Acute pancreatitis in a patient with COVID-19: a case report.

The global pandemic of coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is predominantly a respiratory illness, but gastrointestinal (GI) manifestations of variable severity have been reported. In patients with COVID-19 pneumonia, observational studies have demonstrated the elevation of pancreatic enzymes as surrogate markers for pancreatic injury without evidence of acute pancreatitis (AP). We report a case of AP in a patient with COVID-19 with SARS-CoV-2 as possible etiological agent with imaging evidence of pancreatitis. We hypothesize a causal relationship of SARS-CoV-2 in this patient with an otherwise unexplained presentation of AP after excluding the common causes. We postulate that AP in COVID-19 could be related to the abundant expression of angiotensin converting enzyme 2 (ACE 2) receptors in the pancreas which serve as viral entry binding receptors for SARS-CoV-2 or due to direct viral involvement of the pancreas. Although there seems to be an association between diabetes and AP, the available data regarding the etiological role of diabetes in causing AP is very limited. We also propose that imaging studies such as computerized tomography (CT) scan of the abdomen should be considered in the diagnosis of AP in patients with COVID-19 infection to exclude the false positive amylase and lipase.

SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19.

Common manifestations of COVID-19 are respiratory and can extend from mild symptoms to severe acute respiratory distress. The severity of the illness can also extend from mild disease to life-threatening acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection can also affect the gastrointestinal tract, liver and pancreatic functions, leading to gastrointestinal symptoms. Moreover, SARS-CoV-2 can cause central and peripheral neurological manifestations, affect the cardiovascular system and promote renal dysfunction. Epidemiological data have indicated that cancer patients are at a higher risk of contracting the SARS-CoV-2 virus. Considering the multitude of clinical symptoms of COVID-19, the objective of the present review was to summarize their pathophysiology in previously healthy patients, as well as in those with comorbidities. The present review summarizes the current, though admittedly fluid knowledge on the pathophysiology and symptoms of COVID-19 infection. Although unclear issues still remain, the present study contributes to a more complete understanding of the disease, and may drive the direction of new research. The recognition of the severity of the clinical symptoms of COVID-19 is crucial for the specific therapeutic management of affected patients.

NAFLD Epidemiology, Emerging Pharmacotherapy, Liver Transplantation Implications and the Trends in the United States.

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney transplantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as these patients are generally older, obese and more likely to have a number of metabolic risk factors. Bariatric surgery is an option and can be considered if a structured weight loss program does not achieve the sustained weight loss goal. Comprehensive cardiovascular risk assessment and aggressive management of comorbid conditions are crucial in the LT evaluation process to improve post-transplant survival. Recurrent nonalcoholic steatohepatitis after LT is not uncommon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts.

Gastrointestinal Bleeding in Patients with Severe SARS-CoV-2.

Gastrointestinal symptoms are common and frequently reported in Coronavirus Disease-2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is unclear if SARS-CoV-2 is associated with increased risk of gastrointestinal bleeding (GIB). Nevertheless, GIB in COVID-19 patients poses unique challenges to patients due to high-risk of concomitant respiratory failure and to endoscopy personnel due to risk of airborne transmission during endoscopic procedures. Many management issues related to COVID-19 are still being studied. In this case series, we attempt to discuss the important clinical implications related to the management of GIB in COVID-19 patients.

Opioid Use Disorder Increases 30-Day Readmission Risk in Inflammatory Bowel Disease Hospitalizations: a Nationwide Matched Analysis.

