Serum IgG4 cut-off of 70 mg/dL is associated with a shorter time to cirrhosis decompensation and liver transplantation in primary sclerosing cholangitis patients.

BACKGROUND: Primary sclerosing cholangitis (PSC) is an immune-mediated biliary disorder of unknown etiology with no effective treatment. The purpose of this study was to better prognosticate the development of cirrhosis, decompensation, and requirement for liver transplantation (LT) in PSC patients based on serum immunoglobulin G4 (IgG4) levels. METHODS: A retrospective chart review was conducted on PSC patients seen at the University of Alberta Hospital between 2002 and 2017. PSC patients were categorized as high IgG4 group (≥70 mg/dL) or normal IgG4 group (<70 mg/dL). Laboratory parameters, clinical characteristics, and outcomes were compared between the groups. RESULTS: One hundred and ten patients were followed over a mean period of 7.3 (SD 5) years. Seventy-two patients (66%) were male, the mean age at diagnosis of PSC was 35 (SD 15) years, and inflammatory bowel disease (IBD) was present in 80 patients (73%). High IgG4 levels were found in 37 patients (34%). PSC patients with high IgG4 had a shorter mean cholangitis-free survival time (5.3 versus 10.4 years, p = 0.02), cirrhosis-free survival time (8.7 versus 13.0 years, p = 0.02), and LT-free survival time (9.3 years versus 18.9 years, p <0.001). IgG4 ≥70 mg/dL was independently associated with liver decompensation and LT-free outcomes. A cut-off IgG4 value of ≥70 mg/dL performed better than a cut-off value of ≥140 mg/dL to predict time to LT (area under the curve [AUC] 0.68, p = 0.03, sensitivity 72%, specificity 78%). CONCLUSIONS: Serum IgG4 ≥70 mg/dL in PSC predicts a shorter time to cirrhosis decompensation and LT.

Acute hepatitis following mRNA BNT162b2 COVID-19 vaccination.

BACKGROUND: Widespread administration of COVID-19 vaccinations have led to reports of rare but potentially serious side effects. METHODS: We present two cases of acute hepatitis following mRNA BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccination. RESULTS: A 25-year-old male presented to hospital with progressive jaundice 5 days following his second dose of Comirnaty. Initial bloodwork revealed severe hepatocellular enzyme elevation and conjugated hyperbilirubinemia with preserved INR. Extensive serologic workup was negative, with normal imaging. Percutaneous liver biopsy was performed and revealed acute cholestatic hepatitis possibly related to drug-induced liver injury. He was started on prednisone 40 mg daily with good initial response but had a second flare; a biopsy was repeated which showed near-identical findings. Steroids were discontinued given non-response and the patient had gradual near complete resolution of liver enzymes and hyperbilirubinemia. A 32-year-old male presented with a 4-week history of nausea followed by progressive choluria, jaundice, and pruritis. He received his second dose of Comirnaty vaccination two weeks prior to presentation. Initial bloodwork showed mixed enzyme elevation with hyperbilirubinemia. Serological workup and imaging were unrevealing. He underwent liver biopsy which showed severe intrahepatic cholestasis, with drug-induced liver injury being suggested as most likely cause. His course was self-limited with resolution of serological abnormalities and symptoms. CONCLUSIONS: While overwhelmingly safe on a population level, our case series illustrate two cases of acute icteric hepatitis following mRNA BNT162b2 vaccination. Clinicians should be aware of this association with hepatic inflammation and consider vaccine history an important component of evaluating patients with acute liver injury.

Post-liver transplantation chronic kidney disease is associated with increased cardiovascular disease risk and poor survival.

Chronic kidney disease (CKD) is common following liver transplantation (LT). We aimed to investigate the frequency, risk factors, and impact of CKD on cardiovascular disease (CVD), graft, and patient survival. We analyzed 752 patients who received LT at the University of Alberta. Development of CKD was defined as eGFR <60 ml/min for greater than 3 months, intrinsic renal disease or presence of end-stage renal disease requiring renal replacement therapy. 240 patients were female (32%), and mean age at LT was 53 ± 11 years. CKD was diagnosed in 448 (60%) patients. On multivariable analysis, age (OR 1.3; P = 0.01), female sex (OR 3.3; P < 0.001), baseline eGFR (OR 0.83; P < 0.001), MELD (OR 1.03; P = 0.01), de novo metabolic syndrome (OR 2.3; P = 0.001), and acute kidney injury (OR 3.5; P < 0.001) were associated with CKD. A higher tacrolimus concentration to dose ratio was protective for CKD (OR 0.69; P < 0.001). CKD was associated with post-transplant CVD (26% vs. 16% P < 0.001), reduced graft (HR 1.4; P = 0.02), and patient survival (HR 1.3; P = 0.03). CKD is a frequent complication following LT and is associated with an increased risk of CVD and reduced graft and patient survival.

