Sclerosing Cholangitis-Like Changes Due to Drug Induced Liver Injury

A recent study (J Ahmad et al. Clin Gastroenterol Hepatol 2019; 17: 789-90) reviewed subjects in enrolled in drug-induced liver injury (DILI) prospective cohort to determine the frequency of sclerosing cholangitis (SC)-like changes in this population.  SC-like changes have previously been noted in up to 10% of DILI cases (Dig Liv dis 2015; 47: 502-7). In this study, 233 of 1487 subjects had underwent an MRI.

Key findings:

  • Four of 56 (7%) with adequate quality images had SC-like images (4 with intrahepatic stricture and 1 with a common hepatic duct stricture as well)
  • Patients with SC-like changes had a more severe initial injury noted and were more likely to develop chronic injury as noted by persistent lab abnormalities at 6 months

My take: This study indicates that a severe DILI can result in secondary sclerosing cholangitis.

Related blog posts:

 

Liver Briefs -June 2019 part 2

E Cowell et al. JPGN 2019; 68: 695-99. This study reviewed 61 cases of pediatric hepatocellular carcinoma to determine predisposing conditions  (in Houston TX).  The majority did NOT have recognizable predisposing conditions.  25 of 61 (41%) had a predisposing condition including cryptogenic cirrhosis/steatosis (9), genetic (7), biliary pathology (4), viral hepatitis (1), and other (4).  Those without a recognizable predisposing condition were diagnosed later and with more advanced disease/decreased survival.

VA McLin et al. JPGN 2019; 68: 615-22. Useful review on congenital portosystemic shunts.

DE Kaplan et al. Gastroenterol 2019; 156: 1693-1706. This large study form the VA with more than 70,000 patients examined the relationship between statin exposure and survival in patients with cirrhosis.  “Each cumulative year of statin exposure was associated with an independent 8-8.7% decrease of mortality of patients with cirrhosis of Child-Turcotte-Pugh classes A and B.”

AG Singal et al. Gastroenterol 2019; 156: 1683-1692. Direct-acting antiviral therapy was not associated with recurrent hepatocellular carcinoma (HCC) in a multicenter cohort study with 793 patients with HCV-associated HCC. Thus, DAAs appear safe in patients who have achieved a complete response to HCC Rx

Liver Briefs -June 2019

YH Yeo et al. Hepatology 2019; 69: 1385-97.  The prevalence of high risk individuals in the U.S. who are susceptible (not immune) to hepatitis B has decreased from 83% to 69% from 2003 to 2014.  That still leaves 64 million who would benefit from HBV vaccination.

M Sharma et al. Hepatology 2019; 69: 1657-75. This meta-analysis compared therapies for primary prevention of esophageal varices and concluded that nonselective beta-blocker (NSBB) monotherapy may decrease all-cause mortality and carried a lower risk of serious complications than variceal band ligation (VBL). However, the commentary (1382-84 by L Laine) reaches a different conclusion. “Current recommendations for primary prevention with VBL or NSBB or carvediolo still appear to be acceptable…using a shared decision-making approach” to weigh issue such as daily medication or periodic endoscopy.

J Nguyen et al. J Pediatr 2019; 207: 90-6. This study modeled the cost-effectiveness of early treatment with direct-acting antiviral therapy in adolescents with hepatitis C infection.  With pangenotypic agenst, the cost would be $10000 to $21000 per QALY gained.

S Trinh et al. Clin Gastroenterol Hepatol 2019; 17: 948-56. This retrospective hepatitis B study examined the changes in renal function between 239 tenofovir disoproxil fumarte (TDF) treated patients and 171 entecavir treated patients.  Key finding: TDF was not associated with higher risk of worsening renal function in this cohort with a mean followup of 43-46 months in patients with baseline normal renal function.  In patients with renal impairment, deterioration of renal function was noted in TDF-treated patients.  Thus, TDF should be avoided in patients with impaired renal function.

 

Rhododendrom in Sandy Springs

.

Liver Shorts: May 2019

ED Bethea et al. Clin Gastroenterol Hepatol 2019; 17: 739-47. Using a Markov-based mathematical model, the authors “found transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy to a cost-effective strategy that could improve health outcomes.”

A Villanueva. NEJM 2019; 1450-62. This is a succinct review of hepatocellular carcinoma (HCC). Some points:

  • More than 1 million patients will die from liver cancer in 2030.
  • The rate of death from liver cancer increased 43% from 2000 to 2016,.  The 5-year survival rate is grim at only 18%.  Only pancreatic cancer is more lethal.
  • HCC is rare among patients without preexisting liver disease.  Cirrhosis is the main risk factor, though hepatitis B has direct oncologic effects even in the absence of cirrhosis.
  • The authors note that cancer surveillance has no “high-quality randomized controlled trials.” However, this may be due to difficulties with enrollment. In one study, 99%of patients declined to assume the risk of being randomly assigned to the nonsurveillance group. Nonetheless, mathematical models, and lower quality studies all show survival benefits of surveillance.

Related blog post:

  • Liver Shorts April 2019 Obesity/NAFLD and alcoholic liver disease are driving an increase in HCC and liver cancer mortality

Expanding Organ Transplantation with Hepatitis C-Positive Donors

A recent study (AE Woolley et al NEJM 2019; 380: 1606-17) highlighted the outcomes of heart and lung transplant (uninfected) recipients of organs from HCV-infected donors (“DONATE HCV” trial).

In this study, 44 patients (36 lung transplant recipients, 8 heart transplant recipients) were treated preemptively with 4 weeks of sofosbuvir-velpatasvir to block viral replication.

Key findings:

  • 42 of 44 (95%) had a detectable viral load immediately after transplantation.
  • The first 35 (who have all completed 6 months of folllowup) all cleared HCV viremia –undetectable HCV at 6 months post-transplantation
  • No treatment-related complications were noted

In the associated editorial by EA Blumberg (1669-70), it is noted that organs for transplantation are in short supply for the more than 113,000 persons on waiting lists in the U.S.  “In 2018, only 36,500 persons received transplants…and 12,225 persons were removed from the waiting list because of death or progressive illness than rendered them” too sick for transplantation.

HCV donors will expand the donor pool substantially (up to one-third more donors) and these donors are typically younger and with fewer coexisting conditions.

My take: With the high response rate of the newer direct-acting antivirals (100% in this study) along with the (cost) effectiveness of a shorter course, this study shows how promising HCV-positive donors are for improving outcomes in patients in need of organ transplantation.  Long term data are still needed to determine if there are unforeseen problems (eg. late severe relapse of HCV, increased cardiovascular disease).

Related blog post: Increased Organ Availability Related to Opioid Epidemic

Mortality Rate with Autoimmune Hepatitis –Increased if Cirrhosis

Briefly noted: Using a Dutch database to identify 449 patients with autoimmune hepatitis, a recent study (FF van den Brand et al. Clin Gastroenterol Hepatol 2019; 17: 940-7) found that having associated cirrhosis increased the mortality rate over a 10-year followup.  In this circumstance, the standardized mortality ratio (SMR) was 1.9.  In contrast, if cirrhosis was not present, there was no significant increase in SMR (1.2).  Patients with overlapping PSC had the greatest increase in mortality with an SMR of 4.7.

View from Sofia Reina museum. Madrid