Liver transplant listing for hepatitis C‐associated cirrhosis and hepatocellular carcinoma has fallen in the United Kingdom since the introduction of direct‐acting antiviral therapy

Following the introduction of direct‐acting antivirals (DAA), there have been reports of declining incidence of hepatitis C (HCV)‐related liver disease as a liver transplantation indication. In this study, we assessed the impact of DAA on liver transplant indications in the UK and waiting list outcomes for patients with HCV. We assessed UK adult elective liver transplant registrants between 2006 and 2017. The aetiology of liver disease at registration was reclassified using an accepted hierarchical system and changes were assessed over time and compared before and after the introduction of DAA. Registration UKELD scores and 1‐year waiting list outcomes were also compared. The proportion of waiting list patients registered with HCV‐related cirrhosis reduced after the introduction of DAA from 10.5% in 2013 to 4.7% in 2016 (P < 0.001). Alcohol‐related liver disease (ARLD) was the leading indication for liver transplantation followed by liver cancer (26.1% and 18.4% in 2016, respectively). The proportion of registrations with Hepatocellular carcinoma (HCC) associated with HCV reduced from 46.4% in 2013 to 33.7% in 2016 (P = 0.002). For patients with HCV‐related cirrhosis at one year the outcomes of death, transplantation, delisting due to improvement or deterioration and awaiting a graft at 1 year were similar. For patients with HCV‐related HCC, the proportion dying at 1 year reduced significantly from 2.9% to 0.0% (P = 0.04). These data demonstrate an association between DAA and reduced listing rates for HCV‐related cirrhosis and HCC, but no significant changes in waiting list outcomes other than reduced mortality in the HCC group.     

Depression in Patients with Cirrhosis (Impact on Outcome)

The impact of depression (assessed by the BeckDepression Inventory) on quality of life and outcome wasprospectively assessed in adult patients with cirrhosis.Patients with depression had significantly poorer perceived quality of life (P = 0.006),poorer adaptive coping (P = 0.001), and lower functionalstatus, ie, Karnofsky performance score (P = 0.06), ascompared to the nondepressed patients. Survival after transplantation was not different betweendepressed and nondepressed patients. However, thepatients with depression were significantly more likelyto die while awaiting transplantation than thenondepressed patients (P = 0.02). The difference inmortality between the depressed and the nondepressedpatients with end-stage liver disease could not beexplained by the severity of illness variables;Child-Pugh score, complications of liver disease, renal function,serum albumin, prothrombin time, frequency and durationof hospitalizations were not significantly different fordepressed and nondepressed patients. Symptoms of depression should be sought in patients withcirrhosis since depression is a modifiable illness thatis amenable to treatment.     

Characteristics of hepatitis C in renal transplant candidates

GOALS: To characterize hepatitis C in renal transplant candidates and to compare hepatitis C-related liver disease between patients with end-stage renal disease (ESRD) and well-matched control subjects without renal disease. BACKGROUND: Hepatitis C is common in dialysis patients and can cause morbidity and mortality in renal transplant recipients. Patients with advanced hepatitis C often are excluded from renal transplantation. STUDY: Forty-six renal transplant candidates and 46 control subjects matched for age, sex, and race without renal disease were included. Demographic, laboratory, and histologic data were compared between patients with ESRD and control subjects. RESULTS: Alanine aminotransferase levels were significantly lower in patients with ESRD (p < 0.001). Hepatitis C virus RNA levels were similar between groups. Patients with ESRD had less inflammatory activity (p < 0.001) and a lower proportion of bridging fibrosis or cirrhosis (13%) than control subjects (30%, p = 0.043). Clinical and laboratory features did not predict histologic grade or stage of hepatitis C in patients with ESRD. Two complications of percutaneous liver biopsy occurred per three diagnoses of cirrhosis in patients with ESRD. No complications occurred with transjugular liver biopsy in this group. CONCLUSIONS: Patients with ESRD had less severe hepatitis C than did control subjects. Clinical measurements did not predict histologic findings in renal transplant candidates. Transjugular liver biopsy should be considered to stage hepatitis C in renal transplant candidates due to the risk of percutaneous biopsy in uremic patients.     

PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence

Background and aim: The PNPLA3 rs738409 C>G polymorphism has been found to be strongly associated with non‐alcoholic fatty liver disease and with alcoholic liver disease. Whether the PNPLA3 rs738409 polymorphism could be a risk factor for the development of hepatocellular carcinoma (HCC) in cirrhosis patients is unknown. Methods: This study included 483 (344 males) consecutive Italian patients of Caucasian ethnicity affected by cirrhosis, of whom 279 had undergone transplantation for end‐stage liver disease while 204 had been referred to our liver and transplant unit for the diagnosis of cirrhosis. The aetiologies were hepatitis C virus=209, hepatitis B virus=76, alcohol=166, metabolic=32. Ile148Met rs738409 transversion was genotyped using an restriction fragment length polymorphism‐based assay. Results: The genotype frequencies of the rs738409 polymorphism were distributed differently in patients with cirrhosis C/C=168, C/G=220, G/G=95 vs controls C/C=218, C/G=175, G/G=35 (P<0.0001). Among cirrhotics, the G allele was over‐represented in alcoholic/metabolic (0.505) vs viral (0.368, P<0.001) liver disease. Patients with cirrhosis complicated by HCC were more likely to be G/G homozygotes (38/141) than the remaining patients (57/342, P<0.02). At multivariate analysis, the PNPLA3 rs738409 polymorphism was confirmed to be an independent predictor of HCC occurrence (odds ratio 1.76, 95% confidence interval 1.06–2.92, P<0.05). HCC rates increased from 13/116 (11.2%; female C/^* carriers), to 97/295 (32.9%; male C/^*carriers and female G/G homozygotes), to 31/72 (43.1%; male G/G homozygotes) (P<0.0001). Conclusions: The PNPLA3 rs738409 C>G polymorphism is associated with cirrhosis. In synergy with gender, this polymorphism is a strong predictor of HCC occurrence among patients with cirrhosis.     

Effects of Hepatitis C-Induced Liver Fibrosis on Survival in Kidney Transplant Candidates

We sought to investigate survival among kidney transplant candidates with varying degrees of liver fibrosis. We studied 108 patients with hepatitis C+ who underwent pre-kidney transplant liver biopsy (1992–2004). Eighteen patients had advanced fibrosis (bridging fibrosis or cirrhosis), and 90 had lesser degrees of fibrosis. Advanced fibrosis patients were younger and had lower prevalence of diabetes. Survival was similar between those with and without advanced fibrosis among all 108 patients (P = 0.92) and among the 58 patients who underwent kidney transplantation (P = 0.83). Fibrosis stage was associated with a 1.1 (0.72, 1.7; P = 0.65) adjusted hazards ratio for mortality among all 108 patients and a 0.64 (0.24, 1.73; P = 0.38) adjusted hazards ratio among the 58 patients who underwent kidney transplantation. These data support the premise that non-liver disease comorbidities are more important outcome determinants in this population. Kidney transplantation alone may be considered in patients with hepatitis C with compensated cirrhosis or bridging fibrosis.     

Non-alcoholic fatty liver disease after liver transplantation in patients with non-alcoholic steatohepatitis and cryptogenic cirrhosis: the impact of pre-transplant graft steatosis

BackgroundNonalcoholic fatty liver disease (NAFLD) may occur in liver transplant recipients. This study aimed to investigate the prevalence and risk factors of NAFLD after liver transplantation in patients with NASH and cryptogenic cirrhosis, focusing on the impact of graft steatosis.MethodsPatients with NASH and cryptogenic cirrhosis who had undergone liver transplantation in Shiraz transplant center between March 2010 and March 2017 were included. NAFLD was diagnosed after liver transplantation using ultrasonography and transient elastography.Results73 patients with NASH and 389 with cryptogenic cirrhosis were included. NAFLD was diagnosed in 33 patients (56.9%) in NASH group and 96 patients (26.7%) in cryptogenic group (OR: 3.61; CI: 2.04–6.39; P-Value < 0.001), using ultrasound. Obesity and post-transplant hyperlipidemia were independent predictors of NAFLD after liver transplantation (P < 0.05). NAFLD was diagnosed in 32.9% of patients with graft macrosteatosis compared to 29.9% in patients without graft macrosteatosis (OR: 1.51; 95%CI: 0.755–1.753). 28% of the patients with macrosteatosis ≥30% had NAFLD after liver transplantation compared to 31.4% with macrosteatosis <30% (OR: 1.175; 95% CI: 0.346–2.091).ConclusionLiver graft steatosis before transplantation was not associated with the occurrence of NAFLD after liver transplantation.     

