Antiviral therapy (AVT) for chronic hepatitis B (CHB) can prevent liver disease progression. Because of its stringent reimbursement criteria, significant numbers of patients with untreated minimally active (UMA)-CHB exist, although they are still subject to disease progression. We thus performed a cost-effectiveness analysis to assess the rationale for AVT for UMA-CHB.

We compared cost and effectiveness (quality-adjusted life years, QALYs) in virtual UMA-CHB cohorts of 10,000 50-year-olds receiving AVT (scenario 1) vs no treatment (scenario 2) for 10 years. A Markov model, including 7 health states of CHB-related disease progression, was used. Values for transition probabilities and costs were mostly obtained from recent South Korean data.

The simulation of AVT vs no treatment predicted $2,201 incremental costs and 0.175 incremental QALYs per patient for 10 years, with an incremental cost-effectiveness ratio (ICER) of $12,607/QALY, suggesting cost-effectiveness of AVT. In sum, if 10,000 patients received AVT, 720 incident hepatocellular carcinoma and 465 CHB-related more deaths could be averted in 10 years relative to no treatment. When the simulated analysis period was extended to 20 years, AVT was also highly cost-effective with an ICER of $2,036/QALY. Although hepatocellular carcinoma-related mortality was a major factor influencing ICER, its fluctuation can be accepted within willingness to pay of $33,000 in South Korea. According to probabilistic sensitivity analysis with the threshold of willingness to pay, the probability of AVT cost-effectiveness was 83.3%.

Long-term AVT for patients with UMA-CHB may contribute positively toward individual clinical benefit and national health care budget.

Sustained hepatitis B surface antigen (HBsAg) loss or 'functional cure' (FC) is considered an optimal treatment endpoint by international clinical guidelines for chronic hepatitis B (CHB), yet rarely is this achieved with current standard of care (SoC). This leads to an under-reporting of FC in clinical trials, observational studies and health economic (HE) models. This paper systematically identifies and assesses how FC is incorporated in published HE models of CHB.

A systematic literature review was conducted in PubMed and Embase (conducted February 2019) to review how HBsAg loss is captured in HE models. The following items were extracted: rate of (and transition probabilities to) HBsAg loss, HBsAg loss health state costs, and HBsAg loss health state utilities.

Sixty-five economics evaluations were identified, and < 50% of these (27/65) incorporated HBsAg loss in their models. Only 15/27 stated HBsAg loss health state costs, 15/27 stated HBsAg loss health state utilities, and 11/27 mentioned treatment-specific transition probabilities to HBsAg loss. The majority of sources these inputs were derived from are not transparent.

The benefits of FC in current HE models are not well captured, as FC is often not reported or not directly related to modelled treatments. This has the potential for novel agents with higher efficacy compared with SoC to be overlooked and undervalued if their worth is not appropriately communicated. In order to ensure optimal access for patients to new and effective therapies, it is important that the benefits of FC are better assessed and captured within HE models.

Hepatitis B virus (HBV) reactivation may occur in >10% of patients with lymphoma and resolved HBV infection who undergo rituximab-containing chemotherapy. Preventive strategies may have marked impact on resource allocation in HBV endemic areas. This study aims to compare the cost-effectiveness between prophylactic antiviral therapy and HBV DNA monitoring for the prevention of HBV-related complications.

Data sources are studies of HBV-related events and survival for patients with lymphoma and resolved HBV infection published since 2006. Decision tree analysis was used to compare the incremental cost-effectiveness ratio (ICER) of preventing HBV-related death or liver decompensation for patients who undergo first-line rituximab-containing chemotherapy. Sensitivity analysis was performed to examine the impact of the preventive efficacy, the duration of prophylactic antiviral therapy, and the cost of different interventions. The direct medical cost was derived from the database of the NHI Administration, Taiwan. The time frame of our analysis was set to 3 years after the completion of chemotherapy.

The median ICER of prophylactic antiviral therapy, according to current practice guidelines, ranged between USD 150,000 and 250,000 if we apply the guidelines generally. When a long-course (12 months after completion of chemotherapy according to clinical guidelines) prophylactic therapy was assumed, Option A was cheaper and more effective only in the anti-HBs-negative subgroup (median ICER US$149,932 vs. US$161,526, p = 0.013).