BACKGROUND AND AIMS: The opioid epidemic has become increasingly concerning, with the ever-increasing prescribing of opioid medications in recent years, especially in inflammatory bowel disease [IBD] patients with chronic pain. We aimed to isolate the effect of opioid use disorder [OUD] on 30-day readmission risk after an IBD-related hospitalization. METHODS: We retrospectively extracted IBD-related adult hospitalizations and 30-day, any-cause, readmissions from the National Readmissions Database [period 2010-2014]. OUD and 30-day readmission trends were calculated. Conventional and exact-matched [EM] logistic regression and time-to-event analyses were conducted among patients who did not undergo surgery during the index hospitalization, to estimate the effect of OUD on 30-day readmission risk. RESULTS: In total, 487 728 cases were identified: 6633 [1.4%] had documented OUD And 308 845 patients [63.3%] had Crohn's disease. Mean age was 44.8 ± 0.1 years, and 54.3% were women. Overall, 30-day readmission rate was 19.4% [n = 94,546], being higher in OUD patients [32.6% vs 19.2%; p < 0.001]. OUD cases have been increasing [1.1% to 1.7%; p-trend < 0.001], while 30-day readmission rates were stable [p-trend = 0.191]. In time-to-event EM analysis, OUD patients were 47% more likely (hazard ratio 1.47; 95% confidence interval [CI]:1.28-1.69; p < 0.001) to be readmitted, on average being readmitted 32% earlier [time ratio 0.68; 95% CI: 0.59-0.78; p < 0.001]. CONCLUSION: OUD prevalence has been increasing in hospitalized IBD patients from 2010 to 2014. On average, one in five patients will be readmitted within 30 days, with up to one in three among the OUD subgroup. OUD is significantly associated with increased 30-day readmission risk in IBD patients and further measures relating to closer post-discharge outpatient follow-up and pain management should be considered to minimize 30-day readmission risk.

Opioid use disorder in admissions for acute exacerbations of chronic pancreatitis and 30-day readmission risk: A nationwide matched analysis.

BACKGROUND: The opioid epidemic in the United States has been on the rise. Acute exacerbations of chronic pancreatitis (AECP) patients are at higher risk for Opioid Use Disorder (OUD). Evidence on OUD's impact on healthcare utilization, especially hospital re-admissions is scarce. We measured the impact of OUD on 30-day readmissions, in patients admitted with AECP from 2010 to 2014. METHODS: This is a retrospective cohort study which included patients with concurrently documented CP and acute pancreatitis as first two diagnoses, from the National Readmissions Database (NRD). Pancreatic cancer patients and those who left against medical advice were excluded. We compared the 30-day readmission risk between OUD-vs.-non-OUD, while adjusting for other confounders, using multivariable exact-matched [(EM); 18 confounders; n = 28,389] and non-EM regression/time-to-event analyses. RESULTS: 189,585 patients were identified. 6589 (3.5%) had OUD. Mean age was 48.7 years and 57.5% were men. Length-of-stay (4.4 vs 3.9 days) and mean index hospitalization costs ($10,251 vs. $9174) were significantly higher in OUD-compared to non-OUD-patients (p < 0.001). The overall mean 30-day readmission rate was 27.3% (n = 51,806; 35.3% in OUD vs. 27.0% in non-OUD; p < 0.001). OUD patients were 25% more likely to be re-admitted during a 30-day period (EM-HR: 1.25; 95%CI: 1.16-1.36; p < 0.001), Majority of readmissions were pancreas-related (60%), especially AP. OUD cases' aggregate readmissions costs were $23.3 ± 1.5 million USD (n = 2289). CONCLUSION: OUD contributes significantly to increased readmission risk in patients with AECP, with significant downstream healthcare costs. Measures against OUD in these patients, such as alternative pain-control therapies, may potentially alleviate such increase in health-care resource utilization.

Pre-Operative Delta-MELD is an Independent Predictor of Higher Mortality following Liver Transplantation.

