Factors impacting survival after transarterial radioembolization in patients with hepatocellular carcinoma: Results from the prospective CIRT study.

Background & Aims: Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is an established treatment option for patients with hepatocellular carcinoma (HCC). However, optimising treatment application and patient selection remains challenging. We report here on the effectiveness, safety and prognostic factors, including dosing methods, associated with TARE for HCC in the prospective observational CIRT study. Methods: We analysed 422 patients with HCC enrolled between Jan 2015 and Dec 2017, with follow-up visits every 3 months for up to 24 months after first TARE. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every 3-month follow-up visit. We used the multivariable Cox proportional hazard model and propensity score matching to identify independent prognostic factors for effectiveness outcomes. Results: The median OS was 16.5 months, the median PFS was 6.1 months, and the median hepatic PFS was 6.7 months. Partition model dosimetry resulted in improved OS compared to body surface area calculations on multivariable analysis (hazard ratio 0.65; 95% CI 0.46-0.92; p = 0.0144), which was confirmed in the exact matching propensity score analysis (hazard ratio 0.56; 95% CI 0.35-0.89; p = 0.0136). Other independent prognostic factors for OS were ECOG-performance status >0 (p = 0.0018), presence of ascites (p = 0.0152), right-sided tumours (p = 0.0002), the presence of portal vein thrombosis (p = 0.0378) and main portal vein thrombosis (p = 0.0028), ALBI grade 2 (p = 0.0043) and 3 (p = 0.0014). Adverse events were recorded in 36.7% of patients, with 9.7% of patients experiencing grade 3 or higher adverse events. Conclusions: This large prospective observational dataset shows that TARE is an effective and safe treatment in patients with HCC. Using partition model dosimetry was associated with a significant improvement in survival outcomes. Impact and implications: Transarterial radioembolization (TARE) is a form of localised radiation therapy and is a potential treatment option for primary liver cancer. We observed how TARE was used in real-life clinical practice in various European countries and if any factors predict how well the treatment performs. We found that when a more complex but personalised method to calculate the applied radiation activity was used, the patient responded better than when a more generic method was used. Furthermore, we identified that general patient health, ascites and liver function can predict outcomes after TARE. Clinical trial number: NCT02305459.

Management of splanchnic vein thrombosis.

The expression splanchnic vein thrombosis encompasses Budd-Chiari syndrome and portal vein thrombosis. These disorders have common characteristics: they are both rare diseases which can cause portal hypertension and its complications. Budd-Chiari syndrome and portal vein thrombosis in the absence of underlying liver disease share many risk factors, among which myeloproliferative neoplasms represent the most common; a rapid comprehensive work-up for risk factors of thrombosis is needed in these patients. Long-term anticoagulation is indicated in most patients. Portal vein thrombosis can also develop in patients with cirrhosis and in those with porto-sinusoidal vascular liver disease. The presence and nature of underlying liver disease impacts the management of portal vein thrombosis. Indications for anticoagulation in patients with cirrhosis are growing, while transjugular intrahepatic portosystemic shunt is now a second-line option. Due to the rarity of these diseases, studies yielding high-grade evidence are scarce. However, collaborative studies have provided new insight into the management of these patients. This article focuses on the causes, diagnosis, and management of patients with Budd-Chiari syndrome, portal vein thrombosis without underlying liver disease, or cirrhosis with non-malignant portal vein thrombosis.

Cirrhosis and COVID-19: Diffuse venous thrombosis and its clinical implication.

A 60-year-old woman with Hepatitis C infection, cirrhosis, recurrent hepatic hydrothorax, and hepatocellular carcinoma was hospitalized with Coronavirus disease-2019 (COVID-19). After her initial discharge, she was re-admitted three weeks later with decompensated liver disease. Imaging revealed extensive thrombosis in the portal vein, superior mesenteric vein, splenic vein and bilateral brachial veins. Given the acute onset and extent of the thrombosis, the patient received therapeutic anticoagulation despite elevated prothrombin time/ international normalized ratio, thrombocytopenia and low fibrinogen. Cirrhotic patients with COVID-19 maybe at high risk of thrombosis, which can present with significant hepatic decompensation.

