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In This Issue:
Alan Franciscus, Editor-in-Chief
This month Alan discusses Daklinza and Sunpreva from BMS, AbbVie's 3D, the Olysio/Sovaldi combination and the side effects of some of these new medications. Read more...
Lucinda K. Porter, RN
Lucinda reviews studies on genotype 3, cirrhosis and cancer; HCV and end-stage kidney disease; alternatives to liver biopsy, and testing policy. Read more...
Lucinda K. Porter, RN
This month Lucinda talks about hepatic encephalopathy, and what happens when liver disease hijacks the brain. Read more...
Alan Franciscus, Editor-in-Chief
This month Alan talks about extrahepatic manifestations of hepatitis C, such as vasculitis, glomerulonephritis, cryoglobulinemia and non-Hodgkin lymphoma and the need for physician awareness of these conditions—especially now that the new treatments are becoming available. Read more...
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—Alan Franciscus, Editor-in-Chief
This month’s column, I am going to take a different path: I will report on the drugs in development and the most common side effects reported as well as offer some self-help tips to help manage the less severe ones. In addition, I will report on a new drug combination that was approved in Japan.
BMS Approval in Japan
On July 7, 2014 the Japanese Ministry of Health, Labor and Welfare (MHLW) approved Daklinza (daclatasvir—HCV NS5A inhibitor) and Sunvepra (asunaprevir—HCV protease inhibitor) for the treatment of chronic hepatitis C genotype 1 for a treatment period of 24 weeks. According to a Bristol-Myers Squibb (BMS) company press release, of the HCV genotype 1b patients treated 84.7% were cured. The number of people in Japan with hepatitis C is estimated at 1.2 million, and approximately 70% have HCV genotype 1b. Among patients 65 years of age or older who were either interferon-ineligible or intolerant, 91.9% were cured. In the patients with compensated cirrhosis the cure rates were 90.9%. The treatment discontinuation rate due to adverse events was 5%. The rate of serious adverse events (SAEs)reported was 5.9%, and the press release stated that “few SAEs were experienced by more than one patient.”
• Nasopharyngitis: The most common side effect (30.2%) reported in the study was nasopharyngitis (upper respiratory system inflammation, infection, the common cold).
Self-help tips: Standard care for the common cold – bed rest, over-the-counter cold remedies, and nasal sprays including saline.
AbbVie / Gilead
The Food and Drug Administration (FDA) is expected to approve Gilead’s sofosbuvir/ledipasvir by October 10, 2014, and AbbVie’s 3D combination by December 22, 2014. The new oral combination therapies have higher cure rates, lower side effects and shorter treatment durations than some of the current drug regimes. However, all drugs have side effects and this article will focus on the most frequent side effects reported in the Phase 3 clinical trials. For this article, I am going to combine the most frequent side effects reported for both drugs in the clinical trials. It is important to know, however, that in clinical trials every symptom is reported whether or not it is related to the study drug, so you could potentially have a symptom of hepatitis C during the study period that would be listed as a side effect of the study drug. Another issue is that many times the patient population of clinical studies is made up of patients who are typically ‘the easiest to treat.’ Therefore, many health issues and side effects may not emerge until the medications are taken by many more people with the condition who may have a wide range of other health issues that may affect the tolerability, adherence and side effects of the newly approved drugs. Another issue is that the side effects listed in the Phase 3 studies are not rated by severity so some of them might be mild and others might be severe. However, the number of people who discontinued treatment due to side effects in both Gilead’s and AbbVie’s Phase 3 clinical trials was less than 1% which would indicate that the majority of side effects were mild to moderate.
Below are some of the most frequent side effects that occurred and some common tips for managing them. If you do experience these side effects or others that become more than annoying they should be reported to a medical provider before they become worse.
• Fatigue: The most common symptom of hepatitis C is fatigue and it is also the most common side effect of the new medications. Fatigue can range from feeling mildly tired to feeling totally exhausted. It can interfere with almost every area of life including work, family and social interactions and it can also lead to anxiety, depression and isolation.
Self-help tips: Be sure to get enough sleep and daily exercise. Take short naps (no more than 10 to 20 minutes and do not nap too close to bedtime). Make sure the fatigue is not caused by something else—talk with your medical provider. Ask for help! Get organized! Try deep breathing—watch your breathing. Many people who are tired and stressed hold their breath which can lead to more stress and fatigue.
