Advances in the treatment of hepatitis C.

The health care burden caused by hepatitis C is projected to increase significantly in the next 20 years, on the basis of modeling estimates of cirrhosis, hepatic decompensation, and HCC likely to be seen in this population in the future. The number of cases of HCV-induced liver decompensation and mortality in the United States is projected to be approximately 4 times higher by the year 2018 than is currently seen, because of the aging of those presently infected. HCV also poses a significant quality-of-life decrement in the majority of individuals with chronic infection. Quality-of-life assessment in these patients has shown substantial reductions in both somatic and physical functioning compared with the general population, regardless of disease severity. The impact of chronic HCV on quality-of-life issues has been equated to that of non-insulin-dependent diabetes. Thus, HCV imparts a considerable toll on individual level of functioning and on overall health care resources. Hepatitis C evolves into a chronic infection in approximately 85% of individuals exposed to the virus, and progression to cirrhosis occurs in 20% to 30% of patients, with a disease duration up to 20 years. Hepatic decompensation will occur in approximately 20% and HCC in about 10% of those with HCV-related cirrhosis within 5 years of the determination of cirrhosis. End-stage liver disease caused by HCV is now the most common indication for liver transplantation in this country. Patients in whom liver decompensation develops should be considered for liver transplant evaluation, with referral to appropriate centers if these complications arise. Individuals with decompensated disease should not be treated with any of the current regimens available for HCV eradication, because these agents can accelerate hepatic dysfunction and will not mitigate the clinical outcome after the onset of decompensation. Available treatment options for HCV are rapidly changing, with INF as the standard and combination therapy with INF plus ribavirin rising to prominence as the optimal option. The need for abstinence from alcohol cannot be underestimated, given its documented synergistic effects on hepatotoxicity when combined with chronic HCV. Patients must be counseled in this regard and provided with the rationale for this recommendation. The benefits of therapy from a medical resource standpoint have recently been defined through analyses of cost-effectiveness. Bennett et al. used a mathematical model to estimate the cost-effectiveness of INF in the treatment of mild chronic HCV (no bridging fibrosis or cirrhosis). Therapy was found to be cost-saving for patients aged 20 to 35 years and was found to increase life expectancy by 3 and 1.5 years, respectively, at the spectrums of this age range. Kim et al. found the cost-effectiveness of a 12-month course of INF to compare favorably to other accepted medical interventions in the United States in patients younger than 60 years. Similar data for combination therapy has not yet been reported but would be expected to be comparable. Interferon monotherapy for 12 months is the current standard treatment recommendation for individuals with chronic HCV and elevated ALT levels. The explosive expansion of information now available to, and frequently quoted by, HCV patients seeking treatment will increasingly make this option less acceptable to a great many of this group. Combination therapy has emerged as the most efficacious option to date, both as initial treatment and for patients who relapse after standard INF. Unless data appear to the contrary, combination therapy should be considered first-line treatment in these groups. A suggested treatment algorithm for chronic HCV is outlined in Figure 2. Patients intolerant to ribavirin should be considered for continuation of INF to complete a 12-month course, dependent upon the assessment of HCV PCR status at week 12 of therapy. (ABSTRACT TRUNCATED)

Splenosis presenting as an ulcerated gastric mass: endoscopic and endoscopic ultrasonographic imaging.

A case of an ulcerated gastric wall mass ultimately found to be splenosis is presented in which the index patient had endoscopic and endoscopic ultrasonographic evaluation prior to resection. Although no visual features identified this mass as a splenic implant preoperatively, the lesion appeared to be atypical for leiomyoma, which led to surgical intervention. The role of endoscopic ultrasonography in assessing isolated gastric masses is discussed.

Correlation of liver density by magnetic resonance imaging and hepatic iron levels. A noninvasive means to exclude homozygous hemochromatosis.

The diagnosis of hemochromatosis requires liver biopsy and the quantification of hepatic iron. Magnetic resonance imaging (MRI) of the liver shows a characteristic decrease in tissue signal intensity in iron overload states, but its role in the diagnosis of hemochromatosis has not been fully delineated. Forty-three patients (31 men and 12 women) were referred for the evaluation of hemochromatosis based upon a fasting transferrin saturation > 55% and/or a serum ferritin > 400 ng/ml in males or > 300 ng/ml in females. Each patient prospectively underwent MRI of the liver prior to percutaneous liver biopsy and quantitative hepatic iron determination. Homozygous hemochromatosis was diagnosed in 10 patients based upon an hepatic iron/age index > or = 2. MRI was performed with a 1.5 Tesla system using standard spin-echo sequences (T1; TR = 300-500 ms, TE = 13-17 ms, PD; TR = 2,000-2,600 ms, TE = 30 ms). Signal intensity values were blindly determined for regions of interest in liver and skeletal muscle at T1 and proton density. Ratios of liver to muscle (LM) for T1 and proton density (PD) calculated from these values showed a significant correlation with quantitative iron by multiple regression analysis. The LMPD ratio provided the best correlation with hepatic iron (r = -0.6946; p < 0.001). Linear regression analysis also provides an equation that can be used to predict hepatic iron based upon the LMPD ratio; micrograms/g of hepatic iron = (-5,174 x LMPD) + 9,932. All patients with LMPD ratios of > 0.5 had hepatic iron/age indices of < 2.0, thereby excluding homozygous hemochromatosis. These results suggest that LMPD ratios derived from MRI of the liver can accurately predict hepatic iron content. These ratios can be clinically useful in the evaluation of hemochromatosis among patients who either refuse or have contraindications to liver biopsy.