Selective Internal Radiation Therapy for Hepatocellular Carcinoma Across the Barcelona Clinic Liver Cancer Stages.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common lethal cancer, and there is a need for effective therapies. Selective internal radiation therapy (SIRT) has been increasingly used, but is not supported by guidelines due to a lack of solid evidence. AIMS: Determine the efficacy and safety of SIRT in HCC across the Barcelona Clinic Liver Cancer (BCLC) stages A, B, and C. METHODS: Consecutive patients that received SIRT between 2006 and 2016 at two centers in Canada were evaluated. RESULTS: We analyzed 132 patients, 12 (9%), 62 (47%), and 58 (44%) belonged to BCLC stages A, B, and C; mean age was 61.2 (SD ± 9.2), and 89% were male. Median survival was 12.4 months (95% CI 9.6-16.6), and it was different across the stages: 59.7 (95% CI NA), 12.8 (95% CI 10.2-17.5), and 9.3 months (95% CI 5.9-11.8) in BCLC A, B, and C, respectively (p = 0.009). Independent factors associated with survival were previous HCC treatment (HR 2.01, 95% CI 1.23-3.27, p = 0.005), bi-lobar disease (HR 2.25, 95% CI 1.30-3.89, p = 0.003), ascites (HR 1.77, 95% CI 0.99-3.13, p = 0.05), neutrophil-to-lymphocyte ratio (HR 1.11, 95% CI 1.02-1.20, p = 0.01), Albumin-Bilirubin (ALBI) grade-3 (HR 2.69, 95% CI 1.22-5.92, p = 0.01), tumor thrombus (HR 2.95, 95% CI 1.65-5.24, p < 0.001), and disease control rate (HR 0.62, 95% CI 0.39-0.96, p = 0.03). Forty-four (33%) patients developed severe adverse events, and ALBI-3 was associated with higher risk of these events. CONCLUSIONS: SIRT has the potential to be used across the BCLC stages in cases with preserved liver function. When using it as a rescue treatment, one should consider variables reflecting liver function, HCC extension, and systemic inflammation, which are associated with mortality.

Quantitative blood flow evaluation of vasodilation-stress compared with dobutamine-stress in patients with end-stage liver disease using 82Rb PET/CT.

BACKGROUND: Our aim was to determine if end-stage liver disease (ESLD) is associated with an attenuated response to vasodilator-stress or dobutamine-stress using 82Rb-PET MPI with blood flow quantification. METHODS AND RESULTS: Pre-liver transplant patients who had a normal dipyridamole-stress (n = 27) or dobutamine-stress (n = 26) 82Rb PET/CT MPI study with no identifiable coronary artery calcium were identified retrospectively and compared to a prospectively identified low-risk of liver disease dipyridamole-stress control group (n = 20). The dipyridamole-stress liver disease group had a lower myocardial flow reserve (MFR) (1.89 ± 0.79) than the control group (2.79 ± 0.96, P < .05). The dobutamine-stress group had a higher MFR than both other groups (3.69 ± 1.49, P < .05). A moderate negative correlation between MELD score and MFR was demonstrated for the dipyridamole-stress liver disease group (r = - 0.473, P < .05). This correlation was not observed for the dobutamine-stress liver disease group (r = - 0.253, P = .21). The liver failure group as a whole (n = 53) had a higher resting myocardial blood flow (0.97 ± 0.33 mL/min/g) than the control group (0.82 ± 0.26, P < .05). CONCLUSION: Dipyridamole demonstrates an attenuated vasodilatory response in ESLD patients compared to a non-ESLD control group related to higher resting blood flow and comparatively reduced stress blood flow. Dobutamine does not demonstrate this effect implying it may be the preferred pharmacologic MPI stress agent for ESLD patients.