Health-related quality of life in patients with compensated and decompensated liver cirrhosis

BackgroundCompensated (Child-Pugh [CP] A) and decompensated (CP B/C) liver cirrhosis significantly differs in terms of impairment of health-related quality of life (HRQoL). However, sufficient data on potentially treatable factors associated with HRQoL in both stages of the disease are still lacking. Consequently, aims of this study were to determine differences in HRQoL between patients with compensated and decompensated liver cirrhosis and to identify potentially treatable factors associated with HRQoL.Methods218 patients with liver cirrhosis were enrolled into this study. Chronic Liver Disease Questionnaire (CLDQ) was used to assess HRQoL. Covert hepatic encephalopathy (CHE) was diagnosed according to a combination of Psychometric Hepatic Encephalopathy Score and Critical Flicker Frequency. Frailty was assessed by Clinical Frailty Scale (CFS).ResultsHRQoL differed between patients with CP A (n = 133) and CP B/C (n = 85) liver cirrhosis (CLDQ total score: 5.6 vs. 4.8, p < 0.001). Multivariate analysis identified a history of falls in the recent year, presence of CHE, female gender, active smoking, higher CFS, and higher serum levels of CRP as independent predictors of impaired HRQoL (all p < 0.05) in patients with CP A liver cirrhosis. In patients with CP B/C liver cirrhosis, female gender, a history of overt hepatic encephalopathy, and lower hemoglobin were independently associated with impaired HRQoL (all p < 0.05).ConclusionsPredictors of impaired HRQoL differ in patients with CP A or CP B/C liver cirrhosis. Focusing on treatable factors in routine clinical practice may improve HRQoL in all stages of liver cirrhosis.     

The impact of advanced patient age in liver transplantation: a European Liver Transplant Registry propensity-score matching study

BackgroundThe futility of liver transplantation in elderly recipients remains under debate in the HCV eradication era.MethodsThe aim was to assess the effect of older age on outcome after liver transplantation. We used the ELTR to study the relationship between recipient age and post-transplant outcome. Young and elderly recipients were compared using a PSM method.ResultsA total of 10,172 cases were analysed. Recipient age >65 years was identified as an independent risk factor associated with reduced patient survival (HR:1.42 95%CI:1.23–1.65,p < 0.001). After PSM, 2124 patients were matched, and the same association was found between elderly recipients and patient survival and graft survival (p < 0.001). As hepatocellular carcinoma and alcoholic cirrhosis were independent prognostic factors for patient and graft survival a propensity score-matching was performed for each. Patient and graft survival were significantly worse (p < 0.05) in the alcoholic cirrhosis elderly group. However, patient and graft survival in the hepatocellular carcinoma cohort were similar (p > 0.05) between groups.ConclusionLiver transplantation is an acceptable and safe curative option for elderly transplant candidates, with worse long-term outcomes compare to young candidates. The underlying liver disease for liver transplantation has a significant impact on the selection of elderly patients.     

Prolongation of QTc interval: relationship with etiology and severity of liver disease,mortality and liver transplantation

