C-reactive protein but not procalcitonin may predict antibiotic response and outcome in infections following major abdominal surgery.

We aimed to evaluate the usefulness of C-reactive protein (CRP) and procalcitonin (PCT) as markers of infection, sepsis and as predictors of antibiotic response after non-emergency major abdominal surgery. We enrolled, from June 2015 to June 2019, all patients who underwent surgery due to abdominal infection (peritoneal abscess, peritonitis) or having sepsis episode after surgical procedures (i.e. hepatectomy, bowel perforation, pancreaticoduodenectomy (PD), segmental resection of the duodenum (SRD) or biliary reconstruction in a Tertiary Care Hospital. Serum CRP (cut-off value < 5 mg/L) and PCT (cut-off value < 0.1mcg/L) were measured in the day when fever was present or within 24 h after abdominal surgery. Both markers were assessed every 48 h to follow-up antibiotic response and disease evolution up to disease resolution. We enrolled a total of 260 patients underwent non-emergency major abdominal surgery and being infected or developing infection after surgical procedure with one or more microbes (55% mixed Gram-negative infection including Klebsiella KPC, 35% Gram-positive infection, 10% with Candida infection), 58% of patients had ICU admission for at least 96 h, 42% of patients had fast track ICU (48 h). In our group of patients, we found that PCT had a trend to increase after surgical procedure; particularly, those undergoing liver surgery had higher PCT than those underwent different abdominal surgery (U Mann-Whitney p < 0.05). CRP rapidly increase after surgery in those developing infection and showed a statistical significant decrease within 48 h in those subject being responsive to antibiotic treatment and having a clinical response within 10 days independently form the pathogens (bacterial or fungal). Further we found that those having CRP higher than 250 mg/L had a reduced percentage of success treatment at 10 days compared to those < 250 mg/mL (U Mann-Whitney p < 0.05). PCT did not show any variation according to treatment response. CRP in our cohort seems to be a useful marker to predict antibiotic response in those undergoing non-emergency abdominal surgery, while PCT seem to be increased in those having major liver surgery, probably due to hepatic production of cytokines.

The role of minimally invasive surgery in the treatment of cholangiocarcinoma.

Cholangiocarcinoma (CC) is the second most common type of primary liver cancer after hepatocellular carcinoma. Surgical resection is considered the only curative treatment for CC. In general, laparoscopic liver surgery (LLS) is associated with improved short-term outcomes without compromising the long-term oncological outcome. However, the role of LLS in the treatment of CC is not yet well established. In addition, CC may arise in any tract of the biliary tree, thus requiring different types of treatment, including pancreatectomies and extrahepatic bile duct resections. This review presents and discusses the state of the art in the laparoscopic and robotic surgical treatment of all types of CC. An electronic search was performed to identify all studies dealing with laparoscopic or robotic surgery and cholangiocarcinoma. Laparoscopic resection in patients with intrahepatic CC (ICC) is feasible and safe. Regarding oncologic adequacy, as R0 resections, depth of margins, and long-term overall and disease-free survival, laparoscopy is comparable to open procedures for ICC. An adequate patient selection is required to obtain optimal results. Use of laparoscopy in perihilar CC (PHC) has not gained popularity. Further studies are still needed to confirm the benefit of this approach over conventional surgery for PHC. Laparoscopic pancreaticoduodenectomy for distal CC (DCC) represents one of the most advanced abdominal operations owing to the necessity of a complex dissection and reconstruction and has also had small widespread so far. Minimally invasive surgery seems feasible and safe especially for ICC. Laparoscopy for PHC is technically challenging notably for the caudate lobectomy. Not least as for the LLR, the robotic approach for DCC appears technically achievable in selected patients.

Liver Transplantation and Abuse of Drugs and Alcohol: A Correlation Between Scales of the MMPI-2.

