Updated Health Warnings Needed For Alcohol & More on COVID-19/Paxlovid

AH Grummon, MG Hall. NEJM 2022; 387: 772-774. Updated Health Warnings for Alcohol — Informing Consumers and Reducing Harm

This article makes a compelling case that most U.S. consumers do not know the true risks of alcohol intake; this is likely in part due to the >$1 billion spent each year on marketing by the alcohol industry.

Leading causes of alcohol-related harms:

  • Fatal and nonfatal injuries resulting from acute intoxication (including injuries caused by motor vehicle crashes)
  • Chronic diseases including hypertensive heart disease, cirrhosis, pancreatitis and several types of cancer.2 Even light or moderate drinking increases the risk of these conditions, particularly cancer (eg. breast, colon, and stomach)2
  • Risks during pregnancy include miscarriage, preterm birth, and fetal alcohol syndrome (these risks are not specifically addressed in this commentary)
  • Also not noted in this article, alcohol is considered a major contributor to violence, including intimate partner violence

Key points –Scope of Problem and Informing Consumers:

  • “In April 2022, the Centers for Disease Control and Prevention (CDC) released new mortality statistics showing that alcohol consumption now accounts for more than 140,000 deaths per year in the United States, or more than 380 deaths per day. The Covid-19 pandemic has exacerbated alcohol-associated harm in the United States, with alcohol-related deaths increasing by 25% during the first year of the pandemic as compared with the previous year”(White AM, Castle IP, Powell PA, Hingson RW, Koob GF. Alcohol-related deaths during the Covid-19 pandemic. JAMA 2022;327:1704-1706).
  • “A national survey of U.S. adults, for example, found that nearly 70% are unaware that alcohol consumption increases the risk of cancer.3…Some alcohol companies even seek to link their products to health campaigns. Several companies, for example, have sold seasonal, pink ribbon–themed alcoholic drinks during October to promote their efforts to raise funds for breast-cancer research — despite compelling evidence that alcohol increases the risk of developing breast cancer.”
  • The authors advocate for better warning labels. They argue that “updated alcohol warnings would provide new risk information to many Americans, … implementing such warnings would be a sensible policy for addressing industry dominance over alcohol-related information, even if warnings’ effects on consumption are fairly small.”

Related article: NBC News 11/4/22: Alcohol deaths spiked among middle-aged adults, especially women, during pandemic “Alcohol-related deaths rose by 26% from 2019 to 2020, a new report published Friday by the Centers for Disease Control and Prevention finds.”

Related blog post:

More on COVID-19:

Eric Topol: Paxlovid and Long Covid This in-depth article reviews the benefits of paxlovid (early) and later, including the reduction of Long Covid in 26% in a recent study. It also provides a table for potential drug interactions (Thanks to Jeff Lewis for sharing).

This recent study is reviewed in NY Times (11/7/22): Paxlovid May Reduce Risk of Long Covid in Eligible Patients, Study Finds

Leaning Tower of Niles (1934) (near Chicago, IL). The “Papa Chris Place” sign should help distinguish this landmark for the one in Pisa.

Dietary Therapy for Adults with Crohn’s Disease

H Yanai et al. The Lancet 2021; The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomised trial https://doi.org/10.1016/S2468-1253(21)00299-5

In this open-label trial of adults with mild-to-moderate biologic naive Crohn’s disease, key findings:

  • At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618)
  • Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group)
  • 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group)

My take: Dietary therapy may be effective option for motivated adult patients with Crohn’s disease.

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Alcohol -More Deadly Than Opioids

NPR: U.S. Alcohol-Related Deaths Have Doubled, Study Says

An excerpt:

Death certificates spanning 2017 indicate nearly 73,000 people died in the U.S because of liver disease and other alcohol-related illnesses. That is up from just under 36,000 deaths in 1999…

Overall, researchers found men died at a higher rate than women. But when analyzing annual increases in deaths, the largest increase was among white women…

Only cigarettes are deadlier than alcohol: More than 480,000 people die each year in the U.S. because of smoking-related illnesses.

Related blog post:

Liver Shorts Feb 2019

ZM Younossi et al. Hepatology 2019; 69: 564-72. This study, using Markov models for nonalcoholic steatohepatitis (NASH), estimated that there are 6.65 million adults with NASH in the U.S. and that lifetime costs will be $.222.6 billion.

