Table 1.
Clinical studies investigating changes in VWF and ADAMTS13 parameters in chronic liver diseases.
| Cohort | VWF | ADAMTS13 | VWF: ADAMTS13 | Other | Ref | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Ag | Act | Ratio | HMW Multimers | Ag | Act | Ratio | Ratio | |||
| Decompensated Cirrhosis (n=10) | ↑ | ↑ | ↓ | ↓ | NA | Heightened VWF proteolysis. Evidence of plasmin-cleaved VWF fragments | [65] | |||
| Cirrhosis Child A,B,C Cholestasis excluded (n=32) | ↑ in Child B & C | ↑ in Child B & C | NA | ≡ | NA | Normal proteolysis, no evidence of novel VWF fragments | [72] | |||
| Cirrhosis with PH, mixed etiology, Child-Pugh score <9 or ≥9 (n=27) | ↑ with disease severity | NA | VWF:Ag higher in patients with ascites than without. | [74] | ||||||
| Decompensated Cirrhosis (n=42) | ↑ | ↑ | ↓ | NA | NA | ↓ | NA | [69] | ||
| Liver disease patients who underwent liver resection, mixed etiology (biliary disease &viral hepatitis) (n= 19) | ↑ | NA | Correlation between VWF levels and FVIII levels. Hepatic VWF mRNA increased in cirrhotic patients. More VWF staining in liver of patients with cirrhosis. | [139] | ||||||
| Cirrhosis (n=54) and ALF (n=5), mixed etiologies, Child A,B,C | ↑ with disease severity, highest in ALF | ↑ with disease severity, highest in ALF | ↓ with disease severity, lowest in ALF | ↓ | Variable, not different | Variable, not different | NA | Increased platelet adhesion over collagen surface. VWFpp ↑ with disease severity | [59] | |
| Cirrhosis Child C alcohol-induced (n=3), Child B viral hepatitis (n=1) | NA | Decreased platelet adhesion over collagen and fibrinogen coated surface, but normal when corrected for lower platelet count. | [56] | |||||||
| Cirrhosis Child A,B,C (n=90) | ↑ with disease severity | NA | NA | Shift from LMW to normal to UL-VWF as liver function deteriorated | ↓ with disease severity | ↓ with disease severity | ≡ | NA | PVT often observed in advanced disease patients. IgG autoantibodies present in severe ADAMTS13 deficiency. | [67] |
| Cirrhosis, mixed etiology (n=109) and chronic hepatitis (n=33) Child A,B,C | ↑ with disease severity | ↑ with disease severity | ↓ with disease severity | Variable. 53% had normal, 30% had loss of HMW, 16% had UL-VWF | ↓ with disease severity | ↓ with disease severity | NA | ↑ with disease severity | Patients with UL-VWF had lowest ADAMTS13 levels. ADAMST13 was lowest when complicated with HCC | [47] |
| Cirrhosis (Cholestasis excl) with PH (n=42) | ↑ correlated with Child-Pugh score and MELD score | NA | Positive correlation between VWF levels and portal pressure. VWF levels predict poor outcome (death, portal hypertension-related complications or transplant) | [75] | ||||||
| NCIPH (n=18), other chronic liver disease (n=25) | Not different | ↓ in NCIPH | NA | Variable | ↓ in NCIPH | ↓ in NCIPH | ↓ in NCIPH | NA | [140] | |
| Cirrhosis with PH (n=211) or without PH (n= 75) and compensated (n=189) or decompensated (n=97) | ↑ higher in decompensated vs compensated, higher in PH patient than without PH. Higher in patients who died. | NA | ↑ VWF associated with varices and ascites. Correlation between VWF and portal pressure. VWF predicted mortality in compensated and decompensated patients | [76] | ||||||
| Cirrhosis, mixed etiology (n=108) Child A,B,C | ↑ with disease severity | ↑ with disease severity | ↓ with disease severity | Variable, degraded and normal in Child B, majority normal in Child C but UL-VWF found in 24% | NA | ↓ with disease severity | NA | ↑ with disease severity | Inhibitor against ADAMTS13 in 83% of patients. Survival lowest in patients with severe to moderate ADAMST13 deficiency. Child A with HCC had a significantly lower ADAMTS13:AC than those without HCC | [66] |
| Chronic Hepatitis C (n=294) | ↑ with stage of fibrosis | NA | VWF level predicts advanced liver fibrosis and cirrhosis | [141] | ||||||
| Stable Cirrhosis with (n=31) or without (n=114) HPS, mixed etiology Child A,B,C | ↑ in HPS patients and in patients with complications (ascites, encephalopathy, GI bleeding, transplant/death) | NA | Association between high VWF and HPS, VWF predictor for presence of HPS | [142] | ||||||
