Association between thyroid dysfunction and chronic hepatitis C genotype 4 virus infection and effect of interferon therapy on it

Autoimmune thyroid dysfunction, a cluster of conditions in which the immune system can either attack or stimulate thyroid tissue, has been associated with HCV infection. Autoimmune thyroid disease can take various forms, from the symptoms of hypothyroidism to the palpable goiters. Therefore, this work aimed to estimate the prevalence of thyroid dysfunction in HCV genotype 4 Egyptian patients and assess the effect of interferon therapy on it. Also to study the association between thyroid disorders, TNF-alpha and liver function parameters among HCV infected patients. A case control study was conducted on 253 HCV genotype 4 patients selected randomly, attended to National liver Institute, Monuflya University, The patients were divided into two groups. 220 chronic HCV patients not treated with any anti-viral therapy. 33 chronic HCV patients, treated with pegylated interferon [Peg-IFN] combined with ribavirin for 12 months. For both groups of patients, PCR test were done. Also liver biopsy was performed before treatment to assess hepatic fibrosis using histological hepatic activity index [HAI] of Knodell et al and modification of Ishak et al. In addition to 19 healthy individuals without any thyroid dysfunction or liver diseases used as control group. Levels of thyroid-stimulating hormone [TSH], total thyroxine [T4], triiodothyronine [T3] and tumor necrosis factor alpha, also all liver function tests were measured. The overall prevalence of thyroid disorders among non treated group was 13.6 percent [30 cases], 63.3 percent of them were females, 13 [5.9 percent] were hyperthyroidism, 8 [61.5 percent] of them were females, and 17 [7.7 percent] were hypothyroidism, 11 [64.7 percent] of them were females. While the prevalence among HCV treated patients were 15.1 percent [5 cases], all of them had hypothyroid function only, 4 [80 percent] of them were females .The serum tumor necrosis factor alpha [TNF- alpha] levels significantly increased in HCV infected non treated patients when compared with control group [p< 0.001], and in treated patients when compared with non-treated group [p < 0.001]. TNF-alpha level showed significant positive correlation with thyroid stimulating hormone [TSH] in HCV treated group and significant negative correlation with albumin and aspartate transaminase [AST] in the HCV non-treated group. HCV infection are associated with thyroid dysfunction especially after interferon and ribavirin treatment TNF-alpha may play a role in inducing autoimmune thyroid disorders. This implies that these patients should be screened for thyroid function on a periodic basis especially interferon treated cases

Histopathological changes in anti-HCV positive subjects with persistently normal aminotransferase levels

Approximately 30% of patients with chronic hepatitis C have normal serum alanine transaminase [ALT] levels; most of those patients have mild degrees of inflammation with mild or no fibrosis and the rate of disease progression is reduced compared to that in patients with elevated ALT levels. Is to study the histopathological characteristics of anti-HCV positive subjects with persistently normal aminotransferase levels in comparison with those patients having elevated aminotransferase levels. A comparative case control study was conducted on 80 patients who asked medical advice in outpatient clinics of National Liver Institute, Menoufiya University and Specialized Medical Hospital, Mansoura University. They were classified into two groups. Group I: were forty anti-HCV-positive subjects with normal enzymes. They were 28 males, 12 females. Their age ranged from 18 to 50 years with a mean age of 31 +/- 8.47 years. Group II: were forty chronic hepatitis C patients [31 males and 9 females] their age ranged between 17-53 years with a mean age 32.12 +/- 7.70 years with elevated ALT levels [one and half or more times of the upper limit of normal for at least six months], Both groups were subjected to thorough history taking and physical examination, complete blood counts [CBC], routine liver tests, abdominal ultrasound and percutaneous ultrasound guided liver biopsy to assess the severity of the necro-inflammatory process using histological activity index [HAT] of Knodell et al. and modification of Ishak et al. This research showed that the majority of anti-HCV positive patients with persistently normal ALT have histological features of minimal to mild necro-inflammation [HAT]. The severity of histological necro-inflammation is reduced in anti-HCV positive patients with persistently normal ALT compared with that of patients with elevated ALT levels. Also they have no or minimal to mild stage of fibrosis compared with that in patients with elevated ALT levels. Persistently normal ALT patients with steatosis had higher HAT grades and fibrosis stages than patients without steatosis and a significant correlation was found between steatosis and increased BMI. Moderate significant correlation was found between low platelet counts and fibrosis stage in patients with elevated ALT levels. The majority of anti-HCV positive patients with persistently normal ALT have histological-pathological changes of variant degrees of severity specially patients having steatosis. So it is recommended that patients with chronic hepatitis C should not be excluded from therapy based on ALT levels alone and the treatment must be individualized according to each patient