Occult central pontine myelinolysis post liver transplant: A consequence of pre-transplant hyponatremia.

Rapid overcorrection of chronic hyponatremia can lead to osmotic demyelination syndrome or central pontine myelinolysis (CPM), a diagnosis often triggered by observing the characteristics of neurological abnormalities developed as a result of CPM. However, anyone with chronic hyponatremia and overcorrection of serum sodium is at risk of physiological CPM despite the lack of clinical symptoms. We report an adult patient who presented as post-op delirium, had incidental finding of CPM by magnetic resonance imaging (MRI) of the head after a liver transplant. Despite his non-typical presentation, the patient had the typical risk factors of CPM such as chronic hyponatremia, rapid overcorrection of serum sodium and cirrhosis undergoing a transplant. As hyponatremia and neurological disorder such encephalopathy simultaneously affect patients with cirrhosis, CPM may be more common than once thought in the chronic liver disease population and inappropriate hyponatremia management has important medical consequences that can go unnoticed.

A review of direct-acting antivirals for the treatment of hepatitis C in patients with advanced chronic kidney disease.

Historically, standard treatment of hepatitis C virus (HCV) infection in patients with renal impairment has been limited by low cure rates and poor tolerability. The introduction of direct-acting antivirals (DAAs) has revolutionized the treatment of HCV with impressive cure rates >90% and low rates of adverse events. Despite these major advancements, treatment of patients with HCV and advanced chronic kidney disease (CKD) is a major challenge due to the lack of efficacy and safety data in this patient population. The purpose of this review is to summarize the available data for efficacy and safety of the following DAAs in treating HCV patients with advanced Stage 4 and 5 CKD: simeprevir, sofosbuvir, ledipasvir, ombitasvir, paritaprevir, dasabuvir, grazoprevir, elbasvir and daclatasvir.

Interaction of Gender and Hepatitis C in Risk of Chronic Renal Failure After Liver Transplantation.

BACKGROUND: Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. OBJECTIVES: To examine the risk factors in the development of CRF in these patients. MATERIAL AND METHODS: Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. RESULTS: Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. CONCLUSIONS: In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.

Lamivudine, Entecavir, or Tenofovir Treatment of Hepatitis B Infection: Effects on Calcium, Phosphate, FGF23 and Indicators of Bone Metabolism.

BACKGROUND: Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. OBJECTIVE: To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. MATERIAL AND METHODS: This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. RESULTS: No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF-treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (<-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. CONCLUSION: Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.

Successful Treatment of Hepatitis C with Simeprevir, Sofosbuvir, and Ribavirin in an HIV Coinfected Liver Transplant Patient with Advanced Chronic Kidney Disease.

Although major advances have occurred in treating patients with hepatitis C virus (HCV) with the development of new direct-acting antivirals (DAAs), treatment of liver transplant recipients with HCV, human immunodeficiency virus (HIV) coinfection, and renal disease is challenging due to the lack of efficacy and safety data in this population. We report a case of successful HCV therapy in a postliver transplant HIV coinfected patient, with stage 4 chronic kidney disease, using an all-oral regimen of simeprevir, sofosbuvir, and ribavirin. The 51-year-old male achieved SVR24, and no specific HIV-related or transplant-related adverse events were documented during the treatment period. The new DAAs show promise for HIV coinfected patients and those with severe to end-stage renal disease (ESRD); however, robust clinical trials or large cohort studies will need to be conducted to confirm the efficacy and safety of these newer agents in this setting.

Drug Interactions With Direct-Acting Antivirals for Hepatitis C: Implications for HIV and Transplant Patients.

