Viral Hepatitis: Viral Hepatitis: Hepatitis C Screening to Cure

0:00Welcome to Board Pearls. This is episode three of three of the Viral Hepatitis chapter, in the Liver Disease module. This episode is hepatitis C, from screening to cure and through the special populations. A man with a positive antibody on screening shows why hepatitis C is now curable, who gets screened, how the antibody is confirmed, what has to be checked before treatment, which two regimens cure almost everyone, and what sustained virologic response, SVR, twelve means. A man who relapsed shows the salvage regimen. Then three patients don't fit the standard pathway: a woman with decompensated cirrhosis awaiting transplant, who also shows who still needs cancer surveillance after cure, a man on dialysis, and a pregnant woman.

0:43Here's the first patient. A thirty-six-year-old man has a positive hepatitis C antibody on routine screening. He injected drugs in his twenties and has been in recovery for six years. He feels well. His alanine aminotransferase, ALT, is sixty-one, and the rest of his liver panel is normal. He's never been treated and assumes he'll need injections for a year, as a friend did a decade ago.

1:07His positive antibody points to hepatitis C infection, and his friend's year of injections is out of date, because hepatitis C is now curable with pills. Direct-acting antivirals target the nonstructural proteins the virus needs to replicate and assemble, and they come in three classes named by suffix. The NS3/4A protease inhibitors end in "previr": glecaprevir, voxilaprevir, and grazoprevir. The NS5A inhibitors end in "asvir": velpatasvir, pibrentasvir, ledipasvir, and elbasvir. The NS5B polymerase inhibitors end in "buvir," with sofosbuvir the nucleotide analog and dasabuvir the non-nucleoside. Combinations achieve a sustained virologic response in more than ninety-five percent of patients across genotypes, and that response is a durable cure, with relapse under one percent at five years. His treatment will be pills for weeks.

2:04He was found because screening is universal. The American Association for the Study of Liver Diseases, AASLD, and the Infectious Diseases Society of America, IDSA, recommend screening every adult eighteen and older at least once, and yearly for people who inject drugs, men with human immunodeficiency virus, HIV, who have unprotected sex with men, and other high-risk groups. Universal screening replaced birth-cohort screening because new infections have shifted to adults aged twenty to thirty-nine, driven by injection drug use.

2:37Some risk factors prompt testing at any age. They include injection drug use ever; intranasal cocaine; long-term hemodialysis; percutaneous or parenteral exposure in unregulated settings; a mother with hepatitis C; a transfusion or organ transplant before July nineteen ninety-two, when donor screening began; clotting factor concentrates before nineteen eighty-seven; incarceration; HIV; starting HIV pre-exposure prophylaxis; undiagnosed chronic liver disease; and a raised ALT.

3:08His antibody alone doesn't prove current infection, so the sequence is the antibody first, with a reflex to hepatitis C virus, HCV, ribonucleic acid, RNA. Antibody with RNA means infection, acute or chronic. Antibody without RNA means a resolved infection or a false-positive antibody. Spontaneous clearance occurs in fifteen to fifty percent, more often after a symptomatic acute illness, in women, at younger ages, and with the IL28B CC genotype. A forty-nine-year-old woman with a positive antibody and an undetectable reflex RNA has no active infection and needs no treatment.

3:47The antibody can also lag behind the infection. It turns positive one to three months after infection, so a negative antibody in a patient with suspected acute infection doesn't settle anything, and HCV RNA is checked directly. RNA without antibody is rare, and it means a false-positive RNA, an early acute infection before seroconversion, or infection in an immunosuppressed host who can't make antibody. Acute infection, once viremia is documented, is treated promptly with the same regimens and durations as chronic infection, because waiting for spontaneous clearance trades cures for chronic infection. His RNA is one point two million international units per milliliter, and six years without drug use means his infection is chronic.

4:30He has chronic hepatitis C, and before treatment he needs a short workup. It includes a chemistry panel and blood count, HIV testing, hepatitis B serology, a quantitative HCV RNA, fibrosis assessment by elastography or by the aspartate aminotransferase-to-platelet ratio index, APRI, and the Fibrosis-4 index, FIB-4, and a pregnancy test when relevant. Hepatitis B surface antigen, surface antibody, and core antibody are checked because hepatitis B reactivation during direct-acting antiviral therapy has been reported in patients positive for surface antigen. Genotype testing is optional with pangenotypic regimens and is reserved for treatment-experienced patients and special situations.

5:14His HIV test and all his hepatitis B markers are negative, so he has nothing to reactivate, and he's vaccinated against hepatitis B. His FibroScan is six kilopascals, without cirrhosis.

5:26Without cirrhosis, he can take either of the two preferred regimens. Sofosbuvir-velpatasvir, an NS5B nucleotide inhibitor with an NS5A inhibitor, is given for twelve weeks to treatment-naive patients with or without compensated cirrhosis across genotypes one through six, and with ribavirin it's the regimen for decompensated cirrhosis. Glecaprevir-pibrentasvir, a protease inhibitor with an NS5A inhibitor, is given for eight weeks to treatment-naive patients without cirrhosis or with compensated cirrhosis across genotypes one through six, extended to twelve to sixteen weeks in selected treatment-experienced patients. The choice comes down to duration, interactions, and cost. Sofosbuvir-ledipasvir and grazoprevir-elbasvir remain for genotype-specific niches.