• Headache: The second most common side effect of the new medications is headache.
Self-help tips: Limit caffeine in coffee, sodas, teas, chocolate, and tobacco. Avoid loud noises, bright lights and strong odors. Cold compresses on the head may help. Use over-the-counter pain aids. If a headache is very painful or persists over time talk to a medical provider.
• Insomnia: This is a common symptom of hepatitis C that is also a common side effect of the new all-oral therapies. Insomnia can lead to fatigue, headaches and a whole host of other symptoms.
Self-help tips: Stay away from caffeine, as mentioned above, especially too close to bedtime. Avoid a partner who snores or makes a lot of noise when they sleep. The room should be dark, and not too cold or hot. Don’t eat too much food before bed but don’t go to bed hungry. Establish healthy and regular sleeping habits—going to bed the same time every night, developing a routine such as reading a non-stimulating book before bedtime, trying to turn off your mind before bedtime. If you find that you can’t sleep, get up and do something boring; then go back to bed. Chronic insomnia can be effectively treated with medications.
• Nausea: Feeling sick to your stomach is a common symptom of hepatitis C as well as a side effect of the all-oral therapies.
Self-help tips: Eat some dry crackers; avoid food and odors that act as triggers; stay away from spicy, greasy, and deep-fried foods. Eat small frequent healthy meals instead of three large meals a day. Chew food slowly; try over-the counter medications for nausea; try peppermint, chamomile, or ginger tea to help calm the stomach; chew or suck on ginger. Acupuncture or acupressure (also wristbands) may offer relief. The BRATT diet (bananas, rice, applesauce, toast and tea) is also recommended.
• Asthenia (lack of muscle strength): This can go hand in hand with fatigue and can lead to balance issues and accidents that can be dangerous.
Self-help tip: Be careful when getting up from a sitting position and when walking. Talk to your medical provider if this issue becomes worse.
• Diarrhea: Persistent diarrhea can be much more than annoying—it can lead to and exacerbate many of the symptoms above and can affect the absorption of medications and nutrients.
Self-help tip: Drink plenty of clear fluids (water, weak tea or broth); eat popsicles or gelatin, eat small frequent meals, keep track of bowel moments; eat banana and potatoes (high in potassium); stay away from high-fiber foods such as whole-grain breads and cereals, spicy, fried and greasy food, alcohol, caffeinated drinks and tobacco products. Try the BRATT diet (see above).
• Rash/ Pruritus (itching): The rash seen in the all-oral therapies is not as severe as the rashes seen in previous HCV drug combinations and was only reported in a minority of patients.
Self-help tips: There are many strategies to combat dry skin and rashes including, and most importantly, drinking clear fluids; avoid soap—especially scented soaps; apply moisturizer especially after a shower; avoid hot showers and baths; oatmeal baths and lotions can sooth the itching. Over-the-counter antihistamines can relieve the itching.
• Irritability: Persistent irritability can be a sign of or a precursor to depression.
Self-help tip: Try deep breathing, meditation and prayer. If irritability worsens talk to a professional.
• Cough: A cough can simply be from a dry throat or could possibly be a symptom of a cold or lung infection.
Self-help tip: Drink plenty of clear fluids as listed above; suck on cough drops; If the cough is persistent or if there is a fever—see a doctor.
Janssen (Olysio) / Gilead (Sovaldi)
Janssen submitted a supplemental new drug application (sNDA) to the Food and Drug Administration (FDA) in June. On July 15, 2014, Janssen announced that the FDA designated the sNDA a Priority Review.
The most common side effects of Sovaldi are discussed above. The most common side effect of Olysio is rash and photosensitivity. Rash is discussed above. Photosensitivity is discussed below.
• Photosensitivity: basically means that your skin is allergic to the sun. This is caused by many different drugs or substances that trigger a person’s immune system to react to the sun. The symptoms can be a mild rash to itchy red bumps and welts. It can last for minutes, hours or days. If the rash becomes serious it should be evaluated by a medical provider. There is no particular diagnostic test for photosensitivity—diagnosis is usually made by observing the skin rash. However, a physician may want to get at the cause and do certain other tests. But since the cause is known to be a reaction to Olysio it is unlikely that further testing will be done.
