Recently, controversies have arisen about whether hepatitis B e antigen (HBeAg) seroconversion can result in regression of fibrosis, thus improving the clinical outcome of Chinese patients with chronic hepatitis B. In this study, we determined if spontaneous HBeAg seroconversion is associated with regression of fibrosis in Chinese chronic hepatitis B patients. We evaluated the histology of liver samples from 128 HBeAg-positive treatment-naive Chinese patients who had undergone 2 liver biopsies over the years. Regression of fibrosis was defined as a decrease in fibrosis stage of at least 1 point. Sustained disease remission was defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA < 10(4) copies/ml at follow-up liver biopsy. The mean duration (+/- standard error of the mean) between the initial and follow-up liver biopsies was 43.9 +/- 3.4 months. Regression of fibrosis was higher in patients with sustained disease remission (5 of 13 [38.5%] versus 22 of 115 [19.1%], P < 0.00005), patients who were younger (20-29 years old) at initial liver biopsy (17 of 54 [31.5%] versus 10 of 74 [13.5%], P = 0.0004), and patients with genotype B (17 of 43 [39.5%] versus 10 of 85 [11.8%], P = 0.004). On multivariate analysis, sustained disease remission (relative risk [RR] 3.00, 95% confidence interval [95% CI] 1.29-7.01, P = 0.01) and being 20-29 years old at initial liver biopsy (RR 2.94, 95% CI 1.01-8.62, P = 0.04) were independently associated with regression of fibrosis. The rate of fibrosis progression was lower in patients with sustained disease remission than in those who remained HBeAg positive (median 0 fibrosis units/year, range -2.00 to -0.70 fibrosis units/year, versus median 0.51 fibrosis units/year, range 0 to +2.03 fibrosis units/year, P = 0.02).Spontaneous sustained remission of disease is associated not only with little progression of fibrosis but also with regression of fibrosis.
Abstract Hepatitis B virus (HBV), a serious infectious and widespread human pathogen, represents a major health problem worldwide. Chronic HBV infection has a very high risk of evolving into hepatocellular carcinoma. Although considerable progress was made during the recent past, the pathogenesis of HBV infection is still elusive and a definite diagnosis of HBV infected liver information still relies on biopsy histological test. In this report, we used proteomics technology to globally examine HBV infected serum samples aiming at searching for disease‐associated proteins that can be used as serological biomarkers for diagnosis and/or target proteins for pathogenetic study. By comparing with normal and HBV negative serum samples, we found that at least seven proteins were significantly changed in HBV infected sera. These greatly altered proteins were identified to be haptoglobin β and α2 chain, apolipoprotein A‐I and A‐IV, α1‐antitrypsin, transthyretin and DNA topoisomerase IIβ. The alteration of these proteins is displayed not only in quantity but also in patterns (or specificity), which can be correlated with necroinflammatory scores. In particular, apolipoprotein A‐I presents heterogeneous change in expression level with different isoforms and α1‐antitrypsin produces evidently different fragments implying diverse cleavage pathways. These unique phenomena appear specific to HBV infection. A combination simultaneously considering the quantities and isoforms of these proteins could be a useful serum biomarker (or index) for HBV diagnosis and therapy.
Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions.A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable.Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naïve patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China.Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility.
Abstract Non‐alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western industrialized countries, affecting 20–40% of the general population. Large population‐based surveys in China, Japan, and Korea indicate that the prevalence of NAFLD is now 12% to 24% in population subgroups, depending on age, gender, ethnicity, and location (urban versus rural). There is strong evidence that the prevalence of NAFLD has increased recently in parallel with regional trends in obesity, type 2 diabetes, and metabolic syndrome; and that further increases are likely. The relationship between NAFLD, central obesity, diabetes, and metabolic syndrome is clearly evident in retrospective and prospective Asian studies, but the strength of association with these metabolic risk factors is only appreciated when regional definitions of anthropometry are used. Pathological definition of NAFLD, particularly its activity and the extent of liver fibrosis, requires histological examination, but liver biopsy is often not appropriate in this disorder for logistic reasons. An alternative set of operational definitions is proposed here. Clinicians need guidelines as how best to diagnose and manage NAFLD and its associated metabolic disorders in countries with scant healthcare resources. The Asia–Pacific Working Party (APWP) for NAFLD was convened to collate evidence and deliberate these issues. Draft proposals were presented and discussed at Asia–Pacific Digestive Week at Cebu, Philippines, in late November 2006, and are published separately in this issue of the Journal as an Executive Summary. The present document reviews the reasoning and evidence behind the APWP‐NAFLD proposals for definition, assessment, and management of NAFLD in the Asia–Pacific region.
