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

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DILI, DILI -Two Studies on Drug-Induced Liver Injury

A Benesic et al. Clin Gastroenterol Hepatol 2018; 16: 1488-94. This prospective study found that monocyte-derived hepatocyte-like (MH) cells isolated from patients could be used to test and identify drugs that triggered acute liver injury.  Among 40 patients, 13 patients had 10 drugs identified which were toxic to MH cells.  Overall, they reported the MH test as having a 92% sensitivity and 100% specificity.

I Medina-Caliz et al. Clin Gastroenterol Hepatol 2018; 16: 1495-1502. Using the Spanish DILI registry (1994-2016), the authors identified 32 of 856 cases of DILI that were due to dietary supplements.  Patients were more often female (63%), and had a mean ALT level 37-fold above ULN.  3 patients (9.4%) progressed to acute liver failure. Many of these supplements were promoted as helpful for weight loss. The authors speculate that reported cases of DILI due to herbal supplements are ‘the tip of the iceberg’ due to under-reporting of cases.

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Lake Moraine, Banff

HCV Treatment and “MELD Purgatory”

A recent study (A Kwong et al. Liver Transplantation 2018; 24: 735-43) and associated editorial (P Martin, pg 727-8) highlight an unintended consequence of HCV therapeutic success –“MELD purgatory.”

The study notes that with the availability of more effective direct-acting antivirals for HCV, there has been a decrease in wait-list mortality and a decrease in disease severity.  This was determined by reviewing 3 timed cohorts (2004 n=2408, 2009 n=2402, and 2014 n=2817) from the Organ Procurement and Transplantation database.

  • For example, the 2014 had a 21% lower risk of wait-list death (HR 0.79) than the 2009 cohort.  This is in contrast to other (non-HCV) disease in which there was no change in mortality.
  • Also, the MELD rate of change was 2.35 per year for the 2009 cohort compared to 1.90 for the 2014 group.
  • In their discussion, the authors note that while patients with HCV can achieve a sustained virologic response, those with advanced liver disease still need liver transplantation.  In these patient, there is a much lower prospect of attaining a high enough MELD score to receive organ offers –“leaving them with persistent complications and a decreased quality of life.”  This situation has been termed “MELD purgatory.”

The editorial notes that in the five years since the introduction of sofosbuvir, HCV has been displaced as the single commonest indication for liver transplantation by nonalcoholic fatty liver disease.  These agents have led to a decrease in advance HCV-related liver disease.  In addition, in the past, HCV infection had near universal recurrence after transplantation and this is no longer the situation.

My take: Undeniably, the advent of DAA have made a huge dent in progressive HCV liver disease. However, those with advanced liver disease may be stuck in a purgatory between good health and poor quality of life even after clearance of HCV infection.

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Interleukin 6 and Liver Disease Mortality

Briefly noted: J Remmler et al. Clin Gastroenterol Hepatol 2018; 16: 730-7.  This retrospective study with 474 patients showed that blood levels of interleukin 6 were associated with mortality.  In this cohort, those with levels in the lowest quartile (< 5.3 pg/mL) had zero fatalities within 1 year.  In those with the highest quartile (37 pg/mL or more), had a 67.7% mortality rate within 1 year.  The associated editorial (pg 630-32) notes that IL6 functions include liver regeneration, infection defense, and metabolic homeostasis.  “IL6 is synthesized during inflammatory conditions…persistent activation of the IL6 pathway may have detrimental effects in the livers and in other tissues.”

Pine Mountain Trail

New Treatment for Primary Biliary Cholangitis

Another treatment is emerging for biliary cholangitis (PBC):  C Corpechot et al (NEJM 2018; 378: 2171-81) shows that an inexpensive medication, bezafibrate, is effective in patients with PBC who have not responded adequately to ursodeoxycholic acid. An associated editorial (2234-35 by Elizabeth Carey) notes that this medication is not available in the U.S., though a similar medicine, fenofibrate “has shown similar efficacy” in PBC (off-label).

Comprehensive 2018 AASLD Guidance for Chronic Hepatitis B

NA Terrault et al. Hepatology 2018; 67: 1560-99. Here’s the full link: Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance

Some of the key points:

Table 4 (pg 1565): provides a refresher on interpretation of serology

Table 5 (pg 1567): Children and Adults Who Are HBsAg Positive:

  • Can participate in all activities, including contact sports
  • Should not be excluded from daycare or school participation and should not be isolated from other children
  • Can share food and utensils and kiss others

Figure 1 (pg 1571) Treatment algorithms.

  • For both HBsAg-positive/HBeAg-positive and HBsAg-positive/HBeAg-negative patients, treatment is recommended if ALT ≥2 x ULN.
  • For both groups, treatment is NOT recommended for those with ALT ≤ULN and low HBV DNA levels (<20,000 IU/mL for HBeAg-positive and <2,000 IU/mL for HBeAg-negative).
  • In those who do not fall into these categories, ongoing monitoring is recommended

Figure 1 from AASLD Guidance Link

Guidance Statements for HCC Screening in HBsAg‐Positive Persons

  • All HBsAg‐positive patients and high risk adults (see page 1574) with cirrhosis should be screened with US examination with or without AFP every 6 months.
  • There are insufficient data to identify high‐risk groups for HCC in children. However, it is reasonable to screen HBsAg‐positive children and adolescents with advanced fibrosis (F3) or cirrhosis and those with a first‐degree family member with HCC using US examination with or without AFP every 6 months.

Treatment: 

  • In adults: The AASLD recommends peg‐IFN, entecavir, or tenofovir (TDF) as preferred initial therapy for adults with immune‐active CHB
  • In children: The AASLD suggests antiviral therapy in HBeAg‐positive children (ages 2 to <18 years) with both elevated ALT and measurable HBV‐DNA levels, with the goal of achieving sustained HBeAg seroconversion.

Perinatal transmission:

  • The AASLD suggests antiviral therapy to reduce the risk of perinatal transmission of HBV in HBsAg‐positive pregnant women with an HBV‐DNA level >200,000 IU/mL..The only antivirals studied in pregnant women are lamivudine, telbivudine, and TDF. Of these 3 options, TDF is preferred to minimize the risk of emergence of viral resistance during treatment. Interim studies show high efficacy of TDF in preventing mother‐to‐child transmission.
  • The infants of all HBsAg‐positive women should receive immunoprophylaxis (HBV vaccination with or without hepatitis B immunoglobulin, per World Heath Organization and Centers for Disease Control and Prevention recommendations)

Treatment & prevention of HBV reactivation in patients receiving immunosuppressive or cytotoxic drugs (section 6 pages 1577-9)

  • HBsAg and anti‐HBc (total or immunoglobulin G) testing should be performed in all persons before initiation of any immunosuppressive, cytotoxic, or immunomodulatory therapy.
  • HBsAg‐positive, anti‐HBc–positive patients should initiate anti‐HBV prophylaxis before immunosuppressive or cytotoxic therapy.
  • HBsAg‐negative, anti‐HBc–positive patients could be carefully monitored with ALT, HBV DNA, and HBsAg with the intent for on‐demand therapy, except for patients receiving anti‐CD20 antibody therapy (e.g., rituximab) or undergoing stem cell transplantation, for whom anti‐HBV prophylaxis is recommended.

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.