OBJECTIVE: Review pharmacokinetics of new direct-acting antivirals (DAAs) for hepatitis C (HCV) infection and interactions with concomitant immunosuppressant and antiretroviral therapies (ART). DATA SOURCES: MEDLINE (1948-January 2015), EMBASE (1964-January 2015), International Pharmaceutical Abstracts (1970-January 2015), Google, and Google Scholar were searched combining the terms simeprevir, sofosbuvir, ledipasvir, daclatasvir, paritaprevir, ABT-450, ombitasvir, dasabuvir, pharmacokinetics, drug interaction, drug metabolism, HIV, antiretroviral, immunosuppressant, transplant. Articles, conference proceedings, abstracts, and product monographs were reviewed. STUDY SELECTION AND DATA EXTRACTION: Literature on pharmacokinetic or pharmacodynamic interactions with DAAs and immunosuppressants or ART was considered for inclusion. Pertinent information was extracted and summarized in the review. In the absence of data, pharmacokinetic and pharmacodynamic principles were used to predict the likelihood of interactions. DATA SYNTHESIS: DAA pharmacokinetics are reviewed and drug interaction data are presented with provision of management strategies. Fixed-dose combination paritaprevir/ritonavir/ombitasvir plus dasabuvir is most susceptible to drug interactions with immunosuppressants and ART mainly due to the influence of ritonavir on multiple enzymes. Simeprevir is also prone to drug interactions because of cytochrome P450(CYP) 3A4, CYP1A2, P-glycoprotein, and OATP1 involvement and is not recommended for use in combination with several HIV antiretrovirals (ARVs). Close therapeutic drug monitoring of calcineurin inhibitors is required with concomitant simeprevir. Few clinically significant interactions are expected with sofosbuvir or ledipasvir. Limited data suggest that daclatasvir may be coadministered with immunosuppressants but requires dose adjustments with certain ARVs. CONCLUSIONS: None of the DAAs are completely free of drug interactions. Awareness and management of drug interactions is critical to optimize outcomes and minimize adverse effects in these patient populations.

First confirmed case of native polyomavirus BK nephropathy in a liver transplant recipient seven years post-transplant.

Renal dysfunction frequently occurs in liver transplant recipients and is associated with increased morbidity and mortality. BK virus is a human polyoma virus that reactivates during immunocompromised states and is a known cause of renal allograft dysfunction in renal transplant recipients. However, BK nephropathy of native kidneys is rare in non-renal transplant recipients. There is no published data linking BK virus and renal dysfunction in liver transplant recipients. We describe the first confirmed case of native polyomavirus BK nephropathy in a liver transplant recipient. BK nephropathy should be considered in the differential diagnosis of new renal failure in liver transplant recipients.

Antimitochondrial antibody serocoversion post-liver transplant during hepatitis C treatment with peginterferon α, ribavirin and telaprevir.

Pegylated interferon alpha (PEG-IFN α), a key component of chronic hepatitis C therapy, has been linked to the development of auto-antibodies and autoimmune disease. We report the first case of antimitochondrial antibody (AMA) seroconversion during PEG-INF α based therapy after liver.1-4 transplantation. A fiftyseven year-old man five months after liver transplantation was initiated on hepatitis C triple therapy with PEG-INF α, ribavirin and telaprevir. He had failed previous PEG-IFN α and ribavirin 12 years pre-transplant and his AMA remained negative pre-transplant. After twelve weeks of antiviral therapy, he developed elevated liver enzyme tests associated with an AMA seroconversion to seropositivity. A liver biopsy failed to show histological evidence of primary biliary cirrhosis or graft rejection. He was initiated on urseodeoxycholic acid with subsequent improvement of his liver enzymes. This case demonstrates that despite adequate immunosuppression, AMA seroconversion may occur post-transplant during interferon-based therapy. As AMA seroconversion did not occur during the pre-transplant PEG-IFN therapy, we speculate that donor allograft antigens in combination with PEG-IFN may have been a factor in the post-transplant seroconversion.

HIV and liver transplantation: The British Columbia experience, 2004 to 2013.

