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The COVID-19 pandemic is having substantial impacts on the health status of individuals with alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). AUD and ALD have both been impacted throughout the pandemic, with increases in alcohol use during the early stages of the pandemic, reduced access to treatment during the mid-pandemic, and challenges in managing the downstream effects in the post-COVID era. This review will focus on how the COVID-19 pandemic has impacted AUD and ALD epidemiology and access to treatment, and will discuss to address this rising AUD and ALD disease burden. [ABSTRACT FROM AUTHOR]

Conflicting data exist on the impact of alcohol use on risk of liver disease progression in patients with steatotic liver disease. We aimed to evaluate the effect of longitudinal alcohol use on risk of cirrhosis among veterans with steatotic liver disease. US veterans with steatotic liver disease were identified from January 2010 through December 2022. Alcohol use was assessed using documented Alcohol Use Disorders Identification Test-Concise (AUDIT-C) scores and categorized as no alcohol (AUDIT-C = 0), low-risk alcohol use (AUDIT-C 1–2 for women and 1–3 for men), and high-risk alcohol (AUDIT-C ≥ 3 for women and ≥ 4 for men). Incidence of cirrhosis was evaluated with competing risks Nelson-Aalen methods. Adjusted multivariable regression models evaluated risks of cirrhosis associated with baseline alcohol use and changes in alcohol use during follow-up. There were 1,156,189 veterans with steatotic liver disease identified (54.2% no alcohol, 34.6% low-risk alcohol, and 11.2% high-risk alcohol). Veterans with steatotic liver disease and high-risk alcohol have a 43% higher incidence of cirrhosis compared with patients reporting no alcohol use. Compared with patients with baseline high-risk alcohol who reported no change in alcohol use, those who decreased their alcohol use during follow-up experienced a 39% reduction in long-term risk of cirrhosis (hazard ratio, 0.61; 95% CI, 0.45–0.83; P <.01). One in 9 veterans with steatotic liver disease report concurrent high-risk alcohol use, which is associated with 43% greater risk of cirrhosis compared with no alcohol use. However, reducing alcohol use lowers risk of cirrhosis, emphasizing the importance of timely alcohol use assessment and early interventions to address high-risk alcohol use in steatotic liver disease. [Display omitted] High-risk alcohol use in adults with steatotic liver disease increases the risk of liver disease progression. Timely alcohol use assessment and early interventions to address high-risk alcohol use are critical, particularly in patients with steatotic liver disease. [ABSTRACT FROM AUTHOR]

With the availability of direct acting antivirals (DAA) for hepatitis C virus (HCV) infection, alcoholic liver disease (ALD) has evolved as the leading indication for listing and receipt of liver transplantation (LT) followed by non-alcoholic steatohepatitis and HCV infection. However, data are limited on etiology specific trends on listings and need for LT for hepatocellular carcinoma (HCC). We analyzed UNOS database to examine etiology specific listings and receipt of LT for patients with and without HCC. Listings and receipt of LT in the pre-DAA (2007–2012) era were compared to the DAA (2013–2018) era. The analysis shows that among patients without HCV, there is a decreasing trend on the proportion of patients listed and transplanted for HCV, with simultaneous increase on listings and LT for NASH and ALD. Specifically for listings and transplants for HCC, the leading etiology remains HCV infection followed by NASH and ALD. The analysis also showed that LT for AH contributes to about 20% of increase in listings and receipt of LT for ALD. [ABSTRACT FROM AUTHOR]

Alcoholic hepatitis (AH) is a unique clinical syndrome that affects patients with chronic and active harmful alcohol consumption, and is associated with a high mortality of up to 40% at 1 month from presentation. It is important to assess disease severity and prognosis at time of presentation to identify patients at risk for high mortality and potential candidates for specific therapies. The cornerstone therapy for AH is enteral nutrition and abstinence. Steroids remain the only pharmacological option for severe AH however, adverse effects and lack of long-term benefit limit their routine use. Early liver transplantation is a potential salvage therapy for select severe AH patients. This review article comprehensively covers recent advances on the clinical unmet needs in the field including newer therapies and therapeutic targets, role of liver transplantation, and emerging biomarkers throughout the disease process from diagnosis, assessing prognosis and disease severity, and predicting responsiveness to medical therapies for severe AH. [ABSTRACT FROM AUTHOR]