Clinical decompensation immediately prior to liver transplantation may affect post-liver transplant (LT) outcomes. Using the serial Model for End-Stage Liver Disease (MELD) scores recorded in the United Network for Organ Sharing national registry (2010-2017), we analyzed post-LT mortality among adult LT recipients based on the degree of fluctuation in MELD score during the 30-day period prior to LT surgery. Delta-MELD (D-MELD) was defined as recipient MELD score at LT minus lowest MELD score within the preceding 30 days. Impact of D-MELD as a continuous and categorical variable (D-MELD 0-4, 5-10, >10) on early, 30-day post-LT mortality was assessed. Overall, a total of 12,785 LT recipients were analyzed, of which 8,862 (67.9%) had a pre-operative D-MELD 0-4; 2,574 (20.1%) with a D-MELD 5-10; and 1,529 (12.0%) with a D-MELD > 10. One-point incremental increase in pre-operative D-MELD (adjusted HR, 1.07, 95% CI: 1.04-1.10) was associated with higher 30-day post-LT mortality. Moreover, pre-operative D-MELD > 10 was associated with nearly a two-fold increased risk for 30-day post-LT mortality (adjusted HR, 1.89, 95% CI: 1.30-2.77) compared to D-MELD 0-4. The increased risk of pre-LT mortality associated with severity of clinical decompensation assessed by the magnitude of pre-operative D-MELD persists in the early post-LT period.

Hepatocellular carcinoma is leading in cancer-related disease burden among hospitalized baby boomers.

INTRODUCTION AND OBJECTIVES: Three fourths of chronic hepatitis C virus (HCV) infected adult patients in the United States (US) are born between 1945 and 1965, also known as baby boomers (BB). Prevalence of hepatocellular carcinoma (HCC) is raising in BB due to their advancing age and prolonged HCV infection. We evaluated inpatient hospitalization and mortality in BB associated with HCC. MATERIALS AND METHODS: It is a retrospective cohort study utilizing the Healthcare Utilization Project-National Inpatient Sample (HCUP-NIS) database. From 2003 to 2012, top five primary cancer related hospitalization and mortality among BB were studied. RESULTS: Among 48,733 hospitalizations related to HCC in HCUP-NIS database from 2003 to 2012, BB accounted for 49.6% (24,210) whereas non-BB 50.4% (24,523). Within BB cohort, the top five cancers with the highest proportion of hospitalizations were HCC (46%), prostate (43%), kidney (41%), pancreas (33%), and bladder (21%). From 2003 to 2012, the proportion of HCC related hospitalizations represented by BB almost doubled (33.5 to 57.8%) whereas there was one-third reduction (66.4 to 42.1%) among non-BB. Similarly, HCC-related inpatient mortality in BB decreased by 28% (6.1 to 2.7 per 100,000 hospitalization) but it remained unchanged in non-BB (11.1 to 10.6). HCC accounted for 2nd highest mortality (4960 total deaths) among hospitalized BB behind pancreatic cancer. HCC related to HCV was disproportionately higher in BB compared to non-BB (50.6% vs. 19%; P<0.001). CONCLUSION: HCC ranks number one among the top five cancers with highest proportion of inpatient burden. Future studies should focus on understanding the underlying reasons for this ominous trend.

Changing Trends in Etiology-Based and Ethnicity-Based Annual Mortality Rates of Cirrhosis and Hepatocellular Carcinoma in the United States.

With recent improvements in the treatment of end-stage liver disease (ESLD), a better understanding of the burden of cirrhosis and hepatocellular carcinoma (HCC) is needed in the United States. A population-based study using the US Census and national mortality database was performed. We identified the age-standardized etiology-specific mortality rates for cirrhosis and HCC among US adults ages 20 years or older from 2007 to 2016. We determined temporal mortality rate patterns by joinpoint analysis with estimates of annual percentage change (APC). Age-standardized cirrhosis-related mortality rates increased from 19.77/100,000 persons in 2007 to 23.67 in 2016 with an annual increase of 2.3% (95% confidence interval [CI] 2.0-2.7). The APC in mortality rates for hepatitis C virus (HCV)-cirrhosis shifted from a 2.9% increase per year during 2007 to 2014 to a 6.5% decline per year during 2014 to 2016. Meanwhile, mortality for cirrhosis from alcoholic liver disease (ALD, APC 4.5%) and NAFLD (APC 15.4%) increased over the same period, whereas mortality for hepatitis B virus (HBV)-cirrhosis decreased with an average APC of -1.1%. HCC-related mortality increased from 3.48/100,000 persons in 2007 to 4.41 in 2016 at an annual rate of 2.0% (95% CI 1.3-2.6). Etiology-specific mortality rates of HCC were largely consistent with cirrhosis-related mortality. Minority populations had a higher burden of HCC-related mortality. Conclusion: Cirrhosis-related and HCC-related mortality rates increased between 2007 and 2016 in the United States. However, mortality rates in HCV-cirrhosis demonstrated a significant decline from 2014 to 2016, during the direct-acting antiviral era. Mortality rates for ALD/NAFLD-cirrhosis and HCC have continued to increase, whereas HBV-cirrhosis-related mortality declined during the 10-year period. Importantly, minorities had a disproportionately higher burden of ESLD-related mortality.

