Category Archives: Hepatology

Hepatitis C Prevalence Underestimated

Posted on by

A recent study (BR Edlin et al. Hepatology 2015; 62: 1353-63) provides data suggesting that Hepatitis C virus (HCV) infection has been underestimated.

The number most commonly used is derived from the 2003-2010 National Health and Nutrition Examination Survey (NHANES) which showed 3.6 million in the U.S. with antibodies to HCV and 2.7 million currently infected.

The authors performed a systemic review and note that ~1 million people were excluded from this survey including a large number at high risk for HCV: ~500,000 incarcerated people, and 220,000 homeless people.

Based on their analysis, they conclude that “the number of US residents who have been infected with hepatitis C is unknown but is probably at least 4.6 million…and of these, at least 3.5 million… are currently infected.”

Related blog posts:

HCV Guidelines

Posted on by

The AASLD-IDSA Recommendations for Hepatitis C Virus have been published (Hepatology 2015; 62: 932-954).  The entire report is accessible from hcvguidelines.org and from the link: HCV Guidance 2015. While having a hard copy is easy to work with, the HCVguidelines website is likely to remain more up-to-date.

A few recommendations to highlight:

  • #6. “Antiviral treatment is recommended for all patients with chronic HCV infection, except those with limited life expectancy due to nonhepatic causes (I-A)
  • #7. “If resources limit the ability to treat all infected patients immediately as recommended, then it is most appropriate to treat those at greatest risk of disease complications” (see Tables 3 and 4)
  • #8. “Use of noninvasive testing or liver biopsy is recommended in order to assess the degree of hepatic fibrosis and, hence, the urgency of immediate treatment. (I-A)”

Other Hepatology studies of interest, briefly noted:

Hepatology 2015; 62: 684-93.  Nucleos(t)ide analog “treatment does not increase the risk of renal and bone events in general.  Nucleotide analogs may increase the risk of hip fractures, but the overall event rate is low.”  This study examined 46,454 untreated chronic hepatitis B patients in comparison to 7,046 treated patients.

Hepatology 2015; 62: 715-25. This study looked at the safety of simeprevir and sofosbuvir in hepatitis C-infected patients.  “Adverse safety outcomes were similar to matched untreated controls, suggesting that safety events reflect the natural history of cirrhosis and are not related to treatment.”

Hepatology 2015; 62: 773-83. This study found that “NAFLD is independently associated with subclinical myocardial remodeling and dysfunction.”

Bruce Munro, Atlanta Botanical Gardens

Bruce Munro, Atlanta Botanical Gardens

Changing Narrative on Affordability of HCV Treatments

Posted on by

A recent commentary (J Chhatwal et al. Clin Gastroenterol 2015; 13: 1711-13) makes the point that HCV treatment is looking a lot better lately with regard to cost.

Key points:

  • “Sofosbuvir-based treatment in 2015, on average, costs 54% of the wholesale acquisition cost”
  • When considering the recent discounts, “the cost of treatment decreased to $56,000…and the cost per SVR decreased to $58,000.”  The cost of an SVR with the first generation protease inhibitors, boceprevir and teleprevir, has been estimated to have been $213,000.
  • “The discounted cost of treating 1 person with HIV in the United States is $315,000 in 2014 US dollars.” Thus, curing HCV which is more deadly, at 18% of the cost, looks more favorable.
  • More discounts and more competition are expected.

Bottomline: Based on these cost considerations, the authors state that HCV treatment should be used broadly and not solely in those with advanced fibrosis.

Related blog posts:

Atlanta Botanical Gardens

Atlanta Botanical Gardens

Lack of Survival Benefit With MELD Exception Points in Hepatocellular Carcinoma

Posted on by

Briefly noted:

Another study also looks at transplant utility by showing the use of MELD exception points for hepatocellular carcinoma provides almost no survival benefit: K Berry, GN Ioannou. Gastroenterol 2015; 149: 669-80, editorial 531-34.    The article states that the “survival benefit of patients with HCC was similar to that of patients without HCC who had the same actual MELD score…a much lower mean 5-year survival benefit was achieved by providing liver transplants to patients with HCC (0.12 years/patient) than patients without HCC (1.47 years/patient).”

