Changing Population of Liver Transplant Recipients in the Era of Direct-acting Antiviral Therapy

Background and Aims: With the availability of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection and changing liver disease etiology for liver transplantation (LT), data on the changes in LT recipient population in the DAA era are scanty. Methods: The United Network for Organ Sharing (UNOS) registry (01/2007 to 06/2018) was used to develop a retrospective cohort of LT recipients for HCV, alco-hol-associated liver disease (ALD), and non-alcoholic steato-hepatitis (NASH). LT recipients in the DAA era (2013-2018) were compared with those in the pre-DAA era (2007-2012) era for recipient characteristics. Chi-square and analysis of variance were the statistical tests used for categorical and con-tinuous variables, respectively. Results: Of 40,309 LT recipients (21,110 HCV, 7586 NASH, and 11,713 ALD), the 21,790 in the DAA era (9432 HCV, 7240 ALD, and 5118 NASH) were more likely to be older, female, obese, diabetic, have acute-on-chronic liver failure with a higher model for end-stage liver disease score, receive grafts with a lower donor risk index, and have waited on the LT list for a shorter period compared with their pre-DAA era counterparts. Specific to ALD, LT recipients with alcohol hepatitis were more likely to be younger at the time of LT. Of 9895 LT recipients with hepatocellular carci-noma, recipients in the DAA era were observed to have a higher proportion of HCV (43% vs. 32%,

Alcohol‐Associated Liver Disease Before and After COVID‐19 – An Overview and Call for Ongoing Investigation

The Coronavirus Disease-2019 (COVID-19) pandemic has exacted a heavy toll on patients with alcohol-associated liver disease (ALD) and alcohol use disorder (AUD). The collective burden of ALD and AUD was large and growing prior to the COVID-19 pandemic. There is accumulating evidence that this pandemic has had a large direct effect on these patients and is likely to produce indirect effects via delays in care, psychological strain, and increased alcohol use. Now a year into the pandemic, it is important that clinicians fully understand the effects of the COVID-19 pandemic on patients with ALD and AUD. To fill existing gaps in knowledge, the scientific community must set research priorities for patients with ALD regarding their risk of COVID-19, prevention/treatment of COVID-19, changes in alcohol use during the pandemic, best use of AUD treatments in the COVID-19 era, and downstream effects of this pandemic on ALD. Conclusion: The COVID-19 pandemic has already inflicted disproportionate harms on patients with ALD and ongoing, focused research efforts will be critical to better understand the direct and collateral effects of this pandemic on ALD

Evaluating quality of life tools in North American patients with erythropoietic protoporphyria and X-linked protoporphyria.

BackgroundErythropoietic protoporphyria (EPP) and X-linked Protoporphyria (XLP) are rare photodermatoses presenting with severe phototoxicity. Although anecdotally, providers who treat EPP patients acknowledge their life-altering effects, tools that fully capture their impact on quality of life (QoL) are lacking.MethodsAdult patients with EPP/XLP were given four validated QoL tools: the Patient Reported Outcomes Measurement Information System 57 (PROMIS-57), the Hospital Anxiety and Depression Scale (HADS), the Illness Perception Questionnaire Revised (IPQR), and an EPP-Specific tool. All patients received the PROMIS-57 while the HADS, IPQR, and EPP-Specific tools were introduced at a later date. Associations between responses and clinical phenotypes were explored.ResultsTwo hundred and two patients were included; 193 completed PROMIS-57, 104 completed IPQR, 103 completed HADS, and 107 completed the EPP-Specific tool. The IPQR showed that patients strongly believed EPP/XLP had a negative impact on their lives. Mean scores in anxiety and depression domains of both HADS and PROMIS-57 were normal; however, anxiety scores from HADS were borderline/abnormal in 20% of patients. The EPP-Specific tool revealed a decreased QoL in most patients. The PROMIS-57 showed that 21.8% of patients have clinically significant pain interference. Several tool domains correlated with measures of disease severity, most being from the PROMIS-57.ConclusionsImpaired QoL is an important consequence of EPP/XLP. PROMIS-57 was most sensitive in evaluating impaired QoL in EPP/XLP. Further research is needed to compare the effectiveness of it for assessing response to treatment

The impact of the COVID-19 pandemic on patients with chronic liver disease: Results from the Global Liver Registry

Patients with preexisting chronic liver disease (CLD) may experience a substantial burden from both coronavirus 2019 (COVID-19) infection and pandemic-related life disruption. We assessed the impact of the COVID-19 pandemic on patients with CLD. Patients enrolled in our Global Liver Registry were invited to complete a COVID-19 survey. As of June 2021, 2500 patients (mean age ± SD, 49 ± 13 years; 53% men) from seven countries completed the survey. Of all survey completers, 9.3% had COVID-19. Of these patients, 19% were hospitalized, 13% needed oxygen support, but none required mechanical ventilation. Of all patients including those not infected with COVID-19, 11.3% reported that the pandemic had an impact on their liver disease, with 73% of those reporting delays in follow-up care. The Life Disruption Event Perception questionnaire confirmed worsening in at least one area (food/nutrition, exercise, social life, vocation/education, financial situation, housing, or health care) in 81% and 69% of patients with and without a history of COVID-19, respectively (p = 0.0001). On a self-assessed Likert health score scale (range, 1-10; 10 indicates perfect health), patients with a COVID-19 history scored lower (mean ± SD, 6.7 ± 2.2 vs. 7.4 ± 2.2, respectively; p \u3c 0.0001) despite reporting similar health scores if there was no pandemic (mean ± SD, 8.5 ± 1.4 vs. 8.4 ± 1.6, respectively; p = 0.59). After adjustment for country of enrollment, liver disease etiology and severity, age, sex, body mass index, diabetes, and history of psychiatric comorbidities, COVID-19 was found to be independently associated with lower self-assessed health scores (beta = -0.71 ± 0.14; p \u3c 0.0001). The COVID-19 pandemic resulted in a substantial burden on the daily life of patients with CLD

Light to moderate drinking and therapeutic doses of acetaminophen: An assessment of risks for renal dysfunction

This study investigated the potential effect of therapeutic doses of acetaminophen (APAP) in combination with light-moderate amounts of alcohol on kidney functions controlling for factors such as hypertension, diabetes and obesity that may predispose the kidney to APAP and/or alcohol toxicity. Secondary analysis of the 2003-2004 National Health and Nutrition Examination Survey data was performed using SAS 9.4. Odds ratios (OR) and 95% confidence intervals (CI) comparing the likelihood that individuals who ingested therapeutic doses of APAP and light-moderate amount of alcohol, compared to those who did not, would have kidney dysfunction were generated from multiple logistics regression models by further controlling for potential predisposing factors namely hypertension, diabetes and obesity. Kidney dysfunction was defined based on self-reports and laboratory examination of serum creatinine (SCr), blood urea nitrogen (BUN), glomerular filtration rate (GFR) and albumin creatinine ratio (ABCR). Statistically significant increased odds of renal dysfunction were noted among respondents who reported use of therapeutic doses of APAP and light-moderate amount of alcohol [OR(95% CI) = 1.64(1.28-2.10) self-report, 2.18(1.81-2.63) SCr, 4.60(3.03-7.00) BUN, 3.14(2.42-4.07) GFR, and 1.71(1.36-2.14) ALBCR)] even after adjusting for hypertension, diabetes and obesity [Adjusted OR (95% CI) = 1.78 (1.22-2.58) self-report, 2.05 (1.07-3.92) GFR]. The toxic effects of APAP and alcohol on the kidney were hypothesized. The threshold doses at which these effects begin to occur are unknown. The findings of this study suggest that even therapeutic doses of APAP and light-moderate amount of alcohol could be health problematic if consumed concomitantly

Acute Alcoholic Hepatitis: Natural History and Predictors of Mortality Using a Multicenter Prospective Study

Objective: To examine the natural history of acute alcoholic hepatitis (AH) and identify predictors of mortality for AH using data from a prospective multicenter observational study. Participants and Methods: We analyzed data from 164 patients with AH and 131 heavy-drinking controls with no liver disease. Participants underwent clinical/laboratory assessment at baseline and 6 and 12 months after enrollment. Multivariable analyses were conducted to identify variables associated with mortality and examine the association between coffee drinking and risk of AH. Results: Thirty-six patients with AH died during follow-up, with estimated 30-day, 90-day, 180-day, and 1-year survival of 0.91 (95% CI, 0.87-0.96), 0.85 (95% CI, 0.80-0.91), 0.80 (95% CI, 0.74-0.87), and 0.75 (95% CI, 0.68-0.83), respectively. In the multivariable analysis, higher serum bilirubin level (hazard ratio [HR]=1.059; 95% CI, 1.022-1.089), lower hemoglobin level (HR=1.263; 95% CI, 1.012-1.575), and lower platelet count (HR=1.006; 95% CI, 1.001-1.012) were independently associated with mortality in AH. Compared with controls, fewer patients with AH regularly consumed coffee (20% vs 44%; P<.001), and this association between regular coffee drinking and lower risk of AH persisted after controlling for relevant covariates (odds ratio=0.26; 95% CI, 0.15-0.46). Time-dependent receiver operating characteristic curve analysis revealed that Model for End-Stage Liver Disease; Maddrey Discriminant Function; age, serum bilirubin, international normalized ratio, and serum creatinine; and Child-Pugh scores all provided similar discrimination performance at 30 days (area under the curve=0.73-0.77). Conclusion: Alcoholic hepatitis remains highly fatal, with 1-year mortality of 25%. Regular coffee consumption was associated with lower risk of AH in heavy drinkers