Self-help tip: Treatment consists of avoiding the sun, wearing clothing to prevent exposure to the sun and the use of corticosteroid ointments to relieve the pain and itching. In severe cases UV light therapy might offer some relief. After treatment the condition will resolve.
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—Lucinda K. Porter, RN
Article: HCV Genotype 3 Is Associated with an Increased Risk of Cirrhosis and Hepatocellular Cancer in a National Sample of U.S. Veterans with HCV—Fasiha Kanwal, et al.
Source: Hepatology July 2014 Volume 60, Issue 1, pages 98–105
Hepatocellular carcinoma (HCC) is the most common cause of death in patients with hepatitis C virus (HCV)-induced cirrhosis. Compared to genotype 2, HCV genotype 1 is associated with a higher risk of developing HCC; genotype 1b may have a higher risk of HCC than genotype 1a. This study examined risk of cirrhosis and HCC in patients with genotype 3.
Collecting data from 2000 through 2009, Veteran Administration researchers adjusted for age, race, gender, HIV infection, alcohol use, body mass index, diabetes, and history of antiviral treatment. Of the 110,484 HCV-positive veterans, nearly 80% (88,348) had genotype 1, almost 12% (13,077) had genotype 2, 7.5% (8,337) had genotype 3, and less than 1% (1,082) had genotype 4 infection.
The Bottom Line: Compared to genotype 1 patients, those with HCV genotype 3 had a 31% higher risk of developing cirrhosis and an 80% increased risk for HCC. This risk was independent of age, diabetes, body mass index, or antiviral treatment.
Editorial Comment: This is particularly distressing because treatment for genotype 3 patients has not progressed as rapidly as treatment has for genotypes 1 and 2. For more information about treatment in the pipeline, see Drugs in Development: Genotype 2 and 3 by Alan Franciscus.
Article: Hepatitis C Virus Infection Increases Risk of Developing End-Stage Renal Disease Using Competing Risk Analysis—Jia-Jung Lee, et al.
Source: PLoS One June 27, 2014; 9(6): e100790
This prospective study conducted in Taiwan, enrolled 4,185 subjects with chronic kidney disease. The study group was 59% male, the mean age was 62 yrs, and it took place from 2002 through 2009. HCV prevalence was 7.6%, a prevalence that increased as chronic kidney disease stages increased. The prevalence of hepatitis B (HBV) was nearly identical (7.4%), but was not associated with trends in kidney disease stages. There were 446 deaths and 1,205 patients advanced to End-Stage Renal Disease.
The Bottom Line: Those with HCV, but not HBV, had higher risk of developing End-Stage Renal Disease compared to those without HCV (52.6% vs. 38.4%).
Editorial Comment: The prevalence of kidney disease is increasing in the US. Patients with HCV, especially if they have cirrhosis, are at risk for chronic kidney disease. Kidney disease has vague symptoms in its early stages, symptoms much like HCV. Kidney disease and HCV will be the subject of next month’s Healthwise.
Article: Combination of Blood Tests for Significant Fibrosis and Cirrhosis Improves the Assessment Of Liver-Prognosis In Chronic Hepatitis C–J. Boursier, et al.
Source: Alimentary Pharmacology & Therapeutics July 2014 Volume 40, Issue 2, pages 178–188
Noninvasive tests that assess liver fibrosis are making their way into mainstream medical practice. How do they stack up? This study compared the accuracy of six blood fibrosis tests and liver biopsy to see how well they predicted liver-related events in chronic HCV. Additionally, the researchers evaluated whether a combination of blood fibrosis tests would improve the liver-prognosis assessment.
This 9.5-year French study enrolled 373 HCV patients; none had decompensated cirrhosis, other liver disease, or high alcohol use. In addition to undergoing a liver biopsy, patients had fibrosis blood tests (APRI, FIB4, Fibrotest, Hepascore, FibroMeter), and the CirrhoMeter blood test if they had cirrhosis.
The Bottom Line: The blood tests measuring fibrosis were as good as or better than liver biopsy when predicting liver disease prognosis. Combining FibroMeter and CirrhoMeter had the best results.
Editorial Comment: This month there were at least four published papers about non-invasive liver fibrosis tests (blood and Fibroscan). The evidence suggests that when used correctly, especially when combined with more than one test, noninvasive tests yield results that are comparable to liver biopsy. Noninvasive tests have clear advantages—for patients and their medical providers. It looks like we are moving out of the HCV dark ages.
Article: Trends in HCV RNA Testing among HCV Antibody Positive Persons in Care, 2003-2010—Philip Spradling, et al.
Source: Clinical Infectious Diseases Advance Access first published online July 2, 2014
An HCV-antibody assay is the first test ordered to determine if a person may have HCV. A positive antibody result merely means that a person was exposed to HCV; it does not mean that HCV is present. A viral load (HCV RNA) is required for proper diagnosis. This study analyzed HCV RNA testing practices by collecting data from four major healthcare systems in the US. Of the 87,431 (9.2%) who had an HCV antibody test, 5,860 (6.7%) had a positive result.
Nearly 61% of those who were HCV antibody-positive had an HCV RNA test performed. Reasons for inadequate testing varied. Providers’ lack of knowledge regarding follow-up testing was cited, as was patients not returning for follow-up testing. Low income was associated with decreased chances of follow-up with viral load testing.
The Bottom Line: Less than two-thirds of those who tested positive for HCV antibody had the necessary follow-up HCV RNA testing for proper HCV diagnosis. The researchers recommended reflex testing, a system that automatically triggers an HCV RNA test after a positive HCV antibody result.
Editorial Comment: These findings are disturbing, not least of which is that a large percentage of patients who weren’t properly tested are walking around with insufficient information that could help them manage and perhaps cure HCV.
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HEALTHWISE: Hepatic Encephalopathy— When Liver Disease Hijacks the Brain
—Lucinda K. Porter, RN
In 2010, Karen Hoyt noticed that her feet and abdomen were swollen. She had ridden her bike in 100-degree heat, and blamed these symptoms on the temperature. A friend insisted that Karen see a doctor. Upon examining her, the nurse practitioner sent Karen to the hospital. She would learn that she had cirrhosis caused by hepatitis C. Karen was in end-stage liver disease, and she was dying.
Karen didn’t believe any it, and tried to check herself out of the hospital against medical advice. Karen is bright, but at that moment, her intelligence was useless; she was cognitively impaired and didn’t know it. Karen didn’t have the ability to comprehend her diagnosis because she had hepatic encephalopathy (HE), a brain disorder that develops when the liver is unable to remove toxins in the body. One toxin is ammonia, produced by the body when proteins are digested. If ammonia builds up in the bloodstream, it can damage the nervous system.
HE is a horrific complication of liver disease. Not only does it affect patients, it can be devastating for those caring for a loved one with HE. It is like watching your loved one become someone else, someone that you don’t know. This pain is captured in the movie, “He’s Back: Wrestling the Monster” at www.hesback.com.
About seven out of ten people with cirrhosis develop HE, although many cases are mild. Early HE diagnosis is critical, and may help reduce HE progression. People with chronic liver disease are at greater risk of developing a more chronic form of the disorder where symptoms get worse or continue to come back, known as “HE recurrence.”
HE may begin with subtle changes in behavior, mental state, and thinking ability. HE is graded on a scale of zero to four.
Grade 0 is hard to detect. In this stage, there are memory changes, impaired concentration, slight decrease in intellectual function, or loss of coordination.
Grade 1 includes a short attention span, sleep problems and mood changes such as depression or irritability.
Grade 2 is when forgetfulness is noticeable. Energy levels are low; speech may be slurred; doing simple mental tasks such as math or spelling may be difficult. Patients may have tremors, deterioration of handwriting and decreased small motor coordination. They may have shaking of the hands or “flapping” when the arms are held up front of the body with hands lifted like someone making a motion telling someone to “stop.”
Grade 3 is severe HE. Patients in this stage don’t know where they are, what the day is, or who the president is. They are confused and sleepy. Patients feel anxious and their behavior may be strange.
Grade 4: The last stage of HE is when the patient is comatose.
Don’t try to diagnose yourself. Most of us have days when we feel like we have grade 2 HE. Low energy and forgetfulness happen to everyone, even those without liver disease. If you have cirrhosis and those around you suspect that you have HE, see your doctor.
Dehydration and electrolyte abnormalities may trigger HE. Karen’s bike ride in extreme heat explains why her symptoms showed up on that particular day. Other conditions that may lead to HE are metabolic abnormalities, infection, constipation, surgery, eating too much protein, kidney problems and insufficient levels of oxygen in the body.
A variety of medications are used to treat HE, the most common being lactulose. Lactulose is a laxative that absorbs ammonia from the blood and carries it out via the colon. Lactulose is effective in reducing HE symptoms, but it comes with a price: diarrhea, flatulence, bloating, and other gastric problems. Neomycin, rifaximin, metronidazole, zinc, and probiotics are also used to treat HE. An article published June 2014 in Clinical Gastroenterology and Hepatology found that three months of probiotic administration significantly reduced measurable signs of HE, and was effective in preventing HE in patients with cirrhosis. (“Probiotics Prevent Hepatic Encephalopathy in Patients with Cirrhosis,” by Manish Kumar Lunia, et al.)
Patients with HE should consult with their medical providers before taking all medications. Drugs that suppress the central nervous system, such as sedatives and tranquilizers may worsen the symptoms. Alcohol and recreational drugs may also intensify HE. Drugs containing ammonium, including certain antacids, should be avoided.
Treating the underlying liver condition or liver transplantation may reverse HE or improve the symptoms. Since hepatitis C is a leading cause of end-stage liver disease, it makes sense that if hepatitis C is cured, patients will be spared the misery of HE. However, access to healthcare is still limited. I think about this every time I read another piece about the cost of the new hepatitis C drug, sofosbuvir. Some state Medicaid programs are unable to pay the high cost of treatment. Hepatitis C patients with HE are unable to advocate for themselves. It is up to us to fight for them.
“HE makes you feel very vulnerable. You can’t tell when you are in the middle of it. You must maintain relationships so people around you can tell if you are going off course. At the same time, HE hurts your social skills, so you are isolated and unable to communicate,” Karen told me. “You can’t think your way through to a solution. In fact, you may not know you aren’t cognitively sharp.” Can you imagine having HE and trying to navigate a cumbersome healthcare system? I can’t.
Karen is one of the lucky ones; she underwent hepatitis C treatment and the virus is now gone. Karen has not taken lactulose in two years. She still bikes, but her cadence is gentle and she rides in the morning when it is cool. Although we don’t have research on exercise and HE, there is plenty of evidence showing that regular physical activity is the best way to prevent brain deterioration. Karen follows strict exercise guidelines set by her liver specialist, guidelines that don’t increase pressure on the fragile vessels in her esophagus.
Karen is scrupulous about her diet. She knows how much protein she needs, limits her sodium, and eats food that is whole, fresh, and chemical-free. Most of all, Karen keeps her life simple. She meditates, does Yoga and practices acceptance. “I accept who I am,” says Karen. Sounds to me like a sensible way of life for us all.
Lucinda K. Porter, RN, is a long-time contributor to the HCV Advocate and author of Free from Hepatitis C and Hepatitis C One Step at a Time. Her blog is www.LucindaPorterRN.com
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Patients First: Extrahepatic Manifestations
—Alan Franciscus, Editor-in-Chief
In last month’s Patients First column I wrote about reporting symptoms to your medical provider and making sure that any symptoms are included in your medical records. I also touched briefly on extrahepatic manifestations (EH). In this month’s column I would like to discuss some of the more serious extrahepatic manifestations in greater detail for a variety of reasons—the main reason is that many medical providers are unaware of these serious conditions: Diagnosing HCV-related extrahepatic manifestations is important so they can be treated and also because successfully treating these conditions will add to the body of evidence that HCV treatment is recommended and needed. The more serious extrahepatic manifestations I will discuss are cryoglobulinemia and conditions associated with cryoglobulinemia including glomerulonephritis (kidney disease) and vasculitis, as well as a certain type of cancer called non-Hodgkin Lymphoma (NHL).
Cryoglobulinemia that is associated with hepatitis C is called mixed cryoglobulinemia. Hepatitis C accounts for more than 90% of cases of mixed cryoglobulinemia and it is the most common disorder that is related to the hepatitis C virus. It is caused by abnormal proteins in the blood called cryoglobulins that clump together when the blood is chilled and then dissolve when warmed. The proteins can be deposited in the small and medium sized blood vessels which then restricts the flow of blood and can lead to further problems. To diagnose cryoglobulinemia a blood test is given to detect the proteins called cryoglobulins. Important note: the blood sample must be kept at room temperature and handled correctly. Fortunately, while the markers are common in people with HCV the symptoms and disorders are uncommon.