Background: A prolonged QTc interval has been reported in patients with liver disease. The objectives of our study were to determine whether a prolonged QTc interval was an independent predictor of mortality in patients with cirrhosis and to examine the effect of liver transplantation (LT) on QTc interval. Patients and methods: We retrospectively studied two cohorts of patients – QTc interval was measured in 409 patients (pre‐transplant group), and in 162 patients (transplant group) before and 6 months after LT. QT interval (mean) corrected (QTc) for ventricular rate was read from a 12‐lead EKG. Patients with known cardiovascular disease or other risk factors that are known to cause a prolonged QTc interval were excluded. Results: Pre‐transplant group. One hundred and sixty‐two patients (40%) had a prolonged QTc interval (>440 ms). By binary logistic regression, age (P=0.005), alcoholic cirrhosis (P=0.007) and Child–Pugh scores (P=0.007) were independent predictors of prolonged QTc interval. Sixty‐six patients died during a mean follow‐up of 8.9 years. Although the Kaplan–Meier survival curve showed a lower survival in patients with a prolonged QTc interval (P=0.03 by log rank test), when survival was adjusted for the Child–Pugh score by Cox regression survival analysis, there were no survival differences in patients with and without prolonged QTc interval. Cox regression analysis showed that the Child–Pugh score (hazard ratio 1.5, CI 1.3–1.6, s<0.001) was the only independent predictor of survival. Transplant group. In this cohort, 91 patients (56%) had prolonged QTc (>440 ms) before LT. Mean QTc improved significantly after LT (429 ± 29 ms vs. 450 ± 39 ms P<0.002). Of the 91 patients with prolonged QTc, 50 (55%) normalized, three (3.3%) remained unchanged, 12 (13.3%) showed further prolongation, and 26 (28%) showed improvement but remained above normal limits. An additional nine patients who had normal QTc before LT developed prolonged QTc (>440 ms) after LT. Conclusion: A prolonged QTc interval was common in patients with cirrhosis, but its presence had no independent effect on mortality. Prolonged QTc returns to normal values in about half of the patients after LT, suggesting that liver disease plays a role, but may not be the only factor in the pathogenesis of prolonged QTc.     

Hepatitis B vaccination in liver transplant candidates

Liver transplantation has become the treatment of choice for patients with end-stage liver disease. De novo hepatitis B infection after liver transplantation is a rare event and usually runs a mild clinical and histological course. Despite the favourable outcome, a wide spectrum of hepatitis B virus (HBV)-associated liver disease may develop, ranging from asymptomatic carriage to severe chronic active hepatitis or cirrhosis and even fulminant hepatic failure. The achievement of protective titres of anti-HBs through vaccination has been suggested to be protective against the development of de novo HBV infection. The results of vaccination in cirrhotic patients awaiting for liver transplant have been very disappointing. High-dose/short-term schedules have been tried in transplant candidates in order to increase the response rate. New and more immunogenic formulations (containing new adjuvants or additional pre-S1/pre-S2 recombinant antigens), and, more importantly, early vaccination of potential transplant candidates at earlier stages of their liver disease should further prevent de novo hepatitis B in transplant recipients.     

Functional gastrointestinal disorders in inflammatory bowel disease: impact on quality of life and psychological status

Background and Aim: In inflammatory bowel disease (IBD), ongoing gastrointestinal (GI) symptoms consistent with coexistent functional GI disorders (FGID) might occur. It is uncertain what effect these symptoms have on health‐related quality of life (HRQoL) and psychological comorbidity. The aim of the present study was to identify interrelationships among IBD, symptoms consistent with FGID, HRQoL, and psychological comorbidity. Methods: A total of 256 consecutive IBD patients had diagnoses and disease activity verified at case‐note review. Patients completed a contemporaneous survey assessing HRQoL, anxiety/depression, and GI symptoms (classified by Rome III criteria). Results: Of 162 respondents (response rate: 63%), 95 (58.6%) had Crohn's disease and 63 (38.8%) had ulcerative colitis. By Rome III criteria, 66% met criteria for at least one FGID. Those with significant (Hospital Anxiety and Depression Scale ≥ 8) anxiety and/or depression were more likely to meet criteria for coexistent FGID (78% vs 22% and 89% vs 11%, respectively; each P < 0.001). A “load effect” was noted, such that the number of symptoms consistent with FGID in each patient correlated positively with anxiety and depression and negatively with HRQoL. Symptoms of any coexistent FGID were highly prevalent, even in those with currently‐inactive IBD (57%). Conclusions: Symptoms consistent with FGID are highly prevalent in IBD and correlate with greater psychological comorbidity and poorer HRQoL in a “load‐dependent” fashion. Therapy directed either at symptom load or psychological comorbidity might independently improve HRQoL in IBD.     

