Outcomes in liver transplantation: does sex matter?

A growing literature has highlighted important differences in transplant-related outcomes between men and women. In the United States there are fewer women than men on the liver transplant waitlist and women are two times less likely to receive a deceased or living-related liver transplant. Sex-based differences exist not only in waitlist but also in post-transplant outcomes, particularly in some specific liver diseases, such as hepatitis C. In the era of individualized medicine, recognition of these differences in the approach to pre and post-liver transplant care may impact short and long-term outcomes

Autoimmune Hepatitis: A Review of Current Diagnosis and Treatment

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by periportal inflammation, elevated immunoglobulins, autoantibodies, and a dramatic response to immunosuppression. An environmental agent is hypothesized to trigger an immune-mediated attack directed against liver antigens in genetically predisposed individuals. A plethora of clinical presentations can be seen ranging from chronic indolent disease to fulminant hepatic failure, and diagnosis requires exclusion of other causes of liver disease. Corticosteroid therapy must be instituted early and modified in an individualized fashion. Treatment decisions are often complicated by the diverse clinical manifestations, uncertainty about natural history, evolving ideas about treatment end points, and a multitude of alternative immunosuppressive agents. Achieving normal liver tests and tissue is the ideal treatment end point, but needs to be weighed against the risk of side effects. Decompensated patients may benefit from early liver transplantation. Long-term prognosis is excellent with early and aggressive initiation of therapy. Our paper discusses AIH, giving a detailed overview of its clinical presentation, risk factors, immunopathogenesis, up-to-date diagnostic criteria, current updates in therapy with a brief discussion of AIH in pregnancy, and long-term implications for cirrhosis and hepatocellular carcinoma in AIH patients

Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease

BACKGROUND & AIMS: There are no effective and safe treatments for chronic hepatitis C virus (HCV) infection of patients who have advanced liver disease. METHODS: In this phase 2, open-label study, we assessed treatment with the NS5A inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and ribavirin in patients infected with HCV genotypes 1 or 4. Cohort A enrolled patients with cirrhosis and moderate or severe hepatic impairment who had not undergone liver transplantation. Cohort B enrolled patients who had undergone liver transplantation: those without cirrhosis; those with cirrhosis and mild, moderate, or severe hepatic impairment; and those with fibrosing cholestatic hepatitis. Patients were assigned randomly (1:1) to receive 12 or 24 weeks of a fixed-dose combination tablet containing ledipasvir and sofosbuvir, once daily, plus ribavirin. The primary end point was sustained virologic response at 12 weeks after the end of treatment (SVR12). RESULTS: We enrolled 337 patients, 332 (99%) with HCV genotype 1 infection and 5 (1%) with HCV genotype 4 infection. In cohort A (nontransplant), SVR12 was achieved by 86%-89% of patients. In cohort B (transplant recipients), SVR12 was achieved by 96%-98% of patients without cirrhosis or with compensated cirrhosis, by 85%-88% of patients with moderate hepatic impairment, by 60%-75% of patients with severe hepatic impairment, and by all 6 patients with fibrosing cholestatic hepatitis. Response rates in the 12- and 24-week groups were similar. Thirteen patients (4%) discontinued the ledipasvir and sofosbuvir combination prematurely because of adverse events; 10 patients died, mainly from complications related to hepatic decompensation. CONCLUSION: The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks produced high rates of SVR12 in patients with advanced liver disease, including those with decompensated cirrhosis before and after liver transplantation. ClinTrials.gov: NCT01938430

Risks and Rewards of Bariatric Surgery in Advanced Chronic Liver Diseases.

