Table A1.
Main characteristics of the three new cases and all included patients.
| Study, Year (Ref) | n (Sex) | Age (Years) | Gene | CC | Transplant Indication/s | Pretransplant Clinical Characteristics | CO (L/min)/CI (L/min/m2) | Pre-LT Related Treatments |
|---|---|---|---|---|---|---|---|---|
| Case 1 | 1 (F) | 33 | ACVRL1 | 4 | HOCF + Ischemic cholangitis | Right-upper abdominal pain, polymicrobial bacteriemia. | - | PAVMs embolization. |
| Case 2 | 1 (F) | 60 | Negative | 1 | HOCF + Hepatic encephalopathy | Heart failure, hepatic encephalopathy | - | - |
| Case 3 | 1 (F) | 55 | Negative | 2 | Hepatic encephalopathy + Ischemic cholangitis | Grade 4 hepatic encephalopathy | - | - |
| Perrodin, 2022 [57] | 1 (F) | 72 | Negative | 2 (E, V) | Ischemic cholangitis | Pulmonary hypertension with dyspnea NYHA III, recurrent ischemic cholangitis episodes with multiple abscesses | BVZ (6 doses) Sildenafil |
|
| Olsen, 2020 [26] |
1 (F) | 65 | ACVRL1 | 2 * (E, V) | HOCF + Ischemic cholangitis | Dyspnea NYHA II, peripheral edema and AF. PAVMs previously embolized. | -/6.6 | - |
| Morales, 2020 [27] | 1 (F) | 63 | - | 2 * (E, V) | HOCF | Dyspnea NYHA III-IV, PHTN, AF and recurrent epistaxis and episodes of upper GI bleeding. | 5.9/- | BVZ Sildenafil |
| Vazquez, 2020 [28] | 2 (F/M) | 36/45 | - | 2 * (T, V) | HOCF | P1: Dyspnea NYHA III-IV. P2: Dyspnea NYHA III-IV. Many previous cardiac comorbidities (prosthetic aortic valve, tricuspid valve plasty, closure of a congenital interventricular communication, AF). |
P1: 9.3/6.2 P2: 8/4.1 |
Both received BVZ. |
| Iyer, 2019 [11] |
5 (all F) | 40/57/57/50/69 | - | P1: 2 * (V, FH) P2: 3 * (E, V, FH) P3: 3 * (E, V, FH) P4: 3 * (E, V, FH) P5: 3 * (E, V, FH) |
P1: ischemic cholangitis + HOCF P2,3,4 and 5: HOCF |
P1: Hepatic abscesses and MSSA bacteremia + arrhythmia. P2: Shortness of breath and volume overload signs. P3, P4 & P5: Shortness of breath and volume overload signs + PHTN |
P1: 10.2/6 P2: 8.6/4.7 P3: 9.1/4.1 P4: 5.3/5.7 P5: 8.5/4.3 |
Some received BVZ (not identified) |
| Dumortier, 2019 [29] | 1 (F) | 60 | - | 2 * (V, FH) | HOCF + Hepatic encephalopathy | Dyspnea, fluctuating confusion and somnolence. | -/4.9 | BVZ |
| Álamo, 2019 [30] | 1 (F) | 62 | - | 1 * (V) | HOCF | Severe heart failure | 7.1/- | BVZ Sildenafil |
| Ejiri, 2019 [31] | 1 (F) | 52 | - | 4 | HOCF and PHTN secondary to hepatic AVMs | WHO class IV (dyspnea at rest) | 9/- | - |
| Ionescu, 2018 [32] | 1 (M) | 59 | 2 * (E, V) | HOCF | MEN-I, transitory ischemic attack, and AF. | 15.3/7.6 | - | |
| Barajas, 2018 [33] | 1 (F) | 40 | ACVRL1 | 3 * (E, T, V) | HOCF + Hepatic encephalopathy | Numerous admissions due to HOCF, respiratory infections and hepatic encephalopathy | 12/- | - |
