Liver transplantation offers live-saving therapy for patients with complications of cirrhosis and stage T2 hepatocellular carcinoma. The demand for organs far outstrips the supply, and innovations ...aimed at increasing the number of usable deceased donors as well as alternative donor sources are a major focus. The etiologies of cirrhosis are shifting over time, with more need for transplantation among patients with alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease and less for viral hepatitis, although hepatitis B remains an important indication for transplant in countries with high endemicity. The rise in transplantation for alcohol-associated liver disease and nonalcoholic/metabolic fatty liver disease has brought attention to how patients are selected for transplantation and the strategies needed to prevent recurrent disease. In this review, we present a status report on the most pressing topics in liver transplantation and future challenges.
Preclinical evidence suggests that modulation of the gut microbiome could represent a new therapeutic target in nonalcoholic fatty liver disease (NAFLD).
The aim of this study was to evaluate the ...most current evidence for liver-specific and metabolic effects of microbiome-targeted therapies (MTTs) in persons with NAFLD.
We searched multiple electronic databases for randomized controlled trials (RCTs) published from January 1, 2005 to December 1, 2018 that enrolled persons with NAFLD who received MTT rather than placebo or usual care. MTT was defined as antibiotics, probiotics, synbiotics, or fecal microbiota transplantation (FMT). Clinical outcomes were pooled with the use of random-effects models and heterogeneity was assessed with the I2 statistic. A random-effects meta-regression was performed to determine sources of heterogeneity in prevalence estimates between studies.
Twenty-one RCTs (1252 participants) were included; 9 evaluated probiotics and 12 evaluated synbiotics, with treatment duration ranging from 8 to 28 wk. No RCTs examined the efficacy of antibiotics or FMT. Probiotics/synbiotics were associated with a significant reduction in alanine aminotransferase activity ALT, weighted mean difference (WMD): −11.23 IU/L; 95% CI: −15.02, −7.44 IU/L and liver stiffness measurement (LSM) by elastography (reflecting inflammation and fibrosis) (WMD: −0.70 kPa; 95% CI: −1.00, −0.40 kPa), although analyses showed heterogeneity (I2 = 90.6% and I2 = 93.4%, respectively). Probiotics/synbiotics were also associated with increased odds of improvement in hepatic steatosis, as graded by ultrasound (OR: 2.40; 95% CI: 1.50, 3.84; I2 = 22.4%). No RCTs examined sequential liver biopsy findings. Probiotics (WMD: −1.84; 95% CI: −3.30, −0.38; I2 = 23.6%), but not synbiotics (WMD: −0.85; 95% CI: −2.17, 0.47; I2 = 96.6%), were associated with a significant reduction in body mass index.
The use of probiotics/synbiotics was associated with improvement in liver-specific markers of hepatic inflammation, LSM, and steatosis in persons with NAFLD. Although promising, given the heterogeneity in pooled analyses, additional well-designed RCTs are needed to define the efficacy of probiotics/synbiotics for treatment of NAFLD. This study was registered with PROSPERO as CRD42018091455.
The liver disorders unique to pregnancy include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy, and preeclampsia-associated hepatic impairment, ...specifically hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP). Their importance lies in the significant maternal and fetal/neonatal morbidity and mortality. Expeditious diagnosis and clinical evaluation is critical to ensure timely, appropriate care and minimize risks to the pregnant woman and her fetus/baby. A multidisciplinary approach is essential, including midwives, maternal-fetal-medicine specialists, anesthetists, neonatologists, and hepatologists.