Y Chang et al. Hepatology 2019; 69: 64-75.  This study with 58,927 Koreans with non-alcoholic fatty liver disease (NAFLD), found that nonheavy alcohol consumption was “significantly and independently associated with worsening of noninvasive markers of fibrosis, indicating that even moderate alcohol consumption might be harmful.”

Related blog posts:

KA Forde et al. Hepatology 2019; 69: 270-81.  This study examined screening for hepatopulmonary syndrome (HPS) in patients (n=363) evaluated for liver transplantation (LT). It found that pulse oximetry had low sensitivity for detecting HPS. Overall, 21% of the cohort had HPS. “We found that pulse oximetry essentially performed no better than chance (i.e.. a ‘coin flip’) in the discrimination of patients with HPS from all-comers.” 18% of patients with an SpO2 of 96% or higher had HPS. Based on their findings, the authors recommend that routine screening of LT candidates include ABG and contrast-enhanced echocardiograpy.

From Joshua Tree National Park..Gorgeous views from Ryan Mountain

Alcohol in the Setting of Non-alcoholic Fatty Liver Disease

Briefly noted: V Ajmera et al. Clin Gastroenterol Hepatol 2018; 16: 1511-20.  This study with 285 participants showed that modest alcohol consumption was associated with a lower odds of NASH resolution on biopsy over 4 years compared with no alcohol consumption (OR 0.32). The associated editorial (pg 1404-6) provides a table with 8 studies that reveal conflicting results on this issue.

My take (borrowed from editorial): “Clinicians should not recommend modest drinking” as a way of improving liver health.

Related review article:D Fuster, JH Samet. “Alcohol Use in Patients with Chronic Liver Disease”  NEJM 2018; 379: 1251-61. For NAFLD (and all chronic liver disease): “abstinence should be the goal.”

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Lake Moraine, Banff

Liver Shorts August 2018

M Yakoot et al. JPGN 2018; 67: 86-89. This prospective, open-label, unblinded study from Egypt indicated that 29 of 30 (96.7%) pediatric (12-17 yr) patients with HCV (genotype 4) attained an SVR12 with sofusbuvir/daclatasvir.  No serious adverse effects were evident.  The one patient who did not achieve SVR12 was lost to followup but had viral negativity after completing treatment.

Related blog post: New HCV Treatment Effective in Adolescents –Important Study Now Published Online

O El-Sherif, ZG Jiang et al. Gastroenterol 2018; 154: 2111-21. This study showed that a “BE3A Score” based on BMI <25, no Encephalopathy, no Ascites, Albumin >3.5 and ALT >60 IU/L could be used to discriminate the likelihood of reducing the Child-Pugh-Turcotte (CPT) score to class A in patients with hepatitis C virus-associated decompensated cirrhosis who received DAA therapy.  This retrospective  analysis was based on 4 trials of a sofusbuvir-therapy with 502 CPT class B and 120 CPT class C patients.

AH Ali et al. Hepatology 2018; 67: 2338-51.  This study convincingly shows that surveillance for hepatobiliary cancers improves outcomes in patients with primary sclerosing cholangitis.  Among their cohort of 830 patients (Mayo clinic), 79 developed malignancies.  Of those under surveillance (n=40), the 5-year survival was 68% compared to 20% for those who had not been under surveillance.  While the true cynic might ascribe some of the difference to ‘lead-time’ bias, this is unlikely to account for this difference at 5 years.

F Aberg et al. Hepatology 2018; 67: 2141-49.  This Finish-population prospective study, over an 11 year follow-up, using a nationally-representative cohort (n=6771) showed that even moderate alcohol consumption worsened outcomes (eg hepatic decompensation, hepatocellular carcinoma) in patients with nonalcoholic fatty liver disease.  In addition, the authors showed that diabetes the most significant predictor of poor outcome (HR 6.79). In a related commentary, pg 2072-73, the authors state that this article “put an end to the ongoing ddebate whether moderate alcohol drinking (less than 20 g of alcohol/day or 2 drinks per day) could be helpful.”

Legalized Cannabis Associated with Increased Vomiting and Dependency But What About Alcohol?

In politics, one hears a lot of “What about?”  If a problem is identified, many times a politician will try to divert the focus and/or justify a contentious issue to a related issue with a “what about” question. In medicine, when we see problems with marijuana, one could ask, ‘What about alcohol?’

A recent retrospective study (M Al-Shammari et al. Clin Gastroenterol Hepatol 2017; 15: 1876-81) found an increase in cannabis dependency unspecified (CDU) (ICD code) coinciding with the legalization of marijuana. Thanks to Seth Marcus for pointing out this study.