Temporal Trends Associated With the Rise in Alcoholic Liver Disease-related Liver Transplantation in the United States.

BACKGROUND: In the United States, alcoholic liver disease (ALD) has recently become the leading indication for liver transplantation. METHODS: Using the United Network for Organ Sharing registry, we examined temporal trends in adult liver transplant waitlist (WL) registrants and recipients with chronic liver disease (CLD) due to ALD from 2007 to 2016. RESULTS: From 2007 to 2016, ALD accounted for 20.4% (18 399) of all CLD WL additions. The age-standardized ALD WL addition rate was 0.459 per 100 000 US population in 2007; nearly doubled to 0.872 per 100 000 US population in 2016 and increased with an average annual percent change of 47.56% (95% confidence interval, 30.33% to 64.72%).The ALD WL addition rate increased over twofold among young (18-39 years) and middle-aged (40-59 years) adults during the study period. Young adult ALD WL additions presented with a higher severity of liver disease including Model for End-Stage Liver Disease score compared to middle aged and older adults (≥60 years). The number of annual ALD WL deaths readily rose from 2014 to 2016, despite an overall annual decline in all CLD WL deaths. Severe hepatic encephalopathy, low body mass index (<18.5) and diabetes mellitus were significant predictors for 1-year WL mortality. CONCLUSIONS: Alcoholic liver disease-related WL registrations and liver transplantation have increased over the past decade with a disproportionate increase in young and middle-aged adults. These subpopulations within the ALD cohort need to be evaluated in future studies to improve our understanding of factors associated with these alarming trends.

Changing Trends in Etiology-Based Annual Mortality From Chronic Liver Disease, From 2007 Through 2016.

BACKGROUND & AIMS: Although treatment of hepatitis C virus (HCV) infection has improved, the prevalence of alcoholic liver disease (ALD) has been increasing, so we need an updated estimate of the burden and etiology-specific mortality of chronic liver diseases. We studied trends in age-standardized mortality of chronic liver diseases in adults at least 20 years old in the United States from 2007 through 2016. METHODS: We collected data from the US Census and National Center for Health Statistics mortality records and identified individuals with HCV infection, ALD, nonalcoholic fatty liver disease, or hepatitis B virus infection using ICD-10 codes. We obtained temporal mortality rate patterns using joinpoint trend analysis with estimates of annual percentage change (APC). RESULTS: Age-standardized HCV-related mortality increased from 7.17 per 100,000 persons in 2007 to 8.14 per 100,000 persons in 2013, followed by a marked decrease in the time period at which patients began receiving treatment with direct-acting antiviral agents (from 8.09 per 100,000 persons in 2014 to 7.15 per 100,000 persons in 2016). The APC in HCV mortality increased 2.0%/year from 2007 through 2014 but decreased 6.4%/year from 2014 through 2016. In contrast, age-standardized mortality increased for ALD (APC 2.3% from 2007 through 2013 and APC 5.5% from 2013 through 2016) and nonalcoholic fatty liver disease (APC 6.1% from 2007 through 2013 and APC 11.3% from 2013 through 2016). Mortality related to hepatitis B virus decreased steadily from 2007 through 2016, with an average APC of -2.1% (95% CI -3.0 to -1.2). Etiology-based mortality in minority populations was higher. HCV-related mortality (per 100,000 persons) was highest in non-Hispanic blacks (10.28) and whites (6.92), followed by Hispanics (5.94), and lowest in non-Hispanic Asians (2.33). Non-Hispanic Asians had higher mortality for hepatitis B virus infection (2.82 per 100,000 vs 1.02 for non-Hispanic blacks and 0.47 for non-Hispanic whites). CONCLUSION: In our population-based analysis of chronic liver disease mortality in the United States, the decrease in HCV-related mortality coincided with the introduction of direct-acting antiviral therapies, whereas mortality from ALD and nonalcoholic fatty liver disease increased during the same period. Minorities in the United States have disproportionately higher mortality related to chronic liver disease.

