□ CASE REPORT □

Rapidly Progressive HCV in a Hypogammaglobulinemic Patient

Fatih Ermis, Filiz Akyüz, Kadir Demir, Fatih Be"ısık, Güngör Bozta" and Zeynel Mungan

Abstract

Contrary to the widely known view of the insidious, slowly progresive pattern of C, a rapidly progressive cirrhotic form can devolop in immunodeficient conditions. Hepatitis C leads to cirrhosis in im- munocompetent hosts after 20 years of infection however in hypogammaglobulinemic patients disease pro- gresses faster, leading to cirrhosis and death within 10 years of diagnosis and frequently earlier. Here we pre- sent a 57-year-old woman with common variable immunodeficiency infected with hepatitis C after antral and duodenal resection and gastrojejenostomy operation in another hospital for lymphoma mimicking duodenal nodular hyperplasia which then rapidly progressed to decompansated cirrhosis in less than two years.

Key words: Hepatitis C, Cirrhosis, Hypogammaglobulinemia

(Inter Med 47: 415-417, 2008) (DOI: 10.2169/internalmedicine.47.0535)

to 30 years. CVI may not become obvious until young, mid- Introduction dle or even late adult life (5-7). A prevalence of HCV infec- tion ranging from 9% to 38% has been reported in hy- Hepatitis C virus (HCV) is the most common blood-borne pogammaglobulinemic patients (8, 9). The high rate of HCV infection and the leading cause of chronic . infection in hypogammaglobulinemic patients could be re- Hepatitis C is an indolent, often subclinical disease that may lated to several nosocomial routes of transmission, including lead to cirrhosis and hepatocellular carcinoma after decades. intravenous immunoglobulin (IVIG) administration, but However in hypogammaglobulinemic patients with hepatitis HCV seroprevalence in those who did not receive IVIG C, disease progresses faster, leading to cirrhosis approxi- therapy is very rare in this group of patients (10). mately in 10 years (1). Here, we present a 57-year-old woman with common variable immunodeficiency infected Case Report with hepatitis C after antral and duodenal resection and gas- trojejenostomy operation in another hospital for lymphoma A 57-year-old woman was referred to our outpatient mimicking duodenal nodular hyperplasia and then rapidly clinic with recurrent respiratory tract infections, dyspepsia progressed to decompansated cirrhosis in less than two and weight loss (8 kilograms in the previous 6 months). In years. her history, there were episodes of short duration of diar- Common variable immunodeficiency (CVI) is the second rhea. She had subtotal gastrectomy, duodenectomy and gas- most common type of hypogammaglobulinemia after the se- trojejenostomy operation in 2004 for lymphoma suspicion in lective IgA (immunoglobulin) deficiency. CVI is character- an another hospital. Anti-HCV which was negative before ized with decreased levels of IgG, IgA, IgM and frequent operation and first found seropositive six months after the respiratory tract infections, gastrointestinal symptoms and operation suggesting HCV transmission during operation. autoimmune diseases (2). Gastrointestinal manifestations of She was hospitaliazed for further examination. On physical CVI have been associated with T cell defects (3). It is a rare examination the right lobe of the liver was atrophic and the disorder that occurs at a rate of approximately 1 case per left lobe 3 cm was palpable below the costal margin. She 100,000 births (4). Although the typical age of onset is 20 also had 4 cm splenomegaly, mild ascites, telangiectasias

Department of Gastroenterohepatology, Istanbul University, Istanbul Faculty of Medicine, !stanbul Received for publication August 17, 2007; Accepted for publication December 3, 2007 Correspondence to Dr. Fatih Ermis, [email protected]

415 Inter Med 47: 415-417, 2008 DOI: 10.2169/internalmedicine.47.0535 and palmar erythema. On admission to hospital her labora- for chirrosis and discharged from hospital in order to come tory results were as follows: the erythrocyte sedimentation as an outpatient. rate was 7 mm/hour. AST (aspartate aminotransferase): 89 IU/L (normal, to 42 IU/L), ALT (alanine aminotransferase): Discussion 61 IU/L(normal, to 45 IU/L), ALP (alkaline phosphatase) : 665 IU/L (normal, to 260 IU/L), GGT (γ-glutamyltran- Hepatitis C is very aggressive in primary hypogam- sferase) : 349 IU/L(normal, to 85 IU/L), total bilirubin: 2,17 maglobulinemia and progresses to cirrhosis in a short period mg/dl (direct bilirubin 1,36 mg/dl), prothrombin time: 14,9 of time. Anti-HCV seropositivity was first found six months seconds (normal, to 13 seconds). Total blood count results after the gastrojejenostomy operation in 2004, and there was were as follows:White blood cell: 6,700/ml, (: no determined risk factor before the operation. She did not 3,900/ml, lymphocyte: 1,900/ml), hemoglobin: 10 g/dl, he- receive IVIG either. CVI without IVIG therapy and cirrhosis matoctrit: %29.7, platelet: 164.000/ml. She was negative for combination is really rare (10). The natural history of hepa- both HBsAg and anti-HBs. HBV DNA was also negative. titis C in an immunocompetent host is that of slow, insidi- Anti-HCV antibody was positive and HCV RNA level was ously progressive disease that leads to cirrhosis in approxi- high as 10.502.432 copies/ml (HCV RNA 3.0 assay, Versant mately 20% of patients after 20 years of infection. Age at Bayer). Her genotype was group 1b. Total protein: 5.1 g/dl infection, consumption of 50 g or more per day and

