Risk of Hepatocellular Carcinoma in Patients with Porphyria: A Systematic Review

Abstract

Acute porphyrias are a group of metabolic disorders resulting in defective porphyrin synthesis and reduced heme production, which carries a risk of malignancy. Porphyrias are inborn defects in the heme biosynthesis pathway resulting in neurovisceral manifestations and cutaneous photosensitivity attacks with multi-systemic involvement. Its estimated prevalence nears 5 per 100,000 patients worldwide. Subclinical liver disease is common, which can progress into transaminitis, fibrosis, cirrhosis, and malignancy. However, data on the incidence of primary liver cancer are lacking. We aim to determine the risk of hepatocellular carcinoma (HCC) in patients with porphyria. A systematic review and pooled analysis were conducted through 2021 on studies assessing blood tests, imaging, cancer development, liver transplant, surgical resection, and outcomes in porphyria. In total, 19 studies, which included 7381 patients with porphyria (3476 females), were considered for the final review. In eight studies, alpha-fetoprotein levels were elevated between 200 and 1000 IU/mL. Of the total cohort of patients with porphyria, primary liver cancer was diagnosed in 351 patients (4.8%), of whom 243 (3.3% of the total) were found to have HCC. A subset of patients was found to have cholangiocarcinoma (n = 18; 0.3% of the total). Interestingly, advanced liver disease or cirrhosis was not a prerequisite for the formation of HCC in a small group of patients. Of the total cohort, 30 patients underwent liver resection, 48 patients underwent liver transplantation, and 327 patients died. Patients with porphyria are at risk of developing primary liver malignancy. Further studies should aim to develop diagnostic and prognostic models aimed at the early detection of HCC in porphyria.

Intrahepatic Cholangiocarcinoma and Acute Intermittent Porphyria: A Case Report

“…Primary liver cancer is the most reported tumor in patients with acute hepatic porphyria, predominantly HCC and with rare occurrence of CCA. A recent meta-analysis included 7381 patients with porphyria (3476 females) and reported occurrence of primary liver cancer in 4.8% of patients, precisely 3.3% diagnosed with HCC and 0.3% of the total diagnosed with CCA [16]. Due to the rarity of the disease, screening and follow-up of patients and their relatives must take into account the balance of benefits, costs and harms.…”

“…Any form of surveillance is potentially harmful, for example by causing anxiety to otherwise asymptomatic individuals and by generating some false positive screening tests. For a pragmatic approach to surveillance, in Sweden annual abdominal ultrasound monitoring is recommended for patients over 50 years of age, whereas α-fetoprotein does not appear to be relevant for monitoring AHP patients [16][17][18][19].…”

The Hepatic Porphyrias: Revealing the Complexities of a Rare Disease

“…The American Association for the Study of Liver Diseases (AASLD) provides guidelines recommending liver ultrasound with or without alfa-fetoprotein (AFP; a tumor marker used to detect and diagnose certain cancers and liver diseases) every 6 months for surveillance of HCC. 99 Liver resection has been reported as the most common treatment in AIP patients with malignancy as well as locoregional therapy in other patients. Liver transplantation has been successfully conducted in AIP but not in patients comorbid for AIP and HCC.…”

An Overview of Acute Hepatic Porphyrias: Clinical Implications, Diagnostic Approaches, and Management Strategies

“…Porphyria guidelines generally recommend screening AIP patients every 6-12 months by imaging and measurement of alpha-fetoprotein levels beginning from the age of 50 years. 15 , 16 …”