BACKGROUND: Clinical practice requires an accurate psychological assessment of subjects with clinical history of alcohol abuse and/or substance abuse (abuse history [AH]) for therapeutic choice. This study aims to identify significant correlations between the Minnesota Multiphasic Personality Inventory (MMPI)-2 scales in patients awaiting liver transplantation. METHODS: We evaluated a personality questionnaire containing MMPI-2 scales in the sample of 308 patients (81.8% males and 18.2% females) awaiting liver transplantation. The AH group composed 44.49% of patients and in the abuse free (AF) group, 55.51%. Scales were compared using Shapiro-Wilk test and Mann-Whitney U test. Interrelationships were examined using Spearman's correlation. RESULTS: This analysis found 27 scales of the MMPI-2 that were statistically different between 2 groups (AF and AH). In the AH group, we found a significant correlation between the following pairs of scales: Schizophrenia Scale (Sc) with the Addictions Potential Scale, Social Introversion scale (Si) with the Psychopathic Deviate scale (Pd), and Social Discomfort scale with Pd; the ES scale was negatively correlated with the Sc and Si scales. This interim study showed that the understanding of these indicators is crucial both for the assessment accuracy and for a prediction of the degree of therapy compliance after the transplantation. CONCLUSIONS: The scales of the MMPI-2 indicated a marked tendency to emotional rigidity, a lack of self-esteem and susceptibility judgment. Social introversion and social discomfort trends lead to impulsive behavior and deviant actions that combine poorly with good compliance with treatment.

The ALPPS procedure for hepatocellular carcinoma.

BACKGROUND: The main limiting factor to major hepatic resections is the amount of the future liver remnant (FLR). Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy (ALPPS) is a procedure which induces a rapid hypertrophy of the FLR in patients with non-resectable liver tumours. METHODS: ALPPS is a surgical technique of in-situ splitting of the liver along the main portal scissura or the right side of the falciform ligament, in association with portal vein ligation in order to induce a rapid hypertrophy of the left FLR. RESULTS: The median FLR volume increase was 18.7% within one week after the first step and 38.6% after the second step. At the first step the median operating time was 300 min, blood transfusions were not required in any case, median blood loss was 150 cc. At the second step median operating time was 180 min, median blood loss was 50 cc, none of the patients required intra-operative blood. All patients are alive at a median follow up of 9 months. CONCLUSIONS: This novel strategy seems to be feasible even in the context of a cirrhotic liver, and demonstrates the capacity to reach a sufficient FLR within a shorter interval of time.

Downstaging Hepatocellular Carcinoma with Yttrium-90 radioembolization: resection or transplantation?

Trans Arterial Radio Embolization with Yttrium 90 in the treatment of Hepatocellular Carcinoma is becoming a new interesting tool in the treatment of patients that are considered non resectable and non transplantable. A successful downstaging could improve the number of patients that could benefit from a resection or a liver transplantation, but some points still need to be addressed.

Hanging of the hepatic veins septa: a safe control prior and during outflow anastomosis in liver transplantation.

Inferior vena cava (IVC) preservation during orthotopic liver transplantation (OLT) is known as the "piggyback" technique. The end-to-side anastomosis is constructed between the graft's IVC and recipient's hepatic veins using a Satinsky side clamp applied in a transverse position. To stabilize the large Satinsky clamp and preserve a sufficient vascular stump after hepatectomy and before graft implantation, we propose a technical innovation consisting of hanging the septa between the left and middle hepatic vein and between the middle and right hepatic vein using 2 tapes. This technique showed some advantages when performing the caval outflow anastomosis, representing a further technical refinement of the piggyback end-to-side technique for the implantation on the 3 hepatic veins. From November 2001 to September 2012, we performed 272 consecutive OLT at our institution with the piggyback technique using the hanging of the hepatic veins septa in all cases. In conclusion, the hanging of the 3 hepatic veins septa presented in this study represents a simple, safe and reproducible technique for the outflow anastomosis using the piggyback technique.

De novo malignancies following liver transplantation: results from a multicentric study in central and southern Italy, 1990-2008.