INTRODUCTION More than 600,000 people die of hepatocellular carcinoma (HCC) each year. Worldwide research on the disease needs to be intensified in both the medical and pharmaceutical fields, especially with a focus on providing help to areas where resources are limited. Treatment approaches depend on the stage of the disease at diagnosis and on access to complex treatment regimens. However, advanced disease is not curable, and management of advanced disease is expensive and only marginally effective in increasing quality-adjusted life years. The delivery of healthcare services for HCC can be improved by developing centers of excellence. Concentrating medical care in this way can lead to an increased level of expertise, so that resections are performed by surgeons who understand liver disease and the limitations of resection and other relevant procedures. Promising new agents are beyond the reach of those who would benefit most: in low-resource countries, sorafenib is out of the question for general use. For example, “snapshot” cost indications of monthly pharmacy prices for sorafenib are: $7300 in China, $5400 in the United States, $5000 in Brazil, €3562 in France, and $1400 in Korea (source: N Engl J Med. 2008;359:378–390; PMID 18650519). From a global perspective, therefore, the most urgent task is to prevent the occurrence of HCC. The only effective strategy is primary prevention of viral hepatitis, and in most countries this is already in place in the form of hepatitis B vaccination of newborns. Prevention of alcohol abuse and preventing the spread of hepatitis C virus (HCV) and metabolic syndrome are also relevant. Another important task is to prevent aflatoxin formation through proper care of crops and food storage. The next best approach is to increase awareness among the healthcare community to promote surveillance of patients who are at risk and achieve earlier diagnosis and resection or ablation of small lesions. Global Prevalence and Incidence HCC is the sixth most common malignancy worldwide. It is the fifth most common malignant disease in men and the eighth most common in women. It is the third most common cause of death from cancer, after lung and stomach cancer. HCC is the most common malignant disease in several regions of Africa and Asia. At least 300,000 of the 600,000 deaths worldwide occur in China alone, and the majority of the other 300,000 deaths occur in resource-challenged countries in sub-Saharan Africa. These devastating figures are most likely due to: Failure to recognize those at risk (with hepatitis B and/or C) High prevalence of risk factors in the population Lack of medical expertise and facilities for early diagnosis Lack of effective treatment after diagnosis Other important factors include poor compliance, with inadequate attendance or absent in surveillance programs and thus late presentation of patients with large tumors; low awareness of the benefits of HCC treatment and ways of preventing underlying liver disease; and a negative opinion among some physicians about screening. In Japan, the United States, Latin America, and Europe, hepatitis C is the major cause of HCC. The incidence of HCC is 2% to 8% per year in patients with chronic hepatitis C and established cirrhosis. In Japan, the mortality from HCC has more than tripled since the mid-1970s. HCV infection is responsible for 75% to 80% of cases and hepatitis B virus (HBV) for 10% to 15% of cases. HCV-related HCC has been linked to blood transfusions in the 1950s and 1960s, intravenous drug use, and the reuse of syringes and needles. In many (but not all) countries, the spread of HCV is declining, but due to migration the disease burden has not changed. In Asia, Africa, and in some eastern European countries, chronic hepatitis B is the prime cause of HCC, far outweighing the impact of chronic hepatitis C (Fig. 1). There are 300 million people infected with HBV, 120 million of whom are Chinese. In China and Africa, hepatitis B is the major cause of HCC; approximately 75% of the HCC patients have hepatitis B.FIGURE 1.: The worldwide geographic distribution of chronic hepatitis B virus infection (source: Centers for Disease Control, 2006).HCC Risk Factors HCC is associated with liver disease independently of the specific cause of the disease: Infectious: chronic hepatitis B or C. Nutritional and toxic: alcohol, obesity (nonalcoholic fatty liver disease), aflatoxin (cofactor with HBV), tobacco. Genetic: tyrosinosis, hemochromatosis (iron overload). However, iron overload as a cause per se and as a result of dietary intake (due to cooking in iron pots) is a subject of controversy. α1-antitrypsin deficiency. Immunologic: autoimmune chronic active hepatitis, primary biliary cirrhosis. The major risk factors for HCC are: Chronic HBV or HCV infection. Alcoholic cirrhosis. Nonalcoholic steatohepatitis. Diabetes (metabolic syndrome is the likely risk process). Cirrhosis by itself, of whatever cause. In Europe, North America, and Japan, HCC occurs mainly in patients with established cirrhosis. The risk of developing HCC in patients infected with HBV increases with: The viral load Male sex Older age The presence of cirrhosis Exposure to aflatoxins Location in sub-Saharan Africa, where patients develop HCC at a younger age The risk of developing HCC in patients infected with HCV and cirrhosis increases in combination with: Concurrent alcohol abuse Obesity/insulin resistance Previous or concurrent infection with HBV. Primary Care Physical findings: If the tumor is small: often without symptoms Physical signs may not be found at all Signs related to the chronic liver disease and/or underlying cirrhosis In more advanced cases: Palpable mass in the upper abdomen, or a hard, irregular liver surface Tenderness in the upper right abdominal quadrant Splenomegaly, ascites, jaundice (also symptoms of cirrhosis) Hepatic arterial bruit (heard over the tumor) Signs that should raise a suspicion of HCC in patients with previously compensated cirrhosis: Rapid deterioration of liver function New-onset (or refractory) ascites Acute intra-abdominal bleeding Increased jaundice Weight loss and fever New-onset encephalopathy Variceal bleeding Patients with late-stage HCC may present with: Right upper quadrant abdominal pain Symptoms and signs of underlying cirrhosis Weakness Abdominal swelling Nonspecific gastrointestinal symptoms Jaundice Loss of appetite Weight loss Anorexia Laboratory findings: Usually nonspecific Signs of cirrhosis: Thrombocytopenia Hypoalbuminemia Hyperbilirubinemia Coagulopathy Electrolyte disturbances Liver enzymes abnormal, but nonspecific Elevated α-fetoprotein (AFP; requires definitionsof levels and appropriate setting) Elevated alkaline phosphatase Follow-up to assess the patient after therapy—to be performed every 3 to 6 months: Physical examination Laboratory blood tests Computed tomography (CT), magnetic resonance imaging, and ultrasonography Referring to a specialist may help in: Confirming the diagnosis (and excluding possible alternatives—eg, liver diseases). Determining the extent of hepatic involvement and (remaining) liver function. Excluding extrahepatic disease. Choosing the best therapeutic option, including palliative care. If expert centers are within reach, it is generally recommended that HCC patients should be referred there, where care and options are optimally applied with all the expertise required from different areas of knowledge. Diagnosis Initial patient evaluation: Complete history Full physical examination Initial laboratory tests: Complete blood count Serum glucose Renal function and serum electrolytes AFP Albumin Prothrombin time Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin Hepatitis B surface antigen and anti-HCV (if not already known) Chest x-ray and/or CT scan Ascitic fluid cytology may also be considered, despite its low sensitivity—it is simple and practicable in Africa. Diagnostic Tests (Table 1) Sufficient to establish a diagnosis of HCC is a combined finding of: the classic appearance on one of the imaging modalities—that is, a large and/or multifocal hepatic mass with arterial hypervascularity; and elevated serum AFP, against a background of chronic (generally asymptomatic), generally cirrhotic-stage liver disease.TABLE 1: Tests Used to Diagnose Hepatocellular CarcinomaUltrasound Imaging, CT, or Magnetic Resonance Imaging Radiology and/or biopsy are the definitive diagnostic tools. Contrast-enhanced ultrasound may produce false-positive findings for HCC in patients with intrahepatic cholangiocarcinoma. AFP is an adjunctive diagnostic tool. A persistent AFP level of more than 400 ng/mL or a rapid increase in the AFP level may be a useful diagnostic criterion. In patients with lower AFP levels when radiology is not available, the diagnosis of HCC can only be made by clinical judgment. Even if options for treating HCC are absent or very limited, AFP testing and ultrasound imaging may be available. Cautionary Notes It is important to distinguish the use of AFP testing as a screening tool from its use as a diagnostic tool. Although it is considered to be a useful and feasible screening tool in China, others disagree. Its performance as a diagnostic tool is better. A positive AFP test (above 