Identification of anti-HBs-negative subgroups is critical to improve the cost-effectiveness of prophylactic antiviral therapy in lymphoma patients with resolved HBV infection.

Hospitalizations for advanced liver disease are costly and associated with significant mortality. This population-based study aimed to evaluate factors associated with in-hospital mortality and resource use for the management of hospitalized patients with cirrhosis.Mortality records and resource utilization for 52,027 patients hospitalized with cirrhosis and/or complications of portal hypertension (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, or hepatorenal syndrome) were extracted from a nationally representative sample of Thai inpatients covered by Universal Coverage Scheme during 2009 to 2013.The rate of dying in the hospital increased steadily by 12% from 9.6% in 2009 to 10.8% in 2013 (P < .001). Complications of portal hypertension were independently associated with increased in-hospital mortality except for ascites. The highest independent risk for hospital death was seen with hepatorenal syndrome (odds ratio [OR], 5.04; 95% confidence interval [CI], 4.38-5.79). Mortality rate remained high in patients with infection, particularly septicemia (OR, 4.26; 95% CI, 4.0-4.54) and pneumonia (OR, 2.44; 95% CI, 2.18-2.73). Receiving upper endoscopy (OR, 0.29; 95% CI, 0.27-0.32) and paracentesis (OR, 0.93; 95% CI, 0.87-1.00) were associated with improved patient survival. The inflation-adjusted national annual costs (P = .06) and total hospital days (P = .07) for cirrhosis showed a trend toward increasing during the 5-year period. Renal dysfunction, infection, and sequelae of portal hypertension except for ascites were independently associated with increased resource utilization.Renal dysfunction, infection, and portal hypertension-related complications are the main factors affecting in-hospital mortality and resource utilization for hospitalized patients with cirrhosis. The early intervention for modifiable factors is an important step toward improving hospital outcomes.

Nucleos(t)ide analogue (NA) monotherapies are typically used as the primary treatment for chronic hepatitis B (CHB) patients, including lamivudine (LAM), telbivudine (TBV), adefovir (ADV), entecavir (ETV) and tenofovir (TDF). For high-resistance NAs (LAM, TBV, ADV), they can generate excellent clinical outcomes by using response-guided therapy; however, their pharmacoeconomic profiles remain unclear in China. We aimed to evaluate the cost effectiveness between response-guided therapies and monotherapies of NAs for Chinese hepatitis B e-antigen (HBeAg)-positive and -negative CHB patients.

We constructed a Markov model to simulate CHB progression associated with 12 treatment strategies using effectiveness and cost data from the published literature. We measured the lifetime costs, quality adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity (especially to extend the range of the TDF price) and probabilistic sensitivity analyses were used to explore the uncertainties of the model.

For both HBeAg-positive and -negative patients, no treatment strategy generated the lowest lifetime costs (US$31,185-US$31,338) and QALYs (7.54-7.58). ETV and TDF monotherapies were not dominated by other treatments, whereas, the ICER of ETV monotherapy was the lowest (US$6112/QALY-US$8533/QALY). For each high-resistance NA, compared with its monotherapy, the ICERs of its response-guided therapies were below the willingness-to-pay threshold of US$22,833/QALY. Additionally, TDF monotherapy was the preferred treatment when its price dropped to US$1820/year or lower.

Among 12 treatment strategies evaluated, ETV monotherapy is the most cost-effective treatment for treatment-naive CHB patients in China. The response-guided therapies of high-resistance NAs are more cost-effective than their monotherapies.

Finite treatment of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) with nucleoside/nucleotide analogues (NAs) is important in resource-limited countries. Outcome of treatment discontinuation in patients on long-term lamivudine (LVD) was assessed in a single centre observational pilot study in the current study.

Non-cirrhotic patients on LVD for at least 5 years with undetectable HBV DNA on at least two consecutive assessments were offered to stop treatment. Biochemical, serological and virological measures were determined at 3-6 month intervals after treatment discontinuation. Serum quantitative hepatitis B surface antigen (HBsAg) was determined at treatment discontinuation and 5-6 years thereafter. NA treatment was re-instituted in patients with confirmed viral rebound defined as HBV DNA >20,000 IU/ml. Relapser patients were no longer followed but were re-assessed 6 years after treatment cessation.

