Background Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors. Methods Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent. Patients who acquired HCV were referred to hepatology and treated with direct-acting anti-viral therapies (DAAs). Data collection and analysis were performed with institutional review board approval. Results At the time of HT, mean age of recipients was 53 ± 10 years, and 8 patients (61.5%) were on left ventricular assist device support. After consent to consider an HCV-positive heart, mean time to HT was 11 ± 12 days. Nine of 13 patients (69%) developed HCV viremia after transplant, including 8 who completed DAA treatment and demonstrated cure, as defined by a sustained virologic response 12 weeks after treatment. One patient died during Week 7 of his treatment due to pulmonary embolism. DAAs were well tolerated in all treated patients. Conclusions In the era of highly effective DAAs, the use of HCV-positive donors represents a potential approach to safely expand the donor pool. Additional follow-up is needed to elucidate long-term outcomes.

Early outcomes using hepatitis C-positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies.

Alcohol abuse is the leading cause of liver related morbidity and mortality. Chronic or binge alcohol drinking causes hepatic steatosis which can develop to steatohepatitis, cirrhosis and ultimately hepatocellular carcinoma. The pathogenesis of alcoholic liver disease (ALD) is poorly characterized, however several recent studies point to a major role of mitochondria in this process. Mitochondria play a crucial role in cellular energy metabolism and in reactive species formation. Alcohol treatment causes mitochondrial DNA damage, lipid accumulation and oxidative stress. Studies in both animal models and in humans showed that alcohol administration causes changes in the mitochondrial morphology and function suggesting a role of these changes in the pathogenesis of ALD. We review recent findings on mechanisms by which alcohol negatively impacts mitochondrial biogenesis and function and we will discuss the specific intracellular pathways affected by alcohol consumption. Interestingly, recent findings indicate that a large number of mitochondrial proteins are acetylated and that mitochondrial proteins acetylation and sirtuins are modulated by alcohol. Understanding the mechanisms behind alcohol mediated impaired mitochondrial biogenesis and function may help identify potential therapeutic targets for treating ALD in humans.

Role of mitochondria in alcoholic liver disease.

Background and Aim:
Percutaneous thermal ablation using radiofrequency ablation (RFA) and microwave ablation (MWA) are both widely available curative treatments for hepatocellular carcinoma Despite significant advances, it remains unclear which modality results in better outcomes This meta-analysis of randomized controlled trials (RCT) and observational studies was undertaken to compare the techniques in terms of effectiveness and safety

Methods:
Electronic reference databases (Medline, EMBASE and Cochrane Central) were searched between January 1980 and May 2014 for human studies comparing RFA and MWA The primary outcome was the risk of local tumor progression (LTP) Secondary outcomes were complete ablation (CA), overall survival, and major adverse events (AE) The ORs were combined across studies using the random-effects model

Results:
Ten studies (two prospective and eight retrospective) were included, and the overall LTP rate was 136% (176/1298) There was no difference in LTP rates between RFA and MWA [OR (95% CI): 101(067–150), P = 09] The CA rate, 1- and 3-year overall survival and major AE were similar between the two modalities (P > 005 for all) In subgroup analysis, there was no difference in LTP rates according to study quality, but LTP rates were lower with MWA for treatment of larger tumors [188(110–323), P = 002] There was no significant publication bias or inter-study heterogeneity (I2   01) observed in any of the measured outcomes

Conclusion:
Overall, both RFA and MWA are equally effective and safe, but MWA may be more effective compared to RFA in preventing LTP when treating larger tumors Well-designed, larger, multicentre RCTs are required to confirm these findings

Percutaneous thermal ablation for primary hepatocellular carcinoma: A systematic review and meta-analysis.

Background: Microwave ablation (MWA) has several advantages over radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). We aimed to compare the efficacy and safe...

Comparison of microwave ablation and radiofrequency ablation for hepatocellular carcinoma: a systematic review and meta-analysis

Purpose Percutaneous ablation techniques, including microwave ablation (MWA) and radiofrequency ablation (RFA), have become important minimally invasive treatment options for liver cancer. This systematic review compared MWA with RFA for treatment of liver cancer. Methods The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was conducted for randomized and observational studies published from 2006 onwards. A random-effects model was used for meta-analyses and local tumor progression (LTP), technique efficacy, overall survival (OS), disease-free survival (DFS), intrahepatic de novo lesions (IDL), extrahepatic metastases (EHM), length of stay (LOS), and complications were analyzed. Subgroup and sensitivity analyses were also conducted. Results Of 1379 studies identified, 28 randomized and observational studies met inclusion criteria. The main analysis demonstrated that LTP was significantly reduced by 30% with MWA versus RFA (RR=0.70; P=0.02) (all studies) and by 45% with MWA versus RFA (RR=0.55; P=0.007) (randomized studies only). There were no significant differences between MWA and RFA for other efficacy and safety outcomes. Higher frequency (2450 MHz) and larger tumor size (≥2.5 cm) are amongst variables that may be associated with improved outcomes for MWA. Sensitivity analyses were generally congruent with the main results. Conclusion MWA is at least as safe and effective as RFA for treating liver cancer and demonstrated significantly reduced LTP rates. Future studies should assess time and costs associated with these two treatment modalities.

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Microwave ablation compared with radiofrequency ablation for treatment of hepatocellular carcinoma and liver metastases: a systematic review and meta-analysis.