400 ng/mL, for example, can be considered diagnostic, but an AFP that is negative or below the predetermined cut-off point does not exclude HCC, as up to 40% of HCCs will never produce AFP. However, 90% of black African patients have raised AFP levels that are above the diagnostic level of 500 ng/mL in 70% of patients. However, this in turn may reflect the late presentation of these patients. In Western patients, AFP testing is less useful. Increased AFP and a mass are the diagnostic criteria of malignancy, but it is not possible to distinguish between HCC and cholangiocarcinoma. The incidence of cholangiocarcinoma is increasing, and cirrhosis is a risk factor. If the radiographic findings are conclusive, the diagnosis is certain; but if radiology is not conclusive, a biopsy is recommended to confirm the diagnosis. Cascades—A Resource-sensitive Approach A “cascade” is a hierarchical set of diagnostic, therapeutic, and management options for dealing with risk and disease, ranked by the resources locally available. A gold-standard approach is feasible in regions and countries where liver transplantation is available for the treatment of HCC. Elsewhere, resection and/or local ablation are available, but not liver transplantation. What is it still possible to do in the various settings in which transplantation or resection and/or local ablation are available? To answer this question, this guideline is structured on the basis of resource-sensitive cascades: for minimal-resource and medium-resource areas, the guideline discusses primary and secondary prevention, patient evaluation, and treatment options. For high-resource regions and countries, the guideline published by the American Association for the Study of Liver Diseases (AASLD) should be consulted. MINIMAL RESOURCES Minimal-resource regions are defined as those in which hardly any treatment options are available. The focus is on prevention and symptomatic treatment. At best, resection or local ablation may be available in some areas. Defining the criteria for referral to a specialist is a complex matter. As patients with advanced cases (and these are the majority of cases in resource-challenged countries) have no treatment options except supportive care, referral is generally futile. Only patients with early cases can benefit (imaging technology is required to identify early cases) and should be referred to specialists. All recommendations should focus on primary prevention and on the treatment of viral hepatitis and cirrhosis. Primary HCC Prevention Particularly when potentially curative treatment is unavailable, primary prevention is very important in reducing the risk of HCC (Table 2).TABLE 2: Options for Primary Prevention of Hepatocellular Carcinoma The vaccination prevention strategy against viral hepatitis (HBV) should be carried out worldwide; so far, it has been implemented in 152 countries. It is supported by nongovernmental organizations such as the Gates Foundation and the Global Alliance for Vaccines and Immunization. In Nigeria, vaccination costs less than a dollar; vaccines are also administered free for babies in public hospitals and immunization centers through the National Program on Immunization. Pakistan runs the World Health Organization's “Expanded Program of Immunization,” with free immunization for all newborns. Antiviral therapy should be recommended if needed: In many countries, the problem with antiviral therapy is management (drug resistance), compliance, and education. Costs may also be a problem, although several medications are reported to be relatively inexpensive. One year of lamivudine treatment costs $165 in Sudan; adefovir is inexpensive in India and China; and entecavir in China costs $5/d compared with $22/d in developed countries. Health education on viral hepatitis should emphasize the ways in which it is possible for the disease to spread in relation to local practices involving blood-blood contact, such as circumcision, scarification, tribal marks, and tattoos; in relation to the care of open sores and marks after multiple-use tooth extraction equipment; and in connection to the reuse of needles (or multiple-dose vials). Secondary HCC Prevention—Surveillance Screening should be encouraged in regions in which it is possible to offer curative treatment for HCC. There is little point in carrying out mass screening of a population if the resources for further investigation and treatment are lacking. Screening should only be undertaken if at least one of these management options is available: liver transplantation, resection, transarterial chemoembolization (TACE), or ablation