Screenshots: Peutz-Jeghers Syndrome, Alcohol #1 for Liver Transplantation, Case report Fanconi Syndrome due to Tenofovir Alafenamide

These images (S Sengupta, S Bose. NEJM 2019; 380: 472) show hyperpigmented macules on the lips, oral mucosa and nose in the first frame, a target sign on CT scan indicative of intussception, and a jejunal resection with polyps that triggered the intussception. Related blog post: Update for Peutz-Jegher Syndrome

Cirrhosis and Cardiac Function

Briefly noted: M Izzy, J Oh, KD Watt. Hepatology 2018; 68: 2008-2015.  This concise review discusses the outcome of cirrhotic cardiomyopathy after liver transplantation.

Key point: “Although it is often believed that cirrhotic cardiomyopathy resolves post-LT, the data, albeit limited, do not support this postulation…diastolic function may not improve post-transplant and may actually worsen. Improvement in systolic function was suggested by only two of six studies.”

Related blog post: Cholecardia

This figure from Hepatology November cover depicts a cirrhotic liver restricting the heart filling during diastole. (From Wiley Online Library -free access)

Which Diet is Best For a Fatty Liver?

A recent randomized controlled trial (C Properzi et al. Hepatology 2018; 68: 1741-54) compare the Mediterranean diet (MD) and a low-fat (LF) diet for non-alcoholic fatty liver disease.

A total of 48 patients completed the 12-week study and were analyzed; subjects had a mean BMI of 31.  Both groups consumed a 2400-2600 kcal diet.

Key findings:

  • Despite minimal weight loss, both groups had significant reduction in hepatic steatosis as determined by magnetic resonance spectroscopy (MRS): 25.0% in LF and 32.4% in MD.  Both had wide confidence intervals due to the small number of subjects.
  • Liver enzyme improved in both groups.
  • Weight loss was minimal, 1.6 kg and 2.1 kg in LF and MD respectively
  • Framingham Risk Score (FRS), cholesterol, triglycerides, and hemoglobin A1c were improved with MD but not with LF (all P<0.05)

The associated editorial (pg 1668-71) notes the following:

  • “Considering the current evidence, recommending the MD for patients with NAFLD might be an appropriate therapeutic option, not least because …[of the} increased risk of CVD.”
  • Longer-term RCTs are needed
  • “It has to be stressed that, in most cases, any form of healthy diet (eg. LF or MD), which leads to caloric reduction…should be encourage for patients with NAFLD…The importance of weight loss has been highlighted in patients with biopsy-proven NASH.”

My take: If you have to make a dietary recommendation, this study indicates that MD is probably a better diet than LF in patients with NAFLD.

Related blog posts:

Town of Banff

 

 

Finite Therapy with Oral Antivirals for Chronic Hepatitis B Infection

A recent study (WJ Jeng et al. Hepatology 2018; 68: 425-34) indicates that many patients with Hepatitis B e Antigen-Negative Chronic Hepatitis B benefit from a finite treatment with oral antivirals.

These findings are discussed by P Lampertico and T Berg (editorial 397-400). In the Jeng study, the investigators prospectively followed the effect of antiviral cessation in 691 individuals after patients had undetectable HBV DNA and met Asian Pacific Association for the Study of Liver guidelines for stopping.  HBsAg clearance occurred in 13% who discontinued therapy compared to 3% during nucleos(t)ide treatment.  The authors note that virologic relapse occurred in 79% and that the immune system activation driven by clinical relapse can be beneficial in yielding a cure.  Clinical decompensation was infrequent and most could be retreated; three patients with cirrhosis and decompensation died

My take: These studies show that in carefully-selected and carefully-monitored patients with HBeAg-negative chronic hepatitis B infection, it is feasible to successfully stop oral antiviral therapy.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

  • Near Banff

 

Does Screening for Hepatocellular Carcinoma Improve Outcomes in Patients with Cirrhosis?

Despite widespread recommendations to screen patients with cirrhosis for hepatocellular carcinoma (HCC), a recent study (AM Moon et al. Gastroenterol 2018; 16: 1777-85) found “No Association Between Screening for Hepatocellular Carcinoma and Reduced Cancer-Related Mortality in Patients with Cirrhosis.” The title of the study did not make sense to me based on previous publications that have noted increased risk of HCC in patients with cirrhosis and the presumption that screening would allow effective interventions to prevent death due to HCC.  So I looked at the study a little closer:

Background/Methods: The authors utilized a matched case-control study within the U.S. Veterans Affairs health care system to determine whether ultrasonography (US) or alpha-fetoprotein (AFP) screening was associated with decreased cancer-related mortality.