The Role of Cannabinoids in the Setting of Cirrhosis.

Although the mortality rates of cirrhosis are underestimated, its socioeconomic burden has demonstrated a significant global impact. Cirrhosis is defined by the disruption of normal liver architecture after years of chronic insult by different etiologies. Treatment modalities are recommended primarily in decompensated cirrhosis and specifically tailored to the different manifestations of hepatic decompensation. Antifibrogenic therapies are within an active area of investigation. The endocannabinoid system has been shown to play a role in liver disease, and cirrhosis specifically, with intriguing possible therapeutic benefits. The endocannabinoid system comprises cannabinoid receptors 1 (CB1) and cannabinoid receptor 2 (CB2) and their ligands, endocannabinoids and exocannabinoids. CB1 activation enhances fibrogenesis, whereas CB2 activation counteracts progression to fibrosis. Conversely, deletion of CB1 is associated with an improvement of hepatic fibrosis and steatosis, and deletion of CB2 results in increased collagen deposition, steatosis, and enhanced inflammation. CB1 antagonism has also demonstrated vascular effects in patients with cirrhosis, causing an increase in arterial pressure and vascular resistance as well as a decrease in mesenteric blood flow and portal pressure, thereby preventing ascites. In mice with hepatic encephalopathy, CB1 blockade and activation of CB2 demonstrated improved neurologic score and cognitive function. Endocannabinoids, themselves also have mechanistic roles in cirrhosis. Arachidonoyl ethanolamide (AEA) exhibits antifibrogenic properties by inhibition of HSC proliferation and induction of necrotic death. AEA induces mesenteric vasodilation and hypotension via CB1 induction. 2-arachidonoyl glycerol (2-AG) is a fibrogenic mediator independent of CB receptors, but in higher doses induces apoptosis of HSCs, which may actually show antifibrotic properties. 2-AG has also demonstrated growth-inhibitory and cytotoxic effects. The exocannabinoid, THC, suppresses proliferation of hepatic myofibroblasts and stellate cells and induces apoptosis, which may reveal antifibrotic and hepatoprotective mechanisms. Thus, several components of the endocannabinoid system have therapeutic potential in cirrhosis.

