Aligning policy and clinical guidelines for albumin use in cirrhosis: insights from Indonesia Hepatology Medical Workgroup Meeting

Abstract

Background

Cirrhosis continues to be a major health burden in Indonesia, with high mortality and morbidity related to complications including ascites, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS). Although international guidelines strongly recommend albumin therapy for these complications, in Indonesia the adoption of international guidelines has been limited by universal healthcare policy and albumin indications defined in the National Formulary. The Indonesia Hepatology Medical Workgroup Meeting (December 2025) was convened to address barriers to the implementation of the newly launched National Cirrhosis Guideline, outline potential solutions, and discuss emerging topics such as long-term albumin (LTA) therapy and recombinant albumin (RA).

Methods

Seven hepatology experts from tertiary care centers completed a pre-meeting survey and participated in structured discussions on local barriers to implementation of the National Cirrhosis Guideline, evolution of treatment towards LTA, and clinical considerations for RA.

Results

The workgroup welcomed the National Cirrhosis Guideline for defining clear albumin indications in large-volume paracentesis (LVP), SBP, and HRS that align with international standards and should serve as the primary clinical guidance for management of cirrhosis in Indonesia. Cost-effectiveness evidence supports albumin use for SBP, HRS, and LVP; however, the current real-world management is still suboptimal. The primary barriers to implementation of the National Cirrhosis Guideline were the restricted indications and criteria defined within the National Formulary. The discussion indicated that albumin underutilization, lack of standardized care, and limited adoption of LTA treatment were primarily due to unclear patient selection criteria and dosing guidance. RA was recognized as a novel alternative, but concerns about long-term safety, immunogenicity, and functional equivalence persist.

Conclusions

The National Cirrhosis Guideline represents a critical advancement toward standardized cirrhosis management in Indonesia. Immediate priorities include National Formulary alignment, hospital protocol integration, and clinician education to support evidence-based albumin utilization nationwide. While LTA offers potential disease-modifying benefits, its routine adoption remains constrained by economic and policy considerations, and it should be considered selectively when clinically appropriate. While RA may offer scalability and consistency, long-term safety, immunogenicity, and non-oncotic functional equivalence require further confirmation before routine clinical adoption.

Highlight box.

Key recommendations

• The National Cirrhosis Guideline should be implemented as the primary clinical reference for albumin use in cirrhosis, particularly for large-volume paracentesis (LVP), spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS).

• Alignment of the National Formulary with the National Cirrhosis Guideline may facilitate implementation of guideline-concordant albumin therapy.

• Hospitals should integrate National Cirrhosis Guideline recommendations into local clinical pathways and standard operating procedures, supported by clinician education.

• Long-term albumin (LTA) therapy may be considered for selected patients with decompensated cirrhosis, while recombinant albumin (RA) should currently be regarded as a future alternative, not a replacement, pending further evidence.

What was recommended and what is new?

• International evidence and guidelines have long supported plasma-derived albumin for LVP, SBP, and HRS, with emerging data supporting LTA in selected patients with decompensated cirrhosis. The National Cirrhosis Guideline represents the first nationally endorsed guideline in Indonesia to clearly define evidence-based albumin indications aligned with international standards.

• Compared with prior practice constrained by formulary-driven indications, the National Cirrhosis Guideline introduces clearer clinical guidance aimed at standardizing care across centers.

What is the implication, and what should change now?

• Immediate efforts should focus on harmonizing reimbursement policies and the National Formulary with National Cirrhosis Guideline recommendations to reduce underutilization of albumin.

• Translation of guideline recommendations into routine practice requires structured education, clinical practice protocol development, and audit of adherence.

• Generation of local real-world and cost-effectiveness data will be essential to support sustainable implementation of albumin in clinical practice.

• Although RA may offer future advantages in cost, scalability, and supply, robust long-term data on safety, immunogenicity, and functional equivalence are required before routine clinical adoption.