Management of Refractory Variceal Bleed in Cirrhosis.

Acute variceal bleeding is the major cause of mortality in patients with cirrhosis. The standard medical and endoscopic treatment has reduced the mortality of variceal bleeding from 50% to 10-20%. The refractory variceal bleed is either because of failure to control the bleed or failure of secondary prophylaxis. The patients refractory to standard medical therapy need further interventions. The rescue therapies include balloon tamponade, self-expanding metal stents (SEMS) placement, shunt procedures, including transjugular intrahepatic portosystemic shunt (TIPS), balloon-occluded retrograde transvenous obliteration (BRTO), and endoscopic ultrasound (EUS) guided coiling. In cases where endoscopic variceal ligation (EVL) has failed and the variceal bleeding continues, temporary measures like balloon tamponade can be used to achieve hemostasis and as a bridge to definitive measures. SEMS being in use for refractory bleed is preferred over balloon tamponade due to the reduced complication rate. The shunting procedures are highly effective in reducing portal pressure and represent the gold standard for uncontrolled variceal bleeding. The surgical shunts, as well as nonshunt surgeries such as devascularization have become less popular with the increasing use of minimally invasive techniques like TIPS. TIPS have high success rates in controlling refractory variceal bleeding. The mortality rate is greater in high-risk patients undergoing salvage TIPS, and hence, pre-emptive TIPS should be considered in these patients. BRTO is an interventional radiologic procedure used in the management of bleeding gastric and ectopic varices. The availability of gastrorenal or splenorenal shunts is required for the BRTO procedure, which helps to reach and obliterate the cardiofundal varices through the femoral or jugular vein approach. The EUS guided coiling and glue injection have shown promising results, and further randomized controlled trials are required to establish their efficacy for refractory variceal bleeding.

Stereotactic body radiation therapy for hepatocellular carcinoma: From infancy to ongoing maturity.

Hepatocellular carcinoma (HCC) accounts for 90% of liver tumours and is one of the leading causes of mortality. Cirrhosis due to viral hepatitis, alcohol or steatohepatitis is the major risk factor, while liver dysfunction due to cirrhosis is a deciding factor in its treatment. The treatment modalities for HCC include liver transplant, hepatectomy, radiofrequency ablation, transarterial chemoembolisation, transarterial radioembolisation, targeted therapy, immunotherapy, and radiation therapy. The role of radiation therapy has been refined with the increasing use of stereotactic body radiation therapy (SBRT). Trials over the past two decades have shown the efficacy and safety of SBRT in recurrent and definitive HCC, leading to its acceptance and adoption in some more recent guidelines. However, high quality level I evidence supporting its use is currently lacking. Smaller randomised trials of external beam radiation therapy suggest high efficacy of radiation therapy compared to other treatments for patients with unresectable HCC, and phase III trials comparing SBRT with other modalities are ongoing. In this review, we discuss the rationale for SBRT in HCC and present evidence on its efficacy, associated toxicity, and technological advances.

When Push Comes to Shove! Emergency ABO-Incompatible Pediatric Living Donor Liver Transplant for Acute Wilson's Disease.

ABO-incompatible living donor liver transplantation (ABOi-LDLT) is on the rise as a viable option in countries with limited access to deceased donor grafts. While reported outcomes of ABOi-LT in children are similar to ABO- Compatible liver transplant (ABOc-LT), most children beyond 1-2 years of age will need desensitization to overcome the immunological barrier of incompatible blood groups. The current standard protocol for desensitization is Rituximab that targets B lymphocytes and is given 2-3 weeks prior to LT. However, this timeline may not be feasible in children requiring emergency LT for acute liver failure (ALF) or acute-on-chronic liver failure (ACLF). In this emergency situation of ABOi-LT, a safe multipronged approach may be an acceptable alternative solution. We report a child with acute Wilson's disease with rapidly deteriorating liver function who underwent a successful ABOi-LDLT using a rapid desensitization protocol.