Globally, nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. We assessed the clinical presentation and patient-reported outcomes (PROs) among NAFLD patients from different countries. Clinical, laboratory, and PRO data (Chronic Liver Disease Questionnaire–nonalcoholic steatohepatitis [NASH], Functional Assessment of Chronic Illness Therapy–Fatigue, and the Work Productivity and Activity Index) were collected from NAFLD patients seen in real-world practices and enrolled in the Global NAFLD/NASH Registry encompassing 18 countries in 6 global burden of disease super-regions. Across the global burden of disease super-regions, NAFLD patients (n = 5691) were oldest in Latin America and Eastern Europe and youngest in South Asia. Most men were enrolled at the Southeast and South Asia sites. Latin America and South Asia had the highest employment rates (>60%). Rates of cirrhosis varied (12%–21%), and were highest in North Africa/Middle East and Eastern Europe. Rates of metabolic syndrome components varied: 20% to 25% in South Asia and 60% to 80% in Eastern Europe. Chronic Liver Disease Questionnaire–NASH and Functional Assessment of Chronic Illness Therapy–Fatigue PRO scores were lower in NAFLD patients than general population norms (all P <.001). Across the super-regions, the lowest PRO scores were seen in Eastern Europe and North Africa/Middle East. In multivariate analysis adjusted for enrollment region, independent predictors of lower PRO scores included younger age, women, and nonhepatic comorbidities including fatigue (P <.01). Patients whose fatigue scores improved over time experienced a substantial PRO improvement. Nearly 8% of Global NAFLD/NASH Registry patients had a lean body mass index, with fewer metabolic syndrome components, fewer comorbidities, less cirrhosis, and significantly better PRO scores (P <.01). NAFLD patients seen in real-world practices in different countries experience a high comorbidity burden and impaired quality of life. Future research using global data will enable more precise management and treatment strategies for these patients. [ABSTRACT FROM AUTHOR]

Mesenteric vein thrombosis is increasingly recognized as a cause of mesenteric ischemia. Acute thrombosis commonly presents with abdominal pain and chronic type with features of portal hypertension. Contrast enhanced CT scan of abdomen is quite accurate for diagnosing and differentiating two types of mesenteric venous thrombosis. Prothrombotic state, hematological malignancy, and local abdominal inflammatory conditions are common predisposing conditions. Over the last decade, JAK-2 (janus kinase 2) mutation has emerged as an accurate biomarker for diagnosis of myeloproliferative neoplasm, an important cause for mesenteric venous thrombosis. Anticoagulation is the treatment of choice for acute mesenteric venous thrombosis. Thrombolysis using systemic or transcatheter route is another option. Patients with peritoneal signs or refractory to initial measures require surgical exploration. Increasing recognition of mesenteric venous thrombosis and use of anticoagulation for treatment has resulted in reduction in the need for surgery with improvement in survival. [ABSTRACT FROM AUTHOR]

Alcoholic hepatitis is a distinct clinical syndrome among people with chronic and active alcohol abuse, with a potential for 30%–40% mortality at 1 month among those with severe disease. Corticosteroids or pentoxifylline are the current pharmacologic treatment options, but they provide only about 50% survival benefit. These agents are recommended for patients with modified discriminant function (mDF) ≥32 or Model for End-Stage Liver Disease score ≥18. The Lille score is used to determine response to steroids. Currently, a minimum of 6 months of abstinence from alcohol use is required for patients to receive a liver transplant, a requirement that cannot be met by patients with severe alcoholic hepatitis nonresponsive to steroids (Lille score ≥0.45). Data are emerging on the benefit of liver transplantation in select patients with first episode of severe alcoholic hepatitis. This review also focuses on recent treatment trials in alcoholic hepatitis including liver transplantation and its associated controversies, as well as possible future targets and pharmacologic treatment options for patients with alcoholic hepatitis that are being pursued through upcoming consortium studies. [Copyright &y& Elsevier]

Model for end-stage liver disease (MELD) score, initially developed to predict survival following transjugular intrahepatic portosystemic shunt was subsequently found to be accurate predictor of mortality amongst patents with end-stage liver disease. Since 2002, MELD score using 3 objective variables (serum bilirubin, serum creatinine, and institutional normalized ratio) has been used worldwide for listing and transplanting patients with end-stage liver disease allowing transplanting sicker patients first irrespective of the wait time on the list. MELD score has also been shown to be accurate predictor of survival amongst patients with alcoholic hepatitis, following variceal hemorrhage, infections in cirrhosis, after surgery in patients with cirrhosis including liver resection, trauma, and hepatorenal syndrome (HRS). Although, MELD score is closest to the ideal score, there are some limitations including its inaccuracy in predicting survival in 15–20% cases. Over the last decade, many efforts have been made to further improve and refine MELD score. Until, a better score is developed, liver allocation would continue based on the currently used MELD score. [Copyright &y& Elsevier]