Introduction

In Indonesia, cirrhosis continues to be a major public health challenge with complications such as ascites, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS) associated with significant mortality and morbidity (1). International guidelines including those from the European Association for the Study of the Liver (EASL), American Association for the Study of Liver Diseases (AASLD), and Asian Pacific Association for the Study of the Liver (APASL) (2-4), strongly recommend albumin therapy for these complications. However, translation of these recommendations into clinical practice and adoption of international guidelines in Indonesia are limited by universal healthcare policy and restricted albumin indications outlined in the National Formulary (Formularium Nasional; FORNAS-2023) (5).

The National Formulary, updated in 2023 by the Indonesia Ministry of Health (5), serves as the primary reference for drug procurement, prescribing, and reimbursement within the National Health Insurance program managed by Badan Penyelenggara Jaminan Sosial Kesehatan (BPJS Kesehatan; National Social Security Agency for Health). The National Formulary indication states that albumin can be used in patients with hypoalbuminemia (serum albumin <2.5 g/dL) due to nephrotic syndrome, extensive burns, selected perioperative states, or chronic liver disease. This narrow scope created a gap between clinical evidence and policy, leading to variability and suboptimal standardization of cirrhosis management across healthcare facilities.

To address this disparity, Perhimpunan Peneliti Hati Indonesia [PPHI: Indonesian Association for the Study of the Liver (Ina-ASL)] launched Pedoman Nasional Pelayanan Kedokteran Sirosis-2025 (PNPK Sirosis-2025), i.e., the National Cirrhosis Guideline, during the Liver Update Meeting in 2025, and the Ministry of Health officially endorsed this guideline in November 2025 (6). This marks a pivotal advancement toward standardized cirrhosis management in Indonesia, providing clear indications for acute use of albumin in large-volume paracentesis (LVP), SBP and HRS, and national practice harmonized with international guidelines.

Beyond acute indications, long-term albumin (LTA) therapy may offer disease-modifying benefits in selected patients with decompensated cirrhosis (7). Clinical studies have shown a survival benefit along with a reduced incidence of complications and lower healthcare resource utilization with LTA therapy (8-15). In addition, real-world data show reduced hospitalizations and support personalized dosing (12,14,16). Furthermore, expert bodies, such as the Italian Association for the Study of the Liver and APASL, recommend LTA for selected patients with at least grade 2 non-complicated ascites not responding to moderate doses of diuretics and also for patients with refractory ascites despite optimized diuretics (2,17).

In parallel, recombinant albumin (RA) has gained attention as a potential future alternative to plasma-derived albumin because its manufacturing process may offer advantages in scalability, batch consistency, and supply stability, particularly in resource-limited settings (18-21). A few studies primarily from China suggest that RA can increase serum albumin concentration with acceptable short-term safety, efficacy, and pharmacokinetic/pharmacodynamic profiles (22,23). However, evidence remains preliminary, and substantial gaps persist regarding long-term safety, immunogenicity, and functional equivalence, particularly with respect to albumin’s non-oncotic biological functions.

The Indonesia Hepatology Medical Workgroup Meeting (December 2025) was convened to assess readiness for implementation of the National Cirrhosis Guideline, identify policy- and practice-level barriers within the Indonesian healthcare system, and develop expert-driven, context-specific insights to support translation of guideline recommendations into routine clinical practice. This manuscript synthesizes results from the pre-meeting survey and structured expert discussions to inform clinicians, hospital administrators, and policymakers on priority actions needed to align national reimbursement policies, hospital protocols, and clinical practice. In addition, forward-looking perspectives on LTA therapy and RA are presented to support strategic health-system planning rather than immediate clinical adoption.

Methods

The Indonesia Hepatology Medical Workgroup Meeting was organized in collaboration with the Ina-ASL and Grifols Medical Affairs. Workgroup members were considered if they met several of the following criteria: 5–10 years of specialist clinical experience managing liver disease; authorship or co-authorship of publications on liver cirrhosis; active participation as speakers or resource persons in medical education activities; member of a national clinical guideline development committee; holding an academic appointment or leadership position in hepatology departments or professional societies; and demonstrated engagement in discussions on management of liver cirrhosis through prior advisory boards or professional forums. Seven hepatology experts from tertiary centers in Jakarta completed a pre-meeting survey (Table S1) developed based on the clinical literature, clinical guidelines, and meeting objectives in collaboration with Ina-ASL executive committee members.