| Ahumada, 2017 [34] | 1 (M) | 51 | - | 2 * (T i V) | HOCF | Dyspnea NYHA III. | 7.1/- | HAE (5 procedures) |
| Chavan, 2017 [35] | 1 (F) | - | - | - | HOCF | Dyspnea NYHA III | - | Repeated doses of BVZ without improvement, receiving HAE |
| Felli, 2017 [10] |
1 (F) | 66 | - | 3 * (E, T, V) | HCOF | Cardiac cirrhosis | - | BVZ |
| Lecler, 2015 [36] | 1 (F) | 66 | - | 3 * (E, T, V) | HOCF + ischemic cholangitis | Jaundice and painful hepatomegaly. Biliomas. | 11/6.9 | - |
| Maestraggi, 2015 [37] | 1 (F) | 63 | ACVRL1 | 4 | Ischemic cholangitis | Right-upper abdominal pain. Biliomas. Bilateral pulmonary embolisms, thrombosis in the right atrial cavity and thrombosis of the right hepatic vein. | - | BVZ |
| Maggi, 2013 [15] |
2 (all F) | 44/64 | - | 4 | HOCF | - | P1: 5.6/- P2: 10/- |
- |
| Chawala, 2011 [38] | 1 (F) | 44 | - | 3 * (E, T, V) | HOCF | Palpitations, dyspnea, and hematochezia | 9.1/5.8 | - |
| Cag, 2011 [39] |
4 (M/M/F/M) | 60/65/40/64 | -/ACVRL1/-/- | P1: 3 (E, T, V) P2: 3 (T, V, FH) P3: 4 P4: 2 (T, V) |
P1: VHB induced cirrhosis P2, 3 & 4: HOCF |
P1: HBV-induced cirrhosis + 2 previous renal transplantation P2: - P3: - P4: HBV-induced cirrhosis |
P1: -/- P2: 10.5/- P3: 7.9/4.9 P4: 7.8/4.1 |
No HAE. Medical treatments had been used (not specified). |
| Buscarini, 2011 [40] | 2 (-/-) | -/- | - | All: at least 2 * | P1: HOCF P2: Portal hypertension |
P1: Dyspnea NYHA class III–IV P2: Refractory ascites |
P1: -/6.2 P2: -/- |
- |
| Dupuis-Girod, 2010 [12] (and Dumortier, 2019 [19]) | 13 (12F, 1M) | 36/50/38/43/55/65/57/63/65/58/46/61/33 | ACVRL1 (all 13) | All: 2 * (E, V; except for 1 patient with unknown E) | HOCF: 9 patients Ischemic cholangitis: 3 patients Both: 1 patient |
For the 9 patients with HOCF: dyspnea NYHA II-IV; 1 patient with severe PHTN For the 3 patients with ischemic cholangitis: right upper abdominal pain For the 1 patient with HOCF/ischemic cholangitis: dyspnea NYHA IV and right upper abdominal pain |
Overall, mean CO 8.8 (5.3–14.1). CI values were: P1: -/5.8 P2: -/6.1 P3: -/5.5 P4: -/3.1 P5: -/6.8 P6: -/5.1 P7: -/5.6 P8: -/3.3 P9: -/3.5 P10: -/4.8 P11: -/4.0 P12: -/8.1 P13: unknown |
- |
| Brenard, 2010 [41] | 3 (all F) | 29/53/32 | - ACVRL1 ACVRL1 | All: at least * | P1: Ischemic cholangitis P2: HOCF P3: Ischemic cholangitis |
- | P1: -/- P2: 12.41/- P3: -/- |
- |
| Cura, 2010 [42] |
1 (M) | 50 | - | 2 * (V, FH) | Portal hypertension | Recurrent episodes of haemobilia and GI variceal bleeding. Cirrhosis. | - | Various HAEs. Left hepatic lobectomy and cholecystectomy |
| Lee, 2010 [43] |
1 (M) | 47 | ACVRL1 | 1 | Ischemic cholangitis | Dyspnea on exertion, epigastric pain, jaundice, and fevers. | 18.2/- | - |
| Nuñez Viejo, 2010 [44] | 1 (F) | 48 | - | 3 * (E, T, V) | HOCF | NYHA IV | 10.6/- | - |
