04194 In-depth biochemical investigations in a new case of ALAD deficiency: better understanding for better treatment

Protoporphyric hepatopathy (PPHep) can be a dreaded, longterm complication of erythropoietic protoporphyria (EPP).In fact, PPHep may go unnoticed for years until advanced chronic liver disease (ACLD) develops, leading to cirrhosis and portal hypertension (PH).We present a case of a 31-year-old, lean (BMI 18 Kg/m2) Caucasian male EPP patient, who presented at our Centre with altered liver biochemistry parameters (figure1a) and normal liver function (MELD score 7, Child-Pugh score 5).He had microcytic anaemia, low platelet count (<80000/mm3), and marked splenomegaly (spleen bipolar diameter 15.9 cm, area 93.8 cm2).Although an abdominal ultrasound did not provide clear evidence of ACLD, a liver biopsy was performed, which revealed a picture of cholestatic cirrhosis with fibrous septa, slight chronic inflammation, and diffuse cholestasis, both intracanalicular and intraductal (figure 1b).A gastroscopy detected mild congestive gastropathy without varices.The patient underwent hepatic venous-portal gradient (HVPG) measurement, which revealed a gradient of 7 mmHg, indicating the presence of non-clinically significant sinusoidal portal hypertension (figure 1c).No evidence of vein-to-vein communications was found during venography, which could have led to an underestimation of the gradient.Liver and spleen stiffness were 17.6 kPa and 27.7 KPa, respectively, consistent with the HVPG and other findings.After 3 months of follow-up, during which therapy with ursodeoxycholic acid was started, a dramatic improvement in liver biochemistry abnormalities was observed (figure 1a) with a reduction in liver stiffness (11.6 KPa).Although a definitive confirmation of the type of PH would have required a direct puncture of the portal vein, this case provide indirect evidence that PH in PPHep appears to be strictly sinusoidal, unlike other cholestatic liver diseases such as primary biliary cholangitis.