Liver transplantation and quality of life: relevance of a specific liver disease questionnaire

Aim: A positive effect of liver transplantation on health‐related quality of life (HRQOL) has been well documented in previous studies using generic instruments. Our aim was to re‐evaluate different aspects of HRQOL before and after liver transplantation with a relatively new questionnaire the ‘liver disease quality of life’ (LDQOL). Methods: The LDQOL and the Short Form 36 (SF‐36) questionnaires were applied to ambulatory patients, either in the transplant list (n=65) or after 6 months to 5 years of liver transplant (n=61). The aetiology of cirrhosis, comorbidities, model for end‐stage liver disease (MELD) Child–Pugh scores and recurrence of liver disease after liver transplantation were analysed using the Mann–Whitney and Kruskall–Wallis tests. Results: In patients awaiting liver transplantation, MELD scores ≥15 and Child–Pugh class C showed statistically significant worse HRQOL, using both the SF‐36 and the LDQOL questionnaires. HRQOL in pretransplant patients was found to be significantly worse in those with cirrhosis owing to hepatitis C (n=30) when compared with other aetiologies (n=35) in 2/7 domains of the SF‐36 and in 7/12 domains of the LDQOL. Significant deterioration of HRQOL after recurrence of hepatitis C post‐transplant was detected with the LDQOL questionnaire although not demonstrated with the SF‐36. The statistically significant differences were in the LDQOL domains: symptoms of liver disease, concentration, memory and health distress. Conclusions: The LDQOL, a specific instrument for measuring HRQOL, has shown a greater accuracy in relation to liver symptoms and could demonstrate, with better reliability, impairments before and after liver transplantation.     

The impact of viral hepatitis‐related hepatocellular carcinoma to post‐transplant outcomes

Hepatocellular carcinoma (HCC) is the most common complication of HCV infection leading to liver transplantation. We evaluated the impact of aetiology of liver disease on patient and graft survival following liver transplantation for HCC. From the Scientific Registry of Transplant Recipients (2002–2011), all adults who underwent liver transplantation for HCC were retrospectively included. Aetiology of liver disease was grouped into HCV, HBV, HCV–HBV co‐infection and nonviral liver disease. Of 8,733 liver transplant recipients with HCC, 5507 had HCV, 631 had HBV, 163 were co‐infected, and 2432 had nonviral causes of liver disease. In follow‐up (48 ± 32 months), 8.2% had graft failure and 29.5% died. The mean rates of graft failure were 9.5%, 4.7%, 6.1% and 6.4% in HCV, HBV, HCV–HBV co‐infection and nonviral liver disease, respectively (P < 0.0001). Post‐transplant mortality rate in patients with HBV was 20.2%, HCV 31.0%, HCV–HBV 28.5% and nonviral 28.5% (P < 0.0001). This difference was significant starting one year post‐transplant and became even more prominent later in follow‐up. Five‐year post‐transplant survival was 64.7% in HCV, 77.7% in HBV, 71.0% in HCV–HBV and 69.1% in nonviral HCC (P < 0.0001). A diagnosis of HCV in patients with HCC was also independently associated with an increased risk of both graft failure (adjusted hazard ratio = 1.84 (1.46–2.33), P < 0.0001) and mortality (1.35 (1.21–1.50), P < 0.0001) in multivariate analysis. Patients with HCV‐related HCC are at higher risk of adverse post‐transplant outcomes. These patients should be considered for preemptive interferon‐free antiviral therapy prior to or immediately following liver transplantation.     

Spur cells and spur cell anemia in hospitalized patients with advanced liver disease: Incidence and correlation with disease severity and survival

Aim: Spur cell anemia (SCA) is a form of acquired hemolytic anemia seen in patients with advanced cirrhosis and particularly in patients with alcoholic cirrhosis. The aim of the present study was to evaluate the incidence of spur cells and spur cell anemia in patients with advanced liver disease and to correlate the presence of spur cell anemia with survival. Methods: During a 33‐month period, all patients with advanced cirrhosis (Child–Pugh–Turcott score [CPT]≥7] who were hospitalized in our department for various reasons were included in this study. Results: A total of 54 patients were included in the study; 26 patients had spur cells on peripheral blood smear (median 4, range 1–14). Patients with spur cells had more advanced liver disease compared with those without spur cells (CPT score, P < 0.0001 and MELD score, P < 0.0001), lower hemoglobin levels (P < 0.0001), higher bilirubin levels (total/unconjugated, P < 0.0001), higher reticulocyte count (P < 0.0001) and more prolonged international normalized ratio (INR; P < 0.0001). Patients with 5% spur cells or more had more advanced disease compared with patients with 1–4% spur cells (CPT score, P = 0.004 and MELD score, P = 0.003), lower hemoglobin levels (P = 0.033), more elevated bilirubin levels (total/unconjugated, P = 0.006) and more prolonged INR (P = 0.04). Three‐month survival was lower in patients with spur cells compared with patients without spur cells (P = 0.017 and P = 0.104, respectively). Patients with 5% spur cells or more had lower 3‐month survival compared with those with 1–4% spur cells (P = 0.014). Conclusion: Presence of spur cells in patients with advanced cirrhosis is not always accompanied by spur cell anemia. The presence of 5% spur cells or more and/or hemolytic anemia is associated with poor prognosis and these patients might have to be given priority for liver transplantation.     

