Case report and review
Volume 12, Issue 1, Pages 51-53 (March 2011)
Hisham O. Akbar
Received 11 February 2010; accepted 10 June 2010. published online 08 February 2011.
Abstract
Chronic hepatitis C (CHC) is variably prevalent around the world and is usually a blood-borne infection. Most patients will have subclinical infection at the onset, but patients who develop acute hepatitis can spontaneously clear the virus upon immune activation. Up to 80% of CHC patients will progress to chronic infection. CHC is unlikely to clear spontaneously. This article describes two female patients with transfusion-acquired CHC diagnosed by both positive hepatitis C virus (HCV)-Ab and hepatitis C virus–polymerase chain reaction (HCV–PCR) tests. Both patients cleared the infection spontaneously after more than 5 and 25years of CHC infection, respectively.
Introduction
Chronic hepatitis C (CHC) is a worldwide problem, with an estimated 170–180 million hepatitis C virus (HCV)-infected individuals globally [1]. HCV is a leading cause for chronic liver disease (CLD), with an estimated 75–85% of HCV-infected individuals progressing to CLD with a risk of liver cirrhosis, advanced liver disease and liver cancer [2], [3], [4]. CHC is also a leading indication for liver transplantation [3], [5]. Acute hepatitis C infection can sometimes result in spontaneous clearance of HCV in the first month after the onset of symptoms, but most of the post-acute hepatitis C-infected patients will progress to CLD [3], [6].
Many host factors have been linked to the spontaneous clearance of HCV, which include age. Children and young adults have a higher chance of spontaneous HCV clearance compared with older individuals [7], [8], [9]. Female patients were also found to have a higher chance of viral clearance compared with males [10], [11]. Human leucocyte antigen (HLA) class 1, HLA class 2 and genetic polymorphism at the IL28B gene, which encodes the III interferon (INF-3), were also found to be associated with spontaneous HCV clearance [12], [13], [14].
Viral factors may play a role in spontaneous viral clearance; lower levels of HCV viraemia can predict spontaneous viral clearance [15]; however, the role of the HCV genotype in spontaneous viral clearance is debatable [7], [16].
Spontaneous HCV clearance is thought to be an outcome of virus–host interactions that will activate the host immune system through cellular or antibody responses that will induce viral clearance [17], [18], [19]. Spontaneous HCV clearance has been also reported after acute hepatitis, resulting from infection with other hepatic viruses (A, B and D) [20], [21], [22].
This report describes two patients with CHC, who spontaneously cleared HCV after a long period of infection.
Case presentation
First patient
A 23-year-old female had been followed up at the hepatology clinic since the age of 12years. At the age of 11years, she had complicated perforated acute appendicitis with loculated pelvic collection and severe peritonitis. She underwent emergency laparotomy, and she required transfusion with two units of blood. At the preoperative work-up, her liver function tests were normal, and screening for hepatitis B surface antigen (HBsAg) and HCV antibodies by enzyme-linked immunosorbent assay (ELISA) was negative. The two units of blood that she received also tested negative for the two viruses by ELISA. She had an uneventful postoperative recovery, and she was discharged. Four weeks after the operation, she had jaundice, fever and right upper quadrant abdominal pain. Clinical examination revealed jaundice and right hypochondrial tenderness. Her liver enzymes were elevated (Table 1). Hepatitis serology revealed a positive HCV-Ab test and negativity for hepatitis B and A viruses. Complete blood count was normal. She was also tested for antinuclear–antibody (ANA), immunoglobulin G (IgG) and coeruloplasmin, all of which were normal. One month later, her liver enzymes were still elevated, and she was referred to the hepatology clinic. After a follow-up of 4months, her liver enzymes were down to 1.5–2 times the normal levels (Fig. 1), and they remained at that level. The hepatitis C virus–polymerase chain reaction (HCV–PCR) was positive, with a viral load of 53,304IUml−1. She did not have any follow-up for 1year nor did she receive treatment, and when she returned for a follow-up, her viral load was 70,200IUml−1. She was scheduled to start treatment with a combination of pegylated interferon and ribavirin. The upper gastrointestinal endoscopy and the abdominal ultrasound were normal. A test for the HCV genotype was ordered, and all of her liver enzymes were found to be fluctuating (Fig. 1). Thereafter, she did not have follow-up at the hepatology clinic for 2years. When she was seen again after 2years, her liver enzymes were normal, and she was negative for HCV RNA as tested by PCR. She again denied any type of treatment, including herbal medicine. Currently, her liver enzymes are at normal levels, with undetectable levels of HCV RNA for the past 5years.
Table 1. Laboratory data for both patients.