BACKGROUND: The demand for definitive management of end-stage organ disease in HIV-infected Canadians is growing. Until recently, despite international evidence of good clinical outcomes, HIV-infected Canadians with end-stage liver disease were ineligible for transplantation, except in British Columbia (BC), where the liver transplant program of BC Transplant has accepted these patients for referral, assessment, listing and provision of liver allograft. There is a need to evaluate the experience in BC to determine the issues surrounding liver transplantation in HIV-infected patients. METHODS: The present study was a chart review of 28 HIV-infected patients who were referred to BC Transplant for liver transplantation between 2004 and 2013. Data regarding HIV and liver disease status, initial transplant assessment and clinical outcomes were collected. RESULTS: Most patients were BC residents and were assessed by the multidisciplinary team at the BC clinic. The majority had undetectable HIV viral loads, were receiving antiretroviral treatments and were infected with hepatitis C virus (n=16). The most common comorbidities were anxiety and mood disorders (n=4), and hemophilia (n=4). Of the patients eligible for transplantation, four were transplanted for autoimmune hepatitis (5.67 years post-transplant), nonalcoholic steatohepatitis (2.33 years), hepatitis C virus (2.25 years) and hepatitis B-delta virus coinfection (recent transplant). One patient died from acute renal failure while waiting for transplantation. Ten patients died during preassessment and 10 were unsuitable transplant candidates. The most common reason for unsuitability was stable disease not requiring transplantation (n=4). CONCLUSIONS: To date, interdisciplinary care and careful selection of patients have resulted in successful outcomes including the longest living HIV-infected post-liver transplant recipient in Canada.

HISTORIQUE: La demande d'une prise en charge définitive des maladies organiques terminales chez les Canadiens infectés par le VIH est en hausse. Jusqu'à tout récemment, malgré des données internationales faisant foi de résultats cliniques positifs, les Canadiens atteints d'une maladie hépatique terminale infectés par le VIH n'étaient pas admissibles à une transplantation, sauf en Colombie-Britannique (C.-B.), où le programme de transplantations de BC Transplant les accepte en vue d'un aiguillage, d'une évaluation, de l'inscription sur la liste d'attente et de l'exécution d'une allogreffe du foie. L'évaluation de l'expérience de la C.-B. s'impose pour déterminer les enjeux entourant la transplantation hépatique chez les patients infectés par le VIH. MÉTHODOLOGIE: Les chercheurs ont procédé à l'étude des dossiers des 28 patients infectés par le VIH qui ont été orientés vers BC Transplant pour subir une transplantation hépatique entre 2004 et 2013. Ils ont colligé les données sur l'état du VIH et de la maladie hépatique, l'évaluation initiale de la transplantation et les résultats cliniques. RÉSULTATS: La plupart des patients étaient des habitants de la C.-B. qui avaient été évalués par l'équipe multidisciplinaire de la clinique de C.-B. La majorité présentait des charges virales indétectables du VIH, prenaient des antirétroviraux et étaient infectés par le virus de l'hépatite C (n=16). Les comorbidités les plus courantes étaient l'anxiété et les troubles des humeurs (n=4), ainsi que l'hémophilie (n=4). Parmi les patients admissibles à la transplantation, quatre ont subi une transplantation consécutive à une hépatite auto-immune (5,67 ans après la transplantation), à une stéatose hépatique non alcoolique (2,33 ans), à un virus de l'hépatite C (2,25 ans) et à une co-infection par l'hépatite B et le virus delta (transplantation récente). Un patient est décédé d'une insuffisance rénale aiguë alors qu'il était en attente de transplantation. Dix sont décédés pendant la préévaluation et dix n'étaient pas des candidats adéquats pour la transplantation. La principale raison de ne pas être un candidat adéquat était une maladie stable ne nécessitant pas de transplantation (n=4). CONCLUSIONS: Jusqu'à présent, les soins interdisciplinaires et une sélection attentive des patients permettent d'obtenir des résultats positifs, y compris la présence au Canada du greffé hépatique infecté par le VIH ayant vécu le plus longtemps depuis sa transplantation.