Three core themes were discussed: (I) impact of the National Cirrhosis Guideline on clinical practice and hospital protocols; (II) local barriers to implementation of the National Cirrhosis Guideline and strategies for improvement; and (III) comparative clinical profile evaluation of plasma-derived albumin versus RA. RA was discussed as part of forward-looking health system planning rather than current clinical decision-making, to inform future policy considerations given ongoing global supply constraints and interest in alternative manufacturing platforms.

Given the small number of participants (n=7), survey findings are reported using descriptive statistics. Discussion outputs are summarized as consensus points, defined as agreement among all workgroup members. This manuscript represents an expert opinion and policy implementation report derived from structured workgroup discussion supported by pre-meeting survey data. The workgroup discussions, recommendations, and conclusions were independent of sponsor influence on clinical interpretation or positioning.

Results

The pre-meeting survey was divided into three domains: unmet needs and current practice patterns, guideline implementation readiness (expected changes, barriers, and evidence needs), and considerations for RA. The survey was exploratory and descriptive, designed to capture expert insights rather than quantify national practice patterns.

Unmet needs and current practice patterns

Based on workgroup responses, the key unmet needs in cirrhosis care in Indonesia were underutilization of albumin (n=4), lack of standardized care pathways throughout the country (n=3), delay in early detection and diagnosis (n=3), insufficient preventive measures (n=2), and restricted access to treatment (n=1) (Figure 1).

Figure 1.

Key unmet needs in cirrhosis care in Indonesia. Pre-meeting survey responses from workgroup members (n=7, multiple responses allowed) highlighting gaps in current cirrhosis management.

In regular clinical practice, the workgroup reported that the most common use of albumin was in LVP (n=7). Other uses were management of HRS (n=5) and LTA (n=3). In contrast, albumin was used far less frequently for SBP and hypoalbuminemia, with only two workgroup members reporting use in each of these indications (Figure 2).

Figure 2.

Reported albumin uses by clinical indication. Distribution of albumin utilization across cirrhosis-related indications as reported by workgroup members (n=7, multiple responses allowed).

LTA therapy is prescribed to only a small proportion of patients. Three workgroup members reported use in ≤25% of their cirrhosis patients. Additionally, 25–50% of patients (n=2) and 50–75% of patients (n=1) are offered LTA treatment, while one member indicated no experience in LTA.

Guideline implementation readiness

Following the launch of the National Cirrhosis Guideline, the workgroup members anticipate several key changes in cirrhosis management within their hospitals, primarily related to greater adoption of standardized, protocol-based management with clearer guidance on albumin use, particularly for LVP, SBP, and HRS (n=6).

When asked to identify areas of the National Cirrhosis Guideline requiring clarification for practical implementation, the workgroup highlighted several priorities. To enable consistent and effective adoption across clinical settings, the most frequently cited needs were clarification on albumin dosing and duration (n=7), integration into hospital treatment protocols (n=7), and alignment with albumin indications defined in the National Formulary and reimbursement policy (n=7). Patient selection criteria for albumin use (n=5) and monitoring parameters for treatment response (n=3) were identified as secondary priorities (Figure 3).

Figure 3.

Areas requiring clarification to support implementation of National Cirrhosis Guideline. Survey-identified priorities for translating guideline recommendations into routine clinical practice (n=7, multiple responses allowed). FORNAS, Formularium Nasional (National Formulary).

The workgroup identified several system-level and practice-level barriers to implementing the National Cirrhosis Guideline recommendations (Figure 4). The major barriers were restricted reimbursement policy under the National Formulary indication, hospital formulary limitations, and cost-related concerns (each n=6). Additional barriers reported include limited availability of albumin in hospitals due to the healthcare budget, lack of awareness among healthcare providers, low awareness among patients, insufficient local data to support implementation, lack of guideline-related training for healthcare workers including hospital administrators and policymakers, and reluctance to change (each n=4).