HCV Eradication with Direct-Acting Antivirals Does Not Impact HCC Progression on the Waiting List or HCC Recurrence after Liver Transplantation.

Background: The introduction of direct-acting antivirals (DAA) for HCV has led to high rates of HCV eradication. Treatment of patients awaiting liver transplantation (LT) has been controversial. Recent data suggests that DAA treatment may accelerate recurrent HCC. The impact of DAA on delisting for HCC progression or recurrent HCC post-LT has not been well characterized. Methods: A retrospective review of both waitlist patients and LT recipients at a single institution was performed. Patient demographics, HCV treatment, HCC features and treatments, biopsy results, and graft and patient survival were evaluated. Patients on the LT waitlist or who were transplanted between January 2014 and December 2015 were included. Data was collected through December 2017 to have a minimum of two years of follow-up. Results: In the study period, 128 adult LT were performed. 44 patients were HCV+, and 68.2% (N=30) also had HCC. 38.6% (N=17) of HCV+ patients received DAA pre-LT, and 94.1% (N=16/17) achieved sustained virologic response (SVR) pre-LT. Among untreated HCV+ patients who underwent LT, 81.5% (N=22/27) received DAA post-LT, with 82.6% achieving SVR post-LT (N=18/22). 82.1% (N=23/28) of untreated post-LT patients underwent liver biopsy prior to therapy, and 52.2% had at least F1 METAVIR fibrosis. 87.5% (N=14/16) of active waitlist patients received DAA and achieved SVR. HCV eradication did not result in higher rates of delisting for HCC progression. Due to local HCC listing criteria of total tumor volume and AFP, 60% (N=18/30) of HCV+/HCC patients were beyond Milan criteria at the time of LT. Despite this, there was no difference in HCC recurrence rates post-LT, whether patients achieved SVR pre- or post-LT. Conclusions: These data suggest that HCV eradication pre-LT does not significantly impact waitlist time for HCV+ patients with HCC. HCV eradication does not impact rates of delisting for HCC progression or rates of HCC recurrence post-LT.

Validation of the Model of End-Stage Liver Disease for Liver Transplant Allocation in Alberta: Implications for Future Directions in Canada.

Background. Since 2002, the Model of End-Stage Liver Disease (MELD) has been used for allocation of liver transplants (LT) in the USA. In Canada, livers were allocated by the CanWAIT algorithm. The aim of this study was to compare the abilities of MELD, Child-Pugh (CP), and CanWAIT status to predict 3-month and 1-year mortality before LT in Canadian patients and to describe the use of MELD in Canada. Methods. Validation of MELD was performed in 320 patients listed for LT in Alberta (1998-2002). In October 2014, a survey of MELD use by Canadian LT centers was conducted. Results. Within 1 year of listing, 47 patients were removed from the waiting list (29 deaths, 18 too ill for LT). Using logistic regression, the MELD and CP were better than the CanWAIT at predicting 3-month (AUROC: 0.79, 0.78, and 0.59; p = 0.0002) and 1-year waitlist mortality (AUROC: 0.70, 0.70, and 0.55; p = 0.0023). Beginning in 2004, MELD began to be adopted by Canadian LT programs but its use was not standardized. Conclusions. Compared with the CanWAIT system, the MELD score was significantly better at predicting LT waitlist mortality. MELD-sodium (MELD-Na) has now been adopted for LT allocation in Canada.

Hyperhomocysteinemia is associated with severity of cirrhosis and negative impact after liver transplantation.