OBJECTIVE: The objective of this study was to quantify incidence rates (IR) and risks of de novo tumors (except nonmelanoma skin cancers) in patients who underwent orthotopic liver transplantation (OLT) in central and southern Italy. METHODS: Data were collected on 1675 patients (75.5% males) who underwent OLT in six Italian transplantation centers in central and southern Italy (1990-2008). The time at risk of cancer (person years [PY]) was computed from OLT to the date of cancer diagnosis, death, or last follow-up, whichever occurred first. The number of observed cancer cases were compared with the expected one using data from population-based cancer registries. We computed gender- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: During 10,104.3 PYs (median follow-up, 5.2 years), 98 patients (5.9% of the total) were diagnosed with a de novo malignancy (for a total of 100 diagnoses). Twenty-two of these cancers were post-transplantation lymphoproliferative disorders (PTLD; 18 non-Hodgkin lymphoma [NHL] and 2 Hodgkin's lymphoma [HL]), 6 were Kaposi's sarcoma (KS), and 72 were solid tumors (19 head and neck [H&N], 13 lung, 11 colon-rectum, 6 bladder, and 4 melanoma). The overall incidence was 9.9 cases/10(3) PYs, with a 1.4-fold significantly increased SIR (95% CI, l.2-1.7). Significantly increased SIRs were observed for KS (37.3), PTLD (3.9), larynx (5.7), melanoma (3.1), tongue (7.1), and H&N (4.5) cancers. CONCLUSIONS: These results confirmed that OLT patients are at greater risk for cancer, mainly malignancies either virus-associated or related to pre-existent factors (eg, alcohols). These observations point to the need to improve cancer surveillance after OLT. The on-going enrollment of patients in the present cohort study will help to elucidate the burden of cancer after OLT and better identify risk factors associated with its development.

Fatal sclerosing peritonitis associated with primary effusion lymphoma after liver transplantation: a case report.

Sclerosing peritonitis (SP) after liver transplantation has been described in 10 cases in the literature. The etiology is still unknown; however, SP is considered a consequence of chronic irritation and inflammation. It can be classified as primary (idiopathic) or secondary form. Although pathologically benign, it has a negative course, resulting in unrelenting abdominal pain, small bowel obstruction, malnutrition, and death. Posttransplantation lymphoproliferative disease (PTLD) is one of the leading causes of late death. Its development is related to complex interactions between immunosuppressive drugs and environmental agents. Primary effusion lymphoma (PEL) as an onset presentation of PTLD is relatively uncommon. Most examples of effusion-based PTLD have been secondary to widespread solid organ involvement and associated with Human herpes virus 8 (HHV-8) recurrence. Here in, we report a case of a 55-year-old man who rapidly developed refractory ascites and bacterial peritonitis at 1-year after orthotopic liver transplantation (OLT) with a fatal clinical course at the beginning of the second follow-up year after an uncomplicated liver transplantation due to cryptogenic cirrhosis. The diagnosis of HHV-8-positive lymphoma was established by postmortem examination with multiple solid localizations and massive dense fibrotic adhesions encompassing the small intestine, colon, liver, and porta hepatis without any involvement of body cavities.

Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadjuvant chemotherapy in colorectal liver metastases: POCHER trial.

BACKGROUND: We assessed the effectiveness of cetuximab plus chronomodulated irinotecan, 5-fluorouracil (5-FU), leucovorin (FA) and oxaliplatin (L-OHP) (chrono-IFLO) administered as neoadjuvant chemotherapy to increase the resectability of colorectal liver metastases. METHODS: This was a phase II prospective trial with rate of liver metastases resection as primary end point. Forty-three patients with unresectable metastases were enroled: 9 with metastases >5 cm; 29 with multinodular (>4) disease; 1 with hilar location; 4 with extrahepatic lung disease. Treatment consisted of cetuximab at day 1 plus chronomodulated irinotecan 5-FU, FA and L-OHP for 2-6 days every 2 weeks. After the first 17 patients, doses were reduced for irinotecan to 110 mg m⁻², 5-FU to 550 mg m⁻² per day and L-OHP to 15 mg m⁻² per day. RESULTS: Macroscopically complete resections were performed in 26 out of 43 patients (60%) after a median of 6 (range 3-15) cycles. Partial response was noticed in 34 patients (79%). Median overall survival was 37 months (95% CI: 21-53 months), with a 2-year survival of 68% in the entire population, 80.6% in resected patients and 47.1% in unresected patients (P=0.01). Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction. CONCLUSION: Cetuximab plus chrono-IFLO achieved 60% complete resectability of colorectal liver metastases.

Successful use of extended criteria donor grafts with low to moderate steatosis in patients with model for end-stage liver disease scores below 27.