Figure 4.

Perceived barriers to implementation of National Cirrhosis Guideline. Health-system and clinical practice-level barriers to guideline implementation identified by workgroup members (n=7, multiple responses allowed). FORNAS, Formularium Nasional (National Formulary); HCP, Healthcare Professional.

The most critical evidence needed to support National Cirrhosis Guideline adoption was cost-effectiveness analysis (n=7) demonstrating economic value given current reimbursement constraints. Additionally, local case series or real-world data were highlighted by four workgroup members as essential to contextualize National Cirrhosis Guideline recommendations within Indonesian clinical practice. Local expert consensus was also viewed as valuable, with three workgroup members indicating that nationally aligned professional agreement would help strengthen clinician confidence and facilitate adoption of the guideline.

The key factors limiting cirrhosis management under the current National Formulary framework relate primarily to policy rigidity and cost-related constraints. The most frequently cited issues involved cost limitations (n=7). Restrictive reimbursement criteria, including narrow indications for albumin and lack of alignment with contemporary cirrhosis guidelines, particularly for cirrhosis complications and LTA therapy, were identified by all workgroup members. Six workgroup members faced challenges in tailoring treatment to patients’ specific clinical needs due to limited flexibility for individualized albumin dosing and duration. Three workgroup members also highlighted the administrative and documentation burden associated with albumin reimbursement, which discourages clinicians from proposing strategies beyond the indications defined in the National Formulary.

Considerations for RA

Based on the responses, the workgroup holds a cautiously optimistic view regarding the clinical comparability of RA to plasma-derived albumin. Individual ratings ranged from 5 to 8 on a 10-point scale, with an overall average confidence score of 6.5. While RA was recognized as a promising future technology, members emphasized that confidence remains limited due to insufficient long-term clinical data and absence of real-world experience.

The most important factor when evaluating RA was clinical efficacy data and functional equivalence data with plasma-derived albumin, which was highlighted by all workgroup members as the highest priority. Additional considerations of secondary importance included cost or reimbursement coverage and safety data (each n=4). Long-term data were also viewed as relevant, although mentioned less frequently (n=3). Factors such as regulatory approval status and approved clinical indications were identified by two members, indicating lower relative importance.

Core discussion points

Impact of National Cirrhosis Guideline on clinical practice and hospital protocols

The workgroup members reached consensus that the National Formulary restriction limiting albumin administration to hypoalbuminemia (<2.5 g/dL) was the major barrier and recommended adding the albumin indications outlined in the National Cirrhosis Guideline to the next update of the National Formulary. The National Cirrhosis Guideline clearly defined albumin indications in LVP, SBP, and HRS, and these recommendations are expected to support more consistent cirrhosis management across Indonesia. Incorporation of these guideline recommendations into hospital protocols and clinical pathways, supported by targeted clinician education, may facilitate the implementation of standard cirrhosis management in Indonesia.

Local barriers to implementation of National Cirrhosis Guideline and strategies for improvement

Despite strong guideline recommendations, albumin therapy remains underutilized in clinical practice due to reimbursement restrictions, cost concerns, misconceptions regarding oral albumin formulations equivalent to plasma-derived albumin, and limited awareness of the clinical role of albumin. These challenges are more pronounced outside major hepatology centers, where variability in hospital policies further limits guideline uptake.

To address these barriers, the workgroup reached consensus on the importance of nationwide continuing medical education programs, structured dissemination of the National Cirrhosis Guideline, and engagement with key stakeholders including hospital administrators and government policymakers.

The workgroup mentioned that inclusion of LTA in the next National Formulary update is unlikely in the near term, highlighting the need for regional evidence and alternative financial support mechanisms to improve accessibility. In the interim, LTA may be considered on an individual patient basis when clinically justified, taking into account affordability, monitoring capacity, and local policy constraints.