6:13Everyone with chronic hepatitis C is treated, except those whose short life expectancy can't be changed by cure, transplant, or other therapy. Past or current drug use isn't a reason to defer.

6:26Interactions are checked before prescribing. Sofosbuvir with amiodarone risks symptomatic bradycardia. Ledipasvir depends on stomach acid for absorption, so proton pump inhibitors reduce it. Protease inhibitors interact with drugs such as cyclosporine, and statins need attention. He takes nothing regularly, so he takes glecaprevir-pibrentasvir for eight weeks.

6:50His cure is judged by SVR twelve, an undetectable HCV RNA twelve weeks after the end of treatment, because relapse shows up in that window. It doesn't mean twelve weeks of treatment. His RNA is undetectable twelve weeks after his last dose, so he's cured.

7:07Cure brings more than a negative test. It brings fibrosis regression, with some reversal in up to forty percent of patients with cirrhosis, a lower risk of liver cancer, lower all-cause and liver-related mortality, and modest improvement in the Model for End-Stage Liver Disease, MELD, and Child-Pugh scores of decompensated patients. Disease outside the liver improves too. Most mixed cryoglobulinemia improves, lymphoma associated with hepatitis C can remit with cure alone, porphyria cutanea tarda, membranoproliferative glomerulonephritis, and lichen planus improve, and diabetes and cardiovascular events become less common.

7:46His fibrosis stage decides his follow-up, not his drug. Compensated cirrhosis keeps the same regimens and durations, but it means cancer surveillance every six months indefinitely after cure. He had no cirrhosis at cure, so he doesn't need liver cancer surveillance for hepatitis C.

8:04A failed regimen needs salvage, and a second man shows it. A forty-one-year-old man relapsed after sofosbuvir-velpatasvir, a regimen containing an NS5A inhibitor and sofosbuvir. His salvage regimen is sofosbuvir-velpatasvir-voxilaprevir for twelve weeks, which adds a protease inhibitor, and here genotype and resistance information can still matter.

8:27The standard regimens assume a liver that can handle them, and the third patient shows what happens when it can't. A fifty-nine-year-old woman has hepatitis C cirrhosis with ascites and one episode of hepatic encephalopathy, Child-Pugh class B, with a MELD of fourteen and an albumin of three point one. She's being evaluated for liver transplant and has never been treated. Her referring doctor wants to start glecaprevir-pibrentasvir.

8:51She has decompensated hepatitis C cirrhosis, and that makes glecaprevir-pibrentasvir the wrong drug. The NS3/4A protease inhibitors, glecaprevir, voxilaprevir, paritaprevir, grazoprevir, and simeprevir, are cleared by the liver, accumulate in hepatic impairment, and have been associated with severe decompensation in Child-Pugh B and C cirrhosis. So the Food and Drug Administration, FDA, carries a boxed warning against regimens containing a protease inhibitor in decompensated disease. Compensated cirrhosis tolerates glecaprevir-pibrentasvir, but decompensated cirrhosis doesn't.

9:31Her regimen is sofosbuvir-velpatasvir for twelve weeks, with weight-based ribavirin when feasible, which gave the highest cure rates in decompensated disease, or sofosbuvir-velpatasvir alone for twenty-four weeks when ribavirin is contraindicated. Neither component is a protease inhibitor.

9:48Because she's a transplant candidate, the timing needs a decision, and it turns on what's called MELD purgatory. A patient who clears hepatitis C may improve enough to lower her MELD and her priority for a liver, but not enough to feel well, so cure before transplant can reduce her access to a liver without restoring her quality of life. The rule is to treat before transplant when the MELD is about fifteen to eighteen or lower, the albumin is above two point eight, and the age is under sixty-five, and to defer treatment until after transplant when the MELD is higher. The decision is made with her.

10:23She meets all three criteria, so she's treated now. The same pretreatment workup applies, and her hepatitis B serology matters especially, because a reactivation flare would be dangerous in a decompensated liver. She takes sofosbuvir-velpatasvir with ribavirin for twelve weeks and reaches SVR twelve, and her MELD falls modestly over the next year, a real improvement but rarely a return to normal.

10:47With a MELD of twenty-four, she'd have been transplanted first. Treatment after transplant cures more than ninety-five percent of patients with graft fibrosis of stage zero to three or compensated cirrhosis, using glecaprevir-pibrentasvir, sofosbuvir-ledipasvir, or sofosbuvir-velpatasvir for twelve weeks, and a decompensated graft follows the same rule against protease inhibitors. The challenge after transplant is interactions: calcineurin inhibitors, cyclosporine in particular, with protease inhibitors; statins; amiodarone with sofosbuvir; and proton pump inhibitors with ledipasvir.

11:24Her cure doesn't end her follow-up, because she had cirrhosis. Cure reduces the incidence of liver cancer by roughly seventy percent compared with untreated cirrhosis, but the risk that remains still justifies surveillance. So AASLD recommends ultrasound, with or without alpha-fetoprotein, every six months indefinitely in patients who had cirrhosis at cure, and she stays in surveillance for life.

