Roberto Miraglia

Liver biopsy findings from healthy potential living liver donors: Reasons for disqualification, silent diseases and correlation with liver injury tests

BACKGROUND/AIMS Liver biopsies detect silent donor disease in potential living liver donors and provide material for studies of subclinical non-alcoholic fatty liver disease (NAFLD). Our primary goal was to determine the contribution of biopsy findings to potential donor evaluation. Factors contributing to pre-clinical NAFLD and correlations between liver injury tests and histopathology have been also determined. METHODS Patient records, laboratory tests and results of the histopathologic examination and diagnoses of 284 patients from 2001 to 2005 were retrospectively extracted from the EDIT database. Hepatic histology was correlated with liver injury tests and with general demographic characteristics in an otherwise normal healthy population. RESULTS A minority (n=119; 42%) of biopsies from this population of 143 males/141 females (average age=36.8years; mean BMI=26.6) were completely normal. The remainder showed steatosis (n=107; 37%), steatohepatitis (n=44; 15%), or unexplained low-grade/early stage chronic hepatitis, primary biliary cirrhosis, or nodular regenerative hyperplasia (n=16; 6%). Biopsy findings disqualified 29/56 donors. Independent risk factors for NAFLD by multivariate modeling, which differed by sex, included: BMI (p=0.0001), age (p=0.003), iron (p=0.01), and ALT (p=0.004). CONCLUSIONS Liver biopsies provide valuable information about otherwise undetectable liver disease in potential liver donors. Obesity, age and iron, which are influenced by sex, contribute to NAFLD pathogenesis. Blood tests other than standard liver profiles are needed to detect early NAFLD.

Successful treatment of small‐for‐size syndrome in adult‐to‐adult living‐related liver transplantation: single center series

Abstract:  The portal hyperperfusion, or small‐for‐size syndrome (SFSS), is a widely recognized clinical complication that may occur after segmental liver transplantation. Several surgical strategies have been proposed to reduce portal blood inflow and portal pressure after partial liver transplantation. In particular, splenic artery ligation and splenectomy have been used without a firm hemodynamic basis for these procedures. Our group recently demonstrated that, in patients with cirrhosis and portal hypertension, the occlusion of the splenic artery causes a significant reduction in the portal pressure gradient, which is directly related to the spleen volume and indirectly related to the liver volume. This concept is at the center of our strategy for performing early splenic artery embolization (SAE) for the treatment of SFSS after living‐related liver transplantation (LRLT). Six patients developed small‐for‐size syndrome, defined as: onset within the first week after LRLT of progressive hyperbilirubinemia without mechanical cause; marked cholestasis; centrilobular sinusoidal dilatation and hepatocyte atrophy at liver biopsy; and refractory ascites in the absence of vascular complications. All six patients who underwent SAE rapidly improved their clinical condition, with an evident decrease in the value of bilirubin in the serum, in the production of ascites, and improvement in condition of pancytopenia. Coagulopathy expressed by the international normalized ratio value (INR) was not a reliable early marker of SFSS in this series; in fact a slight improvement in the result of this test was already present immediately after LRLT and before SAE. Because splenic flow clearly contributes to portal hyperperfsion, an early SAE can relieve the partial graft from the deleterious effect of this portal overflow.

Contribution of transjugular liver biopsy in patients with the clinical presentation of acute liver failure

PurposeAcute liver failure (ALF) treated with conservative therapy has a poor prognosis, although individual survival varies greatly. In these patients, the eligibility for liver transplantation must be quickly decided. The aim of this study was to assess the role of transjugular liver biopsy (TJLB) in the management of patients with the clinical presentation of ALF.MethodsSeventeen patients with the clinical presentation of ALF were referred to our institution during a 52 month period. A TJLB was performed using the Cook Quick-Core needle biopsy. Clinical data, procedural complications, and histologic findings were evaluated.ResultsCauses of ALF were virus hepatitis B infection in 7 patients, drug toxicity in 4, mushroom in 1, Wilson’s disease in 1, and unknown origin in 4. TJLB was technically successful in all patients without procedure-related complications. Tissue specimens were satisfactory for diagnosis in all cases. In 14 of 17 patients the initial clinical diagnosis was confirmed by TJLB; in 3 patients the initial diagnosis was altered by the presence of unknown cirrhosis. Seven patients with necrosis <60% were successfully treated with medical therapy; 6 patients with submassive or massive necrosis (≥85%) were treated with liver transplantation. Four patients died, 3 had cirrhosis, and 1 had submassive necrosis. There was a strict statistical correlation (r = 0.972, p < 0.0001) between the amount of necrosis at the frozen section examination and the necrosis found at routine histologic examination. The average time for TJLB and frozen section examination was 80 min.ConclusionIn patients with the clinical presentation of ALF, submassive or massive liver necrosis and cirrhosis are predictors of poor prognosis. TLJB using an automated device and frozen section examination can be a quick and effective tool in clinical decision-making, especially in deciding patient selection and the best timing for liver transplantation.

Changing picture of central nervous system complications in liver transplant recipients

Central nervous system (CNS) complications are common after liver transplantation (LT). According to the literature, the most common causes are infections and the neurotoxicity of immunosuppressive drugs (cyclosporine and tacrolimus). The aim of this study was to evaluate the incidence, clinical presentations, etiologies, and outcomes of CNS complications in a series of 395 consecutive LT recipients whose immunosuppression regimen was designed for low tacrolimus blood levels. An analysis of the 12‐hour trough concentrations of tacrolimus in the study population showed that the target drug levels, which were designed to maintain minimal immunosuppression, were usually achieved. In all, 64 patients (16.2%) developed major neurological symptoms (37 within 30 days of LT). None of the observed CNS complications were caused by infections (viral, bacterial, or fungal), and only 3 of the 395 patients (0.8%) received a diagnosis of tacrolimus‐related leukoencephalopathy. Cerebrovascular disease was identified in 15 patients (3.8%; 8 had cerebral hemorrhages, 5 had ischemic strokes, and 2 had subdural hemorrhages). Pontine myelinolysis was found in 2 patients (0.5%). Notably, no clear cause was identified for the remaining 44 cases (11.1%): brain imaging was negative for 22 cases, and diffuse hypoxic changes were present for the other 22. CNS complications were significantly associated with a reduction in 3‐month patient survival (88.8% versus 95.4%) and 5‐year patient survival (57.3% versus 84.1%). Among the pretransplant variables that were analyzed, the incidence of portosystemic encephalopathy, the peak serum bilirubin levels, and the lowest serum total cholesterol levels were significantly different between the 64‐patient group with CNS complications and the asymptomatic group of 331 patients. Liver Transpl 17:1279–1285, 2011.

Effects of splenic artery occlusion on portal pressure in patients with cirrhosis and portal hypertension

The specific contribution of splenic blood inflow to portal hypertension in patients with cirrhosis is still unclear. In this study, we investigated this contribution by assessing the hemodynamic effects of transient splenic artery occlusion. In 15 cirrhotic patients, portal pressure gradient (PPG) was measured just before inserting a transjugular intrahepatic portosystemic shunt (TIPS), in baseline conditions, for 15 minutes after splenic artery occlusion and 5 minutes after recovery. Splenic artery occlusion caused a significant decrease in PPG (range, −4% to −38%, median −20%, P < 0.001) which promptly returned to baseline values after recovery of the splenic inflow. The decrease in PPG showed a significant correlation with spleen volume (r = 0.70, P < 0.005), liver volume (r = −0.63; P < 0.01), and spleen/liver volume ratio (r = 0.82, P < 0.001). Seven out of eight patients with a spleen/liver volume ratio greater than 0.5 had a marked decrease in PPG (>20%), whereas none of patients with a ratio lesser than 0.5 had a marked PPG response. In conclusion, in cirrhotic patients with portal hypertension, splenic artery occlusion causes a significant reduction in portal pressure (PPG). The drop in PPG is directly related to spleen volume and indirectly related to liver volume. The spleen/liver volume ratio accurately predicts the drop in PPG and may be used to identify patients who could obtain a significant advantage from surgical and nonsurgical procedures decreasing splenic inflow. Liver Transpl 12:1237‐1243, 2006.

Arterial chemoembolization/embolization and early complications after hepatocellular carcinoma treatment: a safe standardized protocol in selected patients with Child class A and B cirrhosis.

PURPOSE To assess the safety of transarterial treatments of hepatocellular carcinoma (HCC), and the statistical correlation of various patient factors with the frequency of complications, in selected patients with cirrhosis when adhering to well-standardized protocols. MATERIALS AND METHODS Three hundred twenty consecutive patients with unresectable HCC were treated with transarterial chemoembolization, oil chemoembolization, and embolization. A total of 712 treatments were performed, with an average of 2.3 treatments for each patient. The epirubicin dose was adjusted according to defined laboratory criteria. An early complication was defined as one that occurred within 4 weeks of treatment. Complications were classified as minor and major and assessed by using clinical and laboratory data. RESULTS Of the 712 procedures, 21 complications (2.9%) occurred in 17 of the 320 patients (5.3%). Major complications included acute liver failure (n = 1, 0.1%), variceal bleeding (n = 2, 0.3%), moderate-to-severe ascites (n = 4, 0.6%), sepsis (n = 3, 0.4%), cholecystitis (n = 1, 0.1%), and diverticulitis (n = 1, 0.1%). Minor complications were hepatic artery damage, including spontaneously resolved dissection (n = 3, 0.4%), mild encephalopathy (n = 1, 0.1%), and aspartate aminotransferase/alanine aminotransferase levels greater than 500 U/L (n = 5, 0.7%). The 30-day mortality rate was 0.003% (n = 1). Constitutional syndrome (P = .0001), Child-Pugh score (P = .0001), ascites (P = .037), and the Model for End-Stage Liver Disease score (P = .02) were found to have a statistically significant correlation with complications after univariate analysis. Child-Pugh score (P = .012) and constitutional syndrome (P = .003) were found to have a statistically significant correlation with complications after logistic regression analysis. CONCLUSIONS Transarterial treatments can be considered safe in patients with Child class A and B cirrhosis when an adjusted dose of epirubicin is used according to body surface, severity of liver disease, and white blood cell count. Accurate patient selection and procedure-related factors may reduce the frequency of complications and help preserve liver function.

Measurement of hepatic vein pressure gradient in children with chronic liver diseases

BACKGROUND & AIMS The aim of this study is to present our preliminary experience with Hepatic Vein Pressure Gradient (HVPG) measurements in pediatric patients with chronic liver disease. METHODS Institutional review board approval was obtained. HVPG was measured in 20 pediatric patients, mean age 82+/-54 months, with chronic liver disease, without extrahepatic portal vein obstruction. In nine patients the end-stage liver disease was secondary to biliary atresia; in the remaining 11, to various causes. Eleven patients had esophageal varices at endoscopy, 14 had perigastric and periesophageal collaterals at imaging scan, three had ascites, 12 had low platelet count, and all had splenomegaly. RESULTS Hepatic vein catheterization was technically possible in all patients without complications. HVPG values were elevated in all but three patients, ranging between 2 and 33 mmHg (mean 11.3+/-7.2 mmHg), thus indicating a sinusoidal component in portal hypertension. A salient finding was the presence of hepatic venovenous shunts in 7 out of 9 patients with biliary atresia; however, the HVPG could still be measured distal to the shunts, but in three patients (with an HVPG of 8 mmHg) it was determined in an area with a small venovenous communication still visible, therefore underestimating the actual portal pressure gradient. No venovenous shunts were detected in the non-biliary atresia patients. CONCLUSIONS HVPG is a feasible procedure in pediatric patients. Patients with biliary atresia very frequently have communicating vessels between hepatic veins. This hitherto unacknowledged finding can lead to the underestimation of portal pressure by HVPG measurement.

Early regeneration of the remnant liver volume after right hepatectomy for living donation: A multiple regression analysis

Early liver regeneration was studied in a series of 70 patients who underwent right hepatectomy for living donation between November 2004 and January 2010. Liver regeneration was evaluated with multidetector computed tomography (MDCT) at a mean of 61.07 days after surgery. Presurgical variables [eg, age, weight, height, body mass index (BMI), liver function tests, creatinine levels, platelet counts, international normalized ratio, and glucose levels] and variables detected with preoperative MDCT imaging [eg, main portal vein diameter, steatosis, original liver volume, and spleen volume (SV)] were investigated as potential predictors of liver regeneration. The future remnant liver volume (FRLV) was preoperatively calculated with a virtual surgical cut. Liver function tests and creatinine levels were recorded on the 30th postoperative day. In addition, the onset of postoperative complications occurring within 90 days of surgery was analyzed, and the complications were codified according to the 5 tiers of the Clavien‐Dindo classification. In 26 of the 70 patients (37.14%), 100% or greater hepatic regeneration had occurred at 2 months. There was no association between the clinical outcome and the liver regeneration rate. A stepwise multiple regression analysis showed that a higher BMI (coefficient = 0.035, P < 0.0001) and preoperative parameters such as a smaller FRLV (coefficient = −0.002, P < 0.0001) and a greater SV/FRLV ratio (coefficient = 1.196, P < 0.0001) were predictors of greater liver regeneration. Liver Transpl, 2012.

Percutaneous transhepatic venous angioplasty in a two-yr-old patient with hepatic vein stenosis after partial liver transplantation.

Abstract:  We report one case of severe hepatic vein stenosis, in a two‐yr‐old pediatric patient with a left lateral split liver transplantation (S2–S3) and severe ascites, in whom color Doppler ultrasound failed to make the diagnosis and transhepatic balloon angioplasty was successfully performed.

Percutaneous recanalization of an occluded hepatico-jejunostomy, using Colapinto needle, in a two-yr-old patient after partial liver transplantation

Abstract:  We report one case of percutaneous recanalization of an hepatico‐jejunostomy, using Colapinto needle, in a two‐yr‐old patient after partial liver transplantation and occlusive anastomotic biliary stricture non‐crossable with conventional interventional radiology techniques. The procedure was successfully performed and followed by biliary trans‐anastomotic catheter placement. Later, the patient underwent multiple session of conventional percutaneous balloon dilatation of the anastomosis as a good flow of contrast from bile ducts to bowel loops was achieved. The patient is now without percutaneous biliary catheter since 10 months in good general conditions and with good liver function tests.