The burden of obesity and metabolic syndrome has determined a sharp increase in bariatric surgery (BS) procedures, which lead to marked weight loss, improved metabolic syndrome, reduced cardiovascular risk, and even improvement in nonalcoholic steatohepatitis (NASH). Despite these promising results, BS in patients with chronic liver disease can rarely lead to worsening of liver function, progression to cirrhosis and its complications, and even liver transplantation. On the other hand, since obesity in patients with cirrhosis is a major cofactor for progression to a decompensated stage of the disease and a risk factor for hepatocellular carcinoma, BS has been used to achieve weight loss in this population. In this review, we critically analyze the existing data on outcomes of BS in patients with cirrhosis and the possible mechanisms leading to fibrosis progression and worsening liver function in patients undergoing BS. Finally, we propose a set of measures that could be taken to improve the multidisciplinary management of liver disease in patients undergoing BS, including early recognition of malnutrition and alcohol misuse

Greater Muscular Strength Is Associated with a Lower Risk of Pulmonary Dysfunction in Individuals with Non-Alcoholic Fatty Liver Disease

This study investigated the combined effect of handgrip strength (HGS) and non-alcoholic fatty liver disease (NAFLD) on pulmonary function using the Korea National Health and Nutrition Examination Survey (KNHANES) from 2016 to 2018. For the present study, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), the FEV1/FVC ratio, handgrip strength (HGS) and the hepatic steatosis index (HSI) to estimate NAFLD were obtained from nationwide cross-sectional surveys. For HGS, subjects were divided into higher HGS (upper 50%) and lower HGS (lower 50%). For NAFLD, subjects were divided into the NAFLD cohort (HSI > 36) and the normal cohort (HSI ≤ 36). Of 1651 subjects (men, n = 601), 25.5% of subjects (n = 421) met the HSI > 36. Based on the normal cohort with high HGS, the normal cohort with low HGS showed an increased risk of reduced FVC (OR = 3.062, 95% CI = 2.46–4.83, p < 0.001) and the NAFLD cohort with low HGS showed a further increased risk of reduced FVC (OR = 4.489, 95% CI = 3.43–7.09, p < 0.001). However, the risk of reduced FVC was not significantly increased in NAFLD with high HGS (OR = 1.297, 95% CI = 0.67–2.50, p = 0.436). After adjusted for covariates such as age, sex, smoking, FBG, HDL-C, TG, SBP, DBP, CRP and alcohol consumption, the results remained similar. More importantly, these results were consistent in the obesity-stratified analysis. The current findings of the study suggest that higher muscle strength is associated with a lower risk of reduced pulmonary function in individuals with NAFLD

Non-tuberculous mycobacteria infection presenting as a hepatic allograft abscess

Nontuberculous mycobacteria (NTM) are mycobacterial species other than Mycobacterium tuberculous and Mycobacterium leprae [1]. They are environmental organisms which have been implicated in a wide array of clinical syndromes. Here we describe a case of a Mycobacterium fortuitum complex liver abscess in a liver transplant recipient

Evaluation of recipients with significant comorbidity - Patients with cardiovascular disease.

Liver transplant(ation) (LT) is the most effective treatment for patients with decompensated liver disease. The increasing prevalence of obesity and type 2 diabetes and the growing number of patients with non-alcoholic fatty liver disease being evaluated for LT, have resulted in a greater proportion of LT candidates presenting with a higher risk of cardiovascular disease. As cardiovascular disease is a major cause of morbidity and mortality after LT, a thorough cardiovascular evaluation pre-LT is crucial. In this review, we discuss the latest evidence on the cardiovascular evaluation of LT candidates and we focus on the most prevalent conditions, namely ischaemic heart disease, atrial fibrillation and other arrhythmias, valvular heart disease, and cardiomyopathies. LT candidates undergo an electrocardiogram, a resting transthoracic echocardiography and an assessment of their cardiopulmonary functional ability as part of their standardised pre-LT work-up. Further diagnostic work-up is undertaken based on the results of the baseline evaluation and may include a coronary computed tomography angiography in patients with cardiovascular risk factors. The evaluation of potential LT candidates for cardiovascular disease requires a multidisciplinary approach, with input from anaesthetists, cardiologists, hepatologists and transplant surgeons