoma. Because disease prevalence is concentrated outside of the United States, it is overlooked, but with expanded vaccination recommendations provided by the Centers for Disease Control and Prevention and recommended screening, as well as heightened awareness by health care providers, we can work toward the eradication of this preventable disease.
•Advances in understanding the natural history of hepatitis B have led to new definitions of the major phases of infection.•New phases are high replicative, low inflammatory (formerly immune ...tolerant) and non-replicative (formerly inactive carrier).•The new concept of trained immunity may alter future hepatitis B treatment strategies.•The current goal of treatment for chronic hepatitis B is a functional cure.•Experimental therapies now under development target viral and host factors and previously inaccessible pathways.
The host immune system plays an important role in chronic hepatitis B (CHB), both in viral clearance and hepatocellular damage. Advances in our understanding of the natural history of the disease have led to redefining the major phases of infection, with the “high replicative, low inflammatory” phase now replacing what was formerly termed the “immune tolerant” phase, and the “nonreplicative phase” replacing what was formerly termed the “inactive carrier” phase. As opposed to the earlier view that HBV establishes chronic infection by exploiting the immaturity of the neonate’s immune system, new findings on trained immunity show that the host is already somewhat “matured” following birth, and is actually very capable of responding immunologically, potentially altering future hepatitis B treatment strategies. While existing therapies are effective in reducing viral load and necroinflammation, often restoring the patient to near-normal health, they do not lead to a cure except in very rare cases and, in many patients, viremia rebounds after cessation of treatment. Researchers are now challenged to devise therapies that will eliminate infection, with a particular focus on eliminating the persistence of viral cccDNA in the nuclei of hepatocytes. In the context of chronic hepatitis B, new definitions of ‘cure’ are emerging, such as ‘functional’ and ‘virological’ cure, defined by stable off-therapy suppression of viremia and antigenemia, and the normalization of serum ALT and other liver-related laboratory tests. Continued advances in the understanding of the complex biology of chronic hepatitis B have resulted in the development of new, experimental therapies targeting viral and host factors and pathways previously not accessible to therapy, approaches which may lead to virological cures in the near term and functional cures upon long term follow-up. This article forms part of a symposium in Antiviral Research on “An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B.”
Mitochondrial dynamics is crucial for the regulation of cell homeostasis. Our recent findings suggest that hepatitis C virus (HCV) promotes Parkin-mediated elimination of damaged mitochondria ...(mitophagy). Here we show that HCV perturbs mitochondrial dynamics by promoting mitochondrial fission followed by mitophagy, which attenuates HCV-induced apoptosis. HCV infection stimulated expression of dynamin-related protein 1 (Drp1) and its mitochondrial receptor, mitochondrial fission factor. HCV further induced the phosphorylation of Drp1 (Ser616) and caused its subsequent translocation to the mitochondria, followed by mitophagy. Interference of HCV-induced mitochondrial fission and mitophagy by Drp1 silencing suppressed HCV secretion, with a concomitant decrease in cellular glycolysis and ATP levels, as well as enhanced innate immune signaling. More importantly, silencing Drp1 or Parkin caused significant increase in apoptotic signaling, evidenced by increased cytochrome C release from mitochondria, caspase 3 activity, and cleavage of poly(ADP-ribose) polymerase. These results suggest that HCV-induced mitochondrial fission and mitophagy serve to attenuate apoptosis and may contribute to persistent HCV infection.
The incidence of cirrhosis-related hepatocellular carcinoma (HCC) is rising. Curative surgical options are available; outcomes are acceptable with early diagnosis. Lens culinaris agglutinin-reactive ...fraction of alpha-fetoprotein (AFP-L3) and des-gamma-carboxy prothrombin (DCP) are HCC risk markers. A high or increasing serum biomarker level can be predictive of the eventual development of HCC, large tumor size, advanced stage, extrahepatic metastases, portal vein thrombosis, and postoperative HCC recurrence. Based on FDA guidelines for HCC risk assessment, clinicians can consider using either the combination of AFP-L3 with DCP, or the combination of AFP-L3 with AFP and DCP.
LINKED CONTENT
This article is linked to Ding et al and Pan papers. To view these articles, visit https://doi.org/10.1111/apt.16043 and https://doi.org/10.1111/apt.16101
Chronic hepatitis delta represents the most severe form of chronic viral hepatitis. The current treatment of hepatitis delta virus (HDV) infection consists of the use of interferons and is largely ...unsatisfactory. Several new compounds are currently in development for the treatment of HDV infection. However, surrogate markers that can be used to develop clinical endpoints in HDV infection are not well defined. In the current manuscript, we aimed to evaluate the existing data on treatment of HDV infection and to suggest treatment goals (possible “trial endpoints”) that could be used across different clinical trials.
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