Key finding:

  • “We observed an increasing trend of CDU or an aggregate of CDU and persistent vomiting…the legalization of marijuana significantly increased the incidence rate during the legalization period (by 17.9%)…compared to the prelegalization period.

Related article: Aaron Carroll Alcohol or Marijuana? A Pediatrician Faces the Question

An excerpt:

The immediate answer, of course, is “neither.” …

The easy answer is to demonize marijuana. It’s illegal, after all. Moreover, its potential downsides are well known. Scans show that marijuana use is associated with potential changes in the brain. It’s associated with increases in the risk of psychosis. It may be associated with changes in lung function or long-term cancer risk, even though a growing body of evidence says that seems unlikely. It can harm memory, it’s associated with lower academic achievement, and its use is linked to less success later in life.

But these are all associations, not known causal pathways…

When I’m debating my answer, I think about health as well…Binge drinking accounted for about half of the more than 80,000 alcohol-related deaths in the United States in 2010, according to a 2012 report by the Centers for Disease Control and Prevention. The economic costs associated with excessive alcohol consumption in the United States were estimated to be about $225 billion. Binge drinking, defined as four or more drinks for women and five or more drinks for men on a single occasion, isn’t rare either. More than 17 percent of all people in the United States are binge drinkers, and more than 28 percent of people age 18 to 24…

Marijuana, on the other hand, kills almost no one…

I think about which is more dangerous when driving. A 2013 case-control study found that marijuana use increased the odds of being in a fatal crash by 83 percent. But adding alcohol to drug use increased the odds of a fatal crash by more than 2,200 percent. A more recent study found that, after controlling for various factors, a detectable amount of THC, the active ingredient in pot, in the blood did not increase the risk of accidents at all. Having a blood alcohol level of at least 0.05 percent, though, increased the odds of being in a crash by 575 percent…

 In 1995 alone, college students reported more than 460,000 alcohol-related incidents of violence in the United States… On the other hand, a 2014 study looking at marijuana use and intimate partner violence in the first nine years of marriage found that those who used marijuana had lower rates of such violence…

[Thus]  if I’m forced to make a choice, the answer is “marijuana.”

My take: While the cited study shows a correlation between cannaboid legalization with both CDU and increased vomiting, the commentary by Dr. Carroll helps provide context to the risks of marijuana use.  From a safety standpoint, the risks posed by alcohol appear much greater.

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Bright Angel Trail, Grand Canyon

Gut microbiome and endogenous alcohol

At first glance, it sounds like an ambitious project -develop a gut microbiome that produces alcohol.  It could obviate the need for “Duff” beer (Duff Beer – Wikipedia, the free encyclopedia).  Yet, a recent article has found that an altered microbiome with increased endogenous alcohol already exists and it is associated with nonalcoholic steatohepatitis (NASH) (Hepatology 2013; 57: 601-609).

In this study, the authors examined three pediatric populations: a healthy control group (n=16), obese group (n=25), and NASH group (n=22).  All NASH patients had undergone liver biopsy and met Kleiner’s criteria; in contrast, the obese group had normal LFTs.

Key study findings:

1. The microbiome from the obese and NASH patients were similar but had some striking differences compared with the control group patients (pie chart –Figure 2):

  • Bacteroidetes (including Bacteroides): 28.65% in healthy controls, 50.28% in obese, and 49.11% in NASH
  • Firmicutes (including Blautia and Faecalibacterium): 66.78% in healthy controls, 42.62% in obese, and 42.39% in NASH
  • Proteobacteria (including Escherichia): 0.87% in healthy controls, 3.13% in obese, and 6.03% in NASH

2. Elevated serum ethanol concentrations only in NASH population: ~26 μM in both control and obese groups compared with ~35 μM in NASH patients.

Under normal conditions, endogenous alcohol is produced in the human body and the intestinal microflora are the major source.  This gut-produced alcohol is quickly metabolized by the liver.  Due to similar histology between NASH patients and patients with alcoholic liver disease, it has been hypothesized that NASH patients may have elevated blood alcohol.  This study adds further evidence to this hypothesis and provides a potential mechanism; namely, increased bacteria like Escherichia and Bacteroides can increase endogenously-produced alcohol.

Will efforts to revert the microbiome to normal have therapeutic effects on NASH?  This important question will need to be addressed given the growing problem of fatty liver disease.

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