TY - JOUR
T1 - Hepatocellular Carcinoma in Acute Hepatic Porphyrias
T2 - Results from the Longitudinal Study of the U.S. Porphyrias Consortium
AU - Saberi, Behnam
AU - Naik, Hetanshi
AU - Overbey, Jessica R.
AU - Erwin, Angelika L.
AU - Anderson, Karl E.
AU - Bissell, D. Montgomery
AU - Bonkovsky, Herbert L.
AU - Phillips, John D.
AU - Wang, Bruce
AU - K.Singal, Ashwani
AU - M.McGuire, Brendan
AU - Desnick, Robert J.
AU - Balwani, Manisha
N1 - Funding Information:
Data were obtained from the Longitudinal Study of the Porphyrias (NCT01561157), which is a long-term observational natural history study conducted by the Porphyrias Consortium. This investigation of the natural history, complications, and therapeutic outcomes in patients with AHP and other porphyrias was conducted in accordance with the Declaration of Helsinki. Each site’s institutional review board approved the study, and informed consent was obtained from all subjects. The clinical, biochemical, and genetic testing findings in the AHP cohort have been described.(24) All patients included had a confirmed diagnosis of AHP with elevated urine PBG and/or a pathogenic HMBS, PPOX (protoporphyrinogen oxidase), CPOX (coproporphyrinogen-III oxidase) mutation. Elevated PBG was defined as urinary PBG greater than 8 mg/24 hours or per gram of creatinine, or greater than 2-fold increase relative to the upper limit of normal of 4 mg/24 hours or per gram of creatinine (https://clinicaltrials.gov/ct2/show/NCT01561157). Medical histories were queried for liver cancer, and diagnoses of HCC were confirmed by review of medical records, liver imaging, and/or pathology. Pathology reports were reviewed when available for patients who had liver biopsies or resections of their HCCs. Data were obtained from the Longitudinal Study of the Porphyrias (NCT01561157), which is a long-term observational natural history study conducted by the Porphyrias Consortium. This investigation of the natural history, complications, and therapeutic outcomes in patients with AHP and other porphyrias was conducted in accordance with the Declaration of Helsinki. Each site’s institutional review board approved the study, and informed consent was obtained from all subjects. The clinical, biochemical, and genetic testing findings in the AHP cohort have been described.(24) All patients included had a confirmed diagnosis of AHP with elevated urine PBG and/or a pathogenic HMBS, PPOX (protoporphyrinogen oxidase), CPOX (coproporphyrinogen-III oxidase) mutation. Elevated PBG was defined as urinary PBG greater than 8 mg/24 hours or per gram of creatinine, or greater than 2-fold increase relative to the upper limit of normal of 4 mg/24 hours or per gram of creatinine (https://clinicaltrials.gov/ct2/show/NCT01561157). Medical histories were queried for liver cancer, and diagnoses of HCC were confirmed by review of medical records, liver imaging, and/or pathology. Pathology reports were reviewed when available for patients who had liver biopsies or resections of their HCCs. All analyses are descriptive. Categorical measures are reported as the number and percentage, and continuous measures are reported as the median and interquartile range. All analyses were conducted using SAS version 9.4 (SAS, Cary, NC).(25)
Publisher Copyright:
© 2020 by the American Association for the Study of Liver Diseases.
PY - 2021/5
Y1 - 2021/5
N2 - Background and Aims: The risk for hepatocellular carcinoma (HCC) is increased in acute hepatic porphyrias (AHP). The aim of this study was to explore the clinicopathologic characteristics, outcomes, and frequency of HCC in patients with AHP in the United States. Approach and Results: This cross-sectional analysis evaluated patients with HCC in a multicenter, longitudinal study of AHP. Among 327 patients with AHP, 5 (1.5%) were diagnosed with HCC. Of the 5 HCC cases, 4 had acute intermittent porphyria and 1 had variegate porphyria, confirmed by biochemical and/or genetic testing. All patients were white females, with a median age of 27 years (range 21-75) at diagnosis. The median age at HCC diagnosis was 69 years (range 61-74). AHP was asymptomatic in 2 patients; 2 reported sporadic attacks; and 1 reported recurrent attacks (>4 attacks/year). All patients had a single HCC lesion on liver imaging that was 1.8-6.5 centimeters in diameter. Serum alpha fetoprotein levels were below 10 ng/mL in all 4 patients with available results. Four patients underwent liver resection, and 1 was treated with radioembolization. No significant inflammation or fibrosis was found in adjacent liver tissues of 3 patients who underwent liver resection. Two patients developed recurrence of HCC at 22 and 26 months following liver resection. All patients are alive with survival times from HCC diagnosis ranging from 26-153 months. Conclusion: In this U.S. study, 1.5% of patients with AHP had HCC. HCC in AHP occurred in the absence of cirrhosis, which contrasts with other chronic liver diseases. Patients with AHP, regardless of clinical attacks, should be screened for HCC, beginning at age 50. The pathogenesis of hepatocarcinogenesis in AHP is unknown and needs further investigation.
AB - Background and Aims: The risk for hepatocellular carcinoma (HCC) is increased in acute hepatic porphyrias (AHP). The aim of this study was to explore the clinicopathologic characteristics, outcomes, and frequency of HCC in patients with AHP in the United States. Approach and Results: This cross-sectional analysis evaluated patients with HCC in a multicenter, longitudinal study of AHP. Among 327 patients with AHP, 5 (1.5%) were diagnosed with HCC. Of the 5 HCC cases, 4 had acute intermittent porphyria and 1 had variegate porphyria, confirmed by biochemical and/or genetic testing. All patients were white females, with a median age of 27 years (range 21-75) at diagnosis. The median age at HCC diagnosis was 69 years (range 61-74). AHP was asymptomatic in 2 patients; 2 reported sporadic attacks; and 1 reported recurrent attacks (>4 attacks/year). All patients had a single HCC lesion on liver imaging that was 1.8-6.5 centimeters in diameter. Serum alpha fetoprotein levels were below 10 ng/mL in all 4 patients with available results. Four patients underwent liver resection, and 1 was treated with radioembolization. No significant inflammation or fibrosis was found in adjacent liver tissues of 3 patients who underwent liver resection. Two patients developed recurrence of HCC at 22 and 26 months following liver resection. All patients are alive with survival times from HCC diagnosis ranging from 26-153 months. Conclusion: In this U.S. study, 1.5% of patients with AHP had HCC. HCC in AHP occurred in the absence of cirrhosis, which contrasts with other chronic liver diseases. Patients with AHP, regardless of clinical attacks, should be screened for HCC, beginning at age 50. The pathogenesis of hepatocarcinogenesis in AHP is unknown and needs further investigation.
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U2 - 10.1002/hep.31460
DO - 10.1002/hep.31460
M3 - Article
C2 - 32681675
AN - SCOPUS:85097374182
SN - 0270-9139
VL - 73
SP - 1736
EP - 1746
JO - Hepatology
JF - Hepatology
IS - 5
ER -