Comparative clinical profile evaluation of plasma-derived albumin versus RA

Plasma-derived albumin remains the standard therapeutic option for the management of complications related to cirrhosis, supported by decades of clinical use and endorsement in international practice guidelines (2-4,24).

RA was viewed as a potential future alternative with theoretical advantages in scalability and supply stability. Workgroup members emphasized that available evidence is limited to short-term biochemical outcomes, with gaps regarding long-term safety, immunogenicity, and non-oncotic functional equivalence (18-23). Clinical endpoints beyond serum albumin concentration, including survival, length of hospital stay, ascites control, quality of life, acute kidney injury, variceal bleeding, dyselectrolytemia, bacterial infections, and hepatic encephalopathy, were considered essential to fully characterize the therapeutic role of RA in liver disease (19-21,25,26).

The workgroup reached consensus that RA should presently be viewed within the context of future health system planning rather than as a routine replacement for plasma-derived albumin. Robust clinical outcomes data, together with guideline endorsement, will be required before broader clinical integration can be considered.

Discussion

The workgroup meeting reaffirmed the National Cirrhosis Guideline as a critical step toward standardizing cirrhosis management in Indonesia, but effective uptake will require alignment between guideline recommendations and real-world policy and practice. Key priorities include alignment of the National Formulary reimbursement criteria with guideline-endorsed indications, enhancing clinician education, and integrating guideline-based pathways into hospital protocols. This article highlights that beyond issuing guidelines, coordinated implementation efforts, including policy engagement, education, and health system integration, are crucial. In preparation for the meeting, a structured 10-item survey (developed with the National Hepatology Society) was formulated based on clinical guidelines, existing evidence, and meeting objectives in order to address conceptual and practical priorities, specifically evaluating current practice patterns, barriers to guideline uptake (such as policy and economic constraints), and expert perceptions of LTA and RA. By focusing on these targeted topics, the survey ensured that the most relevant factors influencing albumin utilization in cirrhosis were explored.

Insights from the pre-meeting survey highlighted persistent challenges in cirrhosis care in Indonesia. While guideline-endorsed indications for acute albumin therapy are well established, their real-world adoption remains inconsistent, largely due to restrictive reimbursement policy, variable institutional protocols, and limited clinician awareness outside major hepatology centers (5,6,27,28). Delayed diagnosis due to limited screening and fragmented referral pathways, and restricted access to advanced therapies such as liver transplantation, also hinder optimal care.

Beyond acute indications, the workgroup stressed uncertainty about how to optimally use albumin in chronic care (e.g., LTA) (2-4). Key barriers include unclear patient selection and dosing for LTA therapy, limited experience with structured outpatient albumin administration, and high out-of-pocket burden (29,30). Similar challenges have been documented in other healthcare systems, where albumin use is often influenced by cost constraints, supply limitations, and variable institutional priorities (31,32).

International experiences highlight challenges in maintaining a reliable albumin supply. For instance, episodic shortages and cost-containment pressures have been reported in the United States and United Kingdom, while Thailand has invested in domestic production capacity to strengthen supply security (29,31-33). These experiences underscore the need for sustainable albumin supply strategies to ensure alignment between clinical evidence and real-world practice (28,31).

Despite concern about cost, a pharmacoeconomic analysis in Indonesia demonstrated that albumin use is cost-effective for SBP and highly cost-effective for HRS and LVP within the Indonesian healthcare setting (30). Moreover, the incremental cost of weekly albumin infusions for LTA is offset by reductions in hospital admissions, paracentesis frequency, and complications, as evidenced in the ANSWER trial and other pharmacoeconomic analyses from Spain, Brazil, and Mexico (8,14,34-36). These data reinforce the value of albumin when appropriately targeted, suggesting that optimized use may improve outcomes while reducing overall healthcare utilization (8,15,34-36).