Long-Term Outcomes of Endoscopic Management of Patients with Symptomatic Portal Cavernoma Cholangiopathy with No Shuntable Veins for Surgery or Failed Surgery.

Background and Aim: Shunt surgery is the definitive treatment for symptomatic patients with portal cavernoma cholangiopathy (PCC), but few patients are non-surgical candidates or fail to improve even after surgery. This study aims to analyze the long-term outcomes of endoscopic therapy in these patients. Methods: Retrospective review of a prospectively maintained database of all patients with symptomatic PCC managed with endoscopic retrograde cholangiography (ERC) followed by stent placement. Outcomes studied included number of biliary interventions, complications, resolution of stricture, development of decompensation and mortality. Results: Thirty-five patients (68.6% males, median age = 35 years) with a median follow-up duration of 46 months (12-112) were included in the analysis. Presentation was only jaundice in 51.4% cases while one-third (37.1%) of the patients presented with cholangitis. Patients underwent a total of 363 endoscopic sessions with a median of 9 procedures (3-29) per patient. Hemobilia was the most common complication of the procedure (6.06%). Ten (28.5%) patients required frequent stent exchanges. Patients who required frequent stent exchanges had higher number of cholangitis episodes and hospitalization. Secondary biliary cirrhosis developed in 4 (11.4%) patients and 2 (5.7%) patients had mortality. Of the 5 (14.3%) patients who were given a stent free trial, 3 patients required restenting due to redevelopment of symptoms. Conclusion: Patients with PCC without shuntable veins for surgery or those who failed to improve after surgery can be managed long-term with repeated endoscopic intervention with a slightly increased risk of non-fatal hemobilia.

Do Natural Portosystemic Shunts Need to Be Compulsorily Ligated in Living Donor Liver Transplantation?

BACKGROUND: Natural portosystemic shunt ligation practices in liver transplant vary widely across transplant centres and are frequently undertaken to prevent the serious consequence of portal steal phenomenon. No concrete indications have so far been convincingly identified for their management in living donor liver transplant. METHODS: We retrospectively studied the outcome of 89 cirrhotic patients who either did (n = 63) or did not (n = 25) undergo shunt ligation during living donor liver transplantation between 2017 and 2020. RESULTS: The incidence of early allograft dysfunction/nonfunction (P = 1.0) and portal venous complications (P = 0.555) were similar between the two groups. Although overall complications, biliary complications, and the composite of Grade III and IV complications were significantly higher in the nonligated group (P = 0.015, 0.052 and 0.035), 1- year graft and patient survival were comparable between them (P = 0.524). CONCLUSION: We conclude that shunt ligation in living donor liver transplantation may not always be necessary if adequate portal flow, good vascular reconstruction, and good graft quality have been ensured.

Role of precipitants in transition of acute decompensation to acute-on-chronic liver failure in patients with HBV-related cirrhosis.