How is this possible?

When patients are transplanted at lesser illness acuity, it takes longer to achieve a transplant benefit because they can live longer without a transplant.  In essence, the survival clock starts ticking much later than the transplant date.

Why this is important (from editorial):

The proportion of patients undergoing liver transplantation for HCC has increased from “4.6% before the introduction of MELD exception to 16.5% currently.” And, “the results, put simply, suggest that allocating donor livers and performing liver transplantation in patients with HCC MELD exception points produces almost no survival benefit.”

My take: Liver allocation policies need to be modified.  This study suggests that prioritizing HCC patients does not make much sense.

Atlanta Botanical Garden

Atlanta Botanical Garden

HCV Update -Fall 2015

Posted on by

Briefly noted:

S Naggie et al. NEJM 2015; 373; 705-13.  Among patients coinfected with HIV-1 and HCV (genotypes 1 and 4), 12 weeks of ledpasvir and sofosbuvir resulted in a 96% sustained HCV virological response.

DL Wyles et al. NEJM 2015; 373; 714-25.  Among patients coinfected with HIV-1 and HCV (genotype 1), 12 weeks of daclatasvir plus sofosbuvir resulted in a 97% sustained HCV virological response.

HA Innes et al. Hepatology 2015; 62: 355-64. Review of a Scottish HCV clinical database showed that a sustained viral response was associated with a reduced liver mortality (adjusted Hazard Ratio 0.24), a reduced non liver mortality (aHR 0.24) and reduced behavioral events (eg. violence-related injury aHR 0.51).  The latter improvement suggests that HCV eradication leads to healthier lives.

Also, seeing as today is ICD-10 Rollout: ICD-10: Source for humor? | gutsandgrowth

View from Signal Lodge, Grand Tetons

View from Signal Lodge, Grand Tetons

Coffee and Caffeine Associated With Less Fibrosis Among Patients with Hepatitis C

Posted on by

Perhaps I need to start drinking coffee.  In the absence of smoking or alcohol, it is reported to have a number of benefits. A recent study (N Khalaf et al. Clin Gastroenterol Hepatol 2015; 13: 1521-31) found that a “modest daily caffeine intake (as little as 100 mg) may protect against advanced hepatic fibrosis in men with chronic HCV infection.” This cross-sectional study of veterans with chronic HCV looked at 910 patients.  Patients were divided into controls with mild fibrosis (F0-F3) based on FibroSURE compared with those with F3/F4-F4 advanced fibrosis.  FibroSURE estimates are based on an algorithm which incorporates α2-macroglobulin, apolipoprotein A1, haptoglobin, total bilirubin, γ-glutamyl -transpeptidase, and alanine amiontransferase. Key findings:

  • Caffeinated coffee was higher among controls than those with advanced fibrosis (1.37 vs 1.05 cups/d, P=.038)
  • Overall caffeine ingestion was also higher in the controls; 66% of controls consumed >100 mg/day compared with 58% of those with advanced fibrosis.

Limitation: observaitonal, retrospective study with self-reported coffee/caffeine consumption. Related blog posts:

Screen Shot 2015-08-23 at 9.25.15 PM

NASH Update -September 2015

Posted on by

Briefly noted:

Obeticholic acid, a Farnesoid X Receptor Ligand, is being studied as a potential agent in nonalcoholic steatohepatitis (NASH).  According to a recent study (Lancet 2015; 385: 956-65), patients assigned to receive obeticholic acid were more likely to have improved liver histology compared with placebo (50/110 [45%] compared with 23/109 [21%]).  The  obeticholic group had increase serum cholesterol and LDL cholesterol. This study looked at a subgroup of patients in the FLINT study who had undergone liver biopsies.

E Vilar-Gomez et al. Gastroenterol 2015; 149: 367-78. This prospective study of 293 patients with histologically-proven NASH were followed after undergoing lifestyle changes for 52 weeks. At week 52, 88 subjects (30%) had lost ≥5% of their weight.  Degree of weight loss was independently associated with improvements in all NASH-related histologic parameters (steatohepatitis, NAS activity score, and fibrosis.

