Nelson Cheinquer

Effect of sustained virologic response on the incidence of hepatocellular carcinoma in patients with HCV cirrhosis

BACKGROUND AND OBJECTIVES Evidence suggests that sustained virologic response to interferon treatment decreases incidence of hepatocellular carcinoma in patients with hepatitis C virus cirrhosis. This study was designed to compare the incidence of hepatocellular carcinoma among cirrhotic patients exposed to interferon based treatment with or without achieving a sustained virological response, in order to evaluate the role of interferon itself in the prevention hepatocellular carcinoma. METHODS A cohort of 85 patients with compensated hepatitis C cirrhosis was followed after treatment with interferon and ribavirin. Sustained virological response was defined as negative polymerase chain reaction assay 24 weeks after the end of treatment. Patients were followed every 6 months with ultrasound and alpha-fetoprotein. Hepatocellular carcinoma was diagnosed by the finding of a focal liver lesion greater than 2 cm with arterial hypervascularization on two imaging techniques and/or by liver biopsy. RESULTS The mean follow-up time was 32.1 ± 20 months for patients who achieved a sustained virological response and 28.2 ± 18 months among 47 patients (55%) without SVR. Hepatocellular carcinoma was diagnosed in 1 (3%) vs. 8 (17%) responders and non responders respectively (p = 0.02). CONCLUSION Patients with cirrhosis due to hepatitis C virus who achieved sustained virological response had significantly lower incidence of hepatocellular carcinoma when compared to those without treatment response. Interferon treatment without achieving sustained virological response does not seem to protect against hepatocellular carcinoma.

HFE gene mutations prevent sustained virological response to interferon plus ribavirin in chronic hepatitis C patients with serum markers of iron overload.

examination revealed left-sided hemiplegia and the upper motor neuron type of left facial (seventh cranial) nerve palsy. Contrast-enhanced CT of the head revealed a hematoma in the right cerebral hemisphere in the parietal lobe. He was managed conservatively. With the help of physiotherapy, power in the limbs improved and he became ambulant and independent. In the meantime, he developed dysphagia with both solids and liquids. Initially, dysphagia was attributed to cerebrovascular accident. However, there was no evidence of ninth or 10th cranial nerve palsy that could have led to dysphagia. Persistence of dysphagia in the presence of progressive improvement in neurological status therefore compelled us to think of an alternative cause for dysphagia. A barium swallow examination showed a moderate symmetrical dilation of the proximal esophagus and a bird’s beak narrowing at the lower end of the esophagus. Upper GI endoscopy revealed a dilated esophagus with puckering of the gastroesophageal junction and failure of opening of the gastroesophageal junction with air insufflation. Furthermore, resistance was felt while negotiating the endoscope through the gastroesophageal junction. These findings were suggestive of achalasia cardia. On asking the patient, he remembered having 2–3 transient episodes of dysphagia 3–4 yr back. Pneumatic balloon dilation of achalasia was performed using an indigenous balloon. He experienced a marked relief in dysphagia initially, but after 6 wk he again had a recurrence of dysphagia. A repeat balloon dilation of achalasia cardia made him asymptomatic. During the initial period after intracerebral bleeding, precipitation of dysphagia might have been contributed by oropharyngeal muscular weakness. However, the predominant cause of dysphagia in the patient was achalasia cardia, as evidenced by resolution of dysphagia after pneumatic balloon dilation. An association between achalasia cardia and neurological disorders such as Parkinson’s disease and hereditary cerebellar ataxia has been described (2, 3). Qualman and colleagues (2) noted Lewy bodies in degenerating ganglion cells of the myenteric plexus and dorsal motor nucleus of the vagus nerve in patients with achalasia and Parkinson’s disease. In a large epidemiological study (4), an association between achalasia cardia and Parkinson’s disease, depressive disorders, and myoneuronal disorders has been noted. The neuropathology in achalasia cardia is not only the loss of ganglion cells in the myenteric (Auerbach’s) plexus of the esophagus, but also a degeneration of the dorsal motor nucleus of the vagus nerve in some patients. Even after an extensive MEDLINE search we did not find another report narrating a precipitation of symptoms of asymptomatic achalasia cardia by an acute neurological event such as cerebrovascular accident as in our patient. One wonders how a hemorrhagic stroke could have made the achalasia cardia symptomatic. The pathophysiological relationship between the two might lie in the dorsal nucleus of the vagus nerve.

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin

CONTEXT Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. OBJECTIVE To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. METHODS A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks. RESULTS Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test). CONCLUSION Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.