Heroin Epidemic Causing Surge in Hepatitis C Infections

From NPR: Heroin Epidemic is Driving a Spike in Hepatitis C Cases

An excerpt:

The number of new Hepatitis C cases leaped nearly 300 percent from 2010 to 2015, according to a report released Thursday by the Centers for Disease Control and Prevention. And the CDC points to the likely culprit behind the spike in cases of the infectious disease: the use of heroin and other injection drugs.

And despite the existence of therapies that can cure more than 90 percent of infections, the organization says the disease remains a deadly threat. In 2013, for instance, the CDC says some 19,000 people died of their infections.

From CNN: New Hepatitis C Infections Triple due to Opioid Epidemic

The number of new nationally reported infections with the virus swelled from 850 in 2010 to 2,436 cases in 2015, with the highest rates among young people, mainly 20- to 29-year-olds, who inject drugs, according to a new report released Thursday by the Centers for Disease Control and Prevention.

Take Two: 1. Mushroom Poisoning 2. Maternal Deaths with Childbirth

The link to the NPR article at the bottom of this blog is highly recommended –though it is a fairly long report.  Sad story for Mother’s Day.

First, from AGA blog summary of recent article: Which Patients Are at Greatest Risk From Mushroom Poisoining

An excerpt:

Maurizio Bonacini et al collected data from 27 patients (15–82 years old) admitted to the emergency department within 24 hours of ingesting wild mushrooms. All presented with nausea, vomiting, abdominal cramps or pain, and diarrhea…

Twenty-three patients survived without liver transplantation, 1 woman underwent liver transplantation on day 20 after mushroom ingestion, and 3 women died of hepatic failure.

Of the 23 patients with peak levels of total bilirubin of 2 mg/dL or more during hospitalization, 4 died or required liver transplantation.

A peak serum level of AST <4000 IU/L identified patients with good outcomes (survival without need for liver transplant) with 100% positive predictive value; use of this cutoff would have saved 10 patients from a transfer to our tertiary center.

Bonacini et al also found that a peak INR value of <2, or a nadir factor V cutoff ≥30%, would have avoided transfer for 7 and 6 patients, respectively.

Also from NPR: Focus on Infants Leaves U.S. Moms in danger

Increasing Incidence of Hepatocellular Carcinoma in the U.S.

A recent study (DL White et al. Gastroenterol 2017; 152: 812-20) provide data showing a striking increase in the incidence of hepatocellular carcinoma (HCC). Using data from the US Cancer Statistics Registry which covers 97% of U.S. population, the authors found the following:

  • HCC incidence rose from 4.4 per 100,000 in 2000 to 6.7 per 100,000 in 2012
  • The annual rate of increase was 4.5% from 2000-2009, but then 0.7% annually from 2010-2012
  • The greatest increase occurred in 55-59 year olds (8.9% annually) and 60-64 year olds (6.4% annually)

The main HCC risk factors are HCV, HBV, and alcoholic liver disease, though obesity-associated HCC is emerging as an important risk factor as well.  The highest rates of HCC are seen in southern and western states, with Texas having the highest rates overall.  The high rate in Texas is in part due to the higher rates of HCC in Hispanics.

Overall, the authors indicate that the rising HCC rates are most closely tied to the peak HCV cohort (1945-65) and speculate that the arrival of direct-acting antivirals may help. At the same time, this HCV cohort is composed “disproportionately [of] minorities and of lower socioeconomic status” and may have less access to these advances in treatment.  Furthermore, in states like Texas which did not adopt Medicaid expansion as part of the Affordable Care Act, there are more uninsured patients who will be less likely to identify preceding risk factors for HCC.

My take: Perhaps in 20 years, we will see HCC incidence maps that are improving as HCV treatments become more widely available.  This presumes that other HCC risk factors, including obesity and alcohol, do not worsen significantly.

Related blog posts:

Opioid Use and Liver Transplantation Outcomes

Not surprisingly, a recent study (HB Randall et al. Liver Transplantation 2017; 23: 305-14) has found that use of opioid medications prior to liver transplantation (LT) increased mortality over 5 years after transplantation.

This retrospective cohort study with data from nearly 30,000 patients correlated outcomes with pre-LT opioid exposure.  Overall, 9.3% of recipients filled opioid prescriptions while on the waiting list. Adjusted hazard ratios for death were 1.28 and 1.52 respectively for opioid use of level 3 and level 4.

In the associated editorial (pg 285-7), the authors note that animal models have shown direct hepatotoxic effects of opioid use, though they speculate that the driver for mortality could be due to “sustained opioid use over time or return to illicit drug use.”

A unrelated commentary by CDC director Tom Frieden (AJC “Protect Ga. families from opioid overdose”, March 18, 2018) explains the scope of the opioid epidemic.  “Since 2000, more than 300,000 of our sons, daughters, brothers, sisters, mothers, fathers, and friends have been killed by opiates.  In 19999, approximately 6,000 Americans died from opiate overdose –including both prescription pain medicines … and heroin.  By 2015 that number increased to more than 33,000.”  This is more than a five-fold increase.

He emphasized that opiates serve as a gateway drug for those addicted to heroin; that is, the majority of those hooked on heroin were started on an opioid medication.

My take: The worsened outcomes of LT due to opioids are unfortunately a tiny part of an enormous tragic problem of the opioid epidemic.