G Lassailly et al. Gastroenterol 2015; 149: 379-88. Between 1994-2013, 109 morbidly-obese patients with histologically-proven NASH underwent bariatric surgery.  One year after surgery, NASH had disappeared from 85% of the patients.

P Angulo et al. Gastroenterol 2015; 149: 389-97. In this retrospective analysis of 619 patients with NAFLD (1979-2005), the authors noted that “fibrosis stage, but no other histologic features of steatohepatitis, were associated independently with long-term overall mortality, liver transplantation, and liver-related events.”

 

Days of Future Past and Declining Liver Graft Quality

Posted on by

In the most recent ‘X-men’ movie (Days of Future Past), the disastrous future is averted by having Wolverine go back in time to correct a mistake. Overall, while there are a good number of movies that have used this trick, this particular movie is pretty clever. For whatever reason, this movie came to mind as I was reading a recent study: “Declining Liver Graft Quality Threatens the Future of Liver Transplantation in the United States” (ES Orman et al. Liver Transpl 2015; 21: 1040-50).  The authors extrapolate data from UNOS to assess what the liver transplantation (LT) picture may look like in 2030. Their results/conclusion:

“If donor liver utilization practices remain constant, utilization will fall from 78% to 44% by 2030, resulting in 2230 fewer LTs.”  “The transplant community will need to accept inferior grafts and potentially worse post transplant outcomes and/or develop new strategies for increasing organ donation.”

The authors note that the national epidemics of diabetes and obesity will result in more cases of NAFLD-related liver failure while at the same time worsen the quality of available grafts. In the associated editorial, (RH Wiesner, pages 1011-12) the author emphasizes that the future is not quite so set.

  • the prevalence of diabetes and obesity in donors for 2030 might not be as great as feared; in addition, medical/surgical advances may diminish the complications associated with obesity
  • there will be a marked decrease in transplants due to hepatitis C virus related cirrhosis and hepatocellular cancer

His conclusion: “in the future, we will be using donor livers that we have never used before and will be achieving similar excellent results as we have today.” Which vision of the liver transplantation future is correct?

Related blog post: AASLD/NASPGHAN 2014 Guidelines for Evaluation of Pediatric …

Bison, Yellowstone

Bison, Yellowstone

Hepatitis C : New and Newer Treatments

Posted on by

A recent study (KR Reddy et al. Hepatology 2015; 62: 79-86) shows that the combination of ledipasvir/sofosbuvir is a safe, effective therapy for patients with genotype 1 Hepatitis C (HCV) and compensated cirrhosis.

The authors performed a post-hoc analysis of seven clinical trials in 513 treatment-naive and previously treated patients; 69% were previously treated. Key findings:

  • Overall, 493 (96%) achieved an SVR12; 98% of treatment-naive patients achieved an SVR12.
  • However, many patients in this analysis had received ribavirin.  In those treated without ribavirin (ledipasvir/sofosbuvir alone), the SVR12 was 90%.
  • Most common adverse effects included headache (23%), fatigue (16-19%), and asthenia (14-16%).

Bottomline: While ledipasvir/sofosbuvir was effective in this population, the 90% SVR12 is not as good as 96%.  This leads to the question of whether ribavirin is needed as well.

Related & briefly noted: SA Alqahtani et al. Hepatology 2015; 62: 25-30.  Ledipasvir/sofosbuvir treatment (8-24 weeks) resulted in SVR of 97% (with or without ribavirin) among the 1952 patients treated in the ION-1, ION-2, and ION-3 studies.

Related blog posts:

From FDA (July 24th): FDA approves new treatment for chronic hepatitis C genotype 3 infections

“The U.S. Food and Drug Administration today approved Daklinza (daclatasvir) for use with sofosbuvir to treat hepatitis C virus (HCV) genotype 3 infections. Daklinza is the first drug that has demonstrated safety and efficacy to treat genotype 3 HCV infections without the need for co-administration of interferon or ribavirin, two FDA-approved drugs also used to treat HCV infection….