(6-8), albumin: 3.22 g/dl (4-4.7), alfa-1:0.38g/dl(0.2- male gender are independent risk factors for disease progres-

0.35), alfa-2: 0.51 g/dl (0.51-0.85), beta-1: 0.36 g/dl (0.34- sion rate. Progression of fibrosis begins to accelerate at 50

0.52), beta-2: 0.18 g/dl(0.23-0.47), gamma: 0.44 g/dl (0.8- years of age independent from duration of infection (12). In 1.35) levels were determined on protein electrophoresis. Im- the present patient, older age can be another factor for rapid munoglobulin subtypes were measured as IgG: 423 mg/dl clinical progression based on the immundeficiency condi- (751-1,560), IgA: 6.67 mg/dl (82-453), IgM: 20.8 mg/dl tion. CVI is a heterogenous group of disorders involving (46-304) respectively. Tumor markers were all in normal both B-cell and T-cell dysfunctions. Main failure is B-cell range. Anti-endomysium IgA antibody was negative. Stool differentiation with immunoglobulin secretion. T-cell abnor- examination was unremarkable for bacterial infections and malities have also been reported, including decreased lym- parasites. In her gastroscopy grade 2 esophageal varices, 2/3 phocyte proliferation to mitogens and antigens, deficiency of distal resected and erosions in the gastrojejenos- antigen primed T cells and reduced production and/or ex- tomy site were seen. Pathological specimen investigation re- pression of especially IL-2 (13, 14). Other vealed findings in the small intestines and in the changes usually seen in CVI include decreased CD4/CD8 anastomosis site. H. pylori negative reactive gastropathy and peripheral T-cell ratio secondary to increased CD8+ T cells. intestinal metaplasia was found in corpus specimens. Nor- Some studies have suggested that these CD8+ T cells func- mal terminal and was found in colonoscopy. tionally abnormal and supress B-cell differentiation. Primary Colonoscopic pathological specimen revealed lymphoplas- -α (TNF-α) has also been mositer and polymorphonuclear leukocyte infiltration in the noted to be elevated and is most likely related to T cell dys- and some in the muscularis mucosa; PAS function (15). In hypogammaglobulinemic patients with (periodic acid-schiff) staining was negative. Liver was atro- hepatitis C, disease progresses faster, leading to cirrhosis phic and lobulated and the left lobe was compensatory hy- and death within 10 years of diagnosis and frequently earlier pertrophic; loculated perihepatic ascites were detected on ab- in the literature (1, 16). Age and hypogammaglobulinemia dominal computerized tomography. There were only small seem to be the most reasonable factors for rapid decompen- lymph nodes (10 mm) surrounding the aorta and there was sation in the present case. The reason for the poor prognosis no finding supporting lymphoma diagnosis. Based on pre in CVI is not clear. HCV is present in the serum in unbound and peroperative pathological specimens of two form or bound form to antibodies. It has been suggested that years previously reevaluated in our department, the infection is slowed by neutralization of virus resulting lymphoid hyperplasia diagnosis was confirmed. Cluster dif- from binding to antibodies. The inability to produce anti- ferentiation (CD) 20, kapa, lambda and CD3 was found to bodies in these immunocompromised patients would allow a be negative on immunohistological analysis. Lymphoma di- higher fraction of unbound virus load, leading to more agnosis was excluded, the present patient had duodenal agressive infection (17). Therefore, high priority should be nodular hyperplasia on the basis of common variable immu- given to detecting and treating such patients with interferon nodeficiency, and she had an unnecessary operation for lym- as early as possible after infection, but sustained viral re- phoma suspicion in another hospital. Since the patient is at sponse to interferon treatment has been found to be poor in increased risk for gastric adenocarcinoma and small-bowel these patients. In the medical literature, rare case reports lymphoma arising in the setting of nodular lymphoid hyper- have been found of patients who sustained biochemical re- plasia, annual gastroscopy and computed tomography are mission and viral remission was obtained after interferon suggested for follow-up program (11). She has taken the therapy (18, 19). Villous atrophy, , duodenal hepatitis B vaccination program (double dose vaccination nodular hyperplasia can be observed in common variable program), and she was given symptomatic medical treatment immunodeficient patients and there is an increased risk of

416 Inter Med 47: 415-417, 2008 DOI: 10.2169/internalmedicine.47.0535 malignancy compared to the normal population. Unneces- progressive cirrhotic form can devolop in CVI. Decompen- sary operative procedures should be prevented with suffi- sated cirrhosis can develop in a shorter time, in less than cient follow-up programs (20). two years as we have seen in the present patient. Therefore In conclusion contrary to the widely known view of in- HCV infection in CVI patients should be treated as soon as sidious, slowly progressive pattern of hepatitis C, a rapidly possible after diagnosis.

References

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