BACKGROUND & AIMS: Hyperhomocysteinemia constitutes an independent risk factor for thrombosis and cellular injury promoted by oxidative stress. The clinical significance of hyperhomocysteinemia in cirrhosis and outcomes post-liver transplantation is poorly documented. In this study, we aimed to determine the prevalence of hyperhomocysteinemia in cirrhosis, evaluate its association with thrombosis and severity of liver disease, and its impact on survival after liver transplantation. METHODS: We analysed 450 patients with cirrhosis who received a liver transplant between 2001 and 2010. Data were recovered from medical charts and homocysteine serum levels were determined before liver transplantation in all patients. RESULTS: Median age was 53 years (range, 18-72 years) and 308 patients were males (68%). Cirrhosis aetiology was hepatitis C (37%), autoimmune liver disease (22%), alcohol (16%) and others (25%). The median homocysteine level was 11 µmol/L (range, 4-221 µmol/L) and 165 patients (37%) had hyperhomocysteinemia. The MELD (23 ± 10 vs. 20 ± 9 points, P < 0.001), and Child-Pugh (11 ± 2 vs. 9 ± 2 points, P < 0.001) scores were higher in patients with hyperhomocysteinemia. Episodes of thrombosis occurred in 91 patients (20%), but there was no significant difference in patients with or without hyperhomocysteinemia (19 vs. 21%, P = 0.6). Hyperhomocysteinemia was associated with reduced graft (105 ± 4 vs. 119 ± 2 months; P = 0.005), and patient survival (125 ± 33 vs. 131 ± 2 months; P = 0.006). CONCLUSIONS: Hyperhomocysteinemia is frequently present in patients with cirrhosis and is associated with severe liver disease and reduced graft and patient survival after liver transplantation. The negative impact hyperhomocysteinemia has on graft and patient survival is not related to thrombosis.

Increased duration of dual pegylated interferon and ribavirin therapy for genotype 1 hepatitis C post-liver transplantation increases sustained virologic response: a retrospective review.

BACKGROUND/AIM: In patients with advanced post-transplant hepatitis C virus (HCV) recurrence, antiviral treatment (AVT) with interferon and ribavirin is indicated to prevent graft failure. The aim of this study was to determine and report Canadian data with respect to the safety, efficacy, and spontaneous virologic response (SVR) predictors of AVT among transplanted patients with HCV recurrence. PATIENTS AND METHODS: A retrospective chart review was performed on patients transplanted in London, Ontario and Edmonton, Alberta from 2002 to 2012 who were treated for HCV. Demographic, medical, and treatment information was collected and analyzed. RESULTS: A total of 85 patients with HCV received pegylated interferon with ribavirin post-liver transplantation and 28 of the 65 patients (43%) with genotype 1 achieved SVR. Of the patients having genotype 1 HCV who achieved SVR, there was a significantly lower stage of fibrosis (1.37 ± 0.88 vs. 1.89 ± 0.96; P = 0.03), increased ribavirin dose (total daily dose 1057 ± 230 vs. 856 ± 399 mg; P = 0.02), increased rapid virologic response (RVR) (6/27 vs. 0/31; P = 0.05), increased early virologic response (EVR) (28/28 vs. 18/35; P = 0.006), and longer duration of therapy (54.7 ± 13.4 weeks vs. 40.2 ± 18.7; P = 0.001). A logistic regression model using gender, age, RVR, EVR, anemia, duration of therapy, viral load, years' post-transplant, and type of organ (donation after cardiac death vs. donation after brain death) significantly predicted SVR (P < 0.001), with duration of therapy having a significant odds ratio of 1.078 (P = 0.007). CONCLUSIONS: This study identified factors that predict SVR in HCV-positive patients who received dual therapy post-transplantation. Extending therapy from 48 weeks to 72 weeks of dual therapy is associated with increased SVR rates. Future studies examining the role of extended therapy are needed to confirm these findings, since the current study is a retrospective one.

Sarcopenia as a prognostic index of nutritional status in concurrent cirrhosis and hepatocellular carcinoma.

BACKGROUND AND AIMS: Abnormal body composition such as severe skeletal muscle depletion or sarcopenia has emerged as an independent predictor of clinical outcomes in a variety of clinical conditions. This study is the first study to report the frequency and prognostic significance of sarcopenia as a marker of nutritional status in patients with hepatocellular carcinoma (HCC). METHODS: We analyzed 116 patients with HCC who were consecutively evaluated for liver transplant. Skeletal muscle cross-sectional area was measured by CT. Sarcopenia was defined using previously established cutpoints. RESULTS: Ninety-eight patients were males (85%), and the mean age was 58±6 years. Sarcopenia was present in 35 patients (30%). By univariate Cox analysis, male sex (HR, 3.84; P=0.02), lumbar skeletal muscle index (HR, 0.97; P=0.04), INR (HR, 8.18; P<0.001), MELD score (HR, 1.19; P<0.001), Child-Pugh (HR, 3.95; P<0.001), serum sodium (HR, 0.84; P<0.001), TNM stage (HR, 2.59; P<0.001), treatment type (HR, 0.53; P<0.001), and sarcopenia (HR, 2.27; P=0.004) were associated with increased risks of mortality. By multivariate Cox regression analysis, only MELD score (HR, 1.08; P=0.04), Child-Pugh (HR, 2.14; P=0.005), sodium (HR, 0.89; P=0.01), TNM stage (HR, 1.92; P<0.001), and sarcopenia (HR, 2.04; P=0.02) were independently associated with mortality. Median survival for sarcopenic patients was 16±6 versus 28±3 months in nonsarcopenic (P=0.003). CONCLUSIONS: Sarcopenia is present in almost one third of patients with HCC, and constitutes a strong and independent risk factor for mortality. Our results highlight the importance of body composition assessment in clinical practice.

Elevated lipogenesis and diminished cholesterol synthesis in patients with hepatitis C viral infection compared to healthy humans.

UNLABELLED: Hepatitis C virus (HCV) exerts a profound influence on host lipid metabolism. It has been suggested that the synthesis of both fatty acids (FA) and cholesterol is dysregulated in HCV but this has not been directly quantified in humans. The purpose of this study was to measure lipogenesis and cholesterol synthesis using stable isotopes in patients with HCV (n = 5) and healthy control (n = 9) subjects recruited from the University of Alberta hospital. Blood samples were taken at fasting (0 and 24 hours) and after meals over the day to mimic typical food consumption and postprandial metabolism. Isolation of free cholesterol (FC), cholesteryl ester (CE), and triglyceride (TG) from plasma and very low-density lipoproteins (VLDL) was used to measure FA and cholesterol synthesis using deuterium uptake and isotope ratio mass spectrometry. FA composition was analyzed by gas chromatography. VLDL-TG levels of polyunsaturated fatty acids (PUFA), including linoleic and linolenic acid, were lower in HCV compared to control (P < 0.05 for both). Fasting hepatic lipogenesis was significantly higher in HCV (2.80 ± 0.55%) compared to control (1.19 ± 0.27%; P = 0.03). Conversely, fasting whole-body synthesis of FC (HCV 1.64 ± 0.28% versus control 8.78 ± 1.59%) and CE (HCV 0.26 ± 0.08% versus control 1.92 ± 0.25%), as well as hepatic FC synthesis (HCV 1.68 ± 0.26% versus control 8.12 ± 0.77%) was lower in HCV (P < 0.001 for all). CONCLUSION: These data provide evidence that lipogenesis is elevated while cholesterol synthesis is impaired in HCV, supporting previous findings from cellular and animal models. Low PUFA levels combined with elevated lipogenesis suggests a role for dietary PUFA supplementation in HCV patients.

Cardiac work-up protocol for liver transplant candidates: experience from a single liver transplant centre.

BACKGROUND: Ischemic cardiac events can cause significant morbidity and mortality postliver transplantation; however, no validated protocols to screen patients before transplantation exist. OBJECTIVES: To report the introduction of a noninvasive cardiac screening protocol used at the Liver Unit, University of Calgary (Calgary, Alberta); to determine whether the protocol decreases use of coronary angiograms; and to compare cardiac outcomes using the new protocol with an appropriately matched historical control group. METHODS: A new cardiac screening protocol was introduced into the program in 2005, which uses perfusion scintigraphy to screen high-risk cardiac patients, reserving coronary angiograms for abnormal results. Transplanted patients screened using this protocol were compared with matched historical controls. Electronic charts were reviewed for cardiac outcomes intra- and postliver transplantation. RESULTS: A total of 396 patients were screened between April 2005 and February 2009. Eighty-two were transplanted by February 2009 and included in the study. Eighty-one patients were successfully matched according to age, sex, cardiac history and presence of diabetes. Twelve of 82 (14.6%) and 11 of 81 (13.6%) in the study and control groups, respectively, underwent coronary angiograms (P=0.85). Coronary artery disease was found in six of 12 (50.0%) study patients and three of 11 (27.3%) control patients who underwent coronary angiography (P=0.27). The mean (± SD) length of the follow-up period was 1.87±0.91 years and 4.45±1.89 years in the study and control groups, respectively. One of 81 in the control group and zero of 82 in the study group experienced an acute coronary syndrome event postoperatively. CONCLUSIONS: Coronary events are infrequent in liver transplant recipients. The described protocol is an effective method of coronary artery disease screening before liver transplant but does not reduce the number of cardiac investigations performed.

Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value.

As detected by cross-sectional imaging, severe muscle depletion, which is termed sarcopenia, holds promise for prognostication in patients with cirrhosis. Our aims were to describe the prevalence and predictors of sarcopenia in patients with cirrhosis listed for liver transplantation (LT) and to determine its independent prognostic significance for the prediction of waiting-list mortality. Adults listed for LT who underwent abdominal computed tomography/magnetic resonance imaging within 6 weeks of activation were retrospectively identified. The exclusions were hepatocellular carcinoma, acute liver failure, prior LT, and listing for multivisceral transplantation or living related LT. Sixty percent of the 142 eligible patients were male, the median age was 53 years, and the median Model for End-Stage Liver Disease (MELD) score at listing was 15. Forty-one percent were sarcopenic; sarcopenia was more prevalent in males versus females (54% versus 21%, P < 0.001) and increased with the Child-Pugh class (10% for class A, 34% for class B, and 54% for class C, P = 0.007). Male sex, the dry-weight body mass index (BMI), and Child-Pugh class C cirrhosis (but not the MELD score) were independent predictors of sarcopenia. Sarcopenia was an independent predictor of mortality (hazard ratio = 2.36, 95% confidence interval = 1.23-4.53) after adjustments for age and MELD scores. In conclusion, sarcopenia is associated with increased waiting-list mortality and is poorly predicted by subjective nutritional assessment tools such as BMI and subjective global assessment. If this is validated in larger studies, the objective assessment of sarcopenia holds promise for prognostication in this patient population.

Incidence and risk factors associated with de novo autoimmune hepatitis after liver transplantation.

BACKGROUND/AIMS: De novo autoimmune hepatitis (AIH) describes the development of hepatitis with autoimmune features in liver transplant (LT) patients without prior diagnosis of AIH. We aimed to evaluate the incidence and risk factors for de novo AIH. METHODS: A cohort of 576 patients with LT for aetiologies other than AIH was evaluated. RESULTS: De novo AIH was diagnosed in 17 patients (3%) with an overall incidence of 4.0 cases per 1000 patient-years. By univariate Cox analysis, patients who received cyclosporine A had lower risk (HR 0.24, 95% CI 0.07-0.80, P = 0.02), whereas patients who had female donors (HR 3.03, 95% CI 1.11-8.25, P = 0.03), donors ≥40-years (HR 6.95, 95% CI 1.93-25.03, P = 0.003), and those who received tacrolimus (HR 4.39, 95% CI 1.47-13.13, P = 0.008) and mycophenolate mofetil (HR 6.37, 95% CI 1.62-25.13, P = 0.008) had higher risk. Survival was similar in patients with de novo AIH compared with the LT population (mean survival time, 17 ± 1.5 vs. 16 ± 0.5 years, Log-rank test; P = 0.4). CONCLUSIONS: The incidence of de novo AIH is low and does not impact on long-term survival. Recipients of female or older donor grafts, or recipients using tacrolimus, or mycophenolate mofetil as part of their immunosuppressive regimen have a higher risk of de novo AIH, whereas LT recipients maintained on cyclosporine A have a lower risk.

Muscle wasting is associated with mortality in patients with cirrhosis.

BACKGROUND & AIMS: Sarcopenia, defined as a low level of muscle mass, occurs in patients with cirrhosis. We assessed its incidence among cirrhotic patients undergoing evaluation for liver transplantation to investigate associations between sarcopenia and mortality and prognosis. METHODS: We studied 112 patients with cirrhosis (78 men; mean age, 54 ± 1 years) who were consecutively evaluated for liver transplantation and had a computed tomography scan at the level of the third lumbar (L3) vertebrae to determine the L3 skeletal muscle index; sarcopenia was defined by using previously published, sex-specific cutoffs. RESULTS: Of the patients studied, 45 (40%) had sarcopenia. Univariate Cox analysis associated mortality with ascites (hazard ratio [HR], 2.12; P = .04), encephalopathy (HR, 1.99; P = .04), level of bilirubin (HR, 1.007; P < .01), international normalized ratio (HR, 7.69; P < .001), level of creatinine (HR, 1.01; P = .005), level of albumin (HR, 94; P = .008), serum level of sodium (HR, 89; P < .001), Model for End-Stage Liver Disease (MELD) score (HR, 1.14; P < .01), Child-Pugh score (HR, 2.84; P < .001), and sarcopenia (HR, 2.18; P = .006). By multivariate Cox analysis, only Child-Pugh (HR, 1.85; P = .04) and MELD scores (HR, 1.08; P = .001) and sarcopenia (HR, 2.21; P = .008) were independently associated with mortality. The median survival time for patients with sarcopenia was 19 ± 6 months, compared with 34 ± 11 months among nonsarcopenia patients (P = .005). There was a low level of correlation between L3 skeletal muscle index and MELD (r = -0.07; P = .5) and Child-Pugh scores (r = -0.14; P = .1). CONCLUSIONS: Sarcopenia is associated with mortality in patients with cirrhosis. It does not correlate with the degree of liver dysfunction evaluated by using conventional scoring systems. Scoring systems should include evaluation of sarcopenia to better assess mortality among patients with cirrhosis.

Locoregional radiological treatment for hepatocellular carcinoma; Which, when and how?

Hepatocellular carcinoma (HCC) is one of the most frequent and deadliest cancers worldwide. Liver transplantation, surgical resection or local ablation offer the best survival advantages but most patients either present when the tumor is in an advanced stage or the degree of underlying liver disease precludes these options. Several therapies have been proposed for these patients with proven survival benefits. These therapies comprise the locoregional treatment for HCC, and include percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and drug-eluting bead (DEB). PEI and RFA are considered curative treatments for early stage HCC; whereas TACE is a standard of care for intermediate stages. Additionally, evaluation of response to locoregional treatment in HCC is important, as objective response may become a surrogate marker for improved survival. Currently, there are several criteria for response assessment, including the World Health Organization (WHO), the Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver Criteria (EASL), and the modified RECIST (mRECIST); however, there has been poor correlation between the clinical benefit provided by locoregional interventional therapies and conventional methods of response assessment. The aim of our study was to review and analyze the current evidence for radiological interventions in HCC, and to propose evidence based recommendations to improve the management of these patients.

Is pre-treatment liver biopsy necessary for all hepatitis C genotypes?

BACKGROUND: Current practice guidelines recommend liver biopsy prior to treatment of hepatitis C genotype-1 but not for genotype-2/3; this is based on expert opinion, not on published evidence. METHODS: In retrospective analysis of a large trial database prior to the publication of recent guidelines, we compared outcomes in 985 treatment-naïve patients with hepatitis C who did or did not undergo liver biopsy before starting peginterferon alfa-2a plus ribavirin. RESULTS: Physicians elected to treat 141/654 (21.6%) genotype-1 patients and 126/331 (38.1%) genotype-2/3 patients without liver biopsy. There were no differences in baseline characteristics among those with or without pre-treatment liver biopsy, except for female preponderance in genotype-1 patients with liver biopsy. The sustained viral response (SVR) rate was no different amongst genotype-2/3 patients who had a biopsy before treatment with 66.3% SVR vs. 69.8% of those treated without biopsy (p = 0.546), but significantly higher among genotype-1 patients with pre-treatment liver biopsy at 54.6 vs. 44.0% for those treated without a liver biopsy (p = 0.029). In genotype-1 patients with liver biopsy, more patients with cirrhosis had dose adjustments (p = 0.0057) rather than drug discontinuation. There was tendency for earlier discontinuation among patients without pre-treatment liver biopsy. CONCLUSIONS: Pre-treatment liver biopsy was associated with better SVR amongst genotype-1 patients. This improvement may reflect ongoing commitment to completing the treatment course by both patient and physician. In genotype-2/3 patients, pre-treatment liver biopsy may not be essential to maximize SVR rates. This study validates the recommendations of the most recent treatment guidelines for hepatitis C.

Simultaneous liver and kidney transplants: optimizing use of this double resource.

Simultaneous liver and kidney transplantation is a life saving procedure for patients with combined liver and kidney failure; however, it remains controversial because of the need to balance individual patient need versus resource allocation. As waiting lists for transplantation become longer and patients become increasingly ill, there will be greater numbers of patients referred for liver and kidney transplantation. Acute kidney injury even requiring dialysis may potentially be reversible making combined transplant decisions difficult. Similarly, selected compensated cirrhotic patients with renal failure may be managed with renal transplant alone. Shared multicenter experience or clinical trials or both will be required to refine our ability to optimally manage these patients with combined liver and kidney dysfunction.