11:48The lesser fibrosis stages are handled differently. Stage three bridging fibrosis without cirrhosis at cure isn't an indication for surveillance under the twenty twenty-three AASLD guidance. Stage one or two fibrosis with other risk factors, such as ongoing alcohol use, fatty liver disease, or persistent diabetes, should have fibrosis reassessed two to five years after cure. And direct-acting antivirals don't increase cancer recurrence after curative resection or transplant. Chapter twenty-four covers surveillance.

12:19Kidney disease changes the choice in the other direction, and the fourth patient shows it. A sixty-two-year-old man on hemodialysis has hepatitis C without cirrhosis. Sofosbuvir was once avoided in kidney failure, but current guidance doesn't formally restrict it, and trials have shown it's safe and effective below an estimated glomerular filtration rate, eGFR, of thirty, including on dialysis. Still, glecaprevir-pibrentasvir is the easier and preferred choice in advanced kidney disease or dialysis when the liver isn't decompensated, because it contains no nucleotide. Grazoprevir-elbasvir is also safe for the kidneys but limited to genotypes one and four. He takes glecaprevir-pibrentasvir, the best choice for his kidneys and the wrong one for the woman's decompensated liver.

13:09Pregnancy is a named exception to treating everyone, and the last patient shows why. A thirty-one-year-old woman has a positive hepatitis C screen at her first prenatal visit, where AASLD now recommends universal screening. Direct-acting antivirals aren't approved in pregnancy in the United States, so ideally women are treated before pregnancy, and a diagnosis made during pregnancy is treated after delivery.

13:29Her pregnancy is managed around transmission. Vertical transmission occurs in five to fifteen percent, and more often with HIV coinfection. Procedures that expose the fetus to maternal blood, such as scalp electrodes and internal monitors, are avoided when possible. Breastfeeding isn't a transmission risk. Hepatitis C is associated with intrahepatic cholestasis of pregnancy, so that's watched for.

13:52Her treatment and her baby's testing come after delivery. About ten percent of women clear the virus after delivery, so her HCV RNA is rechecked before postpartum treatment. Her baby is tested with HCV RNA at two to six months, and antibody with reflex RNA at eighteen months or later is reserved for children who weren't tested earlier. If ribavirin is ever part of a regimen, it's teratogenic, with a six-month washout after the last dose, both for women taking it and for the female partners of men taking it.

14:24Here are the traps the boards set in these patients. Screening isn't limited to risk factors or a birth cohort. A positive antibody isn't the end of the workup without an RNA. A negative antibody doesn't rule out acute infection. Hepatitis B serology comes before treatment. Genotype testing isn't required before a pangenotypic regimen. And drug use, past or current, isn't a reason to defer treatment.

14:48The regimen traps follow. SVR twelve means twelve weeks after treatment, not twelve weeks of treatment. Glecaprevir-pibrentasvir and every other protease inhibitor are avoided in decompensated cirrhosis, where ribavirin is added, or the course is extended to twenty-four weeks without it. A transplant candidate with a high MELD isn't treated before transplant without weighing access to a liver. Sofosbuvir isn't avoided on dialysis on old grounds. And amiodarone with sofosbuvir, and proton pump inhibitors with ledipasvir, are interactions to catch.

15:23The pregnancy and follow-up traps close the list. Treatment waits until after delivery, and the RNA is rechecked first. An exposed infant is tested with RNA at two to six months, not antibody. Surveillance doesn't stop after cure when cirrhosis was present. And stage three fibrosis alone doesn't call for surveillance.

15:43So, start to finish. Direct-acting antivirals from three classes cure more than ninety-five percent of hepatitis C. Screen every adult at least once with antibody and reflex RNA, yearly with ongoing risk, and check RNA directly when acute infection is suspected. Before treatment, check hepatitis B serology and stage fibrosis, and treat genotype as optional.

16:11Most patients are cured with sofosbuvir-velpatasvir for twelve weeks or glecaprevir-pibrentasvir for eight, including those with compensated cirrhosis, with sofosbuvir-velpatasvir-voxilaprevir after an NS5A or sofosbuvir failure. SVR twelve means an undetectable RNA twelve weeks after treatment ends.

16:30In decompensated cirrhosis, never use a protease inhibitor. Give sofosbuvir-velpatasvir with ribavirin for twelve weeks, or alone for twenty-four, and treat before transplant only with a MELD of about fifteen to eighteen or lower, an albumin above two point eight, and an age under sixty-five. After transplant, watch the interactions. In advanced kidney disease, glecaprevir-pibrentasvir is the easy choice.

16:50Don't treat during pregnancy. Recheck the RNA after delivery, and test the infant with RNA at two to six months. After cure, continue cancer surveillance every six months indefinitely if cirrhosis was present, but not for stage three fibrosis alone.

17:11That completes the Viral Hepatitis chapter. The next chapter is drug-induced liver injury and acute liver failure.

17:19For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode three of three of chapter eighteen, and I'll see you in the next one.