Little observational data exist describing telbivudine (LdT) or lamivudine (LAM) use in late pregnancy for preventing hepatitis B mother‐to‐child transmission (MTCT) in real‐world settings. During ...the period of January 2009 to March 2011, we enrolled hepatitis B e antigen–positive mothers with HBV DNA >6 log10 copies/mL in China. At gestation week 28, the mothers received LdT or LAM until postpartum week 4 or no treatment (NTx). The study endpoints were the safety of LdT/LAM use and MTCT rates. Of the 700 mothers enrolled, 648 (LdT/LAM/NTx = 252/51/345) completed the 52‐week study with 661 infants (LdT/LAM/NTx = 257/52/352). On treatment, viral rebound occurred in 1.6% of mothers, all resulting from medication noncompliance. There was no genotypic mutation detected. At delivery, significantly lower HBV DNA levels were noted in mothers who received LdT or LAM versus NTx. Alanine aminotransferase flares were observed in 17.1% of treated mothers versus 6.3% of untreated mothers (P < 0.001). At birth, hepatitis B surface antigen (HBsAg) was detected in 20% and 24% of newborns in the treated and NTx groups, respectively. At week 52, an intention‐to‐treat analysis indicated 2.2% (95% confidence CI: 0.6‐3.8) of HBsAg+ infants from the treated group versus 7.6% (95% CI: 4.9‐10.3) in the NTx group (P = 0.001) and no difference of HBsAg+ rate between infants in the LdT and LAM groups (1.9% vs. 3.7%; P = 0.758). On‐treatment analysis indicated 0% of HBsAg+ infants in the treated group versus 2.84% in the NTx group (P = 0.002). There were no differences for gestational age or infants' height, weight, Apgar scores, or birth defect rates between infants from the treated and untreated groups. Conclusions: LdT and LAM use in late pregnancy for highly viremic mothers was equally effective in reducing MTCT. The treatment was well tolerated with no safety concerns identified. (Hepatology 2014;60:468–476)
Background
Since immunoprophylaxis failure can occur if maternal serum hepatitis B virus (HBV) DNA levels are >200,000 IU/ml, tenofovir disoproxil fumarate (TDF) therapy has been investigated for ...preventing mother to child transmission (PMTCT).
Methods
A literature search for maternal TDF therapy for PMTCT between 1/1/2015 and 7/1/21 on PUBMED, EMBASE, Cochrane, CNKI, and Wanfang databases was performed. Data from RCTs in English or Chinese were extracted and reviewed. The outcomes of interest included the efficacy and safety of TDF versus placebo for PMTCT.
Results
Among 11 RCTs identified from the databases, the risk-of-bias was low. All studies demonstrated that maternal TDF therapy initiated from the second or third trimester for highly viremic chronic hepatitis B mothers is highly effective and safe in the PMTCT of HBV, except one RCT performed in Thailand which showed no therapeutic advantage on TDF treatment versus placebo for PMTCT (0% vs 3% transmission). Recent emerging data suggest that maternal TDF therapy initiated at the 2nd or early 3rd trimester in mothers with HBV DNA >200,000 IU/ml achieved viremic control before delivery. In the 4-year long follow-up study for maternal TDF therapy, there were no impacts on infants’ physical growth, psychological or mental development, and bone mineral density after fetal exposure to TDF. In the light of updated efficacy and safety data from RCTs, an algorithm was proposed. The approaches in resource-limit areas were discussed.
Conclusions
TDF is safe for both mothers and infants as the preferred therapy for PMTCT in highly viremic mothers. TDF should be initiated at the second or early third trimester in the combination of the appropriate infants’ immunoprophylaxis.
Alcohol-related liver disease (ALD) from excessive alcohol intake has a unique gut microbiota profile. The disease progression-free survival in ALD patients has been associated with the degree of gut ...dysbiosis. The vicious cycles between gut dysbiosis and the disease progression in ALD including: an increase of acetaldehyde production and bile acid secretion, impaired gut barrier, enrichment of circulating microbiota, toxicities of microbiota metabolites, a cascade of pro-inflammatory chemokines or cytokines, and augmentation in the generation of reactive oxygen species. The aforementioned pathophysiology process plays an important role in different disease stages with a spectrum of alcohol hepatitis, ALD cirrhosis, neurological dysfunction, and hepatocellular carcinoma. This review aims to illustrate the pathophysiology of gut microbiota and clarify the gut-brain crosstalk in ALD, which may provide the opportunity of identifying target points for future therapeutic intervention in ALD.
Current therapeutic interventions can only suppress hepatitis B virus (HBV) replication or reduce complications without a cure. Therefore, further development of new treatment methods is critical for ...the global eradication of HBV. Accumulating evidence suggests that the liver and gut share an interconnected relationship referred to as the ‘Gut‐Liver Axis’, where exchanges happen bi‐directionally. The gut itself is the host to a unique microbiota profile which has metabolic, immunological, neurological and nutritional functions. Gut microbiota is not only constantly intersecting with the liver but also associated with hepatic injury when dysbiosis occurs. In recent years, there has been increased interest in gut microbiota and its implications on liver disease treatment. Progress has been made in understanding the complex relationship between chronic hepatitis B (CHB) and gut microbiota. New investigative techniques such as colony‐free sequencing enabled new perspectives into this field. Mouse models and human studies revealed that HBV infection is associated with significant alteration of gut microbiota, which differ depending on the stage of CHB disease progression. Different mechanisms of the hepatic injury from gut microbiota dysbiosis have also been proposed based on findings of increased intestinal permeability to toxins, disruption of normal bacterial metabolism, and colonization of the gut by oral microbiota. New treatment methods targeting gut microbiota in CHB, such as probiotics and faecal microbiota transplant, have also gained promising results in recent years. The current review recapitulated the most recent investigations into the relationship between gut microbiota and CHB to provide research directions towards the new therapeutic target of CHB.