Related posts:

Word of Caution with New Hepatitis C Medications

From NY Times: Are New Drugs for Hepatitis C Safe? A Report Raises Concerns

An excerpt:

Drugs approved in recent years that can cure hepatitis C may have severe side effects, including liver failure, a new report suggests. The number of adverse events appears relatively small, and the findings are not conclusive. But experts said the report was a warning that should not be ignored…

The report will be published online on Wednesday [1/25/17] by the Institute for Safe Medication Practices, a nonprofit in Horsham, Pa., that studies drug safety. Its findings are based on the group’s analysis of the Food and Drug Administration’s database of reports from doctors around the world of adverse events that might be related to medications.

In October, the F.D.A. identified the first major safety problem caused by the nine antiviral drugs. In 24 patients, the drugs wiped out hepatitis C — but also reactivated hepatitis B infections that had been dormant. Two of those patients died, and one needed a liver transplant. The agency said there were probably additional cases that had not been reported.

As a result, the agency required that a boxed warning, its most prominent advisory, be added to the labeling of the newer antivirals, telling doctors to screen and monitor for hepatitis B in all patients taking the drugs for hepatitis C. Infection with both viruses is not common, and how the reactivation occurs is not known. The problem was not detected during premarket testing of the drugs because patients who currently had hepatitis B or who had a history of it were not allowed into the studies…

The other cases of liver failure are a separate problem. He said it was important for doctors prescribing the newer drugs to test patients’ liver function thoroughly first, because liver disease can be deceptive

My take: Overall, these newer Hepatitis C medications represent a tremendous achievement.  However, as with most medications, rare serious problems can occur and in some cases may be preventable.

Related blog posts:

From Twitter Feed-Funny Church Signs

From Twitter Feed-Funny Church Signs

Liver Briefs Feb 2017

JB Schwimmer et al. Gastroenterol 2016; 151: 1141-54.  Using a double-masked trial with 169 children with NAFLD, the use of cysteamine bitartrate for 1 year did not reduce histologic activity scores, but did reduce liver aminotransferase levels.

NA Terrault et al. Gastroenterol 2016; 151: 1131-40. The authors collected data from 2099 participants in the HCV-TARGET study who mainly received ledpasvir-sofosbuvir (311 received therapy in combination with ribavirin).  The study included 25% blacks, 66% with genotype 1A, 41% with cirrhosis, 50% with prior treatment, and 30% who were receiving proton pump therapy.  Key finding: SVR12 rates varied from 95% to 97% based on duration of therapy.  Factors that predicted SVR12 included higher albumin (>3.5 g/dL), lower total bilirubin (<1.2), absence of cirrhosis, absence of proton pump inhibitor therapy.

KR Olson et al. NEJM 2017; 376: 268-78.  This case report of an 18 yo woman with acute liver failure provides a helpful review.  For Wilson’s disease, the article reviews rapid diagnostic criteria: “a screen that shows a ratio of alkaline phosphatase (IU per liter) to total bilirubin (mg per deciliter) of lower than 4.0 and then subsequently shows a ratio of aspartate aminotransferase (IU per liter) to alanine aminotransferase (IU per liter) of higher than 2.2 has been described as 100% sensitive and specific for the diagnosis of Wilson’s disease.”  Making this diagnosis quickly is crucial and allows these patients to be UNOS status 1A, “the only cause of acute liver faliure that allows a patient with preexisting liver disease to be listed as status 1A”

Among children older than 10 years of age, Wilson's disease accounted for 90% of metabolic disease.

Among children older than 10 years of age, Wilson’s disease accounted for 90% of metabolic disease.

Cholecardia

An interesting study (MS Desai et al. Hepatology 2017; 65: 189-201) examines the effect of excess bile acids on the heart.  The abstract is listed below -I’ve highlighted what I find fascinating:

Cardiac dysfunction in patients with liver cirrhosis is strongly associated with increased serum bile acid concentrations. Here we show that excess bile acids decrease fatty acid oxidation in cardiomyocytes and can cause heart dysfunction, a cardiac syndrome that we term cholecardia. Farnesoid X receptor; Small Heterodimer Partner double knockout mice, a model for bile acid overload, display cardiac hypertrophy, bradycardia, and exercise intolerance. In addition, double knockout mice exhibit an impaired cardiac response to catecholamine challenge. Consistent with this decreased cardiac function, we show that elevated serum bile acids reduce cardiac fatty acid oxidation both in vivo and ex vivo. We find that increased bile acid levels suppress expression of proliferator-activated receptor-γ coactivator 1α, a key regulator of fatty acid metabolism, and that proliferator-activated receptor-γ coactivator 1α overexpression in cardiac cells was able to rescue the bile acid-mediated reduction in fatty acid oxidation genes. Importantly, intestinal bile acid sequestration with cholestyramine was sufficient to reverse the observed heart dysfunction in the double knockout mice.

CONCLUSIONS:

Decreased proliferator-activated receptor-γ coactivator 1α expression contributes to the metabolic dysfunction in cholecardia so that reducing serum bile acid concentrations may be beneficial against the metabolic and pathological changes in the heart.

My take: There are a lot of reasons why having elevated bile acids is not a good thing. This study provides good evidence that these bile acids have specific cardiac toxicity.

Cozumel

Cozumel