The symptoms can be mild, moderate or severe.
The symptoms can include:
- Red or purple blotching skin—especially on the lower extremities of the body
- Rashes, sores, and ulcers
- Joint pain and inflammation
- Mild to severe pain
- Generalized pain
- Lymph node enlargement
- Numbness and tingling in the hands, legs and feet due to decreased blood flow and/or inflammation of the peripheral nerves (peripheral neuropathy)
- Stomach pain
- Internal bleeding and blood clot formation
Glomerulonephritis is a condition affecting the kidneys. It simply means inflammation of the kidney. It can be caused by many factors including cryoglobulinemia. But it can also be caused by hepatitis C disease progression and from circulating HCV antibodies and viral particles which can damage small blood vessels in the kidney (Membranous nephropathy).
Vasculitis (also called essential cryoglobulinemia vasculitis) is an inflammation of blood and lymphatic vessels caused by cryoglobulins. Vasculitis is sometimes referred to as the ‘hurting disease’ because it is commonly associated with pain. Vasculitis can affect almost every organ of the body.
The most common symptoms and conditions of vasculitis include:
- Purplish red spots usually found on the legs
- Joint aches and swelling as well as arthritis
- Cough, shortness of breath and lung disease
- Kidney disease, loss of protein through the urine
- Low red and/or white blood cells
- Chronic sinus congestion and infection, hearing problems, and inflammation of the nasal passages
- Damage to the vessels of the eyes
- Headaches, difficulty with coordination
- Pain and numbness in the arms and legs (neuropathy)
Diagnosis of vasculitis is similar to the diagnosis of cryoglobulinemia—a blood test to check for cryoglobulins, check for underlying autoimmune disease, skin and tissue biopsy and arteriography (pictures of blood vessels).
Treatment of Cryoglobulinemia and Associated Diseases
HCV Therapy: The treatment consists of treating the underlying cause—hepatitis C, but the results vary by the type of HCV medications used and the types of disorders.
In two studies that treated vasculitis with pegylated interferon, ribavirin and either boceprevir or telaprevir, complete clinical response rates were achieved in 57% and 79% of the patients treated.
To date there have not been any published studies of the newer HCV inhibitor therapies to treat cryoglobulemina or the conditions associations with it, but they are now recommended since the treatment duration is shorter, the HCV cure rates are higher and side effects are less severe.
Treating hepatitis C is generally recommended as a first line of treatment for cryoglobulemina.
Plasmapheresis: This procedure removes blood from the body, chills it and filters and removes the cryoglobulins and returns the blood back to the body.
Rituximab: An immunosuppressant drug that has been found to be successful when used to treat cryoglobulinemia and some of the conditions associated with it. It is usually given if HCV treatment does not work, but has also been found useful when used in combination with HCV therapies.
Non-Hodgkin Lymphoma (NHL) is a form of cancer that starts in the lymphatic system. The lymphatic system is an important network of lymph vessels that carry a clear fluid called lymph, made up of a type of white cell that helps to fight infection.
Lymphoma occurs when white blood cells divide continuously without pause, which prevents the cells from maturing. This causes the overproduction of immature cells that crowd out the mature white cells, platelets and red blood cells.
NHL is uncommon in people with hepatitis C and when it does occur it is usually after many years of ongoing HCV infection.
The symptoms of NHL include:
- Swollen, but painless lymph nodes—neck, armpits and groin
- Unexplained weight loss
- Fever and/or night sweats
- Coughing, trouble breathing, or chest pain
- Constant weakness and fatigue
- Pain, swelling, or a feeling of fullness in the abdomen
Diagnosis is usually made with a series of blood tests, physical tests, chest x-rays and possibly a biopsy to look at lymph tissue. In people with hepatitis C, the usual recommendation is to treat hepatitis C since it is believed that hepatitis C infection causes NHL.
Treatment of HCV-related NHL consists of closely monitoring NHL, but most likely the underlying cause—hepatitis C —will be treated. Hepatitis C treatment (especially successful treatment) has been found to lead to successful remission of NHL. This happens only in people with HCV-related NHL, which validates that hepatitis C causes NHL.
Hopefully, there will be studies with the newer HCV inhibitors soon to treat this and many other under-recognized HCV-related extrahepatic manifestations.
Get Tested. Get Treated. Get Cured.
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