First successful treatment of post-liver transplant hepatitis C fibrosing cholestatic hepatitis with boceprevir, peginterferon and ribavirin in a pre-transplant null responder.

Fibrosing cholestatic hepatitis (FCH) is a less common but well-recognized severe complication of recurrent hepatitis C virus (HCV) infection post-liver transplant. This condition is fatal without successful treatment and to date; post-transplant antiviral interferon-based antiviral therapy has been associated with guarded success. The new era of protease inhibitors in the treatment of chronic HCV infection may alter the dismal outcome of this condition. To date, however, the experience with protease inhibitors in this condition is unreported. We report a post-liver transplant recipient with HCV associated FCH treated successfully with boceprevir, peginteferon and ribavirin for severe FCH. The patient was young woman who was a null responder pre-transplant to peginterferon and ribavirin. The peak serum bilirubin 391 µmol/L normalized to 15 µmol/L by week 8 of therapy. The pre-treatment HCV viral load of > 78 million IU/mL, decreased to 78 IU/mL at week 8 of therapy and was undetectable by week 12 and at the end of 48 week of treatment. 12 weeks post treatment, the HCV viral load remains undetectable. Significant anemia and neutropenia were encountered. Tacrolimus dosage titrated to trough levels, required marked reduction to 0.5 mg three times weekly. Despite the suboptimal peginterferon and ribavirin dosing, limited by adverse effects, full boceprevir dosing was maintained, with resolution of liver dysfunction. Boceprevir was obtained on compassionate grounds from the manufacturer before its licensure in Canada and this was the first use of boceprevir in the world for post-transplant FCH.

Primary hepatic neuroendocrine tumour requiring live donor liver transplantation: case report and concise review.

Primary hepatic neuroendocrine tumours are rare tumours effecting relatively young patients. As metastatic neuroendocrine tumours to the liver are much more common, extensive investigations are crucial to exclude a primary tumour elsewhere. We report a case of a 27 year old woman who presented with fatigue, increased abdominal girth and feeling of early satiety and bloating. Extensive work up failed to show tumour at another primary site. Hepatic artery embolization showed no effect, so the patient underwent total hepatectomy and live-donor liver transplant. Grossly the tumour measured 27 cm. Microscopic examination showed bland, monomorphic cells growing in tubuloglandular and trabecular growth patterns. Cells were positive for neuroendocrine (synaptophysin, chromogranin, CD56) and epithelial markers (MOC31, CK7, CK19). Cytoplasmic dense neurosecretory vesicles were seen on ultrastructural examination. Based on the Ki-67 rate, mitotic count, lack of marked nuclear atypia and absence of necrosis, a diagnosis of primary neuroendocrine grade 2 was conferred.

End stage liver disease etiology & transplantation referral outcomes of major ethnic groups in British Columbia, Canada: A cohort study.

ABSTRACT: Liver disease etiology and transplantation outcomes may vary by ethnicity. We aimed to determine if disparities exist in our province.We reviewed the provincial database for liver transplant referrals. We stratified cohorts by ethnicity and analyzed disease etiology and outcomes.Four thousand nine hundred sixteen referrals included 220 South Asians, 413 Asians, 235 First Nations (Indigenous), and 2725 Caucasians. Predominant etiologies by ethnicity included alcohol (27.4%) and primary sclerosing cholangitis (PSC) (8.8%) in South Asians, hepatitis B (45.5%) and malignancy (13.9%) in Asians, primary biliary cholangitis (PBC) (33.2%) and autoimmune hepatitis (AIH) (10.8%) in First Nations, and hepatitis C (35.9%) in Caucasians. First Nations had lowest rate of transplantation (30.6%, P = .01) and highest rate of waitlist death (10.6%, P = .03). Median time from referral to transplantation (268 days) did not differ between ethnicities (P = .47). Likelihood of transplantation increased with lower body mass index (BMI) (hazard ratio [HR] 0.99, P = .03), higher model for end stage liver disease (MELD) (HR 1.02, P < .01), or fulminant liver failure (HR 9.47, P < .01). Median time from referral to ineligibility status was 170 days, and shorter time was associated with increased MELD (HR 1.01, P < .01), increased age (HR 1.01, P < .01), fulminant liver failure (HR 2.56, P < .01) or South Asian ethnicity (HR 2.54, P < .01). Competing risks analysis revealed no differences in time to transplant (P = .66) or time to ineligibility (P = .91) but confirmed increased waitlist death for First Nations (P = .04).We have noted emerging trends such as alcohol related liver disease and PSC in South Asians. First Nations have increased autoimmune liver disease, lower transplantation rates and higher waitlist deaths. These data have significance for designing ethnicity specific interventions.

