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home - Liver - Hepatitis C - Hepatitis C Extra Hepatic Manifestations Written by Dr Sebastian Zeki

Understands the serological interpretation categorisation and
investigation of patients with chronic hepatitis B and/or C with
particular emphasis on the need for treatment and surveillance

Recognises the particular populations at risk
Aware of national and international agreed guidelines on viral
hepatitis management and use of interferon and antiviral drugs

Aware of hepatitis B reactivation in the context of immunosuppression
Uses appropriate diagnostic modalities including serology
genotyping viral load measurements liver biopsy and related

Monitors anti-viral and immunomodulatory therapies with appropriate

Communicates effectively with patients and relatives in the context of
viral liver disease and underlying social and psychological risk factors

Marshals multi-disciplinary support networks and in particular
recognise the crucial role of nurse practitioners in disease


Hepatitis C Extra Hepatic Manifestations

Monoclonal gammopathies — Hepatitis C (genotype 2a/c) may be a risk factor for the development of monoclonal gammopathies.Lymphoma —B-cell non-Hodgkins lymphoma (NHL) (Inc RR of 25%)Waldenstrom macroglobulinemia; Diffuse large B-cell lymphomaMarginal zone lymphoma; Lymphoplasmacytic lymphoma; Not follicular lymphoma; Immunocytoma has very strong asocationAlso...Primary hepatic lymphoma.; MALT lymphomas; HCV cryoglobulinemia may progress to a NHL Patients with HCV patients t(14;18) translocation with overexpression of the antiapoptotic bcl-2 proto-oncogene and bcl-2 rearrangements suggesting that bcl-2 may be a contributing factor to lymphoma development. Diabetes MellitusHCV genotype 2a is overrepresented among the diabetics .DM may be due to HCV core gene directly involved in insulin resistance development.DM may be due to more parenteral exposures .Cirrhosis may be associated with impaired glucose tolerance. Autoimmune DisordersAutoimmune hepatitis antibodies can flare up with interferon.LKM-1 antibodies in patients with HCV are directed at different epitopes of cytochrome P450 2D6 (CYP2D6, the target antigen) from that seen with autoimmune hepatitis.Thyroid disease occurs in 10% of HCV with 5% getting thyroid disease.Sialadenitis can occur and Sjogren’s syndrome has been described.Autoimmune thrombocytopenic purpura occurs in 20%. ITP patients have HCV either because of transfusion or antibodies develop as a result of ITP.Sarcoidosis has been described. CD81 Virus binding to cd81 on B lymphocytes lowers threshold for antibody production Circulating immune complexes in small to medium sized blood vessels. Treatment of patients with cryoglobulinemia due to HCV should be based upon the presence of cryoglobulinemia symptoms rather than the usual criteria used in patients with chronic hepatitis aloneRituximab has shown promise if cryoglobs are refractory. Essential mixed cryoglobulinemia OTHERFocal segmental glomerular sclerosisProliferative glomerulonephritisFibrillary Immunotactoid glomerulopathiesGlomerular diseases can occur both in native kidneys and renal allografts. Renal Disease MIXED (IgG/IgM) CRYOGLOBULINEMIA — =Systemic vasculitis. 95% with this have HCVPresentation: Nonspecific systemic symptoms; palpable purpura; skin necrosis Hepatosplenomegaly; Hypocomplementemia (C4<C3); Renal disease (hematuria, nephritic range proteinuria, and renal insufficiency(50%), HTN (80%))Labs Type II cryoglobulins - rheumatoid factor is IgM kappa.The complement components, C3, C4 and C1q, are usually low. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS —Esp Type MEMBRANOUS NEPHROPATHY —Also contraversial CLINICALLY SILENT GLOMERULAR DISEASE — On bx without clinical manifest.) Treatment: ACEI or AIIR blockersWe suggest that patients with HCV and MPGN with or without cryoglobulinemia be considered for anti-HCV therapy.The specific antiviral therapy varies based upon the estimated glomerular filtration rate (GFR in mL/1.73m2)): - GFR normal (>50) :Pegylated interferon, plus ribavirin. - GFR (15 - 50) :Monotherapy with pegylated interferon. - GFR <15 : Monotherapy with standard interferonPegylated interferon contraindicated if GFR< 15 Ribavirin contraindicated if GFR <5012 month pegylated interferon course If severe acute disease start antiviral after acute episode treated Screen all HCV patients for:Proteinuria, hematuria, hypertension, and renal functionCryoglobulinemia, complement, and rheumatoid factors.Consider kidney biopsy depending on screen Cognitive dysfunctionHCV is associated with neurocognitive dysfunc-tion even without advanced liver disease. Myocarditis and Cardio-myopathy HCV assoiation has been noted. Ocular Disease:Dry eyes, corneal ulcers (Mooren's ulcer), uveitis, and scleritis and sicca syndrome in patients with HCV-related Sjogren's syndrome.Also, ophthalmologic disorders (retinal hemorrhages, cotton wool spots, and rarely retinal artery or vein obstruction) can occur during interferon therapy Autoantibodies: Antinuclear antibodies.Antibodies directed against the Fc portion of IgG (rheumatoid factor).Anticardiolipin antibodies.Smooth muscle antibodies.Antithyroid antibodies. Haemotological Disorders These are common in HCV (50%), in low titre and usually no extrahepatic disease and include Can arise during interferon therapy Extrahepatic Hep C Diagno-ses Porphyria cutanea tarda and hepatitis C virus infectionStrong assoc. with HCVThe classic presentation consists of photosensitivity and uroporphyrinuria in the setting of chronic liver disease.Labs: High urine uroporphyrin levels.Urinary porphyrins >800 microg/day when photosensitive.Treatment Relies on:1. Avoiding factors that precipitate attacks, such as alcohol, estrogens, and exposure to polyhalogen-ated hydrocarbons. 2. Treatment of the underlying iron overload state, if present.3. Treatment of HCV infection, if present.PCT should be considered an indication for treatment of HCV;(even if mild)Leukocytoclastic vasculitis — Can occur in conjunction with essential mixed cryoglobulinemiaBiopsy: cutaneous vasculitis with dermal blood vessel destruction associated with neutrophilic infiltration in and around the vessel wall Can get same changes in lower limb nerves in vasa nervorum.Lichen planus —Anti-HCV antibodies are present in 10 to 40 percent of these patients but a cause-and-effect relation is uncertain.Necrolytic acral erythema Dermatological Disease Hepatitis C-associated osteosclerosis: Rare. Get marked increase in bone mass during adult life.Periosteal, endosteal and trabecular bone thickening occurs throughout skeleton with exception of cranium. During active disease, forearm and leg pain are common, bone remodeling (turnover) is high, and bone mineral density is 2-3x normalAetiology: Abnormal IGF-I or II or binding proteinsIncreased remodeling responds to bisphospho-nates or calcitonin; spontaneous remission has also described. Musculoskeletal Risk factors for DM development:-Older age; Obesity; Severe liver fibrosis; FH of DMInsulin resistance may contribute to fibrosis progression, particularly with HCV genotypes 1 and 4 and high serum RNA levels.Insulin resistance may also impair the response to antiviral therapy with interferon and ribavirin. Written by Dr Sebastian Zeki

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