Role of Cholecystectomy After Endoscopic Sphincterotomy in the Management of Choledocholithiasis in High-risk Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopic retrograde cholangiography and endoscopic sphincterotomy (ES) with subsequent cholecystectomy is the standard of care for the management of patients with choledocholithiasis. There is conflicting evidence in terms of mortality reduction, prevention of complications specifically biliary pancreatitis and cholangitis with the use of early cholecystectomy particularly in high-risk surgical and elderly patients. AIMS: We conducted this systematic review and meta-analysis of randomized controlled trials to compare the early cholecystectomy versus wait and watch strategy after ES. METHODS: We searched Medline, Scopus, Web of Science, and Cochrane database for randomized controlled trials comparing the 2 strategies in the management of choledocholithiasis after ES. Our primary outcome of interest was difference in mortality. We evaluated several secondary outcomes including difference in development of acute pancreatitis, biliary colic and cholecystitis, cholangitis and recurrent jaundice, nonbiliary adverse events, and length of hospital stay. Risk ratios (RR) were calculated for categorical variables and difference in means was calculated for continuous variables. These were pooled using random effects model. RESULTS: Seven studies with 916 patients (455 cholecystectomy group and 461 wait and watch group) were included in the meta-analysis. Pooled RR with 95% confidence interval for mortality was 1.43 (0.93-2.18), I=9%. In the high-risk patient group, pooled RR was 1.39 (0.64-3.03) and in low-risk population pooled RR was 1.53 (0.79-2.96). Pooled RR for acute pancreatitis was 1.64 (0.46-5.81) with no heterogeneity. There was no difference in the rate of acute pancreatitis patients based on high-risk versus low-risk patients. Pooled RR for occurrence of biliary colic and cholecystitis during follow-up was 9.82 (4.27-22.59), I=0%. Pooled RR for cholangitis and recurrent jaundice was 2.16 (1.14-4.07), I=0%. However, there was no difference in the rate of cholangitis between the 2 groups in low-risk patients. Length of stay was shorter in the wait and watch group with a pooled mean difference was -2.70 (-4.71, -0.70) with substantial heterogeneity. CONCLUSIONS: Although we found no difference in mortality between the 2 strategies after ES, laparoscopic cholecystectomy should be recommended as it is associated with lower rates of subsequent recurrent cholecystitis, cholangitis, and biliary colic down the road even in high-risk surgical patients.

Mechanistic Potential and Therapeutic Implications of Cannabinoids in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is comprised of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). It is defined by histologic or radiographic evidence of steatosis in the absence of alternative etiologies, including significant alcohol consumption, steatogenic medication use, or hereditary disorders. NAFLD is now the most common liver disease, and when NASH is present it can progress to fibrosis and hepatocellular carcinoma. Different mechanisms have been identified as contributors to the physiology of NAFLD; insulin resistance and related metabolic derangements have been the hallmark of physiology associated with NAFLD. The mainstay of treatment has classically involved lifestyle modifications focused on the reduction of insulin resistance. However, emerging evidence suggests that the endocannabinoid system and its associated cannabinoid receptors and ligands have mechanistic and therapeutic implications in metabolic derangements and specifically in NAFLD. Cannabinoid receptor 1 antagonism has demonstrated promising effects with increased resistance to hepatic steatosis, reversal of hepatic steatosis, and improvements in glycemic control, insulin resistance, and dyslipidemia. Literature regarding the role of cannabinoid receptor 2 in NAFLD is controversial. Exocannabinoids and endocannabinoids have demonstrated some therapeutic impact on metabolic derangements associated with NAFLD, although literature regarding direct therapeutic use in NAFLD is limited. Nonetheless, the properties of the endocannabinoid system, its receptors, substrates, and ligands remain a significant arena warranting further research, with potential for a pharmacologic intervention for a disease with an anticipated increase in economic and clinical burden.

Waitlist Outcomes in Liver Transplant Candidates with High MELD and Severe Hepatic Encephalopathy.

BACKGROUND: Organ Procurement and Transplantation Network and United Network for Organ Sharing (OPTN/UNOS) implemented the Share 35 policy in June 2013 to prioritize the sickest patients awaiting liver transplantation (LT). However, Model for End-Stage Liver Disease (MELD) score does not incorporate hepatic encephalopathy (HE), an independent predictor of waitlist mortality. AIM: To evaluate the impact of severe HE (grade 3-4) on waitlist outcomes in MELD ≥ 30 patients. METHODS: Using the OPTN/UNOS database, we evaluated LT waitlist registrants from 2005-2014. Demographics, comorbidities, and waitlist survival were compared between four cohorts: MELD 30-34 with severe HE, MELD 30-34 without severe HE, MELD ≥ 35 with severe HE, and MELD ≥ 35 without severe HE. RESULTS: Among 10,003 waitlist registrants studied, 41.6% had MELD score 30-34 and 58.4% had MELD ≥ 35. Patients with severe HE had a higher 90-day waitlist mortality in both MELD 30-34 (severe HE 71.1% vs. no HE 56.6%; p < 0.001) and MELD ≥ 35 subgroups (severe HE 85% versus no HE 74.2%; p < 0.001). MELD 30-34 patients with severe HE had similar 90-day waitlist mortality as MELD ≥ 35 patients without severe HE (71.1 vs. 74.2%, respectively; p = 0.35). On multivariate Cox proportional hazards modeling, MELD ≥ 30 patients had 58% greater risk of 90-day waitlist mortality than those without severe HE (HR 1.58, 95% CI 1.53-1.62; p < 0.001). CONCLUSION: Patients awaiting LT with MELD score of 30-34 and severe HE should receive priority status for organ allocation with exception MELD ≥ 35.