Health state utilities and quality of life in patients with hepatitis B

BACKGROUND:

The effect of chronic hepatitis B (CHB) infection on health-related quality of life (HRQoL) and health state utilities has not been well characterized.

OBJECTIVE:

To measure utility scores and HRQoL across disease states associated with CHB infection.

METHODS:

Patients attending four tertiary care clinics for CHB were approached between July 2007 and March 2009. Respondents completed version 2 of the Short-Form 36 Health Survey, the EQ5D, a visual analogue scale, the Health Utilities Index Mark 3, standard gamble, and demographics and risk factor surveys in English, Cantonese or Mandarin. Charts were reviewed to determine disease stage and comorbidities.

RESULTS:

A total of 433 patients were studied: 294 had no cirrhosis; 79 had compensated cirrhosis; seven had decompensated cirrhosis; 23 had hepatocellular carcinoma; and 30 had received a liver transplant. The mean standard gamble utilities for these disease states were 0.89, 0.87, 0.82, 0.84 and 0.86, respectively. HRQoL scores in noncirrhotic patients were similar to those of the general population. Scores of patients with compensated cirrhosis were not significantly lower; however, patients with decompensated cirrhosis and hepatocellular carcinoma had significantly lower HRQoL scores compared with noncirrhotic patients (P<0.05). Similar scores were observed among patients on and off oral antiviral treatment. Post-liver transplant patients had a higher HRQoL than patients with decompensated cirrhosis. Age, number of comorbidities and relationship status were significantly associated with HRQoL scores.

CONCLUSIONS:

HRQoL in CHB patients is only impaired in the later stages of liver disease. Neither CHB infection nor antiviral treatment is associated with a lower quality of life.     

Artificial neural network is superior to MELD in predicting mortality of patients with end-stage liver disease

BACKGROUND: Despite its accuracy, the model for end-stage liver disease (MELD), currently adopted to determine the prognosis of patients with liver cirrhosis, guide referral to transplant programmes and prioritise the allocation of donor organs, fails to predict mortality in a considerable proportion of patients. AIMS: To evaluate the possibility to better predict 3-month liver disease-related mortality of patients awaiting liver transplantation using an artificial neural network (ANN). PATIENTS AND METHODS: The ANN was constructed using data from 251 consecutive people with cirrhosis listed for liver transplantation at the Liver Transplant Unit, Bologna, Italy. The ANN was trained to predict 3-month survival on 188 patients, tested on the remaining 63 (internal validation group) unknown by the system and finally on 137 patients listed for liver transplantation at the King's College Hospital, London, UK (external cohort). Predictions of survival obtained with ANN and MELD on the same datasets were compared using areas under receiver-operating characteristic (ROC) curves (AUC). RESULTS: The ANN performed significantly better than MELD both in the internal validation group (AUC = 0.95 v 0.85; p = 0.032) and in the external cohort (AUC = 0.96 v 0.86; p = 0.044). CONCLUSIONS: The ANN measured the mortality risk of patients with cirrhosis more accurately than MELD and could better prioritise liver transplant candidates, thus reducing mortality in the waiting list.     