| Mavrakis, 2009 [45] | 1 (F) | 32 | - | 3 (E, V, FH) | Fulminant hepatic failure and septic shock | At 33 weeks gestation, weight loss, upper quadrant abdominal pain, nausea, and intermittent vomiting. | - | Vaginal delivery. Elective laparoscopic cholecystectomy |
| Skaro, 2006 [13] | 1 (F) | 53 | - | 3 * (T, V, FH) | HOCF | Jaundice, cachexia, and ascites. Chronic refractory anemia despite multiple blood transfusions. | - | None described |
| Domínguez, 2005 [46] | 1 (F) | 32 | - | 2 (V, FH) | Ischemic cholangitis | Right upper quadrant abdominal pain, hyperthermia and jaundice. |
- | Laparoscopic cholecystectomy. PAVM embolized. |
| Thevenot, 2005 [47] | 2 (all F) | 59/62 | ACVRL1 (both) |
P1: 3 * (E, T, V) P2: 4 |
P1: HOCF + Ischemic cholangitis after HAE P2: HOCF |
P1: fever, jaundice, cardiac failure with dilated jugular veins, bilateral pleural effusion, peripheral edema. P2: breathing difficulties. |
P1: 8.4/5.1 P2: 10.7/6.6 |
P1: Left HAE. P2: None |
| Argyriu, 2005 [48] | 2 (F/M) | 36/60 | ACVRL1 (both) |
P1: 3 (E, T, V) P2: 4 |
HOCF | P1: Increased right heart load, dyspnea. P2: Increased right heart load, arrhythmia, dyspnea, ascites, and esophageal varices. |
- | - |
| Sabbà, 2004 [22] | 1 (F) | 49 | - | 2 * (V, FH) | HOCF + Biliary sepsis after hepatic artery ligation. | - | - |
HA ligation |
| Giacomoni, 2004 [24] |
1 (-) | - | - | 1 * (V) | - | - | - | - |
| Aseni, 2003 [49] |
1 (M) | 29 | - | 3 (E, T, V) | Hepatopulmonary syndrome | Severe respiratory distress | - | - |
| Blewitt, 2003 [50] | 1 (F) | 34 | - | 2 * (V, FH) | Ischemic cholangitis | Continuous right upper quadrant abdominal pain | - | Laparoscopic cholecystectomy. |
| Azoulay, 2002 [17] | 6 (F/F/F/F/M/F) | 38/41/49/38/67/48 | - | P1: 3 (E, V, FH) P2: 4 P3: 4 P4: 2 (V, FH) P5: 4 P6: 3 (T, V, FH) |
P1, 3 and 4: Ischemic cholangitis P2: Portal hypertension P5: Portal hypertension P6: HOCF + cholangitis |
P1: Repeated biliary sepsis and abscess drainages P2: Ascites, esophagi varices, hypertensive gastritis. Abscess drainage. P3: -. P4: Esophagi varices, hypertensive gastritis. Abscess drainage P5: Ascites and esophagi varices, hypertensive gastritis. PHTN. P6: - |
- | No HA ligation or HAE. P5: TIPS |
| Pfitzmann, 2001 [51] | 4 (all F) | 45/69/54/55 | ACVRL1 (All) |
P1: 2 * P2: 2 * P3: 2 * P4: 2 * All (T, V) |
P1, 4: HOCF + ischemic cholangitis P2, 3: HOCF |
P1: NYHA III-IV, abdominal pain, weight loss and icterus. P2: NYHA III-IV, GI bleeding, ascites, recurrent pulmonary embolisms, Ventricular arrhythmias. P3: NYHA III-IV, ascites, edema, PHTN, tricuspid insufficiency grade IV. P4: NYHA III-IV, pleural effusions and ventricular arrhythmias. |
P1: 8.8/- P2: 13.3/- P3: 12/- P4: 8/- |
P1: HAE. P2–3: - P4: 6 HAE and surgical HA banding |
| Hillert, 2001 [52] |
1 (F) | 39 | - | 4 | Ischemic cholangitis | At 29 weeks gestation, diffuse abdominal pain and several episodes of GI bleeding. Billroth I resection of the stomach. Hepatic vein thrombosis. | - | Cesarean Delivery Right HAE |
| Le Corre, 2000 [53] | 1 (F) | 40 | - | 3 * (E, V, FH) | HOCF | Previous right pulmonary lobectomy. NYHA II-III. | 12.5/7.35 | - |
| Boillot, 1999 [54] | 3 (all F) | 36/50/42 | - | P1: 3 (E, V, FH) P2: 3 *(E, V, FH) P3: 2 * (E, V) |
P1: HOCF, Ischemic cholangitis P2 and 3: HOCF |
P1: At 13 weeks gestation, right-upper abdominal pain. Cardiac failure associated with PHTN. Multiple Hepatic abscess P2: Refractory ascites and PHTN P3: Acute right-sided HF and massive edema and ascites. |
P1: 9.1/- P2: 11.3/- P3: 10.8/- |
P1: cesarean delivery. cholecystectomy. P2 and P3: - |
| Neuman, 1998 [55] | 1 (F) | 45 | ACVRL1 | 1 * (V) | HOCF + Ischemic cholangitis | Previous partial left pneumonectomy for PAVMs. Esophageal and gastric varices grade IV | 8.8/- | Complete liver dearterialization. Cholecystectomy |
| Odorico, 1998 [56] | 2 (all F) | 48/47 | - | 2 (E, V) | P1: Ischemic cholangitis P2: Ischemic cholangitis |
P1: Large bilomas, multiple hepatic abscesses and polymicrobial bacteriemia. Hepatic encephalopathy after embolization P2: Abdominal pain, jaundice, fever. Multiple bilomas. Polymicrobial bacteriemia (including Candida Albicans). Encephalopathy after embolization |
P1: 6.6/- | P1: cholecystectomy.Embolization of pancreaticoduodenal arteries P2: HAE. Open cholecystectomy |
| Saxena, 1998 [21] (and Ullus 2019 [20]) | 1 (F) | 43 | - | 3 * (T, V, FH) | Ischemic cholangitis | Ascites, pleural effusion, wasting, and extreme fatigue. | - | Previous surgical dearterialization of the HA. |
| Mclnroy, 1998 [25] | 1 (F) | 31 | - | 1 (V) * | Ischemic cholangitis | Gravida. Right upper quadrant pain, low-grade fevers, and elevated liver enzyme levels. Hematemesis. Confirmed bacteriemia. | - | Vaginal delivery. Open cholecystectomy |
| Bauer, 1995 [23] (and Sabbà 2004 [22]) |
1 (F) | 33 | - | 4 | HOCF + Ischemic cholangitis | Severe upper abdominal pain, sepsis with isolation of Streptococcus faecalis due to ischemic cholangitis | - | - |
Abbreviations: AF: atrial fibrillation; BVZ: bevacizumab; CC: Curaçao Criteria; CI: cardiac index; CO: cardiac output; E: epistaxis; F: female; FH: family history; GI: gastrointestinal; HA: hepatic artery; HAE: hepatic artery embolization; HOCF: high output cardiac failure; M: male; NYHA: New York Heart Association Functional Classification; PAVMs: pulmonary arteriovenous malformations; PH: portal hypertension; PHTN: pulmonary hypertension; T: telangiectases; V: visceral involvement. (*) not all Curaçao Criteria described.