MANAGING FULMINANT LIVER FAILURE FROM ANTI-TUBERCULOSIS DRUG-INDUCED HEPATOTOXICITY USING DPMAS: A CASE REPORT

Drug-induced liver injury (DILI) remains one of the most challenging complications in clinical medicine, particularly in regions with high infectious disease burdens where multidrug regimens are often indispensable. Among the most common agents responsible are the first-line anti-tuberculosis (anti-TB) drugs—isoniazid, rifampicin, and pyrazinamide—which are widely used as part of standard treatment protocols for tuberculosis. In the Philippines, where TB remains a major public health concern, DILI poses a substantial clinical problem, contributing to cases of acute liver failure (ALF) that carry high morbidity and mortality (Andrade, 2019).

The management of DILI-related ALF is particularly difficult because anti-TB therapy must often continue despite ongoing hepatotoxicity, as premature discontinuation risks disease relapse or resistance. Liver transplantation remains the definitive treatment for fulminant hepatic failure, but in resource-limited settings, it is often not an available or viable option. This gap in therapeutic options underscores the need for alternative modalities that can provide hepatic support and facilitate recovery until native liver regeneration occurs.

The Double Plasma Molecular Adsorption System (DPMAS) has emerged as a promising extracorporeal liver support therapy. Developed in China, it functions by selectively removing bilirubin, bile acids, and inflammatory cytokines from the circulation without depleting essential plasma proteins. By modulating systemic inflammation and reducing toxin accumulation, DPMAS aims to improve biochemical parameters and bridge patients to either recovery or transplantation (Mao, 2020). Clinical data have demonstrated its benefit in acute and acute-on-chronic liver failure, particularly in patients with hepatitis B virus–related or drug-induced injury (Wu, 2018; Zhang, 2021; Guo, 2021).

While DPMAS is still relatively new in the Philippines, emerging experiences from tertiary centers such as the National Kidney and Transplant Institute (NKTI, 2023) have shown encouraging outcomes in patients with TB-DILI–related ALF who were ineligible for transplantation. These early findings suggest that DPMAS may provide an effective and accessible supportive therapy in the management of severe hepatotoxicity. In this report, we describe the case of a 43-year-old Filipino male with biliary tuberculosis who developed fulminant hepatic failure secondary to anti-TB DILI and was successfully managed with DPMAS in a non-transplant setting.

This is a single case report of a patient admitted to East Avenue Medical Center with fulminant hepatic failure due to anti-TB DILI, managed using the Double Plasma Molecular Adsorption System. Clinical information was obtained from medical records, laboratory data, imaging results, and treatment documentation. The diagnosis was based on clinical findings, biochemical evidence of hepatic dysfunction, and a history of exposure to potentially hepatotoxic anti-TB agents.

All management decisions were guided by a multidisciplinary team involving hepatology, nephrology, and infectious disease specialists. DPMAS therapy was performed according to institutional protocols, with each session lasting approximately four hours. The patient’s liver function tests, coagulation profile, and clinical status were monitored before and after each session to assess response. Ethical approval was obtained from the institutional review board, and written informed consent for publication was provided by the patient and his family.

The patient was a 43-year-old Filipino male with biopsy-proven biliary tuberculosis diagnosed earlier in 2024. He initially presented with progressive jaundice, generalized weakness, and later, a new-onset seizure. Over the preceding months, he had been treated with several anti-TB regimens, each modified in response to rising liver enzyme levels and worsening jaundice. Despite drug substitutions, his condition deteriorated, prompting transfer to East Avenue Medical Center for further evaluation and management.

His past medical history revealed that in March 2024, fatty liver changes were detected on imaging. By May, he reported pruritus and unintentional weight loss, but no medical consultation was sought. When symptoms persisted, he sought treatment in Auckland, New Zealand, where imaging revealed intrahepatic biliary abnormalities, right hepatic lobe atrophy, and chronic portal vein thrombosis. ERCP confirmed biliary tuberculosis, and a liver-sparing regimen was initiated. However, hepatic deterioration continued even after adjustments to minimize drug toxicity. Upon returning to the Philippines, he resumed anti-TB therapy, which included hepatotoxic agents, leading to further biochemical derangement.

On presentation, he was conscious and oriented, with stable vital signs but marked jaundice, ascites, and multiple bruises suggestive of bleeding diathesis. His laboratory findings were consistent with acute liver failure: prothrombin time (PT) activity less than 5%, INR greater than 6, activated partial thromboplastin time (APTT) over 200 seconds, and markedly elevated bilirubin levels (total bilirubin 567 µmol/L, direct 415 µmol/L, indirect 151 µmol/L). Transaminases were elevated (AST 285 U/L, ALT 164 U/L), and anemia was present (hemoglobin 84 g/L), with leukocytosis and reactive thrombocytosis. Electrolyte results showed mild hyponatremia (129 mmol/L) and low magnesium (0.83 mmol/L), while renal function was preserved. Imaging from prior hospitalization confirmed intrahepatic biliary strictures, right lobe atrophy, and chronic portal vein thrombosis. Serologic testing for hepatitis B was negative.

The diagnosis of fulminant hepatic failure was made, likely secondary to cumulative hepatotoxicity from anti-TB drugs on a background of biliary tuberculosis and vascular compromise. Management focused on stabilizing liver function and providing supportive care. Fresh frozen plasma and packed red blood cell transfusions were given to address coagulopathy and anemia. Because transplantation was not feasible, DPMAS therapy was initiated as a bridging intervention.

The patient underwent four sessions of DPMAS on January 9, 11, 13, and 18. Each treatment session aimed to reduce serum bilirubin and circulating hepatotoxins. Following therapy, his biochemical and clinical condition improved significantly. Post-DPMAS laboratory results showed normalization of coagulation parameters (PT 11.30 seconds, INR 0.90) and a marked decline in bilirubin levels (total 308 µmol/L, direct 228 µmol/L, indirect 79 µmol/L). The patient’s mental status stabilized, and his jaundice and bleeding manifestations gradually regressed.

During hospitalization, his anti-TB regimen was carefully adjusted to maintain efficacy while minimizing hepatotoxic risk. Moxifloxacin and ethambutol were retained, while other agents were tapered or reintroduced cautiously as liver function improved. No adverse reactions to DPMAS were observed throughout the treatment course. The patient was eventually discharged in stable condition, with ongoing outpatient follow-up showing continued improvement in hepatic function.

This case highlights the clinical challenges of managing drug-induced liver failure secondary to anti-tuberculosis therapy, especially in resource-limited settings where liver transplantation is not always available. The patient’s course underscores the complexity of balancing effective TB treatment against the hepatotoxic potential of essential medications.

The successful recovery observed in this case demonstrates the potential of the Double Plasma Molecular Adsorption System as an effective adjunctive therapy in acute liver failure. DPMAS facilitated a rapid decline in bilirubin and normalization of coagulation parameters, translating to meaningful clinical improvement. By removing bilirubin, bile acids, and inflammatory mediators, DPMAS provides a supportive mechanism that allows time for hepatic regeneration and recovery without the need for transplantation.

Reports from prior studies have supported similar benefits. Wu and colleagues (2018) demonstrated improved liver function and survival among patients with HBV-related ALF treated with DPMAS, while Zhang (2021) reported its utility in non-viral etiologies of acute liver failure. Guo (2021) described cases of anti-TB DILI showing rapid biochemical and neurologic improvement within days of DPMAS initiation. The results in this case parallel these findings, suggesting that DPMAS can be safely and effectively applied beyond viral causes of liver failure.

In the Philippine context, where tuberculosis is prevalent and liver transplantation remains scarce, DPMAS represents a valuable therapeutic bridge. Its ability to stabilize patients with severe hepatotoxicity can buy critical time for the liver to recover while allowing cautious continuation of TB therapy. Furthermore, its selective adsorption capability minimizes the removal of essential plasma components, making it well-suited for coagulopathic patients.

While this single case cannot establish causality or define treatment protocols, it contributes to the growing body of evidence supporting DPMAS as a viable non-transplant therapeutic option for ALF secondary to drug-induced hepatotoxicity. Continued documentation and local experience will be essential to develop standardized guidelines for its timing, frequency, and patient selection.

In conclusion, DPMAS offers a practical, life-saving intervention in managing fulminant liver failure secondary to anti-TB DILI, especially in regions where transplantation is not accessible. Early recognition of hepatic injury, prompt withdrawal of offending agents, and timely initiation of DPMAS can significantly improve outcomes. This case exemplifies the potential of extracorporeal liver support systems to bridge patients to recovery and redefine management strategies for drug-induced hepatic failure in developing healthcare settings.