Hepatitis C and Cirrhosis in a Vietnam Veteran
A 64-year-old man has moved to your area and will be using your practice for his medical care. His major medical diagnosis is cirrhosis of the liver due to hepatitis C diagnosed 4 years ago prior via a liver biopsy.
He has mild hypertension effectively managed by a thiazide diuretic alone. He has never had variceal bleeding, but had an episode of hepatic encephalopathy 2 years ago after general anesthesia. He used alcohol in the past but has refrained since his diagnosis. He smokes 1 pack of cigarettes every 3 days. He is a retired postal worker and a Vietnam War veteran.
The physical exam reveals a well appearing male in no acute distress. Vital signs—including blood pressure—are all normal. Head, eyes, ears, nose and throat (HEENT) examination is negative for conjunctival pallor and scleral icterus. There are no enlarged lymph nodes. Chest and heart are normal. Abdomen reveals a firm liver edge 1 cm below the right costal margin without nodules or rubs. There is no gross ascities or distended body wall veins. Extremities are negative for edema and neurological exam is normal.
Initial laboratory evaluation reveals normal hemogram and basic chemistry profile. Bilirumin is normal, serum albumin is 3.2 gms/dL, and INR is 1.4 (prothrombin time was 17 seconds vs control of 12 seconds). Serum alanine transaminase was 62 u/L (normal <40 u/L), while serum aspartate transaminase was 100 u/L (normal <25 u/L).
Hepatitis C studies reveal his infection to be genotype 1. His hepatitis C virus (HCV) RNA is 1650 Iu/mL.
This case study addresses the current data on the epidemiology, natural history, and prognosis of hepatitis C—estimated to have infected approximately 1.5% to 2% of individuals, or about 4 million people in the United States.1 The epidemic primarily affects people born between 1946 and 1964 (the “baby boomers”), and is following a course indicating peak infection rates from the mid 1960s through the early 1980s.1
Large surveys indicate that the following significant risk factors help explain the epidemiology of this group: history of IV drug abuse, even casual, and not readily volunteered in initial history taking (relative odds ratio of 148.9); sexual promiscuity defined as >20 partners (5.2); and a blood transfusion prior to 1982 (2.6).2
In addition, the patient falls into the 20% of hepatitis C patients who have progressed to chronic liver disease and even cirrhosis.
Which of the following statements about this patient is correct?
A. Cirrhosis-related hepatocellular carcinoma continues to decrease in incidence and as a cause of mortality in hepatitis C patients.
B. Since he already has cirrhosis, he will not benefit from antiviral therapy.
C. Hepatitis C screening in high-risk population is of little benefit and would not be helpful.
D. A cure is now likely for most people affected by hepatitis C.
(Answer and discussion on next page)
Correct Answer: D
Therapy for hepatitis C infection continues to improve. A variety of effective pharmacologic agents are now available that make viral clearance, and likely a cure, a possibility in a majority of patients. Current data indicate a viral clearance rate of 70% using modern therapy regimens.3,4
Three families of agents comprise the usual therapy for hepatitis C:
• The pegylated form of interferon alfa is part of every regimen. Its mechanism is diverse, but on the whole, it acts by inducing activation of host genes that have antiviral functions.
• The second core of hepatitis C therapy—ribavirin—also seems to have a diverse array of actions but precise mechanisms of action remain unclear.
• Finally, protease inhibitors, boceprevir and teleprevir, now complete what appears to be the most effective treatment regimen for hepatitis C.3
Standard of Care
Using the usual end point of successful therapy as a goal—undetectable HCV RNA serum 24 weeks after treatment has been stopped, which correlates with symptom reduction and reduced rates of negative clinical outcomes—the 2 agent regimen of interferon/ribavirin yield 70% to 80% sustained responses in HCV genotypes 2 or 3 and 45% to 70% in other genotypes.3 The addition of either protease inhibitor has now been shown to bring response rate up to levels approaching 70% in all genotypes, including the most common type 1. Since sustained viral response is correlated to improved clinical outcomes in hepatitis C populations, a cure seems likely for most patients treated in a timely and effective manner (Answer D).
Demographics indicate that a majority of hepatitis C cases are found in populations born between 1945 and 1964. However, many patients are unaware of their diagnosis, which is often only made when transaminase elevation is found on incidental blood studies. Clinical data by the CDC shows that access to hepatitis C care correlated with earlier and more frequent use of antiviral therapy and likely more improved long-term outcomes.1,5 The CDC therefore made the recent recommendation of a one-time test for everyone born between 1945 to 1964 to identify more people who might be candidates for and benefit from earlier diagnosis.5 Thus current data and opinion support screening in that high-risk population and Answer C is incorrect.
The abovementioned therapy regimens are actually most indicated in cases with high HCV RNA and advanced stages of fibrosis since that group is at the highest risk for disease progression. Sustained response results in lower rates of liver failure and risk for liver-related death in this group, a fact that has been firmly established in studies.6,7 Thus, Answer B is incorrect.
Despite the improvements in treating hepatocellular carcinoma (HCC), the improvement in overall survival has significantly shifted the causes of death. Thus, less patients succumb to progressive liver failure, esophageal hemorrhage and infection—but this longer survivorship has resulted in a far higher HCC incidence and subsequent mortality (eg, 33% in 1958-1964 to 55% in 1975-1984).6 Therefore, although there is far improved management of the complication (eg, ablative techniques and transplantation), its incidence and subsequent mortality have so relatively increased that Answer A is an incorrect statement.
Outcome of the Case
The potential benefits, risks, and problems associated with therapy for hepatitis C were discussed with the patient. A decision to proceed with
a triple therapy regimen—pegylated interferon, ribavir, and telapravir—was made.
He was able to sustain therapy for the 24-week period and had undetectable HCV RNA at that time. He is currently continuing therapy and being followed by interval HCV RNA testing.
As drug therapeutics for all genotypes of hepatitis C continue to improve, a cure is now likely for a majority of patients. This improved prognosis covers essentially all subgroups—from asymptomatic to established cirrhosis cases. In fact, the latter may benefit the most. New CDC recommendations suggest screening persons born between 1945 and 1965 to allow for early diagnosis and treatment. Unfortunately, hepatocellular carcinoma remains a complication.
Ronald Rubin, MD, is a professor of medicine at Temple University School of Medicine and chief of clinical hematology in the department of medicine at Temple University Hospital, both in Philadelphia.
1. Deinstag JL. Hepatitis C: A bitter harvest. Ann Int Med. 2006;144:770-771.
2. Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Int Med. 2006;144:705-714.
3. Lang TJ, Ghany MG. Current and future therapies for hepatitis C virus infection.
N Eng J Med. 2013;368:1907-1917.
4. Holmberg SD, Spradling PR, Moorman AC, Denniston MM. Hepatitis C in the United States. N Eng J Med. 2013;368:1859-1861.
5. Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among person born during 1945-1965. MMWR Recom Rep. 2012;61:1-32.
6. Telwalker JA, Kamath PS. Influence of recent advances in medical management on clinical outcomes of cirrhosis. Mayo Clinic Proc. 2005;80:1501-1508.
7. Black M, Thomas R. Antiviral treatment for hepatitis C cirrhosis: is the effort justified? Ann Intern Med. 2008;149:427-428.