Drug and substance abuse remains a major medical problem Alcohol use, abuse and dependence are highly prevalent conditions Alcohol related liver disease can present as simple steatosis, steatohepatitis, alcoholic hepatitis or liver cirrhosis Paracetamol hepatotoxicity secondary to accidental or deliberate overdose is another common problem While the adverse cardiovascular, neurological, renal and psychiatric consequences of various illicit substance abuses are widely studied and publicized, less attention has been directed towards possible hepatotoxic effects Illicit drug abuse can cause a range of liver abnormalities ranging from asymptomatic derangement of liver function tests to fulminant hepatic failure This article reviews the epidemiology, risk factors, clinical manifestations, pathogenesis, investigations, management and prognostic factors of alcohol related liver disease and paracetamol hepatotoxicity as well as the current knowledge pertaining to hepatotoxicity of the more commonly used illicit substances including cannabis, amphetamine type stimulants, cocaine, khat chewing and complementary and alternate medicine

Liver abnormalities in drug and substance abusers.

Background and aimThe risk of local tumour progression (LTP) and factors predicting LTP following percutaneous thermal ablation (PTA) of early-stage hepatocellular carcinoma (HCC) have not been well studied in non-trial settings and may be underestimated. We aimed to assess these outcomes in a multi

High local recurrence of early-stage hepatocellular carcinoma after percutaneous thermal ablation in routine clinical practice.

BACKGROUND Vascular disease is a common cause of death in patients with chronic hepatitis C (CHC) infection; however, the association between CHC and atherosclerosis is unclear. AIMS To determine whether patients with CHC have increased subclinical vascular disease and whether genotype or antiviral treatment modifies this risk. METHODS Fifty CHC patients and 22 age-matched and sex-matched healthy controls underwent clinical and biochemical assessment for vascular risk factors. In addition, vascular risk was assessed by measuring arterial stiffness (aortic augmentation index and carotid-femoral pulse wave velocity (PWV)), endothelial dysfunction (brachial artery flow-mediated dilatation (FMD) and dilatation post-glycerol trinitrate administration) and carotid intima-media thickness (CIMT). Assessment was repeated in subset of CHC patients (n = 12) undergoing antiviral treatment 18 months after initiation of treatment. RESULTS Baseline vascular risk factors and measures of arterial stiffness, endothelial dysfunction and CIMT were not different between cases and controls (P > 0.2 for all). Genotype 1 CHC patients had greater endothelial dysfunction with lower FMD (8.2 ± 3.5% vs 10.9 ± 5.2%, P = 0.03) and higher right CIMT (0.6 ± 0.1 mm vs 0.5 ± 0.07 mm, P = 0.04) compared with non-genotype 1. Patients who achieved sustained virological response (7/12) showed significant improvement in insulin resistance (homeostasis model of assessment of insulin resistance 2.3 ± 1.2 vs 1.8 ± 0.8, P = 0.02) and arterial stiffness (PWV 7.4 ± 1.1 m/s vs 6.5 ± 0.6 m/s, P = 0.04). CONCLUSIONS Subclinical vascular disease is not greater in CHC subjects compared with controls. However, among CHC subjects, genotype 1 infection is associated with greater endothelial dysfunction and increased carotid-intima medial thickness compared with non-genotype 1 infection. Successful viral eradication may improve insulin resistance and arterial stiffness.

The association between chronic hepatitis C infection and cardiovascular risk

Introduction Insertion of transjugular intrahepatic portosystemic shunt (TIPS) is an established therapeutic option to treat the complications of portal hypertension. The purpose of this study is to review the experience of a single Australian institute with TIPS and evaluation of result to emphasize the indication, aetiology of portal hypertension, prognostic factors, complications and survival. Use of TIPS as a bridge to liver transplantation was also analysed. Method A retrospective cohort study of patients treated with TIPS at The Western Australian Liver Transplant Unit, Sir Charles Gairdner Hospital, over a period of 12 years. Kaplan-Meier method was used for survival analysis and cox-regression analysis was used to analyse the predictors of survival. Results Fifty-three patients underwent TIPS between January 2000 and March 2012. The cumulative survival at 1 month, 1 year and 5 years was 90%, 70.9% and 43.9%, respectively. The predictors of survival were indication (variceal bleeding versus ascites, hazard ratio 3.19, CI 95%: 1.164-8.794, P = 0.024) and Model of End Stage Liver Disease score (Hazard ratio 2.513, CI 95%: 1.087-5.810, P = 0.031). Patients who underwent TIPS as a bridge to liver transplant had a 5-year survival of 71% that is comparable to the overall survival of Western Australian liver transplant unit. Conclusion Transjugular intrahepatic portosystemic shunt is a safe and effective method of treatment of complications of portal hypertension. TIPS can be safely used as a bridging therapy to liver transplant. Despite small number of TIPS being performed at our institute, our technical results are comparable to the institutes with bigger number of patients.

Transjugular intrahepatic portosystemic shunt: Indications, complications, survival and its use as a bridging therapy to liver transplant in Western Australia.

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Puraskar Pateria

Papers

Liver abnormalities in drug and substance abusers.

High local recurrence of early-stage hepatocellular carcinoma after percutaneous thermal ablation in routine clinical practice.

The association between chronic hepatitis C infection and cardiovascular risk

Transjugular intrahepatic portosystemic shunt: Indications, complications, survival and its use as a bridging therapy to liver transplant in Western Australia.

Predictors of hepatocellular cancer recurrence post thermal ablation.