Background & Aims: Porphyria cutanea tarda (PCT) is an iron-related disorder caused by reduced activity of hepatic uroporphyrinogen decarboxylase; it can be treated by phlebotomy or low doses of hydroxychloroquine. We performed a prospective pilot study to compare the efficacy and safety of these therapies. Methods: We analyzed data from 48 consecutive patients with well-documented PCT to characterize susceptibility factors; patients were treated with phlebotomy (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low-dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month after they had normal plasma levels of porphyrin). We compared the time required to achieve a normal plasma porphyrin concentration (remission, the primary outcome) for 17 patients treated with phlebotomy and 13 treated with hydroxychloroquine. Results: The time to remission was a median 6.9 months for patients who received phlebotomy and 6.1 months for patients treated with hydroxychloroquine treatment (6.7 and 6.5 mo for randomized patients), a difference that was not significant (log-rank, P = .06 and P = .95, respectively). The sample size was insufficient to confirm noninferiority of hydroxychloroquine treatment (hazard ratio, 2.19; 95% confidence interval, 0.95–5.06) for all patients. Patients who received hydroxychloroquine had substantially better compliance. There were no significant side effects of either treatment. Conclusions: Hydroxychloroquine, 100 mg twice weekly, is as effective and safe as phlebotomy in patients with PCT, although noninferiority was not established. Given these results, higher-dose regimens of hydroxychloroquine, which have more side effects, do not seem justified. Compliance was better and projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long-term studies are needed to compare durability of response. ClinicalTrials.gov number, NCT01573754. [ABSTRACT FROM AUTHOR]

Background: PEG/jejunostomy (PEG/J) is often placed in patients with metastatic gastric cancer for palliating bowel obstruction or for feeding. However, PEG/J placement may not always be possible for many reasons. Objective: We wish to bring attention to the percutaneous transesophageal gastrostomy/jejunostomy (PTEG/J) as a viable alternative to nasogastric decompression in patients who are not candidates for PEG/J. PTEG/J is a largely unknown technique in the United States that designed to gain access to the stomach and proximal small bowel in these patients. We describe the use of PTEG/J in 3 patients with metastatic gastric cancer by using resources and techniques readily available in a well-stocked interventional radiology suite. Patients: In the first case, percutaneous transesophageal gastrostomy (PTEG) was placed for palliation of intractable nausea and vomiting in a 37-year-woman with diffuse gastric cancer and peritoneal carcinomatosis. In the second case, PTEG was extended into the jejunum for feeding a 60-year-old woman with metastatic gastric cancer. In the third case, PTEG extending into the jejunum was placed in a 69-year-old man for palliation of bowel obstruction caused by metastatic gastric cancer and peritoneal carcinomatosis. Methods: After adequate sedation is administered, a 22 × 4-mm balloon catheter is passed into the esophagus over a guidewire just below the thoracic inlet. The balloon is ruptured with a needle passed through the neck under US guidance. A guidewire is then passed through the needle into the balloon and carried into the stomach or proximal small bowel by advancing the balloon catheter. The track is then dilated over the guidewire and a pigtail 45-cm-long 14F nephrostomy tube then passed into the stomach or into the proximal small bowel over the guidewire. The catheter is secured by suturing to the skin of the neck. Results: PTEG/J was effective in achieving palliation or feeding in our patients. No complications occurred. Conclusions: PTEG/J is a safe and effective alternative to standard percutaneous gastrostomy/jejunostomy tube placement for decompression of bowel obstruction or feeding in appropriately selected patients. [Copyright &y& Elsevier]

Background & Aims: The effects of antiviral therapy on prevention of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related cirrhosis are unclear. We performed a systematic review and meta-analysis to assess HCC risk reduction in patients with HCV-related cirrhosis who have received antiviral therapy. Methods: Twenty studies (4700 patients) were analyzed that compared untreated patients with those given interferon (IFN) alone or ribavirin. Risk ratios (RRs) determined effect size using a random effects model. Results: Pooled data showed reduced HCC risk in the treatment group (RR, 0.43; 95% confidence interval [CI], 0.33–0.56), although the data were heterogenous (χ2 = 59.10). Meta-regression analysis showed that studies with follow-up durations of more than 5 years contributed to heterogeneity. Analysis of 14 studies (n = 3310) reporting sustained virologic response (SVR) rates with antiviral treatment showed reduced HCC risk in patients with an SVR, compared with nonresponders (RR, 0.35; 95% CI, 0.26–0.46); the maximum benefits were observed in patients treated with ribavirin-based regimens (RR, 0.25; 95% CI, 0.14–0.46). Meta-analysis of 4 studies assessing the role of maintenance IFN in nonresponders did not show HCC risk reduction (RR, 0.58; 95% CI, 0.33–1.03). No publication bias was detected by the Egger test analysis (P > 0.1). Conclusions: The risk of HCC is reduced among patients with HCV who achieve an SVR with antiviral therapy. Maintenance therapy with IFN does not reduce HCC risk among patients who do not respond to initial therapy. View this article''s video abstract at www.cghjournal.org . [Copyright &y& Elsevier]

