24 August 2026
: Case report 
Refractory Hyperammonemic Encephalopathy as a Paraneoplastic Presentation of Fibrolamellar Hepatocellular Carcinoma: A Case Report
Management of emergency care, Rare disease
Ritwik Dey
ABDEF 1*, Harshitha Popuri ABDEF 1, Virali Gulla BDEF 1, Yagnapriya Chirrareddy EF 1, Satyapriya Paritala EF 1, Daniel Bustamante ABDE 2, Javier Corral ABDEF 3
DOI: 10.12659/AJCR.952819
Am J Case Rep 2026; 27:e952819
Table 3 Summary of cases of fibrolamellar hepatocellular carcinoma with hyperammonemic encephalopathy, treatment, and outcomes.
| No. | Paper | Age (years) | Sex | Timeline of HAE | Ammonia levels (μmol/L) | Treatment for FLHCC | Treatment for HAE | Outcome of FLHCC | Outcome of HAE |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 2008 Chan et al []31 | 22 | F | After 2 days of initiating chemotherapy | 280 | Chemotherapy (doxorubicin, cisplatin, fluorouracil, interferon-alfa) | Arginine, citrulline | Disease progressed | Improved |
| 2 | 2009 Sethi et al []32 | 18 | M | Initial | 137 | Chemotherapy (sorafenib) | Not available | Died | Died |
| 3 | 2012 Berger et al []33 | 22 | F | Initial | 254 | Not available | None | Not available | Not available |
| 4 | 2012 Hashash et al []34 | 18 | F | Presented with HAE | 342 | Multiple resection surgeries | Mannitol, hyperventilation, therapeutic hypothermia, lactulose, rifaximin, and hemodialysis (ineffective); sodium phenylacetate and sodium benzoate (ineffective); then TPN with arginine supplementation | Remission | Improved |
| 5 | 2014 Suliman et al []12 | 20 | F | 6 years after diagnosis | 410 | Left hepatectomy and chemotherapy | IV sodium benzoate and phenylbutyrate infusion; oral sodium benzoate, phenylbutyrate, and arginine | Disease progressed | Improved |
| 6 | 2015 Bender et al []35 | 19 | F | 9 months after initial diagnosis | 264 | Chemotherapy (sorafenib, bevacizumab, erlotinib, platinum, doxorubicin, gemcitabine), surgery, and radiotherapy | Lactulose and rifaximin, sodium phenylbutyrate | Recurrence | Improved |
| 7 | 2016 Alsina et al []36 | 23 | F | Initial | 281 | Chemotherapy (sorafenib) and liver transplantation | Sodium phenylbutyrate, sodium benzoate, arginine | Remission | Improved |
| 8 | 2016 Chapuy et al []1 | 31 | M | 3 days after receiving chemotherapy | 300 | Chemotherapy (GEMOX × 6 cycles) and salvage debulking surgery | Lactulose (initial improvement); ammonia scavenger therapy with citrulline added for subsequent episodes | Stable disease | Improved |
| 9 | 2017 Surjan et al []17 | 31 | M | 1 week after diagnosis | 312 | Chemotherapy (sorafenib and GEMOX) | Neomycin, lactulose, and L-ornithine-L-aspartate; sodium benzoate and arginine | Not available | Improved |
| 10 | 2018 Bartlett et al []37 | 13 | M | 8 days after treatment | 317 | Chemotherapy (sorafenib, GEMOX, nivolumab, cyclophosphamide/topotecan, crizotinib) | Arginine, lactulose, and rifaximin | Disease progressed | Improved |
| 11 | 2018 Bartlett et al []37 | 17 | F | 8th cycle of chemotherapy | 329 | Chemotherapy (sorafenib, GEMOX, cabozantinib, nivolumab) | Arginine and sodium benzoate/sodium phenylacetate | Stable disease | Improved |
| 12 | 2018 Suarez et al []38 | 33 | F | At diagnosis | Not available | Cadaveric liver transplantation | Hemofiltration and ammonium benzoate | No relapse | Improved |
| 13 | 2019 Cho et al []6 | 32 | F | Not available | 300 | Chemoembolization, surgical resections, chemotherapy (nivolumab) | Sodium phenylacetate and benzoate | Not available | Improved within 2 days |
| 14 | 2020 Thakral et al []39 | 32 | F | 6 years after diagnosis | 300 | Chemoembolization, surgical resection, chemotherapy (sorafenib, ponatinib, GEMOX) | Lactulose, sodium phenylacetate, and arginine; L-citrulline, glycerol phenylbutyrate, lactulose, and rifaximin | Died | Died |
| 15 | 2020 Lee et al []40 | 18 | M | At diagnosis of HCC | 393 | Chemotherapy (cisplatin, 5-fluorouracil, doxorubicin, interferon-alfa) and hemi-hepatectomy | Lactulose and rifaximin, then CVVH with sodium benzoate, sodium phenylacetate, arginine, carnitine, and 20% dextrose | Not available | Improved |
| 16 | 2020 Shah et al []41 | 26 | F | Not available | 160 | Surgical resection of liver, colon, and small bowel | Sodium benzoate and L-arginine | Not available | Improved |
| 17 | 2020 Surjan et al []42 | 39 | F | 8 years after diagnosis | 663 | Left hepatectomy with intrahepatic biliodigestive anastomosis | L-ornithine-L-aspartate, polyethylene glycol with lactulose, TPN with amino acid supplementation, hemodialysis, sodium benzoate | Not available | Improved |
| 18 | 2022 Ahmed et al []15 | 28 | M | 9 months after initial diagnosis | 338 | Chemotherapy (FOLFOX, atezolizumab/bevacizumab × 5 cycles, then GEMOX) | Lactulose, ammonia scavenger therapy | Disease progressed | Improved within 24 hours |
| 19 | Present case | 24 | M | 7 years after diagnosis | 271 | TARE, multiple resection surgeries, chemotherapy (nivolumab, cabozantinib, lenvatinib, regorafenib, GEMOX, pembrolizumab/ipilimumab, capecitabine), and radiotherapy | Lactulose and rifaximin, then sodium benzoate–sodium phenylacetate and arginine, intermittent hemodialysis, and CRRT | Disease progressed | Died |
| F, female; M, male; CRRT, continuous renal replacement therapy; CVVH, continuous venovenous hemofiltration; FLHCC, fibrolamellar hepatocellular carcinoma; FOLFOX, folinic acid, fluorouracil, and oxaliplatin; GEMOX, gemcitabine and oxaliplatin; HAE, hyperammonemic encephalopathy; HCC, hepatocellular carcinoma; IV, intravenous; TARE, transarterial radioembolization; TPN, total parenteral nutrition. | |||||||||