Background & Aims: Pre-acute-on-chronic liver failure (ACLF) is a distinct intermediate stage between acute decompensation (AD) and ACLF. However, identifying patients with pre-ACLF and predicting progression from AD to ACLF is difficult. This study aimed to identify pre-ACLF within 28 days, and to develop and validate a prediction model for ACLF in patients with HBV-related decompensated cirrhosis. Methods: In total, 1,736 patients with HBV-related cirrhosis and AD were enrolled from 2 large-scale, multicenter, prospective cohorts. ACLF occurrence within 28 days, readmission, and 3-month and 1-year outcomes were collected. Results: Among 970 patients with AD without ACLF in the derivation cohort, the 94 (9.6%) patients with pre-ACLF had the highest 3-month and 1-year LT-free mortality (61.6% and 70.9%, respectively), which was comparable to those with ACLF at enrollment (57.1% and 67.1%); the 251 (25.9%) patients with unstable decompensated cirrhosis had mortality rates of 22.4% and 32.1%, respectively; while the 507 (57.9%) patients with stable decompensated cirrhosis had the best outcomes (1-year mortality rate of 2.6%). Through Cox proportional hazard regression, specific precipitants, including hepatitis B flare with HBV reactivation, spontaneous hepatitis B flare with high viral load, superimposed infection on HBV, and bacterial infection, were identified to be significantly associated with ACLF occurrence in the derivation cohort. A model that incorporated precipitants, indicators of systemic inflammation and organ injuries reached a high C-index of 0.90 and 0.86 in derivation and validation cohorts, respectively. The optimal cut-off value (0.22) differentiated high-risk and low-risk patients, with a negative predictive value of 0.95. Conclusions: Three distinct clinical courses of patients with AD are validated in the HBV-etiology population. The precipitants significantly impact on AD-ACLF transition. A model developed by the precipitant-systemic inflammation-organ injury framework could be a useful tool for predicting ACLF occurrence. Clinical trial number: NCT02457637 and NCT03641872. Lay summary: It was previously shown that patients with decompensated cirrhosis could be stratified into 3 groups based on their short-term clinical prognoses. Herein, we showed that this stratification applies to patients who develop cirrhosis as a result of hepatitis B virus infection. We also developed a precipitant-based model (i.e. a model that incorporated information about the exact cause of decompensation) that could predict the likelihood of these patients developing a very severe liver disease called acute-on-chronic liver failure (or ACLF).

Risk of further decompensation/mortality in patients with cirrhosis and ascites as the first single decompensation event.

Background & Aims: Although ascites is the most frequent first decompensating event in cirrhosis, the clinical course after ascites as the single index decompensation is not well defined. The aim of this multicentre study was thus to systematically investigate the incidence and type of further decompensation after ascites as the first decompensating event and to assess risk factors for mortality. Methods: A total of 622 patients with cirrhosis presenting with grade 2/3 ascites as the single index decompensating event at 2 university hospitals (Padova and Vienna) between 2003 and 2021 were included. Events of further decompensation, liver transplantation, and death were recorded. Results: The mean age was 57 ± 11 years, and most patients were male (n = 423, 68%) with alcohol-related (n = 366, 59%) and viral (n = 200,32%) liver disease as the main aetiologies. In total, 323 (52%) patients presented with grade 2 and 299 (48%) with grade 3 ascites. The median Child-Pugh score at presentation was 8 (IQR 7-9), and the mean model for end-stage liver disease (MELD) was 15 ± 6. During a median follow-up period of 49 months, 350 (56%) patients experienced further decompensation: refractory ascites (n = 130, 21%), hepatic encephalopathy (n = 112, 18%), spontaneous bacterial peritonitis (n = 32, 5%), hepatorenal syndrome-acute kidney injury (n = 29, 5%). Variceal bleeding as an isolated further decompensation event was rare (n = 18, 3%), whereas non-bleeding further decompensation (n = 161, 26%) and ≥2 concomitant further decompensation events (n = 171, 27%) were frequent. Transjugular intrahepatic portosystemic shunt was used in only 81 (13%) patients. In patients presenting with grade 2 ascites, MELD ≥15 indicated a considerable risk for further decompensation (subdistribution hazard ratio [SHR] 2.18; p <0.001; 1-year incidences: <10: 10% vs. 10-14: 13% vs. ≥15: 28%) and of mortality (SHR 1.89; p = 0.004; 1-year incidences: <10: 3% vs. 10-14: 6% vs. ≥15: 14%). Importantly, mortality was similarly high throughout MELD strata in grade 3 ascites (p = n.s. for different MELD strata; 1-year incidences: <10: 14% vs. 10-14: 15% vs. ≥15: 20%). Conclusions: Further decompensation is frequent in patients with ascites as a single index decompensation event and only rarely owing to bleeding. Although patients with grade 2 ascites and MELD <15 seem to have a favourable prognosis, those with grade 3 ascites are at a high risk of mortality across all MELD strata. Lay summary: Decompensation (the development of symptoms as a result of worsening liver function) marks a turning point in the disease course for patients with cirrhosis. Ascites (i.e. , the accumulation of fluid in the abdomen) is the most common first decompensating event, yet little is known about the clinical course of patients who develop ascites as a single first decompensating event. Herein, we show that the severity of ascites is associated with mortality and that in patients with moderate ascites, the widely used prognostic MELD score can predict patient outcomes.

Portal Vein Thrombosis in Cirrhosis.

Patients with cirrhosis of the liver are at high risk of developing portal vein thrombosis (PVT), which has a complex, multifactorial cause. The condition may present with a myriad of symptoms and can occasionally cause severe complications. Contrast-enhanced computed tomography (CT) is the gold standard for the diagnosis of PVT. There are uncertainties regarding the effect on PVT and its treatment outcome in patients with cirrhosis. The main challenge for managing PVT in cirrhosis is analyzing the risk of hemorrhage compared to the risk of thrombus extension leading to complications. All current knowledge regarding non-tumor PVT in cirrhosis, including epidemiology, risk factors, classification, clinical presentation, diagnosis, impact on natural history, and treatment, is discussed in the present article.

A new choice of stent for transjugular intrahepatic portosystemic shunt creation: Viabahn ePTFE covered stent/bare metal stent combination.

OBJECTIVES: To compare the clinical outcomes in terms of structure and function between the insertion of a transjugular intrahepatic portosystemic shunt (TIPS) created with the Viabahn ePTFE covered stent/bare metal stent (BMS) combination and the Fluency ePTFE covered stent/BMS combination. METHODS: A total of 101 consecutive patients who received a TIPS from February 2016 to August 2018 in our center were retrospectively analyzed. Sixty-four subjects were enrolled in the Viabahn group and 37 were enrolled in the Fluency group. The geometry characteristics of the TIPS were calculated, and the associated occurrence of shunt dysfunction, survival, overt hepatic encephalopathy, and variceal rebleeding were evaluated. RESULTS: The technical success rate was 100%. After the insertion of the TIPS, the rate of shunt dysfunction during the first 3 months was significantly different between the Viabahn and Fluency groups (1.6% and 13.5%, respectively; p â€‹= â€‹0.024). Multivariate analysis indicated that the angle of portal venous inflow (α) was the only independent risk factor for shunt dysfunction (hazard ratio â€‹= â€‹1.060, 95% confidence interval â€‹= â€‹1.009-1.112, p â€‹= â€‹0.020). In addition, 3 months after the TIPS insertion, the α angle distinctly increased from 20.9° â€‹± â€‹14.3°-26.9° â€‹± â€‹20.1° (p â€‹= â€‹0.005) in the Fluency group but did not change significantly in the Viabahn group (from 21.9° â€‹± â€‹15.1°-22.9° â€‹± â€‹17.6°, p â€‹= â€‹0.798). CONCLUSIONS: Shunt dysfunction was related to the α angle owing to the slight effect on the α angle after the implantation of the TIPS. The Viabahn ePTFE covered stent/BMS combination was more stable in structure and promised higher short-term stent patency compared with the Fluency ePTFE covered stent/BMS combination.

Living Donor Liver Transplant in Patients Aged 60 Years or Older: Experience from a Large Volume Centre in India.

BACKGROUND: With ageing population and higher prevalence of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in older patients, more and more living donor liver transplants (LDLTs) are being considered in this group of patients as eligibility for deceased donor liver transplant is restricted to those aged 65 years and younger. However, the short- and long-term outcomes of this group have not been reported from India, which does not have a robust national health scheme. The aim of this study was to provide guidelines for transplant in this group. METHODS: All patients aged 60 years and older (group 1) who underwent LDLT in our centre between January 2006 and December 2017 were studied. A propensity score-matched group in 1:2 ratio was created with comparable sex and Model for End-Stage Liver Disease score (group 2). The 2 groups were compared for duration of hospital stay, surgical complications, hospital mortality and 1-, 3- and 5-year survival. RESULTS: Group 1 consisted of 207 patients, and group 2 had 414 patients. The number of patients in group 1 gradually increased with time from 4 in 2006 to 33 in 2017 accounting for 15% of total cases. Group 1 had more patients with viral hepatitis, NASH and HCC, and they had a higher 30-day mortality due to cardiorespiratory complications. Although 1- and 3-year survival was similar, the 5-year survival was significantly lower in group 1. CONCLUSION: Five-year survival was lower in the elderly group due to cardiorespiratory complications and recurrence of HCC. Outcomes in the elderly group can be improved with better patient selection and preventing HCC recurrence.

Where does TIPS fit in the management of patients with cirrhosis?

In this review, we summarise the current knowledge on the indications and contraindications of transjugular intrahepatic portosystemic shunt (TIPS) placement for the treatment of the complications of portal hypertension in cirrhosis, specifically variceal haemorrhage and ascites. Moreover, we discuss the role of TIPS for the treatment of portal vein thrombosis (PVT) and the prevention of complications after extrahepatic surgery ('preoperative TIPS') in patients with cirrhosis. The position of TIPS in the treatment hierarchy depends on the clinical setting and on patient characteristics. In acute variceal haemorrhage, preemptive TIPS is indicated in patients at a high risk of failing standard therapy, that is those with a Child-Pugh score of 10-13 points or Child-Pugh B with active bleeding at endoscopy, although the survival benefit in the latter group still remains to be established. Non-preemptive TIPS is a second-line therapy for the prevention of recurrent variceal haemorrhage and for the treatment of ascites. Of note, TIPS may also improve sarcopenia. Contraindications to TIPS placement, independent of clinical setting, include very advanced disease (Child-Pugh >13 points), episodes of recurrent overt hepatic encephalopathy without an identifiable precipitating factor, heart failure, and pulmonary hypertension. In patients with PVT, TIPS placement not only controls complications of portal hypertension, but also promotes portal vein recanalisation. Although the severity of portal hypertension correlates with poor outcomes after extrahepatic surgery, there is no evidence to recommend preoperative TIPS placement.

Sarcopenia in Cirrhosis: Fallout on Liver Transplantation.

BACKGROUND: Liver transplantation (LT) is a game changer in cirrhosis. Poor muscle mass defined as sarcopenia may potentially upset the LT scoreboard. AIM: To assess the prevalence and impact of sarcopenia on the intraoperative and early postoperative outcomes in Indian patients undergoing LT. METHODS: Pre LT, single-slice routine computed tomography images at L3 vertebra of 115 LT recipients were analyzed, to obtain cross-sectional area of six skeletal muscles normalized for height in m2 - skeletal muscle index (SMI; cm2/m2). SMI< 52.4 in males and <38.5 in females was called sarcopenia. The intraoperative, postoperative outcome parameters and 90-day mortality were compared between sarcopenics and nonsarcopenics. RESULTS: Sarcopenia was found in 47.8% of patients [M (90.4%); age, 46.3 ± 10; BMI, 24.5 ± 4.3 kg/m2; child A:B:C = 1%:22%:77%; MELD, 20.6 ± 6.3; etiology alcohol: nonalchohol = 53%:47%; Charlson Comorbidity Index (CCI) > 3:≤3 = 56.5%:43.5%]. Sarcopenics vs. Nonsarcopenics; early postoperative complications: [sepsis, 49(89%) vs. 33(55%), P = 0.001; neurologic complications, 16(29.6%) vs. 5(8.8%), P = 0.040; Clavien-Dindo Classification ≥3-24 (43.6%):15 (25.4%),P = 0.041; ancillary parameters (days), duration of ventilation [median (range)] 1.5(1-3) vs. 1 (1-2), P = 0.021; intensive care unit (ICU) stay 12 (8-16) vs. 10 (8-12), P = 0.024; time to ambulation 9 (7-11) vs. 6 (5-7), P = 0.001; drain removal 18.7 ± 7.3 vs. 14.4 ± 6.2, P = 0.001; need for tracheostomy 5 (9%) vs. 0 (%), P = 0.017; preoperative prevalence of acute kidney injury, comorbidities and requirement for dialysis, intraoperative blood loss & inotropic support were significantly higher in sarcopenics. Ninety-day mortality was comparable between sarcopenics 5 (9.09%) and nonsarcopenics 4 (6.6%) P = 0.63. SMI (OR: 0.83; 95% CI: 0.71-0.97, P = 0.016; Acute on chronic liver failure (ACLF) presentation 12.5 (1.65-95.2), P = 0.015 and intraoperative blood loss 3.74 (0.96-14.6), P = 0.046 were predictors of 90-day mortality. CONCLUSION: Almost 50% of LT recipients had sarcopenia, who had a higher incidence of postoperative sepsis, neurological complications, longer ICU stay and ventilatory support. Low SMI, ACLF presentation, and intraoperative blood loss were the independent predictors of early mortality.