Regarding RA, the workgroup acknowledged its potential as an innovative future option with a scalable, pathogen-free manufacturing platform that may offer more consistent batch quality and improved supply stability, attributes particularly relevant for resource-limited settings (18,19). They welcomed the recent clinical findings on RA (22,23) but pointed out several important translational questions that must be resolved before RA can be integrated into clinical practice (19,26). They noted that early RA studies are limited by short follow-up durations and small study populations, providing insufficient evaluation of long-term safety, immunogenicity, repeated exposure in a chronic disease such as cirrhosis, and RA’s ability to replicate human albumin’s non-oncotic functions (22,23,37,38).

With regulatory uncertainty and no current guideline, RA remains a future possibility rather than a near-term replacement for plasma-derived albumin. Robust evidence from adequately powered trials evaluating clinical outcomes, long-term immunogenicity, and functional equivalence is required before RA can be considered for routine use (19,21,26,38). Until such data become available, plasma-derived albumin remains the standard of care for decompensated cirrhosis.

Furthermore, to translate these findings into practice, the workgroup stressed several concrete steps. First, hospitals should establish or update local clinical pathways and standard operating procedures to align with the National Cirrhosis Guideline, ensuring that albumin is prescribed consistently for recommended indications. Second, national and hospital-level education programs (e.g., continuing medical education workshops, seminars, and guideline dissemination sessions) should be implemented to improve healthcare providers’ awareness and knowledge of optimal albumin use, especially in regions beyond major hepatology centers. Third, collaboration with hospital administrators and policymakers is needed to integrate albumin use into quality improvement programs and to advocate for aligning the National Formulary’s reimbursement criteria with contemporary clinical evidence. The workgroup emphasized that these measures, coupled with ongoing monitoring, feedback, and patient education, will facilitate sustainable improvements in cirrhosis care.

A key strength of this manuscript is that it provides the first structured, nationally focused expert perspective on the implementation of the National Cirrhosis Guideline in Indonesia, integrating survey findings with in-depth discussion to address real-world clinical and health system challenges. The participating hepatologists are from high-volume tertiary centers, lending credibility and ensuring recommendations are grounded in contemporary practice and aligned with international evidence while remaining sensitive to local policy and economic constraints. Although efforts were made to ensure independence, the industry-sponsored nature of the meeting may introduce potential perception bias. All participating authors are independent academic clinicians, and the discussions, interpretation of findings, and conclusions were conducted without sponsor influence. Additional limitations include the small number of participants, largely confined to tertiary referral centers, which may reduce generalizability to secondary or rural healthcare settings. Survey findings relied on self-reported practices rather than objective utilization or outcome data, introducing potential reporting bias. In addition, the recommendations are derived from expert consensus and existing literature rather than prospective interventional studies or locally generated outcomes data. Finally, implementation feasibility may vary across institutions and regions within Indonesia, and some recommendations may need further validation through real-world studies and health system evaluations.

Conclusions

The workgroup emphasized that the National Cirrhosis Guideline should remain the primary reference for cirrhosis management in Indonesia. Aligning the National Formulary with guideline-endorsed albumin indications is critical, requiring coordinated engagement across PPHI/Ina-ASL, major hospitals, and the Ministry of Health. However, implementation barriers persist, particularly in the areas of knowledge gaps, financial constraints, and heterogeneous hospital policies, underscoring the need for targeted clinical education, standardized protocols, and improved healthcare infrastructure. LTA provides a clinically promising, mechanistically plausible option for selected patients with decompensated cirrhosis; however, routine adoption will depend on economic feasibility and clearer patient selection and dosing guidance. RA remains a potential future option to improve supply, stability, and scale, but its long-term safety, immunogenicity, and ability to replicate albumin’s non-oncotic benefits require robust evidence before routine clinical adoption. In summary, strengthening national care pathways, improving early diagnosis and monitoring, and broadening clinician and patient education are essential to meet the pressing needs and to improve outcomes across Indonesia.

Supplementary

The article’s supplementary files as

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This manuscript reports findings from an expert medical workgroup meeting and an anonymized pre-meeting survey of practicing hepatologists. No identifiable personal data or patient-level information were collected, and no interventions involving human participants were performed. Ethical approval was therefore not required.