techniques. Treatment with acetic acid (vinegar) is used in some places. One of the starting points for screening is to identify asymptomatic patients with HCC. If patients have cancer symptoms at diagnosis, the outcome is not good and treatment is not likely to be cost-effective. Treatment Options Appropriate treatment options that may or may not be beyond the scope of local medical facilities include: Partial liver resection Percutaneous ethanol injection (PEI) or radiofrequency ablation (RFA) TACE Traditional chemotherapy has no place in the management of HCC. Patients should be offered symptomatic treatment when it is needed and possible. MEDIUM RESOURCES Medium-resource regions are defined as those in which both resection and ablation are available for the treatment of HCC, but transplantation is not an option. In addition to primary HCC prevention (as discussed under “Minimal Resources” above), detailed recommendations can be provided on surveillance, diagnosis, and treatment. The delivery of healthcare services for HCC can be improved by developing centers of excellence—concentrating medical care can lead to an increased level of expertise, so that resections are performed by surgeons who understand liver disease and the limitations of each treatment modality. Secondary HCC Prevention—Surveillance When resection and/or local ablation are available for the treatment of HCC, there should be an emphasis on surveillance. Primary prevention—that is, hepatitis B vaccination of youngsters—is optimal in reducing the risk of HCC. Early diagnosis and treatment are essential for improving survival, but preventing recurrent HCC is still a major challenge. HCC surveillance may improve early detection of the disease. Generally, treatment options are broader when HCC is detected at an earlier stage. Finding early-stage disease is a prerequisite for improved prognosis. Screening should be encouraged in regions in which it is possible to offer curative treatment for HCC. The risk factors for HCC are well known, and this allows cost-effective surveillance. Screening for early detection of HCC is recommended for the groups of high-risk patients listed in Table 3.TABLE 3: Criteria for Hepatocellular Carcinoma ScreeningSurveillance involves establishing screening tests, screening intervals, diagnostic criteria, and recall procedures (Table 4).TABLE 4: Surveillance Techniques Depending on the clinical condition and the available resources, an ultrasound screening interval of 6 to 12 months is recommended. In advanced cases and in patients with cirrhosis, ultrasound screening should be performed every 4 to 6 months. Patient education is an essential prerequisite. Tertiary HCC Prevention—Recurrence Recurrent HCC may result from multicentric carcinogenesis or inadequate initial treatment. Prevention of HCC recurrence requires early diagnosis and complete removal of primary HCC lesions. Currently, there is no proof of the efficacy of tertiary prevention of HCC with any agent, including chemotherapy, HBV and HCV therapy, or interferon. There are no safe and effective chemotherapeutic agents available yet to prevent the recurrence of HCC. Molecular-targeted drugs seem to show promising clinical activity, but the median survival is not satisfactory and these agents are very costly. Anti-HBV oral nucleoside/nucleotide analogs are required for patients with ongoing active chronic hepatitis B with HCC as a complication and who are in Child-Pugh class A or B. Evaluation The management of HCC is changing. In the developed countries, HCC patients are increasingly being evaluated and managed at specialized centers by multidisciplinary teams consisting of hepatologists, oncologists, radiologists, surgeons, and pathologists. The Barcelona Clinic Liver Cancer (BCLC) staging system takes into account variables related to tumor stage, liver function, physical status, and cancer-related symptoms, and links these with treatment options and life expectancy. On the basis of the BCLC staging system, patients may be classified as having: Early HCC: single nodule or three nodules ≤3 cm. These patients may benefit from curative therapies. Intermediate HCC: multinodular. These patients may benefit from chemoembolization. Advanced HCC: multinodular with portal invasion. These patients may benefit from palliative treatments; new agents may be considered. End-stage HCC: very poor life expectancy; symptomatic treatment. After a diagnosis of HCC has been confirmed, liver function is one of the main factors in the treatment selection process; performance status and comorbid conditions need to be