Living Donor Liver Transplantation Using Small-for-Size Grafts: Does Size Really Matter?

BACKGROUND: In living donor liver transplantation (LDLT), graft-to-recipient weight ratio (GRWR) > 0.8% is perceived as the critical graft size. This lower limit of GRWR (0.8%) has been challenged over the last decade owing to the surgical refinements, especially related to inflow and outflow modulation techniques. Our aim was to compare the recipient outcome in small-for-size (GRWR < 0.8) versus normal-sized grafts (GRWR > 0.8) and to determine the risk factors for mortality when small-for-size grafts (SFSG) were used. METHODS: Data of 200 transplant recipients and their donors were analyzed over a period of two years. Routine practice of harvesting middle hepatic vein (MHV) or reconstructing anterior sectoral veins into neo-MHV was followed during LDLT. Outcomes were compared in terms of mortality, hospital stay, ICU stay, and occurrence of various complications such as functional small-for-size syndrome (F-SFSS), hepatic artery thrombosis (HAT), early allograft dysfunction (EAD), portal vein thrombosis (PVT), and postoperative sepsis. A multivariate analysis was also done to determine the risk factors for mortality in both the groups. RESULTS: Recipient and donor characteristics, intraoperative variables, and demographical data were comparable in both the groups (GRWR < 0.8 and GRWR ≥ 0.8). Postoperative 90-day mortality (15.5% vs. 22.85%), mean ICU stay (10 vs. 10.32 days), and mean hospital stay (21.4 vs. 20.76 days) were statistically similar in the groups. There was no difference in postoperative outcomes such as occurrence of SFSS, HAT, PVT, EAD, or sepsis between the groups. Thrombosis of MHV/reconstructed MHV was a risk factor for mortality in grafts with GRWR < 0.8 but not in those with GRWR > 0.8. CONCLUSION: Graft survival after LDLT using a small-for-size right lobe graft (GRWR < 0.8%) is as good as with normal grafts. However, patency of anterior sectoral outflow by MHV or reconstructed MHV is crucial to maintain graft function when SFSG are used.

Is Portal Venous Pressure or Porto-systemic Gradient Really A Harbinger of Poor Outcomes After Living Donor Liver Transplantation?

BACKGROUND: Portal hyperperfusion as a cause of small for size syndrome (SFSS) after living donor liver transplantation (LDLT) remains controversial. Portal venous pressure (PVP) is often measured indirectly and may be confounded by central venous pressure (CVP). METHODS: In 42 adult cirrhotics undergoing elective LDLT, PVP was measured by direct canulation of portal vein and porto systemic gradient (PSG) was obtained after subtracting CVP from PVP. None underwent portal inflow modulation. SFSS was looked in 27 patients after excluding 15 with technical complications. RESULTS: Clinical features of SFSS found in 6 patients, 5 with graft recipient weight ratio (GRWR) > 0.8% and PVP < 20 mm of Hg. One with GRWR < 0.8% could truly be labeled as SFSS. Incidence of SFSS was not higher in patients with elevated PVP > 20 mm of Hg (14.3% vs 0%, P = 0.259) or PSG > 13 mm of Hg (33.3% vs 0%, P = 0.111). Intensive care unit (ICU) stay was longer in patients with elevated PVP (14.55 vs 9.13 days, P = 0.007) and PSG (16.8 vs 9.72 days, P = 0.009). There was no difference in graft functions, post-operative complications and mortality in first month post-LDLT. CONCLUSION: Elevated PVP or PSG increased morbidity but neither predicted SFSS nor affected survival.