Three-Dimensional Multi-Frequency Shear Wave Absolute Vibro-Elastography (3D S-WAVE) With a Matrix Array Transducer: Implementation and Preliminary In Vivo Study of the Liver.

Magnetic resonance elastography (MRE) is commonly regarded as the imaging-based gold-standard for liver fibrosis staging, comparable to biopsy. While ultrasound-based elastography methods for liver fibrosis staging have been developed, they are confined to a 1D or a 2D region of interest and to a limited depth. 3D Shear Wave Absolute Vibro-Elastography (S-WAVE) is a steady-state, external excitation, volumetric elastography technique that is similar to MRE, but has the additional advantage of multi-frequency excitation. We present a novel ultrasound matrix array implementation of S-WAVE that takes advantage of 3D imaging. We use a matrix array transducer to sample axial multi-frequency steady-state tissue motion over a volume, using a Color Power Angiography sequence. Tissue motion with the frequency components {40,50,60} and {45,55,65} Hz are acquired over a (90° lateral) × (40° elevational) × (16 cm depth) sector with an acquisition time of 12 seconds. We compute the elasticity map in 3D using local spatial frequency estimation. We characterize this new approach in tissue phantoms against measurements obtained with transient elastography and MRE. Six healthy volunteers and eight patients with chronic liver disease were imaged. Their MRE and S-WAVE volumes were aligned using T1 to B-mode registration for direct comparison in common regions of interest. S-WAVE and MRE results are correlated with R2 = 0.92, while MRE and TE results are correlated with R2 = 0.71. Our findings show that S-WAVE with matrix array has the potential to deliver a similar assessment of liver fibrosis as MRE in a more accessible, inexpensive way, to a broader set of patients.

Predictors of relapse to significant alcohol drinking after liver transplantation.

BACKGROUND: End-stage alcoholic liver disease is common, with many of these patients referred for liver transplantation (LT). Alcohol relapse after LT can have detrimental outcomes such as graft loss and can contribute to a negative public perception of LT. OBJECTIVE: To identify factors that predict the recurrence of harmful alcohol consumption after LT. METHODS: A total of 80 patients who underwent LT for alcoholic cirrhosis or had significant alcohol consumption in association with another primary liver disease, from July 1992 to June 2006 in British Columbia, were retrospectively evaluated by chart review. Several demographic-, psychosocial- and addiction-related variables were studied. Univariate and multivariate logistic regression analyses were used to test possible associations among the variables studied and a return to harmful drinking after LT. RESULTS: The relapse rate of harmful alcohol consumption post-liver transplant was 10%, with two patient deaths occurring directly as a result of alcohol relapse. Univariate analysis revealed relapse was significantly associated with pretransplant abstinence of less than six months (P=0.003), presence of psychiatric comorbidities (P=0.016), female sex (P=0.019) and increased personal stressors (P=0.044), while age at transplant of younger than 50 years approached significance (P=0.054). Multivariate logistic regression analysis revealed the following independent factors for relapse: pretransplant abstinence of less than six months (OR 77.07; standard error 1.743; P=0.013) and female sex (OR 18.80; standard error 1.451; P=0.043). CONCLUSION: The findings of the present study strongly support a required minimum of six months of abstinence before LT because duration of abstinence was found to be the strongest predictor of recidivism. Female sex, younger age at transplant and psychiatric comorbidities were also associated with relapse to harmful drinking.

