Table 1.
Clinical characteristics of family members.
| Person (Fig. 1A) | MTTP p.Ile564Thr | Sex (male/female) | Liver disease diagnosis (method) | Age diagnosed (years) | Type 2 diabetes | BMI | Hypertension | Liver biochemistry and lipid blood analyses at diagnosis | Other subsequent investigations, treatments, and comorbidities | PNPLA3 p.I148M | TM6SF2 p.E167 K | MTTP p.I128T | MTTP p.Q297H |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| B | IT | F | Cirrhosis and ascites (USS) | 88 | x | <30 | ✓ | ALT = 26, AP = 120, Chol = 3.5, TG = 1.29 | Cardiovascular-related death aged 90 | MM | EK | TT | HH |
| C | TT | F | HCC and cirrhosis (CT/biopsy) | 57 | ✓ | <30 | ✓ | ALT = 38, AP = 129, normal lipids | Liver resection ablation, right hemihepatectomy, HCC recurred; liver-related death | IM | EE | TT | HH |
| D | TT | M | Cirrhosis (MRI) | 60 | x | <30 | ✓ | Bilirubin = 312 μmol/L, normal lipids | Liver screen = normal; died of gallbladder sepsis aged 72 | IM | EE | TT | HH |
| E | IT | M | FL (USS) | 57 | ✓ | 30 | ✓ | ALT = 30, AP = 75, Chol = 2.5, TG = 0.75, HDL = 1.2 mmol/L, LDL = 1.0 mmol/L | Stable for 18 years: TE = 5.8 kPa, CAP = 341, ApoB = 0.94 | IM | EE | nd | HH |
| F | TT | M | Cirrhosis (USS) | 56 | x | 21 | ✓ | ALT = 23, AP = 125, Chol = 2.4, TG = 0.58, HDL = 1.7 mmol/L, LDL = 0.4 mmol/L | No retinitis pigmentosa; vagotomy and pyloroplasty; mild bone marrow failure | IM | EK | TT | HH |
| G | T∗ | M | HCC and cirrhosis (biopsy) | 57 | x | <30 | X | Normal lipids | Multifocal HCC: chemotherapy and hepatectomy; died aged 61 | nd | Nd | nd | nd |
| H | TT | M | HCC, cirrhosis, portal hypertension | 51 | x | <30 | ✓ | Chol = 2.2, TG = 0.2, HDL = 1.6 mmol/L, LDL = 0.5 mmol/L | Liver transplant twice; died of cardiac complications aged 63 | IM | EK | TT | nd |
| I | II | F | FL (USS) | 50 | x | <30 | X | Diet/lifestyle changed: recovered/stable for >5 years: TE = 4.0 kPa; CAP = 223 ApoB = 1.02 | IM | EE | TT | HH | |
| J | TT | F | Cirrhosis (MRI) HCC |
50 54 |
x | 25 | ✓ | ALT = 52, AP = 87, ApoB = 0.32, normal lipids | Liver transplant age 56: recovered/stable for >5 years: TE = 4.6 kPa, CAP = 214, BMI = 20.3; duodenal biopsy: no evidence of abetalipoproteinaemia | IM | EE | TT | HH |
| K | IT | F | NASH (USS) (TE:CAP = 380) |
48 | x | 24 | ✓ | ALT = 79, AP = 108, normal lipids, ApoB = 1.0 | Diet/lifestyle changed: recovered/stable for 10 years: TE = 6.2 kPa, CAP = 298; duodenal biopsy: no evidence of abetalipoproteinaemia | IM | EK | nd | HH |
| L | TT | F | Cirrhosis (USS) | 59 | x | 18 | ✓ | Elevated ALT and AST, normal lipids | Stable for 10 years: TE = 10.3 kPa, CAP = 276, ALT = 104, AP = 87, AST = 73, cardiac arrhythmia, osteoporosis, vitamin D deficiency | IM | EE | TT | HH |
| M | II | M | Healthy | x | x | 26 | X | Normal lipids | TE = 4.6 kPa, CAP = 253, vitamin D deficiency | II | EK | IT | QH |
| N | IT | M | NASH (USS) | 40 | x | 28 | X | TE = 3.6 kPa, CAP=373; lipids and ALT elevated | Lifestyle and diet modified – stable for 7 years | IM | EK | nd | QH |
| O | IT | M | FL (USS) | 38 | x | 27 | X | Lipids elevated | Lifestyle and diet modified – recovered; stable for 19 years: TE = 5.8 kPa, CAP = 341 | II | EK | IT | QH |
| Q | IT | M | FL (USS) | 28 | x | 19 | X | Normal lipids, duodenal Biopsy: evidence of duodenal lipid | Improved after 10 years: TE = 6.3 kPa, CAP = 199 | MM | EE | IT | HH |
For MTTP p.E98D, all tested were EE; for MTTP p.N166S, all tested were NN.
ALT, alanine transaminase (U/L); AP, alkaline phosphatase (U/L); ApoB, apolipoprotein B (g/L); CAP, controlled attenuation parameter (dB/m); Chol, cholesterol (mmol/L); CT, computed tomography; FL, fatty liver; HCC, hepatocellular carcinoma; MRI, magnetic resonance imaging; nd, not determined; TE, transient elastography; TG, triglycerides (mmol/L); USS, abdominal ultrasonographic steatosis score.
∗
Likely T carrier based on pedigree.