Hepatitis B Jeng, Wen-Juei; Papatheodoridis, George V; Lok, Anna S F
The Lancet (British edition),
03/2023, Volume:
401, Issue:
10381
Journal Article
Peer reviewed
Hepatitis B virus (HBV) infection is a major public health problem, with an estimated 296 million people chronically infected and 820 000 deaths worldwide in 2019. Diagnosis of HBV infection requires ...serological testing for HBsAg and for acute infection additional testing for IgM hepatitis B core antibody (IgM anti-HBc, for the window period when neither HBsAg nor anti-HBs is detected). Assessment of HBV replication status to guide treatment decisions involves testing for HBV DNA, whereas assessment of liver disease activity and staging is mainly based on aminotransferases, platelet count, and elastography. Universal infant immunisation, including birth dose vaccination is the most effective means to prevent chronic HBV infection. Two vaccines with improved immunogenicity have recently been approved for adults in the USA and EU, with availability expected to expand. Current therapies, pegylated interferon, and nucleos(t)ide analogues can prevent development of cirrhosis and hepatocellular carcinoma, but do not eradicate the virus and rarely clear HBsAg. Treatment is recommended for patients with cirrhosis or with high HBV DNA levels and active or advanced liver disease. New antiviral and immunomodulatory therapies aiming to achieve functional cure (ie, clearance of HBsAg) are in clinical development. Improved vaccination coverage, increased screening, diagnosis and linkage to care, development of curative therapies, and removal of stigma are important in achieving WHO's goal of eliminating HBV infection by 2030.
LINKED CONTENT
This article is linked to Papatheodoridis et al papers. To view these articles, visit https://doi.org/10.1111/apt.17093 and https://doi.org/10.1111/apt.17117
Background & Aims: Chronic hepatitis B patients are at increased risk for hepatocellular carcinoma (HCC). The effect of medium-term nucleos(t)ide analogue therapy on HCC incidence is unclear; ...therefore, we systematically reviewed all the data on HCC incidence from studies in chronic hepatitis B patients treated with nucleos(t)ide analogues. Methods: We performed a literature search to identify studies with chronic hepatitis B patients treated with nucleos(t)ide analogues for ⩾24 months. Results: Twenty-one studies including 3881 treated and 534 untreated patients met our inclusion criteria. HCC was diagnosed in 2.8% and 6.4% of treated and untreated patients, respectively, during a 46 (32–108) month period ( p = 0.003), in 10.8% and 0.5% of nucleos(t)ide naive patients with and without cirrhosis ( p <0.001) and in 17.6% and 0% of lamivudine resistance patients with and without cirrhosis ( p <0.001). HCC developed less frequently in nucleos(t)ide naive patients compared to those without virological remission (2.3% vs 7.5%, p <0.001), but there was no difference between lamivudine resistance patients with or without virological response to rescue therapy (5.9% vs 8.8%, p = 0.466). Conclusions: Chronic hepatitis B patients receiving medium-term nucleos(t)ide analogue therapy had a significantly lower incidence of HCC compared to untreated patients but treatment does not completely eliminate the risk of HCC. Among the treated patients, cirrhosis, HBeAg negative at baseline and failure to remain in virological remission were associated with an increased risk of HCC.
New epidemiology of hepatitis delta Vlachogiannakos, Jiannis; Papatheodoridis, George V.
Liver international,
February 2020, 2020-Feb, 2020-02-00, 20200201, Volume:
40, Issue:
S1
Journal Article
Peer reviewed
Open access
Hepatitis D virus (HDV) is a defective pathogen that needs hepatitis B virus (HBV) for infection. Co‐infection of HBsAg‐positive individuals with HDV is commonly associated with a more rapid ...progression to cirrhosis, a higher incidence of hepatocellular carcinoma (HCC) and increased mortality. Initial studies have shown that about 5% of chronic HBV carriers worldwide (15‐20 millions) were also infected with HDV. However, recent studies suggest that the prevalence of HDV is at least two‐ to three‐fold higher than previous estimations. Improved diagnostic techniques have shown that HDV infection remains endemic in certain areas of the world. Injection drug users, individuals with high‐risk sexual behaviour and patients co‐infected with human immunodeficiency virus (HIV) represent the major reservoir of the disease in the Western world. Although the burden of HDV infection significantly decreased in Europe in the nineties, there has been no further decrease in the last decade, probably because of migration from HDV endemic countries. Until new and more effective therapies are available, public health measures should be reinforced by increasing prophylactic HBV vaccination programs, preventing transmission of the virus among parenteral drug users and implementing universal HDV screening of all HBV‐infected individuals.
Background and Aims
Treatment for HCC has evolved rapidly, but the risk of HBV reactivation to new therapies is unclear. We systematically reviewed data on HBV reactivation in patients receiving HCC ...therapy in relation to use of HBV antiviral prophylaxis.
Approach and Results
A literature search was performed to identify all published studies including HBsAg‐positive patients with HCC providing data on HBV reactivation. Forty‐one studies with 10,223 patients, all from Asia, were included. The pooled HBV reactivation rate was 5% in patients receiving no specific HCC therapy and was higher in patients undergoing surgical resection (16%), transarterial chemoembolization (19%), or radiotherapy (14%) and intermediate in patients treated with local ablation therapy (7%) or systemic agents (7%). HBV reactivation rates were higher in those without compared to those with HBV prophylaxis (ablation, 9% versus 0%; resection, 20% versus 3%; chemoembolization, 23% versus 1%; external radiotherapy alone, 18% versus 0%; systemic therapy, 9% versus 3%). HBV‐related biochemical reactivation rates varied between 6%–11% and 2% in patients receiving HCC therapies with high and intermediate HBV reactivation risk, respectively. Liver decompensation and death were rarely reported (0%–3%) and only in patients receiving HCC treatment with high HBV reactivation risk.
Conclusions
HBsAg‐positive patients with HCC are at high or intermediate risk of HBV reactivation depending on the type of HCC therapy. Nucleos(t)ide analogue prophylaxis reduces the risk of HBV reactivation, practically eliminates the risk of hepatitis flare, and should be administered regardless of HCC treatment.
A recent study in Asian patients with chronic hepatitis B (CHB) reported that the incidence of hepatocellular carcinoma (HCC) was lower in patients treated with tenofovir disoproxil fumarate (TDF) ...than entecavir (ETV), but this finding remains controversial. We aimed to identify any differences in HCC incidence, or other patient outcomes, between patients receiving TDF or ETV in the well monitored, multicenter European PAGE-B cohort.
We included 1,935 Caucasians with CHB, with or without compensated cirrhosis, treated with ETV (n = 772) or TDF (n = 1,163) monotherapy. Mean follow-up was 7.1 ± 3.0 years from ETV/TDF onset.
The 5-year cumulative HCC incidence was 5.4% in ETV- and 6.0% in TDF-treated patients (log-rank, p = 0.321), with no significant difference in any patient subgroup (with or without cirrhosis, naïve or experienced to oral antiviral(s) total, with or without cirrhosis). In multivariable Cox regression analyses, the hazard of HCC was similar between ETV- and TDF-treated patients after adjustment for several HCC risk factors. ETV- and TDF-treated patients had similar rates of on-therapy biochemical and virological remission, HBsAg loss, liver transplantation and/or death. Elastographic reversion of cirrhosis at year 5 (liver stiffness <12 kPa) was observed in 245/347 (70.6%) patients with pretreatment cirrhosis, being more frequent in TDF- than ETV- treated patients (73.8% vs. 61.5%, p = 0.038).
In Caucasian patients with CHB, with or without cirrhosis, long-term ETV or TDF monotherapy is associated with similar HCC risk, rates of biochemical/virological remission, HBsAg loss and liver transplantation or death, but elastographic reversion of cirrhosis at year 5 was more frequent with TDF.
In a large cohort of Caucasians with chronic hepatitis B treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) monotherapy, cumulative rates of hepatocellular carcinoma did not differ (up to 12 years). Nor did rates of biochemical/virological remission, HBsAg loss and liver transplantation or death. However, elastographic reversion of cirrhosis at year 5 was more frequent in TDF- than ETV-treated patients with pretreatment cirrhosis.
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•Caucasians with chronic hepatitis B treated with entecavir vs. tenofovir had:•Similar rates of hepatocellular carcinoma up to 12 years•Similar rates of biochemical/virological response, HBsAg loss and mortality•Less frequent elastographic reversion of cirrhosis at year 5
Current status of hepatitis delta Papatheodoridi, Margarita; Papatheodoridis, George V.
Current opinion in pharmacology,
06/2021, Volume:
58
Journal Article
Peer reviewed
Hepatitis D virus (HDV) infection in patients chronically infected with hepatitis B virus (HBV) causes the most severe form of chronic viral hepatitis and continues to represent a major health ...problem. The latest data show that the global prevalence is much higher than previously considered. Therefore, screening with the detection of anti-HDV antibodies is mandatory for all chronic HBV patients. In spite of the severity of liver disease, the only recommended treatment today is pegylated interferon-alpha, which has limited efficacy. Novel host-targeting molecules are now under investigation. The current phase 2 clinical trials include pegylated interferon-lambda, bulevirtide, lonafarnib, and REP-2139. This review focuses on the current status of epidemiology, diagnosis, and treatment of HDV infection.
Is hepatitis delta underestimated? Papatheodoridi, Margarita; Papatheodoridis, George V.; Valenti, Luca
Liver international,
June 2021, 2021-06-00, 20210601, Volume:
41, Issue:
S1
Journal Article
Peer reviewed
Open access
Hepatitis D virus may be underestimated because it is a significant problem in HBsAg‐positive patients, especially those who inject drugs, have HIV or HCV co‐infections and/or live in certain endemic ...regions. In the past few decades, the prevalence of HDV was expected to have decreased as a result of improvements in public healthcare policies and universal HBV vaccination programs. However, HDV has continued to spread in low‐income countries, with local outbreaks and migration to less endemic areas, so that its prevalence has remained stable or even increased in certain regions. As a result, research has been focused on the epidemiology of HDV. Contradicting data from three large recent meta‐analyses have reported that the prevalence of HDV may be between 0.16% and 1.00% in the global general population, and 4.5% and 14.6% in HBsAg‐positive patients, with an estimated 12 to 70 million HDV patients worldwide. The exact prevalence and estimated number of HDV patients is still a subject of debate for several reasons, including the unreliable assessment of the infection and a lack of real‐world screening. HDV infection is associated with an increased risk of progression to cirrhosis and the development of HCC compared to patients with HBV mono‐infection, a risk which is even higher in patients with HIV co‐infection. Morbidity and mortality from HDV‐related cirrhosis should not be overlooked. In conclusion, hepatitis D virus is probably underestimated and certainly underdiagnosed, and screening for HDV should be performed in all HBsAg‐positive patients in clinical practice.
•MASLD is the most common liver disease worldwide and the most growing liver transplant indication in Western countries.•The natural course of the disease exhibits significant dynamism and ...bidirectionality.•The fibrosis stage is the most accurate predictor of mortality.•Cardiovascular disease and associated events are the predominant contributing factors to death among MASLD patients.•MASH-related decompensated cirrhosis appears to have worse prognosis than decompensated cirrhosis of other etiologies.
Metabolic dysfunction-associated steatotic liver disease (MASLD), which has been the term for non-alcoholic fatty liver disease (NAFLD) since June 2023, represents the most common liver disease worldwide and is a leading cause of liver-related morbidity and mortality. A thorough knowledge of the disease's natural history is required to promptly stratify patients' risks, since MASLD is a multifaceted disorder with a broad range of clinical phenotypes. The histological disease spectrum ranges from isolated hepatic steatosis, currently named as metabolic dysfunction-associated steatotic liver (MASL), to metabolic dysfunction-associated steatohepatitis (MASH) and eventually may accumulate hepatic fibrosis and develop cirrhosis and/or hepatocellular carcinoma (HCC). Several risk factors for fibrosis progression have been identified, while the disease's progression displays notable dynamism and bidirectionality. When compared to the general population, all MASLD histological stages are substantially related with greater overall mortality, and this association exhibits a disease severity-dependent pattern. Interestingly, the fibrosis stage is the most accurate predictor of mortality among MASLD patients. The mortality attributed to MASLD predominantly stems from issues linked with the liver and cardiovascular system, as well as HCC and extrahepatic cancers. In light of the disease natural course, it is crucial to prioritize the identification of at-risk patients for disease progression in order to effectively address and change modifiable risk factors, hence mitigating disease complications. Further investigation is required to define the phenotype of rapid progressors more precisely as well as to improve risk stratification for HCC in non-cirrhotic individuals.
Abstract Background/Objectives Although lifestyle modifications remain the cornerstone therapy for non-alcoholic fatty liver disease (NAFLD), the optimal lifestyle intervention is still ...controversial. The aim of this meta-analysis was to evaluate the effect of exercise and/or dietary interventions, type or intensity of exercise and type of diet, on liver function outcomes (liver enzymes, intrahepatic fat and liver histology), as well as on anthropometric and glucose metabolism parameters in NAFLD patients. Subjects/Methods Literature search was performed in Scopus and US National Library of Medicine databases to identify all randomized controlled clinical trials (RCTs) in adult patients with NAFLD, diagnosed through imaging techniques or liver biopsy, published in English between January 2005 and August 2016. Studies' quality was evaluated using the Cochrane Risk of Bias Tool. Heterogeneity was tested using the Cochran's Q test and measured inconsistency by I2 . Effect size was calculated as the standardized mean difference (SMD). The meta-analysis was performed in accordance with PRISMA guidelines. Results Twenty RCTs with 1073 NAFLD patients were included. Compared to standard care, exercise improved serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (all P < 0.05). Ιntrahepatic fat also improved, irrespectively of weight change (SMD = − 0.98, 95% CI: − 1.30 to − 0.66). Regarding the type of exercise, aerobic compared to resistance exercise did not yield any superior improvements on liver parameters, whereas moderate-to-high volume moderate-intensity continuous training was more beneficial compared to continuous low-to-moderate-volume moderate-intensity training or high intensity interval training. Interventions combining exercise and diet showed decreases in ALT (P < 0.01) and improvement in NAFLD activity score (SMD = − 0.61, 95% CI: − 1.09 to − 0.13). Moderate-carbohydrate diets yielded similar changes in liver enzymes compared to low/moderate-fat diets. Conclusions Exercise alone or combined with dietary intervention improves serum levels of liver enzymes and liver fat or histology. Exercise exerts beneficial effects on intrahepatic triglycerides even in the absence of weight loss.
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