PNPLA3 gene polymorphism is associated with predisposition to and severity of alcoholic liver disease

The genetic polymorphism with an isoleucine-to-methionine substitution at position 148 (rs738409 C>G) in the patatin-like phospholipase domain protein 3 (PNPLA3) gene confers risk of steatosis. PNPLA3 polymorphism is shown to be associated with alcoholic liver disease (ALD). We performed a systematic review and meta-analysis to examine association of this genetic polymorphism with ALD spectrum and its severity.METHODS:Medline, Embase, and Cochrane Library were searched for studies on association of PNPLA3 polymorphism and ALD spectrum: alcoholic fatty liver (AFL), alcoholic liver injury (ALI), alcoholic cirrhosis (AC), and hepatocellular carcinoma (HCC). Pooled data are reported as odds ratio (OR) with 95% confidence interval. Heterogeneity was assessed using the I 2 statistics and publication bias using Egger's test and Begg and Mazumdar's test. Individual participant data obtained from five studies were used for subgroup analyses.RESULTS:Among 10 studies included in this pooled analysis, compared with controls, OR for rs738409 CG and GG among ALI patients was 1.45 (1.24-1.69) and 2.22 (1.50-3.28), respectively, compared with CC. Respective OR among AC patients was 2.09 (1.79-2.44) and 3.37 (2.49-4.58) and among AC patients with HCC was 2.87 (1.61-5.10) and 12.41 (6.99-22.03). Data for AFL were inconsistent. Among ALD patients, OR of CG and GG genotypes was 2.62 (1.73-3.97) and 8.45 (2.52-28.37), respectively, for AC compared with fatty liver (FL) patients. Similar OR for AC compared with ALI was 1.98 (1.24-3.17) and 3.86 (1.18-12.60). The OR for CG and GG genotypes among AC patients for HCC occurrence was 1.43 (0.76-2.72) and 2.81 (1.57-5.01), respectively. Individual participant data analysis showed age to predispose to AC among ALI patients.CONCLUSIONS:PNPLA3 genetic polymorphism (rs738409 C>G) is associated with increased risk for the entire spectrum of ALD among drinkers including ALI, AC, and HCC. Studies are needed to clarify association of PNPLA3 polymorphism and steatosis in alcoholics. PNPLA3 gene may potentially be a therapeutic target in ALD

Lean non-alcoholic fatty liver disease patients from the global NASH registry

Background and aims: Although vast majority of patients with NAFLD are overweight and obese, NAFLD can be seen among lean individuals. The aim was to assess prevalence of lean NAFLD in different regions of the world. Method: The Global NASH Registry enrolled patients with an established diagnosis of NAFLD from real-world practices in 18 countries (Australia, China, Cuba, Egypt, Greece, Hong Kong, India, Italy, Japan, Saudi Arabia, Malaysia, Mexico, Pakistan, Russia, Spain, Taiwan, Turkey, USA) in 6 out of 7 Global Burden of Disease (GBD) super-regions. Clinical and patient-reported outcomes (PRO) data (CLDQ-NASH, FACIT-F,WPAI) were collected. Lean NAFLD was defined as NAFLD in patients with BMI/m2, or 23 kg/m2 for patients of East Asian origin. Results: There were 6096 NAFLD patients included (as of November 10, 2021): 48% from High-Income super-region, 24% Middle East and North Africa (MENA), 12% Southeast Asia, 7% Latin America, 6% from Eastern Europe and Central Asia, and 3% South Asia super-region. Of these, 7.3% were lean. The rates of lean NAFLD were the highest in Southeast Asia (12%) and South Asia (31%), the lowest in Eastern Europe and Central Asia ( Conclusion: Lean NAFLD patients seen in real-world practices across the world have different clinical and PRO profiles in comparison to NAFLD patients who are overweight or obese

The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term “fatty liver disease” with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients’ self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers’ perception may not adequately reflect patients’ perspective and experience with the disease