They identified 238 patients with cirrhosis who died of HCC between 2013-2015 –all of whom had a diagnosis of cirrhosis at least 4 years before the diagnosis of HCC.  Then, they matched them with a control patient with cirrhosis who did not have HCC and had been identified at least 4 years prior to matched case’s HCC.

Key findings:

  • There was no significant difference between the cases and the controls in the proportions who underwent screening:
  • For U/S screening: 52.9% cases and 54.2% for controls.
  • For AFP (serum) screening, 74.8% vs 73.5% respectively.
  • For either U/S or AFP screening, 81.1% vs 79.4%.
  • For both U/S and AFP screening, 46.6% vs 48.3% respectively.
  • Table 4 provides odds ratios and adjusted odds ratios for the cases compared to controls.  The Adjusted Odds ratios for U/S 0-4 years before index case was 0.95, for AFP 1.08, and for either U/S or AFP 1.11.

The authors found that HCC screening with U/S and/or AFP was not associated with decreased risk of HCC-related mortality.

In their study, the authors note that most studies on HCC screening have been observational which have numerous limitations including lead-time biases (which can overestimate the benefits of screening) and patient selection.  Two randomized controlled trials reached conflicting conclusions; these trials were conducted in China where HCC is mainly associated with hepatitis B infection.

The authors point out that liver societies like AASLD and EASL have recommended U/S every 6 months with or without AFP measurements for HCC surveillance in patients with cirrhosis.  However, non-liver societies have NOT “endorsed HCC screening because of the lack of high-quality data.”  Neither the US Preventive Services Task Force nor the American Cancer Society make recommendations for HCC screening.  And, “the National Cancer Institute found no evidence that screening decreases mortality from HCC but did find evidence that screening could result in harm.”

Strengths of this study:

  • All VA patients have access to medical care; this limits bias due to access to HCC screening
  • The matched-case control design with random controls across a system that delivers care to 8 million veterans across the country indicates that the findings are likely  “typical of community-based settings” and likely to yield “estimates of the impact of screening …[that] approximates the results that would be expected from a randomized controlled trial”

Why Have Previous Studies Indicated that HCC Screening is Worthwhile?

  • According to the authors, even though HCC detected by screening is on average detected at an earlier stage than those detected due to symptoms, “this does not prove that screening leads to earlier detection. Another explanation is that screening is more likely to identify slow-growing tumors, which have a lower stage, and more likely to miss the fast-growing tumors, which are identified at a higher stage by symptoms.”
  • “It is possible that the HCCs most likely to lead to death are the HCCs least likely to be identified by current screening modalities at an early stage.”
  • In addition,  “whether early treatment for HCC in patients with cirrhosis leads to a decrease in case fatality is questionable.”  Patients who receive surgical resection or locoregional treatments remain at risk for recurrent HCC, new HCC and progressive liver dysfunction.  While liver transplantation can cure HCC and cirrhosis, only a “small minority of patients with HCC undergo liver transplantation.”  In 2012, only 1,733 patients received liver transplantation for HCC out of a reported 24,696 incident cases.

My take: This study offers a lot of insight regarding HCC screening and questions its usefulness, though I doubt this study will change how most hepatologists practice.

Related blog posts:

Near Banff

 

Avatrombopag Reduces Need for Platelet Transfusion in Patients with Chronic Liver Disease

Briefly noted: N Terrault et al. Gastroenterol 2018; 155: 705-18. In two trials, ADAPT-1 and ADAPT-2, the use of avatrombopag, a thrombopoietin receptor agonist, was superior to placebo in increasing platelet counts and reducing need for platelet transfusion for bleeding related to procedures.

AbstractAvatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia

Genotyping Still Matters with Hepatitis C

A recent study (R Esteban et al. Gastroenterol 20018; 155: 1120-7) evaluated the efficacy of sofosbuvir and velpatasvir in patients with hepatitis C genotype 3.

Overall, the study shows good efficacy of this regimen with and without ribavirin, though with higher SVR12 and lower relapse with the addition of ribavirin.

The difference in response was driven almost entirely based on whether there were pretreatment NS5A resistance-associated substitutions (RASs) present.

  • In those with NS5A RASs the difference in response with added ribavirin compared to without was 96% vs 84%.
  • In those without NS5A RASs the difference in response with ribavirin compared to without was 99% vs. 96%.

My take:

  • If RAS testing is available and baseline Y93H is absent, then ribavirin is not likely needed
  • Genotyping is still important.  The associated editorial (pg 969-71) labeled genotype 3 ‘the problem child in the era of direct-acting antivirals.”   That is, there are still differences in treatment recommendations based on HCV genotype.

Related blog posts: