Snapshots, by Alan Franciscus, Editor-in-Chief

Originally Published July 15, 2015

Article: Hepatitis C treatment in the elderly: New possibilities and controversies towards interferon-free regimens—Vespasiani-Gentilucci U, et al.
  Source: World Journal of Gastroenterology, 07/06/2015

Results and Conclusions:  In this article the authors discuss some important issues regarding the treatment of elderly patients with interferon-free therapies.  Elderly patients have additional health concerns that affect treatment decisions including:

• A generally faster disease progression to cirrhosis and liver cancer than those who are younger
• More extrahepatic conditions such as fatigue, cognitive issues
• A potential decrease in quality of life
• Possible drug-drug interactions with medications taken by the elderly (diabetes, heart, blood-pressure medications)

The authors recommend that the best case scenario is to treat every elderly patient because of the risk of accelerated disease progression.  If this is not realistic, we should be treating those who need treatment first who are in danger of disease progression.   The patients who are not in immediate need of treatment should be monitored on a regular basis.  As with current recommendations, those who have only a short-term survival are excluded from HCV antiviral treatment.  

The Bottom Line:  In general, the elderly population faces many health complications.  The elderly also face discrimination from healthcare professionals.  It is important that everyone with hepatitis C have an advocate—a family member or friend to help them through the intricacies of monitoring HCV and accessing HCV treatment.  

Editorial Comments:  We now have medications that have fewer side effects and have been found to be safe in people with mild to moderate kidney impairment.  It is important that the newly approved drugs and the investigational drugs be tested with the many medications that are commonly prescribed to the elderly.

Everyone deserves the right to be cured of hepatitis C including the elderly with hepatitis C.  More importantly, don’t we have an obligation to make sure that our elderly population with hepatitis C be treated and cured?  This way they can live their lives in relative health and know that they no longer have to deal with the potential physical and emotional consequences of living with hepatitis C.  

Article:  Hepatitis B Virus Reactivation During Successful Treatment of Hepatitis C Virus with Sofosbuvir and Simeprevir—J. M. Collins et. Al
  Source:  Clinical Infectious Diseases Advance Access

Results and Conclusions: This was a case report of two individuals with hepatitis C. 

The first case was a 55 yo man who was coinfected with hepatitis B and hepatitis C genotype 1a.  He had been previously treated with pegylated interferon plus ribavirin but did not achieve a cure.  He was started on sofosbuvir and simeprevir.  After week 4 he was HCV undetectable, but at week 7 he started to have severe liver symptoms (AST of 1792 IU/L, ALT of 1495 IU/L, total bilirubin of 12.2 mg/dl and INR of 1.96) and his hepatitis B viral load rose to 22 million.  His other tests (antinuclear antibody, ferritin, a-fetoprotein, etc.) were also abnormal.

The HCV treatment was discontinued, and hepatitis B treatment (tenofovir/emtricitabine) was started and the hepatitis B viral load subsequently decreased to less than 20 IU/mL.  The hepatitis B treatment was continued for ongoing hepatitis B suppression.

The second case was a 57 yo man with HCV genotype 1a.  He had been treated for HCV with pegylated interferon plus ribavirin but had not been cured. He was positive for the hepatitis B virus, but the hepatitis B viral load was below the level of detection (20 IU/mL).  He was started on HCV treatment—sofosbuvir and simeprevir and his HCV and hepatitis B viral loads were monitored every two weeks.  After two weeks, his HCV viral load was undetectable and his hepatitis B viral load increased to 353 IU/mL.  After four weeks of HCV treatment, HCV was still undetectable, but the hepatitis B viral load increased to 11,255 IU/mL.  The liver function tests were normal, and there were no other signs of liver disease.  The patient remained on sofosbuvir/simeprevir treatment.  Tenofovir was added to the HCV treatment regime to treat hepatitis B. 

The Bottom Line:  The reactivation of HBV in people who were coinfected with HBV and HCV was rare in the days of pegylated interferon based therapies.  This was most likely because PEG works against HBV whereas the new HCV direct acting antivirals do not have antiviral properties that will suppress hepatitis B while treating HCV.   

Editorial Comment:  A couple of important points:

• Everyone with hepatitis C should be tested for hepatitis B (and A), and if not previously infected should be vaccinated.
• People who are chronically infected with HBV and HCV who are being treated with the direct-acting antiviral medications (Harvoni or Viekira Pak) should be monitored very closely—every two weeks as listed in the second study—for HBV flares and treated for HBV as needed. 

http://hcvadvocate.org/news/newsLetter/2015/advocate0715_mid.html#4

Snapshots, by Alan Franciscus, Editor-in-Chief

Article: Depression rather than liver impairment reduces quality of life in patients with hepatitis C—LD Silva, et al
  Source: Rev Bras Psiquiatr. 2015 Jan-Mar;37(1):21-30. doi: 10.1590/1516-4446-2014-1446

 

Results and Conclusion: In the current study there were 124 patients (72 females; 52 males; mean age 53 yo).  The patients were given various clinical and psychiatric evaluations.  No patients were receiving HCV treatment.  Various in-person interviews were given to determine socio-economic information, health-related quality of life, income, smoking, alcohol and drug use. 

The study results found that 30.6% had major depressive disorder, which is consistent with other studies. The degree of major depressive disorder and other psychiatric disorders found in people with hepatitis C is associated with health-related quality of life rather than tied to the degree of liver fibrosis.  The authors noted that more attention needs to be devoted to “the implementation of integrated medical, psychiatric, and [that] psychological care may be helpful.”

 

The Bottom Line: Up to 70% of people with chronic hepatitis C have depressive disorders—this is a seven-fold higher rate than the general population.

 

Editorial Comment: Does HCV cause depression?  Many experts believe that the hepatitis C virus causes depression, but the exact mechanism hasn’t been completely understood.  There have been some studies that have shown that the hepatitis C virus passes the blood-brain barrier and there have been viral particles found in brain tissue.  Another possible reason for depressive disorders could potentially be the results of the immune system cells fighting off the virus in brain tissue.   

Regardless of what causes depression in people with hepatitis C, it is clear that curing hepatitis C also can increase the quality of life leading to a wide variety of improvements in health including mental health. It’s time that we recognize that we should treat everyone with hepatitis C regardless of the degree of liver damage—hepatitis C is NOT just a liver disease.

 

Article: Changes in characteristics of hepatitis C patients seen in a liver center in the United States during the last decade—N Talaat et al.
  Source: Journal of Viral Hepatitis Volume 22,Issue 5, pages 481–488, May 2015

 

Results and Conclusion: This was a retrospective study of the records of patients seen in liver clinics 1998-1999 (Era-1) compared to the records of patients seen 2011-2012 (Era-2)

The current study sought to describe the characteristics of people with HCV who were newly referred to liver clinics in Era-1 (538 patients). The records from Era-1 patients were compared to those of patients who were seen in Era-2 (810 patients).  Advanced liver disease was defined as cirrhosis, decompensated cirrhosis, or liver cancer.  

The patients in Era-2 were older (median age 56 vs 45 years), more likely to be Black (17.2% vs 11.6%) and had a longer interval between diagnosis and referral (median 4 years vs 2 years).  Genotype 1 was similar in both Era’s, but genotype 1a was 39.9% vs 53.8% in Era-2.  

Even though there was a higher percentage of treatment-experienced patients in the Era 2 patient group, the comparison showed that more than three quarters of the patients had never been treated.    

Era-2 patients were more likely to have advanced disease at referral (61.6% vs 51.5%)—with an   eightfold higher prevalence of HCC or liver cancer (21.6% vs 2.6%).

 

The Bottom Line:  The changes in the Era-2 patients points to important trends in the hepatitis C population.  These changes occurred over a relatively short period of time:   

• The majority of patients identified had not been treated.
• More patients had HCV genotype 1a – generally a more difficult genotype/subtype to treat.  This also reflects a change in the demographics of the HCV population of the United States.
• The aging of the HCV population is reflective of more advanced disease including an eight-fold increase in liver cancer.

Editorial Comment:  This study speaks volumes.  In this short period of time there has been a major advance in the rate of liver disease progression—most notably the increase in liver cancer is frightening.  


http://hcvadvocate.org/news/newsLetter/2015/advocate0515.html#4

Snapshots —Alan Franciscus, Editor-in-Chief

Article:  Improvement of health-related quality of life and work productivity in chronic hepatitis C patients with early and advanced fibrosis treated with ledipasvir and sofosbuvir—ZM Younossi
  Source: J Hepatol.2015 Mar 17. pii: S0168-8278(15)00192-0. doi: 10.1016/j.jhep.2015.03.014. [Epub ahead of print]

The main goal of HCV treatment is viral eradication or being cured of hepatitis C. However, there are equally important reasons and objectives besides being cured—better overall mental and physical functioning and being able to increase work productivity (and being able to increase income). 

The aim of the current study was to examine what being cured of hepatitis C with sofosbuvir plus ledipasvir with or without ribavirin means with respect to improving health-related quality of life—mainly physical functioning and work productivity.  There were 1,005 patients in the current study that were drawn for the ION-1,2,3 clinical trials.  The patient’s fibrosis stage was determined pretreatment based on the Metavir fibrosis staging system:

• F0: 94 patients (pts);
• F1: 311 pts;
• F2: 301 pts ;
• F3: 197 pts;
• F4:102 pts

Four questionnaires [Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Index: Specific Health Problem (WPAI:SHP)] were administered at baseline, during, and after treatment.

The Bottom Line:  It is not surprising that patients with the most advanced fibrosis (F4) had the most impairment in health-related quality of life with respect to physical functioning compared to those who were stage F0. 

This continued during and post-treatment.  After being cured there was a significant improvement from baseline in most areas of health-related quality of life regardless of the level of fibrosis stage. 

After analysis, not surprisingly, advanced fibrosis was associated with impairment of health-related quality of life and work productivity. However, it was noted that health-related quality of life and work productivity after being cured was not related to the stage of fibrosis.

Editorial Comment: This is an important study because it proved that curing people of hepatitis C improved physical well-being and work productivity.  I am eager to see more of these types of studies because we all need more information about every aspect of being cured of hepatitis C—this helps people living with hepatitis C to make the treatment decision and it will further justify the expense and need to treat people with hepatitis C.

Abstract: Chronic hepatitis C virus infection and lymphoproliferative disorders: Mixed cryoglobulinemia syndrome, monoclonal gammopathy of undetermined significance, and B-cell non-Hodgkin lymphoma—GP Caviglia
  Source: J Gastroenterol Hepatol.2015 Apr;30(4):742-7. doi: 10.1111/jgh.12837.

The researchers reviewed a study of 1,313 HCV patients who had enrolled in previous studies from January 2006 and December 2013.  There was a total of 121 people with HCV and lymphoproliferative disorders (LPDs) and 130 without LPDs.  The two groups were evenly divided between age and gender.  In the groups with LPDs—25 had mixed cryoglobulinemia (MCS)*; 55 had monoclonal gammopathy of undetermined significance (MGUS)**; 41 had B-cell non-Hodgkin Lymphoma (B-HNL)***.  The patients with LPDs did not differ in age, severity of disease, HCV genotype, and response HCV therapy. 

The Bottom Line:  After analyzing the data, it was found that there was an association between MGUS and B-NHL and cirrhosis, but there was no association between MCS and cirrhosis. 

Editorial Comment:  It is interesting that there was a correlation between MGUS and cirrhosis.  However, both conditions typically take many years before serious disease progression occurs.  In regards to MCS it can occur earlier in the course of HCV infection.  Still, it is important that people living with hepatitis C understand this information and talk with their medical providers to be tested for these conditions and for medical providers to make sure they are tested.  If someone infected with hepatitis C does have these serious conditions they may be more likely to qualify for treatment.  It would be, however, best medical and patient practice to nip these and HCV in the bud by treating and curing hepatitis early before any disease or associated condition has a chance to occur. 

*Mixed cryoglobulinemia (MCS) is one of the most common disorders associated with hepatitis C.  Cryoglobulinemia (cryo for short) is a blood disorder caused by abnormal proteins in the blood called cryoglobulins that precipitate or clump together when blood is chilled and then dissolve when warmed.  Cryo can lead to many other disorders. 

**Monoclonal gammopathy of undetermined significance (MGUS) are abnormal proteins in the blood.   They can be associated with another disease (such as hepatitis C).  They rarely cause disease, but in some people with certain conditions, such as hepatitis C, MGUS’s can progress to other diseases. 

***B-cell non-Hodgkin Lymphomas (B-HNL) are cancers of the lymphoid tissues.  The cancers are typically uncommon and usually occur after many years of infection with hepatitis C. 

More detailed information can be found on our fact sheet page.

http://hcvadvocate.org/news/newsLetter/2015/advocate0415_mid.html#1

Snapshots—Lucinda K. Porter, RN

Article: Systematic Review: Patient-Reported Outcomes in Chronic Hepatitis C - The Impact of Liver Disease and New Treatment Regimens - Z. Younossi and L. Henry
  Source: Alimentary Pharmacology and Therapeutics January 23, 2015

How do we measure successful hepatitis C (HCV) treatment? Is it strictly by clinical trial data showing how safe and effective a treatment is? Alternatively, is it by patients’ experiences, outcomes, and overall quality of life? This ambitious study examined patients’ experiences of living with hepatitis C and its treatment. 

They found that current data support the fact that HCV patients suffer substantially. This burden was much worse during interferon/ribavirin treatment and worse yet if that treatment used telaprevir or boceprevir. The newer interferon-free treatments showed that patients reported improvements in quality of life and productivity; and even bigger improvements with ribavirin-free regimens. Patients who reported easier treatment were more likely to complete therapy and respond to it.

This study also looked at fibrosis stage, finding significant fatigue and impairment among those with early stage liver disease. Patients with early fibrosis reported significant benefits, similar to the gains achieved by those with advanced fibrosis.

 

The Bottom Line: Using fibrosis stage to limit the cost of HCV treatment does not take in to account the other costs of HCV, such as its effect on work productivity, quality of life, etc.

 

Editorial Comment: This study validates what patients have been reporting for decades—that having hepatitis C is hard, and that the newer treatments offer hope for improved quality of life. Denying access to treatment violates human rights.

Article: Seven Years of Chronic Hepatitis C Virus Infection in an HIV-Infected Man without Detectable Antibodies – Joost Vanhommerig, et al.
  Source: AIDS 2015, Vol 29 No 3

After an HCV exposure, about half of those exposed will form antibodies in 5 to 10 weeks.

It averages 10 to 13 weeks for HCV antibodies to be detectable in HCV/HIV-coinfected men who have sex with men (MSM). There have been reports of some HIV-infected individuals for whom HCV antibodies didn’t show up for more than 3 years. In this case study, an HIV-positive man had positive HCV viral load results for 7 years but never had a positive HCV-antibody test result. 

The Bottom Line: These researchers recommend HCV viral load testing rather than relying solely on antibody testing for HIV-infected MSM.

 

Editorial Comment: I am both fascinated and irritated when there are rare exceptions in medical science, but they do exist. 

Article: Hepatitis C Virus Infection: A Risk Factor for Parkinson’s Disease – Wendy Wu, et al.
  Source: Journal of Viral Hepatitis January 21, 2015

Recent evidence indicates that HCV may invade the central nervous system.  In rat studies, researchers observed that HCV and Parkinson’s disease both overexpress inflammatory biomarkers. Analyzing data from 62,276 subjects, researchers found similarities between HCV and Parkinson’s.

 

The Bottom Line: This study demonstrated an association between HCV infection and Parkinson’s and confirms the observation of dopaminergic toxicity of HCV similar to that found in rats.

 

Editorial Comment: As horrifying as these results are, perhaps this research will shed light on the nature of “brain fog,” which is experienced by so many HCV patients. 

Article: Hepatitis A hospitalizations in the United States, 2002-2011 – Melissa Collier, et al.
  Source: Hepatology February 2015

This study reviewed hospitalization rates for hepatitis A from 2002-2011. The number of hepatitis A-related hospitalizations hasdeclined significantly, but patients who are hospitalized for hepatitis A are older and more likely to have liver diseases and other comorbid medical conditions.

 

The Bottom Line: Immunization could prevent hepatitis A infection and ensuing hospitalizations.

 
Editorial Comment: Hepatitis A vaccination is recommended for hepatitis C patients.

http://hcvadvocate.org/news/newsLetter/2015/advocate0315.html#4

Snapshots —Lucinda K. Porter, RN

Article: Next-Generation Sequencing Sheds Light on the Natural History of Hepatitis C Infection in Patients Who Fail Treatment – Tamer Abdelrahman, et al.
  Source: Hepatology January 2015; Volume 61, Issue 1, pages 88–97

Reports show high rates of HCV reinfection among injecting drug users with history of HCV, along with reports of sexually transmitted HCV infection and reinfection in HIV-infected men who have sex with men. This research investigated viral quasispecies dynamics in patients who failed HCV treatment to determine whether treatment failure was associated with reinfection or reemergence of preexisting infection. Previous studies interpreted the evidence as reinfection; this study identified the subjects as having preexisting resistant HCV variants.