Course of thrombocytopenia of chronic liver disease after transjugular intrahepatic portosystemic shunts (TIPS). A retrospective analysis.

Thrombocytopenia associated with chronic liver disease presents a difficult management issue. Most reports conclude that portocaval and distal splenorenal shunts do not improve platelet counts in this setting. The response of thrombocytopenia after transjugular intrahepatic portosystemic shunt placement has not been studied. All platelet counts of 21 patients undergoing intrahepatic shunt placement were determined retrospectively to accumulate values at one month prior to procedure, weekly for the first month after the procedure, and monthly thereafter to six months. Comparison of pre- and postshunt platelet means showed a significant increase in counts in patients with a postshunt portal pressure gradient < 12 mm Hg, with the increment evident by one week after the procedure. This response was not seen when preshunt thrombocytopenia was used as the lone variable. This study suggests that the transjugular intrahepatic portosystemic shunt may improve the thrombocytopenia associated with liver cirrhosis when these pressure gradients are attained.

A 39 year old man with chronic hepatitis.

The diagnosis of primary sclerosing cholangitis in association with autoimmune hepatitis was made in this case after the discovery of inflammatory bowel disease prompted a cholangiogram. Immunosuppressive therapy with cyclosporine prior to ERCP resulted in a significant decrease in serum aminotransferase. Liver histology and autoimmune serologies favored a diagnosis of AIH, while cholangiographic findings suggested PSC. A review of similar cases describing the simultaneous occurrence of AIH and PSC is presented. The shared autoimmune characteristics of the two diseases, such as serum autoantibodies, peripheral lymphocyte subsets and HLA haplotypes, raises the question of whether similar mechanisms of immune dysfunction can result in both processes. The existence of a PSC-AIH overlap syndrome may help provide the linkage between the two diseases.

Transient focal hepatic defects related to sustained-release niacin.

Hepatotoxicity is a potential side effect of niacin therapy for hypercholesterolemia, ranging from mild aminotransferase elevation to fulminant hepatic failure. Although uncommon with plain forms, liver dysfunction has increasingly been associated with sustained-release preparations. This case illustrates transient focal liver defects seen on computed tomography with symptomatic elevation of liver-associated enzymes during treatment with sustained-release niacin. The masses were not evident on radionuclide liver scan, suggesting focal fatty liver. After niacin was discontinued, these abnormalities resolved, and aminotransferases returned to normal. This is the first such reported case.

Radioimmunoassayable N-Tyr-MIF-1-like activity in rat brain is increased by pinealectomy.

Levels of N-Tyr-MIF-1-like immunoreactivity were measured in rat brain by radioimmunoassay (RIA). Although the highest levels were found in the pineal and hypothalamus, the striatum and thalamus also contained significantly more immunoreactivity than the other parts of the brain. Since oxytocin cross-reacts 5.4% with the antibody for N-Tyr-MIF-1, oxytocin-like immunoreactivity was also measured by RIA, but could not account for the levels of radioimmunoassayable N-Tyr-MIF-1 found in these experiments. There was a significant increase in N-Tyr-MIF-1-like immunoreactivity after pinealectomy, a tendency for a decrease after stress, but essentially no change after hypophysectomy. A diurnal rhythm was observed with the highest levels at night and lowest levels during the day. The results demonstrate the presence in brain tissue of a novel immunoreactive peptide, the levels of which can be altered by neuroendocrine manipulations.

Radioimmunoassay of MIF-1/Tyr-MIF-1-like material in rat pineal.

The hypothalamic peptide MIF-1 (Pro-Leu-Gly-NH2) was coupled to thyroglobulin and injected into rabbits. The resulting antiserum reacted with the tetrapeptide Tyr-MIF-1 to a greater extent than with the tripeptide MIF-1, presumably because of a better conformation for antibody binding. By radioimmunoassay (RIA), immunoreactive MIF-1/Tyr-MIF-1-like material was found in the pineal gland of each of the 100 rats examined. The tendencies for slightly higher levels in pineals obtained from rats kept in constant darkness for two weeks, from rats in a normal light cycle decapitated at noon, or from rats which had been hypophysectomized were not statistically significant. Gel filtration of pineal extracts on a column of Sephadex G-10 revealed that by RIA one immunoreactive peak eluted near MIF-1 and oxytocin, and another peak near Tyr-MIF-1. The results suggest the presence in pineal tissue of an MIF-1-like material as well as a novel peptide containing Tyr-Pro-Leu-Gly-NH2 or a closely related structure for which oxytocin is unlikely to be the precursor.