Liver transplantation in a patient with complete portal vein thrombosis, is there a surgical way out? A case report.

INTRODUCTION: Due to the complexity of the surgical procedure portal vein thrombosis (PVT) has long been considered an absolute contraindication to liver transplantation (LT). The presence of a large splenorenal shunt (SRS) could make portal anastomosis a valid option. PRESENTATION OF CASE: We report the case of a 37-year-old female patient with Grade III PVT and a large SRS, who underwent orthotopic LT. Liver was implanted using a 1992-Belghiti piggyback technique and portal anastomosis was performed using the large spleno-renal shunt. We observed good graft reperfusion and postoperative Doppler ultrasound showed normal portal vein flow. She was discharged on postoperative day 7, with an excellent graft function. At six months follow-up, patient is alive with normal hepatic vascularization. DISCUSSION: Due to paucity of reports, there is currently no consensus on the indication to LT and/or surgical technique. In the present case, once the transplant benefit was evaluated, the Grade III PVT was not considered a contraindication to LT. CONCLUSION: The presence of a Grade III PVT associated with a large SRS should not be considered a contraindication for LT, and the use of the shunt vein should be considered a feasible option to perform portal anastomosis.

PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q, and Prothrombin 20210A in Splanchnic Vein Thrombosis: Analysis of Individual Patient Data From Three Prospective Studies.

BACKGROUND: There are no univocal opinions on the role of genetic thrombophilia on splanchnic vein thrombosis (SVT). We defined genetic thrombophilia the presence of one of these thrombophilic genetic factors (THRGFs): PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q, and prothrombin 20210A. OBJECTIVES: To evaluate the frequencies of these THRGFs in SVT patients, we analyzed individual data of 482 Caucasian patients, recruited from 2000 to 2014 in three prospective studies. SVT was defined as the presence of thrombosis of portal (PVT), mesenteric (MVT), splenic (SPVT), cava (CT), and hepatic vein (Budd Chiari syndrome, BCS). Pre-hepatic SVT (pre-HSVT) was defined as PVT with or without MVT/SPVT, without BCS. Post-hepatic SVT (post-HSVT) was BCS with or without PVT/MVT/SPVT. METHODS: We compared 350 patients with liver cirrhosis (LC), 47 hepatocellular carcinoma (HCC), 37 myeloproliferative neoplasm (MPN), 38 associated disease (AD), 10 without any associated disease (WAD), vs 150 healthy controls (HC); 437 patients showed pre-HSVT and 45 post-HSVT. RESULTS: Thrombophilia was present in 294/482 (60.9%) patients: 189/350 LC (54.0%), 31/47 (66.0%) HCC, 29/39 (74.4%) MPN, 35/38 AD (92.1%), and 10/10 (100%) WAD, and 54/150 (36.0%) in HC. In the total group, we found 175 PAI-1 4G-4G, 130 MTHFR 677TT, 42V Leiden 506Q, and 27 prothrombin 20210A; 75 patients showed presence of >1 TRHGF; the more frequent association was PAI-1 4G-4G/MTHFR 677TT, in 36 patients. PAI-1 4G-4G and MTHFR 677TT were significantly more frequent in patients with SVT (P values <0.005), whereas V Leiden Q506 and prothrombin G20210A were not. PAI-1 4G-4G and MTHFR 677TT distributions deviated significantly from that expected from a population in Hardy-Weinberg equilibrium. Thrombophilia was significantly less frequent in patients with pre-HSVT (250/437, 57.2%) than in patients with post-HSVT (44/45, 97.8%). CONCLUSIONS: Our study shows the significant prevalence of PAI-1 4G-4G and MTHFR 677TT in SVT, mainly in post-HSVT.