While abstinence-promoting behavioral and pharmacotherapies are part of the therapeutic foundation for alcohol use disorder (AUD) and alcohol-associated liver disease (ALD), these therapies, along with alcohol screening and education, are often underutilized. Our aim was to examine provider attitudes and practices for alcohol screening, treatment and education in patients with liver disease. We conducted a survey of primarily (89%) hepatology and gastroenterology providers within (80%) and outside the United States (20%). Surveys were sent to 921 providers with 408 complete responses (44%), of whom 343 (80%) work in a tertiary liver transplant center. While alcohol screening rates in liver disease patients was nearly universal, less than half of providers reported practicing with integrated addiction providers, using alcohol biomarkers and screening tools. Safe alcohol use by liver disease patients was felt to exist by 40% of providers. While 60% of providers reported referring AUD patients for behavioral therapy, 71% never prescribed AUD pharmacotherapy due to low comfort (84%). Most providers (77%) reported low addiction education and 90% desired more during GI/hepatology fellowship training. Amongst prescribers, baclofen was preferred, but with gaps in pharmacotherapy knowledge. Overall, there was low adherence to the 2019 AASLD practice guidance for ALD, although higher in hepatologists and experienced providers. While our survey of hepatology and gastroenterology providers demonstrated higher rates of alcohol screening and referrals for behavioral therapy, we found low rates of prescribing AUD pharmacotherapy due to knowledge gaps from insufficient education. Further studies are needed to assess interventions to improve provider alignment with best practices for treating patients with AUD and ALD. [Display omitted] [ABSTRACT FROM AUTHOR]

We aimed to synthesize evidence for most effective treatments for minimal hepatic encephalopathy (HE) and prevention of overt HE in patients with cirrhosis. We performed a systematic search of the PubMed, EMBASE, OvidSP, and Cochrane Central Register of Controlled Trials databases through July 26, 2018, for randomized controlled trials evaluating treatments for minimal HE in patients with cirrhosis, with primary outcomes of reversal of minimal HE or prevention of overt HE. We conducted a meta-analysis and then used network meta-analysis and surface under cumulated ranking (SUCRA) to pool the direct and indirect estimates and rank the different treatments. We appraised study quality using the Grading of Recommendations Assessment, Development and Evaluation system. Our meta-analysis and network meta-analysis included 25 trials, comprising 1563 participants. Agents found to be effective in reversing minimal HE compared with placebo or no treatment included rifaximin (odds ratio [OR], 7.53; 95% predictive interval [PrI], 4.45–12.73; SUCRA, 89.2%; moderate quality), lactulose (OR, 5.39; 95% PrI, 3.60–8.0; SUCRA, 67.2%; moderate quality), the combination of probiotics and lactulose (OR, 4.66; 95% PrI, 1.90–11.39; SUCRA, 52.4%; low quality), L-ornithine L-aspartate (OR, 4.45; 95% PrI, 2.67–7.42; SUCRA, 47.2%; low moderate quality), and probiotics (OR, 3.89; 95% PrI, 2.52–6.02; SUCRA, 34.1%; low quality). Agents found to be effective in preventing episodes of overt HE compared with placebo or no treatment included L-ornithine L-aspartate (OR, 0.19; 95% PrI, 0.04–0.91; SUCRA, 75.1%; high moderate quality), lactulose (OR, 0.22; 95% PrI, 0.09–0.52; SUCRA, 73.9%; moderate quality), and probiotics (OR, 0.27; 95% PrI, 0.11–0.62; SUCRA, 59.6%; low quality). In a meta-analysis of data from 25 trials, we found rifaximin and lactulose to be most effective for reversal of minimal HE in patients with cirrhosis. L-ornithine L-aspartate and lactulose are most effective in the prevention of overt HE. Lactulose was the only agent that was effective in reversing minimal HE, preventing overt HE, reducing ammonia, and improving quality of life, with tolerable adverse effects. International prospective register of systematic reviews ID: 107003. [ABSTRACT FROM AUTHOR]