......................Lab test (normal range)...... First patient ...Second patient
Liver function tests .......ALTUl−1 (5–50)................ 558................ 25
....................................ASTUl−1 (5–55)................ 737................ 14
...................................ALPUl−1 (0–136)............ 1034................. 88
...............................Albumingl−1 (35–50)............... 43.................. 38
...............................Total bilirubin (0–17).............. 266................... 5
Complete blood count...WBCKμl−1 (4.5–11.5)....5.66................ 4.2
.....................................Hbdl−1 (12–15) ..............12.8...............13.2
......................PlateletsKμl−1 (150–450)............... 180............. 1309
HCV–PCR.............. Undetectable........53,304IUml−1...... 17,871IUml−1
Fig. 1. The results liver function tests for the first patient at different dates.
Second patient
A 52-year-old female was discovered to have CHC by HCV-Ab ELISA testing at the age of 50years during an investigation for the cause of fatigability at that time. She had received a blood transfusion more than 20years prior during a caesarean delivery, but she never had a history of jaundice. She denied any recent exposure to risk factors for HCV transmission, such as getting a tattoo, and there was no family history of HCV infection. Transaminases and complete blood count were normal (Table 1), as was the abdominal ultrasound and upper gastrointestinal endoscopy. She maintained normal liver enzyme levels all thorough her follow-up period. She was positive for HCV RNA by PCR, with a viral load of 17,871IUml. On the next visit, her viral load was 7852IUml, and the genotype result was genotype 1. She was advised to start treatment, but she preferred to delay the treatment because she did not have many symptoms, and she was worried about the side effects of the treatment. She had regular outpatient follow-up every 3–4months, and her viral load declined spontaneously over time (Fig. 2). She denied any treatment, including herbal medicines. At her latest follow-up, HCV RNA was undetectable, but she planned to continue follow-up at the hepatology clinic with HCV RNA testing every 4–6months to check for possible viral recurrence.
Fig. 2. The results of HCV–PCR for the second patient at different dates.
Discussion
These two patients represent unusual outcomes of chronic CHC. Both patients had HCV clearance after documented chronic infection, and had a transfusion-acquired HCV infection. In the case of the first patient, the transfused blood was tested for HCV by an ELISA HCV-Ab test, which was negative. This negative result could be due to the donor having been infected in the window period before the development of HVC-Ab [23], [24]. This is the reason that blood banks around the world currently include HCV–PCR methods for the accurate detection of early infection during donor screening [25], [26]. The second patient received a blood transfusion before donor screening for HCV was started.
Both patients were females; thus, the outcomes of these patients are consistent with the findings of Grebely et al., who reported a higher rate of HCV clearance in infected female patients as compared with males [11]. The first patient had acute hepatitis at the age of 12years; however, she did not immediately clear HCV, and she progressed to CHC, with documented positive HCV–PCR tests for up to 5years after infection. Then, she had spontaneous HCV clearance. Similarly, Wietzke et al. and Lehmann et al. reported a high probability of HCV clearance in young individuals [7], [16]. Because of her poor compliance with follow-up, close viral load monitoring and genotyping were not obtained for the first patient. Therefore, gradual reduction of the viral load was not documented.
The second patient had better compliance with follow-up and monitoring after she was diagnosed. Acute hepatitis, followed by clearance of HCV, was again unlikely in her case because her liver function was monitored at 3-month intervals and was normal on all occasions. Although there is no cut-off level for HCV RNA that is reported to be associated with clearance of the virus, this patient was documented to have gradual declines in her HCV–PCR results over time, until she had completely cleared the virus. She was also found to have HCV genotype 1. Lehmann et al. showed that HCV genotype 1 is less likely to be spontaneously cleared than genotype 3 [16]. Fortunately, this patient preferred to delay treatment because of fear of side effects. If she had received HCV treatment with a combination of pegylated interferon and ribavirin, this HCV viral clearance would have been considered a treatment response. The second patient had also complained of fatigue and joint pain that resolved after viral clearance. Barrett et al. reported an association between positive HCV–PCR tests and either rheumatological symptoms or positive autoantibodies [27]. As compared with most of the previous data on HCV clearance after chronic infections, which relied on the detection of HCV-Ab [10] (which may give false positive results in some patients) and negative HCV–PCR, both patients had documented positive HCV–PCR tests.
The presence of underlying genetic predictors is possible, but most of the putative genetic associations have not yet been confirmed; thus, routine genetic testing of such patients is not justified [28]. Neither of the two patients had genetic tests nor HLA-typing performed.
Based on this report, and on previously reported data about HCV clearance, in the future, more recognition of viral and host factors involved in spontaneous HCV clearance may allow physicians to avoid prescribing unnecessary HCV treatment, especially in young adults or adolescents who are expected to have higher chances of spontaneous viral clearance and lesser risk of progression to CLD.
Conflicts of interest
The authors declared that there was no conflict of interest.
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doi:10.1016/j.ajg.2011.01.010
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