Table 3.
State transition probabilities and test characteristics for biopsy, AFP, and USS combined and fibroscan that are used within the model
| HCV natural history/mortality rates | State transition rate and test characteristics |
Definition information/source reference | Sensitivity analysis | |
|---|---|---|---|---|
| Low | High | |||
| HCV natural history (TR) | ||||
| No cirrhosis to fibrosis stage Metavir 1 | Rate: 0.1098 Annual TP: 0.1040 |
Townsend et al. [10]; (Thein et al. [6]—0.1244) | 0.054 | 0.154 |
| Metavir 1 to Metavir 2 | Rate: 0.0954 Annual TP: 0.0910 |
Townsend et al. [10]; (Thein et al. [6]—0.0888) | 0.075 | 0.096 |
| Metavir 2 to Metavir 3 | Rate: 0.0954 Annual TP: 0.0910 |
Townsend et al. [10]; (Thein et al. [6]—0.1278) | 0.054 | 0.133 |
| Incidence of cirrhosis from Metavir 3 | Rate: 0.1233 Annual TP: 0.1160 |
Thein et al. [6]-transition from F3-F4 (Townsend et al. [10]—similar value calculable via probabilities and assumptions) |
0.104 | 0.129 |
| Decompensation of cirrhosis | Rate: 0.0429 Annual TP: 0.0420 |
The Global Burden of Hepatitis C Working Group [66], Chen et al. [67], Limits Townsend et al. [10] |
0.0161 | 0.0888 |
| HCC natural history | ||||
| Incidence of HCC in patients with Metavir 3 | Rate: 0.0080 Annual TP: 0.0020 |
Lok et al. [15]. (sensitivity from no risk without cirrhosis to same risk as in cirrhosis) |
0.0 | 0.0202 |
| Incidence of HCC in patients with cirrhosis | Rate: 0.0202 Annual TP: 0.0050 |
Salomon et al. [63] | 0.015 | 0.030 |
| Growth of HCC—from operable to inoperable | Rate: 0.145 Annual TP: 0.1349 |
Naugler and Sonnenberg [62], Lin et al. [38] | 0.1 | 0.7 |
| Mortality rates (probability) | ||||
| Biopsy | <40 years: 0.0005 40–59 years: 0.0011 60–79 years: 0.0048 >80 years: 0.0065 |
Population database study by West and Card [24] | <40: 0.0002 40–59: 0.0008 60–79: 0.0039 >80: 0.0028 Tornado: 0.00 |
0.0010 0.0016 0.0059 0.0127 Tornado: 0.0127 |
| Compensated cirrhosis | 0.084 | Fleming et al. [57] | 0.079 | 0.089 |
| Decompensated cirrhosis | 0.14 | The Global Burden of Hepatitis C Working Group [66], Chen et al. [67] |
0.10 | 0.30 |
| HCC with fibrosis stage Metavir 3 | 0.598 | Greten et al. [59] | 0.231 | 1.040 |
| HCC and compensated cirrhosis | 0.494 | Greten et al. [59] [–ln(0.49)] | 0.2466 | 1.188 |
| HCC with decompensated cirrhosis | 1.514 | Greten et al. [59] [–ln(0.8)] | 0.6397 | 2.0790 |
| Resection (perioperative) | 0.04 | Llovet and Ducreux [19], Lin et al. [38], Chang et al. [17] | 0.013 | 0.108 |
| Ablation (perioperative) | 0.03046 | Lin et al. [38], Livraghi et al. [60], Mondazzi et al. [61] | 0.0101 | 0.0618 |
| Patients who have received successful resection or ablation |
0.0693 | Llovet and Ducreux [19], Fong et al. [58], Bruix and Sherman [20] |
0.05 | 0.08 |
| Transplant (perioperative) | 0.0975 | Adam et al. [55]. Mortality is 9 % in first 6 months | 0.1450 | 0.2900 |
| Transplant recipients | 0.0301 | Mazzaferro et al. [68], Llovet et al. [69], Bismuth et al. [70], Bruix and Sherman [20] |
0.025 | 0.050 |
| HCC recurrence | 0.7713 | Ladabaum et al. [71] | 0.5108 | 0.9163 |
| HCC given palliative care in line with NICE recommendations (including Sorafanib) |
1.1215 | Carr et al. [72] | 0.895 | 1.245 |
| Test characteristics: biopsy | ||||
| Sensitivity of biopsy | 0.669 | Regev et al. [23]: 33.1 % false negatives; Bedossa et al. [4] | 0.60 | 1.00 |
| Likelihood of being biopsied through routine surveillance when asymptomatic |
0.2309 | Foster et al. [21]: 50 % of chronic HCV patients without already diagnosed cirrhosis will receive a biopsy in 3 years; Sweeting et al. [22] from two cohorts: 54 % at 16 years and 87 % in 7.6 years (rate = 0.2310) |
0.0354 | 0.5358 |
| Probability of biopsy when symptoms develop (includes probability that patient is suitable for biopsy) |
0.4 | Freeman et al. [8]: 59 % in community studies, none from UK; Sweeting et al. [22]: 0.33 in UK population (Trent group) |
0.3 | 0.6 |
| Probability of incidental HCC being diagnosed on routine biopsy | 0.0379 | Based on data of incidental diagnosis from Trevisani et al. [64] |
0.00 | 0.0488 |
| Test characteristics: AFP and USS | ||||
| Sensitivity of combined AFP and USS screening | 0.85 | Lin et al. [38] | 0.55 | 0.95 |
| Specificity of combined AFP and USS screening for HCC in HCV | 0.8 | Lin et al. [38] | 0.70 | 0.90 |
| Test characteristics: fibroscan | ||||
| Probability of patient not being suitable for fibroscan: e.g.>BMI |
0.031 | Castera et al. [27] [BMI[30]; High parameter limit informed from UK obesity statistics |
0.00 | 0.461 |
| Probability of scan failure (10 valid shots not achieved) | 0.2 | Degos et al. [32], Stamuli et al. [40] (sensitivity analysis high limit informed by Castera et al. [27]) |
0.01 | 0.417 |
| Probability of incidental diagnosis of HCC during fibroscan | 0 | Fibroscan measures only liver stiffness and does not produce images; no evidence of assessment or calibration of any changes in output in HCC |
0 | 0 |
| Sensitivity of fibroscan in diagnosing Metavir 3 | 0.82 | Tzochatzis et al. [31] | 0.77 | 0.87 |
| Sensitivity of fibroscan for diagnosing cirrhosis | 0.83 | Tzochatzis et al. [31] | 0.79 | 0.86 |
| Specificity of fibroscan for diagnosing Metavir 3 | 0.86 | Tzochatzis et al. [31] | 0.80 | 0.91 |
| Specificity of fibroscan for diagnosing cirrhosis | 0.91 | Tzochatzis et al. [31] | 0.84 | 0.95 |
TR Transition rate, BMI body mass index, NICE UK National Institute of Clinical Evidence
Probability of false positive results is 1 – specificity and the probability of a false negative is 1 – sensitivity. References for values used and the upper and lower limits used in the sensitivity analysis