Hepatitis C virus infection and health-related quality of life

Hepatitis C virus (HCV) hepatitis and other diseases related to HCV, such as cryoglobulinemia, lymphoma and renal failure, impair health-related quality of life (HRQoL). In addition, HCV per se might directly influence HRQoL via colonization of microglia in the brain or, indirectly, via the effect of systemic inflammatory cytokines which, in turn, can trigger brain interleukin production. The treatment of HCV-related disorders with interferon (IFN) has an effect on HRQoL. Initially, IFN causes a transient deterioration of HRQoL, due to the induction of depression and other side effects of treatment. Subsequently, the subjects who obtain a sustained virologic response experience an improvement in HRQoL. Only rarely does interferon treatment causes permanent detrimental effects on HRQoL, due to residual psychiatric or neurologic side effects. Liver transplantation is the only treatment for end-stage HCV-related liver disease. HRQoL generally improves massively a few months after transplantation, except in the case of serious complications of the transplant procedure. Furthermore, high levels of anxiety and neuroticism pre-transplant are associated with lower HRQoL one year after transplant. Additionally, six months after transplant, patients with HCV who experience virologic recurrence show significantly greater depression, anxiety, phobic anxiety, and paranoid ideation than anti-HCV-negative patients. In conclusion, optimal care for the overall well-being of patients with HCV infection requires adequate knowledge of their neurological and psychological status.     

Cardiac catheterization in patients with end‐stage liver disease: Safety and outcomes

Introduction : Patients with end‐stage liver disease (ESLD) awaiting transplant are at increased risk of bleeding. Nevertheless, these patients routinely undergo cardiac catheterization for various indications. Safety and outcomes of cardiac catheterization in these patients are not well reported. Methods : In a case–control study 43 patients with ESLD who underwent angiography for liver transplant work‐up were compared to 43 age and gender‐matched controls with no liver dysfunction. In‐hospital outcomes and procedural variables were compared. Results : Patients with ESLD had a lower baseline hemoglobin (12.1 ± 2.1 vs. 13.7 ± 1.8, P < 0.0005), lower platelet counts (86.8 ± 66 vs. 247 ± 80, P < 0.0001) and higher international normalized ratio (INR) (1.4 ± 0.2 vs. 1.1 ± 0.2, P < 0.0001) than controls. Among ESLD group, five (11.6%) patients received platelet transfusions, one received blood transfusion, and three patients (7%) with INR > 1.6 received fresh frozen plasma (FFP) compared with none in the control group. Smaller size (four French) vascular sheaths were used more frequently in the group with ESLD (16% vs. 4%, P = 0.04). There were no significant vascular or bleeding complications in either group. Conclusions : Elective cardiac catheterization can be safely performed in patients with ESLD with outcomes (vascular and bleeding complications, length of hospital stay and in‐hospital mortality) similar to patients without liver disease despite significant thrombocytopenia and elevated INR in patients with ESLD. Practices such as platelet transfusion for platelets <60,000 μL, prophylactic FFP transfusion for INR ≥≥ 1.6, less frequent use of antiplatelet therapy and more frequent use of smaller vascular sheaths may have contributed to the safety of cardiac catheterization in ESLD patients. © 2010 Wiley‐Liss, Inc.     

Management of bacterial infection in the liver transplant candidate

Bacterial infection(BI) is a common cause of impairment of liver function in patients with cirrhosis, especially in the liver transplant candidates. These patients share an immunocompromised state and increased susceptibility to develop community and hospital-acquired infections. The changing epidemiology of BI, with an increase of multidrug resistant strains, especially in healthcareassociated settings, represents a critical issue both in the waiting list and in the post-operative management. This review focused on the role played by BI in patients awaiting liver transplantation, evaluating the risk of drop-out from the waiting list, the possibility to undergo liver transplantation after recovery from infection or during a controlled infection.     

Liver transplantation in adults: Choosing the appropriate timing

Liver transplantation is indicated in patients with acute liver failure,decompensated cirrhosis,hepatocellular carcinoma and rare liver-based genetic defects that trigger damage of other organs.Early referral to a transplant center is crucial in acute liver failure due to the high mortality with medical therapy and its unpredictable evolution.Referral to a transplant center should be considered when at least one complication of cirrhosis occurs during its natural history.However,because of the shortage of organ donors and the short-term mortality after liver transplantation on one hand and the possibility of managing the complications of cirrhosis with other treatments on the other,patients are carefully selected by the transplant center to ensure that transplantation is indicated and that there are no medical,surgical and psychological contraindications.Patients approved for transplantation are placed on the transplant waiting list and prioritized according to disease severity.Thus,the appropriate timing of transplantation depends on recipient disease severity and,although this is still a matter of debate,also on donor quality.These two variables are known to determine the "transplant benefit"(i.e.,when the expected patient survival is better with,than without,transplantation) and should guide donor allocation.