Direct‐acting antiviral (DAA) therapy, recently approved for patients with decompensated cirrhosis (DC) secondary to hepatitis C virus (HCV), is associated with improved hepatic function. We analyzed ...trends in liver transplant (LT) wait‐listing (WL) to explore potential impact of effective medical therapy on WL registration. This is a cohort study using the Scientific Registry of Transplant Recipients database from 2003 to 2015. A total of 47,591 adults wait‐listed for LT from HCV, hepatitis B virus (HBV), and nonalcoholic steatohepatitis (NASH) were identified. LT indication was defined as DC if the Model for End‐Stage Liver Disease (MELD) at WL was ≥15 or hepatocellular carcinoma (HCC). Era of listing was divided into interferon (IFN; 2003‐2010), protease inhibitor (PI; 2011‐2013), and direct‐acting antiviral (DAA; 2014‐2015). Annual standardized incidence rates of WL were analyzed using Poisson regression. Adjusted incidences of LT WL for DC in HCV patients decreased by 5% in the PI era (P = 0.004) and 32% in the DAA era (P < 0.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (–17%; P = 0.002) and DAA eras (–24%; P < 0.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P < 0.001) and 81% in the DAA era (P < 0.001). WL for HCC in both the HCV and NASH populations increased in both the PI and DAA eras (P < 0.001 for all) whereas HCC WL in HBV remained stable (P > 0.05 for all). Conclusion: The rate of LT WL for HCV complicated by DC has decreased by over 30% in the era of DAA therapy. Further reductions in WL are anticipated with increased testing, linkage to care, and access to DAA therapy. (Hepatology 2017;65:804‐812).
Moderate alcohol consumption in patients with nonalcoholic fatty liver disease (NAFLD) is common, yet the effects on cardiovascular and liver health are unclear. Moderate alcohol use is associated ...with improved insulin sensitivity and decreased cardiovascular mortality in the general population, but whether similar benefits would be observed in persons with NAFLD remains largely unstudied. There is significant overlap in the pathogenesis of alcoholic liver disease (ALD) and NAFLD, although studies of ALD have focused on pathological alcohol intake and few mechanistic studies of moderate alcohol use in NAFLD exist. We undertook a critical review of the effect of moderate alcohol use on cardiovascular and liver disease in patients with NAFLD. A total of seven observational studies met the criteria for inclusion (one for cardiovascular endpoints and six for liver endpoints). Insufficient studies have assessed the association of moderate alcohol use with cardiovascular outcomes. There was a positive association between moderate alcohol use and decreased NASH and fibrosis; however, heavy episodic drinking may accelerate fibrosis progression and moderate alcohol use may increase the risk of hepatocellular carcinoma in patients with advanced fibrosis. Significant methodological limitations were present, including incomplete adjustment for confounding factors and failure to measure lifetime use or the pattern of alcohol intake. Thus, a strong recommendation of benefit of moderate alcohol use in NAFLD cannot be made. There remains a need for additional high‐quality longitudinal studies that evaluate both cardiovascular and liver outcomes among NAFLD patients with moderate or lesser degrees of alcohol use. (Hepatology 2017;65:2090‐2099).
Cirrhosis is an important cause of morbidity and mortality in people with chronic liver disease worldwide. In 2019, cirrhosis was associated with 2.4% of global deaths. Owing to the rising prevalence ...of obesity and increased alcohol consumption on the one hand, and improvements in the management of hepatitis B virus and hepatitis C virus infections on the other, the epidemiology and burden of cirrhosis are changing. In this Review, we highlight global trends in the epidemiology of cirrhosis, discuss the contributions of various aetiologies of liver disease, examine projections for the burden of cirrhosis, and suggest future directions to tackle this condition. Although viral hepatitis remains the leading cause of cirrhosis worldwide, the prevalence of non-alcoholic fatty liver disease (NAFLD) and alcohol-associated cirrhosis are rising in several regions of the world. The global number of deaths from cirrhosis increased between 2012 and 2017, but age-standardized death rates (ASDRs) declined. However, the ASDR for NAFLD-associated cirrhosis increased over this period, whereas ASDRs for other aetiologies of cirrhosis declined. The number of deaths from cirrhosis is projected to increase in the next decade. For these reasons, greater efforts are required to facilitate primary prevention, early detection and treatment of liver disease, and to improve access to care.
Tests to detect the presence and activity of hepatitis B virus (HBV) are the cornerstones of diagnosis and management. Assays that detect or measure serum levels of HB surface antigen, HB surface ...antibody, and HB core antibody are used to identify patients with exposure to HBV, whereas other tests provide information on the level of virus replication, presence of specific variants, and presence of virus reservoirs. Newer diagnostic tests, used only in research settings so far, aim to quantify levels of intrahepatic HBV replication. Other tests have been developed to detect HBV infection in resource-limited settings. We review point-of-care tests (essential in global screening efforts), standard diagnostic tests used in routine clinical management, and newer tests that might be used in clinical trials of agents designed to cure HBV infection.
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