 

The Bottom Line: Resistant HCV strains are more likely the reason for failure to achieve a sustained virological response (SVR) in these study subjects. This could be the result of superinfection or a limitation on the ability to test these HCV strains.

 

Editorial Comment: Few words cause as much fear in me as “superinfection.” What this study did not discuss is whether the lack of SVR could be connected to immune factors in this study group.

Article: Association between Chronic Hepatitis C Virus Infection and Low Muscle Mass in US Adults – Charitha Gowda, et al.
  Source: Journal of Viral Hepatitis December 2014; Volume 21, Issue 12, pages 938–943

The purpose of this cross-sectional study was to see if chronic hepatitis C virus (HCV) infection was associated with low muscle mass among adults.

Among 18,513 adults in the U.S., people with chronic HCV had a higher prevalence of low muscle mass compared to uninfected persons (13.8% vs. 6.7%). Even HCV+ persons without significant liver fibrosis had lower muscle mass.

 

The Bottom Line: Chronic HCV infection is associated with low muscle mass, even in the absence of advanced liver disease.

 

Editorial Comment: Low muscle mass is a risk factor for osteoporosis. This study strengthens the argument that we should treat people with chronic HCV, regardless of fibrosis stage.  

Article: The Epidemiology of Cirrhosis in the United States: A Population-based Study – Steven Scaglione, et al.
  Source: Journal of Clinical Gastroenterology published ahead-of-print October 8, 2014

Hepatitis C is one of many conditions that can cause cirrhosis, a severe scarring of the liver. This study assessed the prevalence of cirrhosis in the US, and defined some of the characteristics of this potentially deadly condition.

The prevalence of cirrhosis is higher in the U.S. than previously estimated (633,323 now versus previously estimated 400,000 adults). The researchers believe that the prevalence is even higher since this research relied on data from the NHANES survey, which did not collect data from people who were in the military, prison, hospitalized, homeless, or institutionalized.

Alcohol abuse, diabetes and hepatitis C were contributing factors for the majority of those with cirrhosis.  Non-Hispanic blacks and Mexican Americans, those living below the poverty level, and those with less than a 12th grade education had the highest prevalence of cirrhosis. Nearly 70% of those who have cirrhosis may not know they have it.

 

The Bottom Line: The prevalence of cirrhosis is significantly higher than previously thought.

 

Editorial Comment: The most common factors associated with cirrhosis are preventable – hepatitis C, diabetes, and alcohol abuse. Hepatitis C is curable; a public health program that identifies and cures this virus may reduce the burden of cirrhosis.

Article: Cognitive Function and Endogenous Cytokine Levels in Children with Chronic Hepatitis C – N. H. Abu Faddan, et al.
  Source: Journal of Viral Hepatitis published ahead-of-print December 15, 2014

Hepatitis C is rarely studied in children, and little is known about the cognitive effects of hepatitis C in young patients. This Egyptian study compared cognitive function in 35 HCV-positive children to 35 HCV-negative children. Compared to HCV-negative children, the children with HCV had reduced function in the areas of vocabulary, comprehension, memory, abstract visual reasoning test, quantitative reasoning test, and intelligence quotients.

 

The Bottom Line: Children with chronic HCV in its early stages showed signs of cognitive impairment, particularly with memory. There appeared to be a correlation between cognitive function and immune response as measured by the production of cytokines.

 

Editorial Comment: This study is particularly heart breaking. Children are often the last to be studied, and the last to be treated. We tend to be afraid to treat children, understandably concerned that we may injure them. This study represents the tip of the iceberg, telling us how little we know about HCV in children.

 

Article: Impact of Hepatitis C Virus Infection on the Risk of Death of Alcohol-Dependent Patients – Daniel Fuster, et al.
  Source: Journal of Viral Hepatitis January 2015; Volume 22, Issue 1, pages 18–24

This longitudinal research assessed the relationship between chronic hepatitis C virus (HCV) infection and survival rates. There were 675 subjects (nearly 80% male), enrolled in two detoxification units, with a median follow-up of three years. 

The Bottom Line: The mortality rate was high for those with alcohol-related liver disease, regardless of HCV-status; more than 11% died (78 subjects). Risk of death was increased among younger HCV-positive participants compared to those who were HCV-negative. HCV/HIV co-infection was associated with increased risk of death.

 
Editorial Comment: This study speaks for itself. I can only add that if alcohol is a problem for you, please get help.


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