Efficacy of maintenance subcutaneous hepatitis B immune globulin (HBIG) post-transplant for prophylaxis against hepatitis B recurrence.

BACKGROUND: Patients who receive liver transplantation for chronic hepatitis B infection require long-term combination therapy with hepatitis B immunoglobulin (HBIG) and oral antiviral medication to prophylax against graft re-infection. This study examines the efficacy and patient preference of subcutaneous (SC) administration of HBIG in maintaining anti HBs titres > 100 IU/L. MATERIALS AND METHODS: 12 patients who were stable while receiving our standard IM HBIG protocol received an alternate formulation by SC injection, consisting of 10 mL (3120 IU) HBIG as 4 x 2.5 mL SC injections. SC injection were repeated as soon as titres reached 100-150 IU/mL during the 3 month study period. A questionnaire was administered upon study entry and exit to subjectively assess patient preference. RESULTS: Anti- HBs Cmax after first injection was 441.6 IU/L +/- 81.5, and Tmax was 7.1 +/- 3.2 days. SC injections were required every 56 days, which compared well to the frequency of required IM injections prior to study enrollment of 45 days. The patients mean ratings of pain on a 0-10 scale were 5 for the IM route and 1.6 for the SC route. All patients preferred the SC injections to the IM. CONCLUSION: SC administration of HBIG can effectively maintain anti HBs levels above the requisite 100 IU/L while substantially decreasing patient discomfort and improving patient satisfaction, and therefore becomes a very attractive alternative to IM HBIG injections. Further studies and wider use of SC HBIG based on this study may alter the standard practice of transplantation centers

Spontaneous clearance of hepatitis C infection post-liver transplant: A rare but real phenomenon? A case report and review of the literature.

Recurrent hepatitis C virus (HCV) infection after liver transplantation is a significant cause of morbidity, mortality and graft loss. Spontaneous clearance of recurrent HCV after liver transplant is a rarely reported phenomenon. We report a case of a 66-year-old woman who underwent liver transplantation for HCV cirrhosis (treatment- naive genotype 2) under immunosuppression with tacrolimus, mycophenolate mofetil (MMF), and short-term corticosteroids. The patient developed histologically proved severe cholestatic recurrence of HCV hepatitis. Immunosuppression was reduced to tacrolimus monotherapy because of cytopenia. She subsequently became RNA negative at week 44 post- transplant while on tacrolimus and MMF despite no antiviral therapy. A spontaneous sustained virologic clearance was confirmed with subsequent HCV nucleotide testing. Only a few similar cases have been reported in the literature with uninterrupted immunosuppression and subsequent spontaneous clearance. Our experience, and the few other published cases in the literature, suggests that spontaneous clearance of HCV after liver transplantation is a rare but real phenomenon. Better understanding of this phenomenon may help to manage recurrent HCV disease after transplantation.

Multimodal therapy for hepatocellular carcinoma: a complementary approach to liver transplantation.

OBJECTIVE: To evaluate the survival benefit of multimodal therapy for the treatment of HCC. BACKGROUND: Orthotopic liver transplantation (OLT) is considered the treatment of choice for selected patients with hepatocellular carcinoma (HCC). However, donor organ shortages and patients whose HCCs exceed OLT criteria require consideration of alternate therapeutic options such as hepatic resection, radiofrequency ablation (RFA), ethanol injection (EI), transarterial chemoembolization (TACE), and chemotherapy (CTX). This study was performed to evaluate the survival benefit of multimodal therapy for treatment of HCC as complementary therapy to OLT. METHODS: A retrospective review was conducted of HCC patients undergoing therapy following multidisciplinary review at our institution from 1996 . 2006 with a minimum of a 2 year patient follow-up. Data were available on 247/252 patients evaluated. Relevant factors at time of diagnosis included symptoms, hepatitis B (HBV) and C (HCV) status, antiviral therapy, Child-Pugh classification, portal vein patency, and TNM staging. Patients underwent primary treatment by hepatic resection, RFA, EI, TACE, CTX, or were observed (best medical management). Patients with persistent or recurrent disease following initial therapy were assessed for salvage therapy. Survival curves and pairwise multiple comparisons were calculated using standard statistical methods. RESULTS: Mean overall survival was 76.8 months. Pairwise comparisons revealed significant mean survival benefits with hepatic resection (93.2 months), RFA (66.2 months), and EI (81.1 months), compared with TACE (47.4 months), CTX (24.9 months), or observation (31.4 months). Shorter survival was associated with symptoms, portal vein thrombus, or Child-Pugh class B or C. HCV infection was associated with significantly shorter survival compared with HBV infection. Antiviral therapy was associated with significantly improved survival in chronic HBV and HCV patients only with earlier stage disease. CONCLUSION: Multimodal therapy is effective therapy for HCC and may be used as complementary treatment to OLT.

Biomarkers for hepatocellular cancer.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. If diagnosed early, curative treatment options such as surgical resection, loco-regional therapies, and liver transplantation are available to patients, increasing their chances of survival and improving their quality of life. Unfortunately, most patients are diagnosed with late stage HCC where only palliative treatment is available. Therefore, biomarkers which could detect HCC early with a high degree of sensitivity and specificity, may play a crucial role in the diagnosis and management of the disease. This review will aim to provide an overview of the different biomarkers of HCC comprising those used in the diagnosis of HCC in at risk populations, as well as others with potential for prognosis, risk predisposition and prediction of response to therapeutic intervention.

The use of sildenafil to treat portopulmonary hypertension prior to liver transplantation.

Portopulmonary hypertension (PPH) is an infrequent, but well-recognized complication of liver cirrhosis. PPH in those with end-stage liver disease has a significant impact on per-operative and intra-operative mortality, with liver transplantation being contraindicated in those individuals with mean pulmonary artery pressure exceeding 50 mmHg. Vasodilatory therapy is the mainstay of pharmacotherapy for PPH, although the evidence of benefit is largely extrapolated from the pulmonary hypertension literature. We report the use of the phosphodiesterase inhibitor, sildenafil, in a patient with end stage liver disease and PPH, with a pulmonary artery pressure before transplantation of 75 mmHg, to reduce pulmonary artery pressure prior to a successful liver transplant.

Late acute celiac and hepatic artery thrombosis with portal vein thrombosis resulting in hepatic infarction 12 years post orthotopic liver transplantation.

Hepatic artery thrombosis (HAT) is relatively infrequent, but possibly a devastating complication of orthotopic liver transplantation (OLT). It often requires urgent retransplantation. Two main forms of HAT are recognized as early and late HAT (diagnosis within or after 30 days following LT). Early HAT typically results in graft failure. Late HAT features biliary obstruction, cholangitis, and hepatic abscess formation. We report here the case of a patient of Wilson's disease who presented twelve years post-liver transplant symptoms typical of acute HAT and hepatic infarction. On diagnostic imaging, celiac axis and hepatic artery were thrombosed, resulting in ischemic necrosis of the left hepatic lobe. The resulting sepsis and transient hepatic insufficiency were managed conservatively, and repeat OLT was avoided. The patient remains stable more than one year later. To the best of our knowledge this case report is unique in the literature for the unusually long interval between OLT and late acute HAT, as well as celiac and portal vein occlusion. The acute presentation of sub massive hepatic necrosis is also uncharacteristic of late HAT and more typical of acute HAT. This report describes our experience in managing this and a literature review of the topic.