The safety and efficacy of Daklinza in combination with sofosbuvir were evaluated in a clinical trial of 152 treatment-naive and treatment-experienced participants with chronic HCV genotype 3 infection. Participants received Daklinza 60 mg plus sofosbuvir 400 mg once daily for 12 weeks and were monitored for 24 weeks post treatment. The studies were designed to measure whether a participant’s hepatitis C virus was no longer detected in the blood 12 weeks after finishing treatment (sustained virologic response), suggesting a participant’s infection had been cured.

Results showed that 98 percent of the treatment-naive participants with no cirrhosis of the liver and 58 percent of the treatment-naive participants with cirrhosis achieved sustained virologic response. Of the participants who were treatment-experienced, 92 percent with no cirrhosis of the liver and 69 percent with cirrhosis achieved sustained virologic response. Daklinza labeling carries a Limitations of Use statement to inform prescribers that sustained virologic response rates are reduced in HCV genotype 3 infected patients with cirrhosis.”

From FDA (July 24th): FDA approves Technivie for treatment of chronic hepatitis C genotype 4

“The U.S. Food and Drug Administration today approved Technivie (ombitasvir, paritaprevir and ritonavir) for use in combination with ribavirin for the treatment of hepatitis C virus (HCV) genotype 4 infections in patients without scarring and poor liver function (cirrhosis).

Technivie in combination with ribavirin is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for co-administration of interferon, an FDA-approved drug also used to treat HCV infection…

The safety and efficacy of Technivie with ribavirin were evaluated in a clinical trial of 135 participants with chronic HCV genotype 4 infections without cirrhosis. Ninety-one participants received Technivie with ribavirin once daily for 12 weeks. Forty-four participants received Technivie once daily without ribavirin for 12 weeks. The studies were designed to measure whether a participant’s hepatitis C virus was no longer detected in the blood 12 weeks after finishing treatment (sustained virologic response), suggesting a participant’s infection had been cured.

Results showed that 100 percent of the participants who received Technivie with ribavirin achieved a sustained virologic response. Of those who received Technivie without ribavirin, 91 percent achieved sustained virologic response.”

Garden of the Gods, Colorado Springs

Garden of the Gods, Colorado Springs

What is Driving Racial Disparities in Access to Living Donor Liver Transplants

Posted on by

Recent articles highlight a huge gap in the availability of living donor liver transplants (LDLTs) when examined based on racial/ethnic background.

  • YR Nobel et al. Liver Transpl 2015; 21: 904-13.
  • A Doyle et al. Liver Transpl 2015; 21: 897-903.

What is the reason for this inequality?

The first study examined UNOS data from 2002-2014 among adult liver transplant recipients.  Of 35,401 recipients, 2171 (6.1%) received a LDLT.

Key findings:

  • Cholestatic liver disease: When compared with white patients, the odds ratios of receiving LDLT were 0.35 for African American, 0.58 for Hispanic, and 0.11 for Asian.
  • Noncholestatic liver disease: When compared with white patients, the odds ratios of receiving LDLT were 0.53 for African American, 0.78 for Hispanic, and 0.45 for Asian.
  • LDLT recipients were more likely to have private insurance

The second study did not look at racial/ethnic background but instead focused on other recipient factors.  Using a retrospective cohort of 491 consecutive patients, they determined that all of the following resulted in a lower likelihood of LDLT:

  • Single — OR 0.34
  • Divorced –OR 0.53
  • Immigrant — OR 0.38
  • Low income quintile — OR 0.44

Together these studies allow speculation on why there is such a disparity.

  • Financial costs, including lost wages, could preclude those with lower socioeconomic status from being available as donors
  • Distrust of donation system and/or fear of surgery

Bottomline: Racial/ethnic differences and financial resources are associated with significant access inequality to living donor liver transplantation.

Related blog posts:

Cascade Canyon, Grand Tetons

Cascade Canyon, Grand Tetons