Liver transplantation may be performed using extended criteria donor grafts (ECDg). The characteristics of ECDg include age >60 years, long intensive care unit (ICU) stay, history of malignancy or steatosis. Grafts are often discarded due to steatosis, which can be macrovesicular (MaS) or microvesicular (MiS). MaS is the variety most frequently involved with unfavorable outcomes due to primary nonfunction (PNF) or primary dysfunction (PDF). As of January 2000, all livers referred to our institution were considered potentially transplantable. Steatosis was defined as the presence of fat droplets in more than 5% of hepatocytes. We observed 35 steatotic grafts. Grafts were stratified according to MaS and MiS as follows: low steatosis (5%-15%), mild steatosis (16%-30%), moderate steatosis (31%-60%), or severe steatosis (>60%). Fifteen grafts with moderate (n = 2) or severe (n = 13) MaS were discarded. Twenty grafts were harvested: 18 of them were transplanted at our institution, the remaining 2, discarded by our donor team, were transplanted by other Italian centers. Low MaS was detected in 10 grafts (50%), mild MaS in 4 (20%), and moderate MaS in 2 (10%). Low MiS was detected in 8 grafts (40%), mild MiS in 5 (25%), and moderate MiS in 1 (5%). Steatotic grafts were transplanted only into recipients with model for end-stage liver disease (MELD) scores <27. The 6-month graft survival was 80%; the PNF rate was 10%; and the PDF rate was 15%. The careful use of ECDg with low to moderate steatosis is possible if particular care is taken to avoid additional risk factors related to the recipient.

First-line liver resection and salvage liver transplantation are increasing therapeutic strategies for patients with hepatocellular carcinoma and child a cirrhosis.

AIM: The present study focused on nine patients with hepatocellular carcinoma (HCC) associated with Child A liver cirrhosis undergoing first-line liver resection and salvage liver transplantation (SLT) for liver tumor recurrence. PATIENTS AND METHODS: Forty-six patients with HCC underwent liver transplantation (OLT); 37 (80.5%) were primary liver transplantations (PLTs) and 9 (19.5%) were SLTs. All patients who underwent SLT received minor transabdominal liver resections. RESULTS: The posttransplant 1-, 3-, and 5-year overall survival rates for SLT (88.9%, 88.9%, and 88.9%) were similar to those for PLT (78%, 62.7%, and 62.7%). Four (10.8%) patients in the PLT group had HCC recurrence, while there was zero recurrence in the SLT group. The 1-, 3-, 5-year disease-free survival rates for PLT (89%, 74%, and 74%) were similar to those for SLT (100%, 100%, and 100%). The 1-, 3-, 5-year disease-free survival rates after PLT were 89%, 74%, and 74%, and after SLT were 100%, 100%, and 100%, respectively. The operative mortality, intraperioperative bleeding, operative time, intensive care unit stay, in-hospital stay, and overall incidence of postoperative complications were similar in the two groups. CONCLUSIONS: In our experience, SLT for HCC is a feasible procedure with similar results in terms of overall survival, disease-free survival, and postoperative complications to those reported for patients who underwent PLT at our institute. An important role exists for SLT as shown by the fact that such a strategy has been used in the 20% of the patients undergoing OLT for HCC.

Modified liver hanging maneuver during orthotopic liver transplantation with inferior vena cava preservation: results after 120 consecutive applications.

The outflow venovenous anastomosis represent a crucial aspect during orthotopic liver transplantation (OLT) with inferior vena cava (IVC) preservation. The modified Belghiti liver hanging maneuver applied to the last phase of hepatectomy, lifting the liver, provides a better exposure of the suprahepatic region and allows easier orthogonal clamping of the three suprahepatic veins with a minimal portion of IVC occlusion. The outflow anastomosis constructed with a common cloacae of the three native suprahepatic veins is associated with a lower incidence of graft related venous outflow complications. The procedure planned in 120 consecutive OLT was achieved in 118 (99%). The outflow anastomosis was constructed on the common cloaca of the three hepatic veins in 111/120 cases (92.5%). No major complications were observed (bleeding during tunnel creation, graft outflow dysfunction, etc) except in one patient with acute Budd-Chiari, who successfully underwent retransplantation.

Liver transplantation in HIV-positive patients.

