Hepatitis C

Mitchell Shiffman, MD: What Challenges Remain in Treating Hep C?

“Are there really any challenges left in treating hepatitis C?”


This question was posed by Mitchell Shiffman, MD, hepatologist at the Bon Secours Liver Institute of Virginia, in his talk at the American College of Gastroenterology (ACG) 2018 Annual Scientific Meeting on October 9.


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The answer? No, explained Dr Shiffman, citing the 2014 advent of highly-effective direct-acting antiviral (DAA) therapies, which have brought us closer to the eradication of hepatitis C virus (HCV) infection than ever before. First- and second-line DAAs are highly effective in the treatment of HCV, often resulting in extremely high sustained virologic response (SVR) rates of 95% to 99%.


Treatment has become possible in a wide range of patients, largely regardless of genotype, race/ethnicity, age, and comorbidities such as obesity, cardiopulmonary disease, anemia, and thrombocytopenia.


DAAs have also aided in significantly lowering the rate of hepatitis C-related liver transplants. HCV infection with or without liver cancer was once the number one indication for liver transplantation, accounting for 68% of all liver transplants in 2000. This rate remained consistent until DAAs emerged in 2014, which ultimately resulted in a 22% decline of liver transplants for this indication over the next 3 years, Dr Shiffman said.


“If we just keep going, we have the possibility of virtually eliminating the need for liver transplantation in patients with hepatitis C in just another 5 to 10 years,” he added.


Although there are no more challenges per se in HCV treatment in the midst of such rapid progress, there are still several concerns that clinicians should be aware of before and upon prescribing DAA therapies to their patients.


Next Page: What Are The Top Remaining Concerns in Treating Hep C?

Treatment Failure


Although rare, treatment failure can be a cause for concern. It only affects 2% to 3% of cases, or approximately 2 in every 1000 patients.


“The most common and most difficult group to treat- whether it’s first-line or repeat therapy- is genotype 3 patients,” Dr Shiffman explained. “Most of the patients who [fail first- and second-line therapy], in my experience, are going to be genotype 3 with cirrhosis. They have the lowest SVR across the board,” he said.


It is important to continue monitoring these patients and screen for liver cancer. Clinicians may also want to consider retreatment, liver transplantation, or whether or not they are engaging in drug use.


Hepatitis B Reactivation


Another key action to take prior to initiating DAAs is to screen for hepatitis B virus (HBV) infection. Patients with evidence of HBV infection need to be monitored closely, even after their hepatitis C has been cured.


In those who are hepatitis B surface antigen (HBsAg) positive, the rate of reactivation is very high, said Dr Shiffman. It can occur during a course of DAA therapy or after it is completed.


As a result, HBsAg-positive patients with inactive disease need to receive prophylactic therapy to prevent reactivation, which could otherwise lead to death.


However, he noted, the rate of reactivation is quite low in those who are HBsAg-negative and only demonstrate evidence of previous infection through HBV core antibody alone (typically less than 1% to 2% of cases).


Could DAAs Induce Liver Cancer?


There is not enough data to support the notion that DAA therapy could induce liver cancer in patients who also have advanced liver disease, said Dr Shiffman. These patients should be still be treated, as untreated HCV is associated with a higher risk of developing liver cancer vs treated HCV.


However, patients with HCV infection and cirrhosis should still be screened for liver cancer, as their risk is likely lifelong.


The risk factors for developing liver cancer, he noted, are the same among DAA-treated and untreated patients: diabetes, older age, and more portal hypertension.


Moreover, decompensation and abnormal or low albumin and platelets are also among the top risk factors for liver cancer in patients with advanced liver disease. These factors can help determine the severity of liver disease, which can in turn affect liver cancer risk.


Treating Active Drug Users


Dr Shiffman addressed another difficult question many clinicians often face: should we treat active drug users?


“[T]he cure rate is the same [among patients with no intravenous drug use, patients on opioid substitution therapy, and those who are still actively injecting drugs],” he said. However, it is still important to consider the recurrence rate of HCV in this patient population.


Research has shown that risk factors for reinfection include drug use, younger age, and lower educational status.


The impact of treating HCV in this patient population could produce a number of positive impacts, Dr Shiffman said. DAA-treated patients receiving opioid substitution therapy tend to remain on this therapy, and DAA receipt also seems to reduce alcohol use.


However, although treating those who inject drugs tends to result in a slight decline in their drug use, these patients often appear to pick up these habits again after treatment has been completed.


Renal Transplant Candidates: To Treat or Not to Treat?


Finally, he outlined considerations clinicians should take prior to treating HCV infection in dialysis patients with end-stage renal disease (ESRD) who are candidates for a renal transplant.


“The thing to do for this patient is not go ahead and treat them,” Dr Shiffman emphasized. “[W]henever I see a patient on dialysis referred for me, the first thing I ask them is, ‘are you a candidate for a renal transplant?’”


Among patients who are candidates for renal transplant, he said, clinicians should assess for renal fibrosis and hold off on administering HCV treatment until after their renal transplant is performed.


Importantly, all renal transplant candidates who defer hepatitis C treatment and accept an HCV-positive kidney will receive a transplant within 3 years, he noted. However, candidates who are first treated for HCV infection and opt to wait for a non-infected kidney face a 15% rate of transplant after 6 years.


—Christina Vogt



Shiffman M. Challenges in hepatitis C management: DAA failures, special populations, and controversies. Presented at: The American College of Gastroenterology 2018 Annual Scientific Meeting; October 9, 2018; Philadelphia, PA.