LVD was discontinued in 23 patients. 8 patients relapsed within 1 year and NA treatment was restarted; 15 patients (65%) were non-relapsers. Thirteen of them were followed for at least 5 years. Two patients had undetectable HBV DNA throughout the follow-up period. In the rest, HBV DNA fluctuated at low levels. Two patients cleared HBsAg 24 and 36 months after stopping treatment. Quantitative HBsAg levels 5-7 years after treatment discontinuation were lower in non-relapser compared to relapser patients (1.21 IU/ml ±0.98 versus 2.71 ±0.76; P=0.002). Of 8 relapser patients 1 patient had HBsAg levels less than 100 IU/ml compared to 11 out of 13 non-relapser patients (P=0.0022).

These data suggest that cessation of NA treatment is a viable option after a reasonable treatment duration in patients with HBeAg-negative CHB and that HBsAg clearance may become an achievable target in these patients.

Advanced liver cirrhosis is usually accompanied by portal hypertension. Long-term portal hypertension results in various vascular alterations. The systemic hemodynamic state in patients with cirrhosis is termed a hyperdynamic state. This peculiar hemodynamic state is characterized by an expanded blood volume, high cardiac output, and low total peripheral resistance. Vascular alterations do not disappear even long after liver transplantation (LT), and recipients with cirrhosis exhibit a persistent systemic hyperdynamic state even after LT. Stability of optimal systemic hemodynamics is indispensable for adequate portal venous flow (PVF) and successful LT, and reliable parameters for optimal systemic hemodynamics and adequate PVF are required. Even a subtle disorder in systemic hemodynamics is precisely indicated by the balance between cardiac output and blood volume. The indocyanine green (ICG) kinetics reflect the patient's functional hepatocytes and effective PVF, and PVF is a major determinant of the ICG elimination constant (kICG) in the well-preserved allograft. The kICG value is useful to set the optimal PVF during living-donor LT and to evaluate adequate PVF after LT. Perioperative management has a large influence on the postoperative course and outcome; therefore, key points and unexpected pitfalls for intensive management are herein summarized. Transplant physicians should fully understand the peculiar systemic hemodynamic behavior in LT recipients with cirrhosis and recognize the critical importance of PVF after LT.

Despite the high burden of hepatitis B virus (HBV) infection in sub-Saharan Africa, absence of widespread screening and poor access to treatment leads to most people remaining undiagnosed until later stages of disease when prognosis is poor and treatment options are limited. We examined the cost-effectiveness of community-based screening and early treatment with antiviral therapy for HBV in The Gambia.

In this economic evaluation, we combined a decision tree with a Markov state transition model to compare a screen and treat intervention consisting of adult community-based screening using a hepatitis B surface antigen (HBsAg) rapid test and subsequent HBV antiviral therapy versus current practice, in which there is an absence of publicly provided screening or treatment for HBV. We used data from the PROLIFICA study to parameterise epidemiological, primary screening, and cost information, and other model parameter inputs were obtained from a literature search. Outcome measures were cost per disability-adjusted life-year (DALY) averted; cost per life-year saved; and cost per quality-adjusted life-year (QALY) gained. We calculated the incremental cost-effectiveness ratios (ICERs) between current practice and the screen and treat intervention. Costs were assessed from a health provider perspective. Costs (expressed in 2013 US$) and health outcomes were discounted at 3% per year.

In The Gambia, where the prevalence of HBsAg is 8·8% in people older than 30 years, adult screening and treatment for HBV has an incremental cost-effectiveness ratio (ICER) of $540 per DALY averted, $645 per life-year saved, and $511 per QALY gained, compared with current practice. These ICERs are in line with willingness-to-pay levels of one times the country's gross domestic product per capita ($487) per DALY averted, and remain robust over a wide range of epidemiological and cost parameter inputs.

Adult community-based screening and treatment for HBV in The Gambia is likely to be a cost-effective intervention. Higher cost-effectiveness might be achievable with targeted facility-based screening, price reductions of drugs and diagnostics, and integration of HBV screening with other public health interventions.

European Commission.