Bleeding from a Small-Intestinal Ulcer Associated with Chronic Hepatitis C

Background

Recently, the development of direct-acting antivirals (DAAs) is changing the therapeutic options for curing chronic hepatitis C virus (HCV) infection. These treatments may be performed for elderly patients who have been suffering from hepatitis for a long time. HCV infection has been associated with several immune-mediated processes, including hematologic disorders such as B cell non-Hodgkin lymphoma (B-NHL). The most common B-NHL subtypes associated with HCV infection include marginal zone lymphoma (MZL), Waldenström’s macroglobulinemia (WM), lymphoplasmacytic lymphoma, and diffuse large B cell lymphoma (DLBL). The risk of lymphoma occurrence was reported to be 60% higher in patients with chronic HCV infection as compared with non-HCV controls [1]. We present a rare case of rapid progression of DLBL in a patient with chronic hepatitis C (CHC) and subsequent formation of a small-intestinal ulcer due to the effect of chemotherapy.

Case Report

A 69-year-old Japanese man who had been diagnosed with CHC (Table 1) was treated with pegylated interferon plus ribavirin therapy and achieved rapid virological response (RVR). The dual therapy was continued for approximately 24 weeks, and then low-echoic masses was detected in the liver by ultrasound, although no mass was detected by computed tomography at the beginning of Peg-RBV treatment. He was finally diagnosed with DLBL in the right axillary lymph nodes, liver (Figures 1, 2) and colon (Figure 3, arrow). There was no lesion in the upper gastrointestinal tract, although he had undergone distal gastrectomy in the past. We administered THP-COP chemotherapy regimen, and consequently, the masses in the liver became reduced in size (Figure 4). After a course of chemotherapy, the patient had significant amounts of melena. We performed an emergent upper endoscopy and observed rapidly disseminated tumors and destruction of the tumor and formation of an ulcer by disrupting the tumor, in the duodenal second portion, which was not detected 6 months earlier (Figure 5). We performed blood transfusion and continued chemotherapy, but the patient finally died of neural invasion from lymphoma.

Discussion

There are reports in the literature describing a possible pathogenetic role of HCV infection in the development of aggressive B cell lymphomas. HCV transgenic mice expressing the full HCV genome in B cells have been shown to develop DLBCL in 25% of cases [2].

The outcome of patients with primary lymphoma in the small intestine is poor compared with that of patients with lymphoma in other locations in the GI tract [3]. Although the common causes of small intestine hemorrhage are vascular lesions, ulcerations, small intestine tumors, and jejunal diverticulum, we herein report a rare case with a duodenal ulcer that was caused by disrupting the aggressive DLBL after chemotherapy. Ulcers in the small intestine are sometimes associated with massive, life-threatening hemorrhage and are difficult to treat because it is difficult to survey the small intestine by the usual upper gastrointestinal endoscopy. Therefore, special diagnostic approaches such as capsule endoscopy or double-balloon endos-copy are necessary, and a flexible spectral imaging color enhancement is useful in detecting small ulcerative lesions [4].

Conclusions

Anti-HCV therapy has been shown to play a significant role in the treatment and prevention of HCV-associated B-NHL diseases. However, systemic therapy of B-NHL in patients with HCV infection requires close monitoring of hepatic function and viral activity. The risk of hematologic disorders should be considered in antiviral therapy, and DAAs are mainly used in outpatient therapy for HCV infection. In such cases, hepatologists need to consider the possibility of HCV-associated systematic diseases [5].