| NCIPH (n=29), Cryptogenic Liver disease (n=22) | ↑ compared to healthy controls, but lower than cryptogenic liver disease | ↓ in NCIPH | ↓ in NCIPH | ↑ compared to healthy controls, no difference between disease groups | [143] | |||||
| Cirrhosis on the transplant waiting list (n=72), mixed etiologies Child A,B,C | ↑ with disease severity | ↑ with disease severity | ↓ | NA | NA | ↓ | NA | NA | Association between VWF and closure time (PFA), VWF higher in thrombocytopenic patients with normal PFA | [144] |
| Early cirrhosis (n=25), or advanced cirrhosis with (n=24) or without (n=31) infection/SIRS, mixed etiology | ↑ with disease severity | ↑ with disease severity | ≡ | ≡ | ↓ in advanced cirrhosis with infection/SIRS compared to early cirrhosis (Child A) | ↓ in advanced cirrhosis with infection/SIRS compared to early cirrhosis (Child A) | NA | NA | ↓ ADAMTS13 and ↑ VWF correlated inflammation markers and organ dysfunction. ↑ VWF in non-survivors, no association with PVT. VWF and ADAMTS13 predict transplant-free survival | [77] |
| Cirrhosis, Hepatitis B (n=60), with or without CSPH, SPH, or EV | ↑, higher in patients with CSPH and SPH, and EV patients than without | NA | ↑ VWF staining in livers of cirrhotic patients, VWF staining correlated with VWF:Ag and PH. VWF is predictor of CSPH and SPH diagnosis, and for presence and degree of EV. | [145] | ||||||
| Cirrhosis with (n=24) or without (n=60) PVT, mixed etiologies | ↑ in PVT patients vs no PVT but not significant | ↑ in PVT patients vs no PVT | ↑ in PVT patients vs no PVT but not significant | ≡ | NA | ↓ in PVT patients vs no PVT | NA | NA | ↑ VWF and ↓ ADAMTS13 was associated with PVT | [82] |
| ACLF (n=50), mixed etiology and Compensated cirrhosis (n=20), Viral Hepatitis | ↑ higher in ACLF than Compensated | ↑ higher in ACLF than Compensated | ↓ lower in ACLF | NA | NA | ↓ lower in ACLF than compensated patients | NA | ↑ in ACLF | VWF higher in patients with poor outcome. Correlated with organ failure. VWF/ADAMTS13 ratio ↑ in patients with poor outcome | [68] |
| Cirrhosis with thrombocytopenia (n=102), Child A,B,C | ↑ with disease severity | NA | VWF ↑ in patients with ascites or varices. VWF independently predicted new-onset ascites, VB, and mortality | [146] | ||||||
| Cirrhosis with (n=198) or without (n=38) CSPH, mixed etiology, Child A,B,C | ↑ with disease severity, ↑ in CSPH vs no CSPH | NA | VWF predicts CSPH, ↑ Vitro score (VWF/platelet ratio) with disease severity, correlates with CSPH, and PH manifestations (EV, ascites, decompensation). | [147] | ||||||
| Compensated (n=99) and AD (n=54) cirrhosis, mixed etiology | ↑ highest in AD patients | ↑ highest in AD patients | ↓ in both groups | Presence of UL-VWF in 25% of patients, majority of them AD | ↓ in AD patients | ↓ in AD patients | NA | NA | ↑ VWF and ↓ ADAMST13 in AD, possible markers and contributors to disease progression | [63] |
| Cirrhosis with CSPH (n=225) | VWF correlated with markers of bacterial translocation, inflammation and C-reactive protein independent of HVPG. VWF was independent predictor of VB, bacterial infections and transplant-free mortality. | [148] | ||||||||
| Decompensated cirrhosis with (n=31) or without (n=33) PVT, mixed etiologies | NA | ↓ Lowest in PVT group | NA | [149] | ||||||
| Cirrhosis (n=109), split by etiology, Child A and B | ↑ across all etiologies | NA | NA | NA | NA | ↑ in NASH, trend towards ↓ in cholestasis | NA | NA | [27] | |
NA, not assessed; PH, portal hypertension; VWFpp, VWF propeptide; PVT, portal vein thrombosis; HCC, hepatocellular carcinoma; AKI, acute kidney failure; HPS, hepatopulmonary syndrome; NCIPH, non-cirrhotic intrahepatic portal hypertension; PFA, platelet function analyzer; SIRS, systemic inflammatory response syndrome; CSPH, clinically significant portal hypertension; SPH, severe portal hypertension; EV, esophageal varices; ACLF, acute-on-chronic liver failure; VB, variceal bleeding; PH, portal hypertension; AD, acute decompensation; NASH, non-alcoholic steatohepatitis.