established. Important aspects in assessing liver function are: Child-Pugh classification: Bilirubin (total) Serum albumin Prothrombin international normalized ratio Ascites Hepatic encephalopathy Optional: hepatic venous pressure gradient. A test result >10 mm Hg would confirm clinically relevant portal hypertension, which is important when surgical resection is planned. Treatment Options Treatment options largely depend on liver function, tumor size, and the presence or absence of metastatic lesions or vascular invasion. In most cases, curative treatments such as resection, RFA, or liver transplantation are not feasible, limiting the options to palliation. Screening of at-risk populations is therefore the only way of detecting tumors at a stage at which they are capable of being treated. Most of the treatment options are expensive and/or require specialized centers. Resection and local ablation are the treatment options most likely to be used in patients with HCC identified during surveillance in developing countries. Both resection and ablation can allow a cure in small tumors. Partial liver resection: Possibly a curative approach for HCC. Only a few of the patients qualify for this option, due to advanced disease stage and/or reduced liver function. Relapse can be either due to residual tumor that was incompletely treated the first time around, or a true recurrence—that is, a second independent tumor arising in a liver that is prone to develop malignancy. PEI or RFA: These are safe and effective when resection is not an option, or when the patient is awaiting transplantation. PEI is universally available, but requires at least ultrasound. PEI and RFA are equally effective for tumors<2 cm. RFA is more effective than alcohol injection in tumors>3 cm. The necrotic effect of RFA is more predictable in all tumor sizes. TACE: This is the standard of care for patients with good liver function and disease that is not amenable to surgery or ablation, but who have no extrahepatic dissemination, no vascular invasion, and no cancer symptoms. Table 5 presents a recent description of treatments, their benefits in HCC, and levels of evidence, developed by an AASLD expert panel.TABLE 5: American Association for the Study of Liver Diseases (AASLD) Expert Panel Description of Treatments, Benefits, and Levels of Evidence in Hepatocellular CarcinomaPalliative Care Patients with Child-Pugh class C cirrhosis should be offered symptomatic treatment only. More recent experimental methods, such as brachytherapy and selective internal radiation therapy, are available at specialized centers. HIGH RESOURCES High-resource regions are defined as those in which liver transplantation is available for the treatment of HCC. For detailed discussion of diagnostic and therapeutic options and interpretation of the results of chemotherapy, the AASLD Practice Guideline should be consulted (Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–1236).FIGURE
Abstract Background The Asia–Pacific (AP) region carries a substantial burden of HBV. Affordable HBV treatment is crucial to attain WHO’s elimination goal. This study assesses the pricing and affordability of HBV treatment in AP. Methods A survey conducted among APASL members from 2 Aug to 30 Oct, 2023, gathered data on antiviral HBV drugs, treatment costs covering stages of chronic hepatitis B (CHB), compensated cirrhosis (CC), hepatocellular carcinoma (HCC), liver transplant, and monitoring expenses. Drug costs for TDF and ETV were compared to international reference price (TDF: $30, ETV: $36 per person per year), generating a median price ratio (MPR) where MPR < 1 indicated an acceptable local price. Affordability was evaluated by comparing yearly CHB treatment cost to yearly minimum wage in each country/area, all converted to 2023 US$. Results ETV costs ranged from $42 per person per year in Pakistan to $2640 in Malaysia, while TDF costs varied from $12 in mainland China to $2446 in Hong Kong. Almost all MPR exceeded 1. Affordability of HBV treatment varied, with CHB patients in Australia paying 1.4% of minimum yearly wage to get 1 year CHB treatment, in contrast to Myanmar’s 78.6%. Affordability disparities were also evident for patients with CC, HCC, and liver-transplant needs, though monitoring costs were generally affordable. Conclusions Despite patent expiration and availability of low-cost generics for TDF and ETV, HBV medication costs in Asia–Pacific region remain high. CHB treatment is generally unaffordable for patients, posing a significant barrier to HBV elimination in this endemic region.
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