Linked ContentThis article is linked to Wang et al and Vyas and Jindal papers. To
view these articles, visit https://doi.org/10.1111/apt.15064 and https://doi.org/10.1111/apt.15123.
Few data are available regarding the use of tenofovir disoproxil fumarate (TDF) during pregnancy for the prevention of mother-to-child transmission of hepatitis B virus (HBV).
In this trial, we ...included 200 mothers who were positive for hepatitis B e antigen (HBeAg) and who had an HBV DNA level higher than 200,000 IU per milliliter. Participants were randomly assigned, in a 1:1 ratio, to receive usual care without antiviral therapy or to receive TDF (at an oral dose of 300 mg per day) from 30 to 32 weeks of gestation until postpartum week 4; the participants were followed until postpartum week 28. All the infants received immunoprophylaxis. The primary outcomes were the rates of mother-to-child transmission and birth defects. The secondary outcomes were the safety of TDF, the percentage of mothers with an HBV DNA level of less than 200,000 IU per milliliter at delivery, and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28.
At delivery, 68% of the mothers in the TDF group (66 of 97 women), as compared with 2% in the control group (2 of 100), had an HBV DNA level of less than 200,000 IU per milliliter (P<0.001). At postpartum week 28, the rate of mother-to-child transmission was significantly lower in the TDF group than in the control group, both in the intention-to-treat analysis (with transmission of virus to 5% of the infants 5 of 97 vs. 18% 18 of 100, P=0.007) and the per-protocol analysis (with transmission of virus to 0 vs. 7% 6 of 88, P=0.01). The maternal and infant safety profiles were similar in the TDF group and the control group, including birth-defect rates (2% 2 of 95 infants and 1% 1 of 88, respectively; P=1.00), although more mothers in the TDF group had an increase in the creatine kinase level. After the discontinuation of TDF, alanine aminotransferase elevations above the normal range occurred more frequently in mothers in the TDF group than in those in the control group (45% 44 of 97 women vs. 30% 30 of 100, P=0.03). The maternal HBV serologic outcomes did not differ significantly between the groups.
In a cohort of HBeAg-positive mothers with an HBV DNA level of more than 200,000 IU per milliliter during the third trimester, the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01488526.).
LINKED CONTENT
This article is linked to Ding et al and Gish & Elmofti papers. To view these articles, visit https://doi.org/10.1111/apt.16043 and https://doi.org/10.1111/apt.16090
Although gut dysbiosis appears in 20%–75% of cirrhotic patients, there are limited data on microbiota profiles in viral hepatitis cirrhotics and its role in progression to cirrhosis. Further ...understanding on the relationship between gut dysbiosis and cirrhosis presents a unique opportunity in not only predicting the development of cirrhosis but also discovering new therapies. Recent advances have been made on identifying unique microbiota in viral hepatitis cirrhotics and adopting the microbiota index to predict cirrhosis. Therapeutic intervention with microbiome-modulating has been explored. Cirrhosis from viral infection has unique bacterial or fungal profiles, which include increased numbers of Prevotella, Streptococcus, Staphylococcaceae, and Enterococcus, as well as decreased Ruminococcus and Clostridium. In addition, the gut microbiota can stimulate liver immunity, effectively helping hepatitis virus clearance. In clinical settings, CDR, GDI, Basidiomycota/Ascomycota, specific POD, and so forth are efficient microbiota indexes to diagnose or prognosticate cirrhosis from viral hepatitis. FMT, probiotics, and prebiotics can restore microbial diversity in cirrhotic patients with viral hepatitis, decrease ammonia serum or endotoxemia levels, prevent complications, reduce rehospitalization rate, and improve prognosis. Cirrhotics from viral hepatitis had unique bacterial or fungal profiles, associated with specific metabolic, immune, and endocrinological statuses. Such profiles are modifiable with medical treatment. The role of gut archaea and virome, implementation of FMT, microbiota metabolites as adjuvant immunotherapy, and microbiota indexes for prognostication deserve attention.
Background
Hepatitis C (HCV)-induced decompensated cirrhosis warrants liver transplantation (LT) as the only ultimate solution. These patients experience liver deterioration, while on the transplant ...waitlist. However, debate remains over the optimal timing for treating HCV relative to before or after LT.
Methods
We performed a literature search between 1/2011 and 1/2022 on PubMed and OVID Medline. Data were extracted from direct antiviral agent (DAA) studies in English. The outcomes of interest included sustained virological response (SVR) rates from various cohorts as well as long- and short-term outcomes in the LT settings.
Results
After screening, 54 studies were eligible and included into the review. In aligning with the EASL and AASLD guidelines and suggestions, many studies supported DAA therapy before LT in patients with Model for End-stage Liver Disease (MELD) scores < 18 and DAA therapy post-LT in MELD scores > 20 through SVR rates, long-term survival factors, liver deterioration, and incidences of severe adverse events. However, uncertainty still lies in the guideline recommendations and unsettled issues remain for various patient cohorts that may benefit from opposing the guideline cutoffs. Based on the recent studies on predictors of treatment outcomes in decompensated patients and the impact of DAA on the waiting list for LT, we proposed an algorithm to manage patients with MELD scores between 18 and 20.
Conclusion
DAA therapy for decompensated patients must be personalized with consideration of different factors, particularly among those with MELD scores between the two cutoff-values proposed by the current associational guidelines.
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