AIMS: The aim of this study was to evaluate the feasibility of liver transplantation (OLT) in human immunodeficiency virus (HIV), hepatitis C virus (HCV) coinfected patients in Italy. METHODS: Between September 2002 and April 2006, 12 HIV(+) coinfected patients (11 men, mean age 42 years) underwent OLT at our Institute. Eleven (91%) patients were HCV-positive and one was hepatitis B virus-positive. Pre-OLT plasma HIV 1-RNA level was undetectable and CD4(+) T-cell count >200 cells/microL for 3 months in all patients. Six patients had to stop highly active antiretroviral therapy (HAART) before OLT because of liver disease severity (n = 2) and for hepato cellular carcinoma (n = 4). RESULTS: The actuarial 1-, 2-, and 3-year survival rates were 83.3%, 58.3%, and 58.3%, respectively, which were significantly lower than those observed among HIV-negative patients transplanted in our center. Six patients are alive with a mean follow-up of 26 months (range: 5 to 46 months). We recorded a low rate of opportunistic infections and rejection. All alive patients have low levels of HIV RNA, and the CD4(+) T-cell counts increased after OLT. Nine patients developed early recurrence of hepatitis C requiring combination therapy with peg-interferon plus ribavirin. Significant improvement in the quality of life was observed in 7/11 patients. CONCLUSIONS: OLT in HIV-positive patients was feasible with good results in the short and medium term. Early severe HCV recurrence may be observed. Key challenges for the management of HIV(+) patients after transplantation included treatment of severe HCV recurrence and attention to the pharmacological interactions of HAART with immunosuppressive drugs.

Incidence and timing of infections after liver transplant in Italy.

BACKGROUND: Infections are one of the main complications that cause high morbidity and mortality in transplant recipients. This study sought to estimate the incidence of infections and their main determinants in liver transplant recipients in the first year after transplantation. PATIENTS AND METHODS: A prospective study was conducted on 103 consecutive patients (72% men) who underwent transplantation in three centers in Northern (Bologna) and Central (Rome) Italy in 2005. Person-years (PY) at risk, incidence rates (IR), IR ratios and 95% confidence intervals were computed for viral, fungal, and bacterial infections. RESULTS: The 103 patients (median age 55 years) contributed a total of 78.2 PYs, with a median follow-up of 286 days (interquartile range: 194 to 365 days). Fifty-eight patients (56.3%) experienced one or more infections, namely, 151 events (IR = 193.2 infections/100 PYs). IR for bacterial, fungal, and viral infections were 110.0, 56.3, and 26.9 infections/100 Pys, respectively. Within the first 30 days after transplantation, 37.9% patients (39/103) developed one or more events. Bacterial infections represented the most frequent event (86/151, 57.0%). Risk factors significantly associated with increased IR were gender (female), age (>50 years), prolonged intensive care stay volume of blood transfused during surgery and posttransplant, and need for retransplantation. CONCLUSIONS: These preliminary results showed the relevance of infectious events after liver transplantation especially those of bacterial etiology, and identified factors mainly associated with their occurrence.

Malignant insulinoma presenting as metastatic liver tumor. Case report and review of the literature.

Insulin-secreting tumors are the commonest hormone-producing neoplasm of the gastrointestinal tract. They occur with an incidence of 4 cases per million per year. About 10% of them are metastatic and malignant insulinomas very rarely observed in children and in elderly. We report a rare case of very large malignant insulinoma in a 71-year-old woman admitted in our Oncological Institute on October 2005. She presented with fasting hypoglicemia (blood glucose 35 mg/dl) and high serum insulin levels (insulin 115.9 microU/ml). A computerized tomographic scan showed a pancreatic tail lesion of about 6 cm in max diameter and multiple liver metastases. A whole body scintiscan using 111In-DTPA-D-Phe1-octreotide was made and an increased uptake in the tail of the pancreas has been found. The patient was submitted to liver biopsy and the diagnosis of a metastatic insulin-secreting tumor was immunoistochemically confirmed. Due to the presence of some hypoglicemic episodes uncontrolled by medical treatment, on December 2005 the patient was admitted to surgical intervention with a body and tail pancreatic resection. Post-operatively the patient experienced again syncope with hypoglycemia and hyperinsulinemia. It was then decided to start a schedule of treatment with somatostatin analog (octreotide subcutaneously 500 microg three times a day) with a good control of blood glucose levels (101 mg/dl). A trans-arterial chemioembolization was planned but the patient died for pancreatic and cardiovascular complications before this treatment started.

[Isolated resection of the caudate lobe in metastasis of colorectal cancer]. / Resezione isolata del lobo caudato per metastasi da cancro colorettale.

The presence of metastatic lesions confined to the caudate lobe (CL or segment I) is quite a rare event. Even more rare is the decision to perform an isolate CL resection. Segmental resection in the liver is justified by the evidence that primary and secondary lesions, in early stage, are confined to the originating segment, and therefore a segmentectomy can be considered for the CL as well. Anatomy of the CL was deeply studied through the years since the surgical approach to this liver segment requires a detailed knowledge of its surgical anatomy and only after 1985 the surgical technique for CL isolate resection was established. We report our experience with 1 case of isolate colo-rectal metastasis confined to the caudate lobe and describe the surgical technique employed.

[Trauma of the liver and hepatic pedicle]. / Le lesioni multifunzionali del fegato.

Traumatic injuries of the liver and hepatic pedicle secondary to blunt abdominal trauma are unusual and often associated with injuries of other abdominal and/or thoracic organs. These lead the patient to an emergency operation for hemorrhagic shock. The diagnosis of trauma severity and hepatic pedicle involvement is made intraoperatively. Often only one anatomical structure of the hepatic pedicle is involved, whereas involvement of two or all three anatomical structures is rare and associated with a bad prognosis. The management of these injuries still remain one of the most challenging scenario in trauma surgery. The overall experience is not significant. Clear treatment guidelines or management algorithms have not yet been established, in part due to the complexity, severity and variability of these injuries and to the lack of large series with these rare events. Three cases of associated liver and hepatic pedicle injuries treated in our unit are reported.

[The modified "hanging maneuver" during orthotopic liver transplantation using a technique for conserving the inferior vena cava]. / Manovra di "hanging" modificata durante trapianto ortotopico di fegato con tecnica di conservazione della vena cava inferiore.

We describe a modification of Belghiti's "liver hanging maneuver" applied to the last phase of hepatectomy during OLT with IVC preservation. The proposed maneuver provides a better exposition of the suprahepatic veins allowing an ortogonal clamping of the suprahepatic confluence and avoiding caval clamping. It allows, moreover, an increase of venous surface available for the anastomosis that results wider and easier to perform. This provides a large outflow anastomotic cloaca and prevents outflow problems of the graft.

[Acute liver toxicity of antiretroviral therapy (HAART) after liver transplantation in a patient with HIV-HCV coinfection and associated hepatocarcinoma (HCC)]. / Tossicità epatica acuta da terapia antiretrovirale (HAART) dopo trapianto di fegato in un paziente con coinfezione da HIV-HCV ed associato epatocarcinoma (HCC).

OLT in HIV infected patients still remains a challenging option requiring a careful monitoring of patients for HCV reinfection, drug interactions and antiretroviral toxicity. Severe adverse events due to HAART have been already reported for post exposure prophylaxis in HIV infected patients. Here we report a case of liver graft toxicity related to HAART in a HIV-HCV co-infected patient (46 yrs-male) with associated a small HCC transplanted with a marginal liver graft. The patient had pre-OLT plasma HIV 1-RNA levels undetectable and CD4+ T-cell count of > 200 cells/microL for 6 months. At day 2 a severe graft dysfunction was observed (AST 1570 U/L, ALT 2180 U/L, BIL tot 8.3 mg/dL, BIL Dir 6.6 mg/dL and PT 35%--INR 2.5). Doppler scan showed hepatic artery always patient. Later the postoperative in-hospital course was complicated by tense ascites and severe cholestasis. Serum bilirubin reached 42 mg/dL in day 12. Hypertransaminasemia ended at day 15 while cholestasis ended after 46 days. Tacrolimus was reintroduced at day 7. A liver biopsy 10 after OLT showed severe intrahepatic cholestasis, centrolobular necrosis and macrovesicular steatosis (30%). The patient was discharged 48 days after OLT with good liver function. After seven months HIV-RNA is still undetectable and HAART has not been restarted. We believe that the early complications we observed may be attributed to a sudden increase in plasma concentration of antiretroviral drugs secondary to drug redistribution from peripheral tissues and hepatic clearance deficiency after OLT. Although a pre-OLT withdrawal of HAART seems unjustified a delayed re-introduction of HAART or the use of less hepatotoxic drugs may be advisable.