Reactivation of hepatitis B after liver transplantation: Current knowledge, molecular mechanisms and implications in management.

Chronic hepatitis B (CHB) is a major global health problem affecting an estimated 350 million people with more than 786000 individuals dying annually due to complications, such as cirrhosis, liver failure and hepatocellular carcinoma (HCC). Liver transplantation (LT) is considered gold standard for treatment of hepatitis B virus (HBV)-related liver failure and HCC. However, post-transplant viral reactivation can be detrimental to allograft function, leading to poor survival. Prophylaxis with high-dose hepatitis B immunoglobulin (HBIG) and anti-viral drugs have achieved remarkable progress in LT by suppressing viral replication and improving long-term survival. The combination of lamivudine (LAM) plus HBIG has been for many years the most widely used. However, life-long HBIG use is both cumbersome and costly, whereas long-term use of LAM results in resistant virus. Recently, in an effort to develop HBIG-free protocols, high potency nucleos(t)ide analogues, such as Entecavir or Tenofovir, have been tried either as monotherapy or in combination with low-dose HBIG with excellent results. Current focus is on novel antiviral targets, especially for covalently closed circular DNA (cccDNA), in an effort to eradicate HBV infection instead of viral suppression. However, there are several other molecular mechanisms through which HBV may reactivate and need equal attention. The purpose of this review is to address post-LT HBV reactivation, its risk factors, underlying molecular mechanisms, and recent advancements and future of anti-viral therapy.

Use of direct-acting antiviral agents in hepatitis C virus-infected liver transplant candidates.

Since the advent of direct acting antiviral (DAA) agents, chronic hepatitis C virus (HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant (LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response (SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.

Nonalcoholic Fatty Liver Disease: Epidemiology, Liver Transplantation Trends and Outcomes, and Risk of Recurrent Disease in the Graft.

In parallel with the rising prevalence of metabolic syndrome globally, nonalcoholic fatty liver (NAFL) disease is the most common chronic liver disease in Western countries and nonalcoholic steatohepatitis (NASH) has become increasingly associated with hepatocellular carcinoma. Recent studies have identified NASH as the most rapidly growing indication for liver transplantation (LT). As a hepatic manifestation of the metabolic syndrome, NAFL disease can be histologically divided into NAFL and NASH. NAFL is considered a benign condition, with histological changes of hepatocyte steatosis but without evidence of hepatocellular injury or fibrosis. This is distinct from NASH, which is characterized by hepatocyte ballooning and inflammation, and which can progress to fibrosis and cirrhosis, hepatocellular carcinoma, and liver failure. As for any other end-stage liver disease, LT is a curative option for NASH after the onset of decompensated cirrhosis or hepatocellular carcinoma. Although some studies have suggested increased rates of sepsis and cardiovascular complications in the immediate postoperative period, the long-term posttransplant survival of NASH cases is similar to other indications for LT. Recurrence of NAFL following LT is common and can be challenging, although recurrence rates of NASH are lower. The persistence or progression of metabolic syndrome components after LT are likely responsible for NASH recurrence in transplanted liver. Therefore, while maintaining access to LT is important, concerted effort to address the modifiable risk factors and develop effective screening strategies to identify early stages of disease are paramount to effectively tackle this growing epidemic.