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      Hepatitis C
      Vinod K Dhawan, MD, FACP, FRCP(C), FIDSA Professor, Department of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Infectious Diseases, Rancho Los Amigos National Rehabilitation Center

      Hepatitis C is an infection caused by the hepatitis C virus (HCV) that attacks the liver and leads to inflammation. The World Health Organization (WHO) estimates that about 3% of the world’s population has been infected with HCV and that there are more than 170 million chronic carriers who are at risk of developing liver cirrhosis and/or liver cancer.

      Although HCV treatment typically is performed by gastroenterologists and hepatologists, a study of 125 urban patients with genotype-1 HCV found that the virus can be effectively treated in a primary care clinic with an interdisciplinary team of physicians, nurse practitioners, and patient navigators. Of the 39 (31%) patients in the study who initiated treatment with triple therapy, consisting of weekly injections of pegylated interferon (PEG-IFN) plus ribavirin, along with telaprevir or boceprevir, 16 patients (45%) achieved posttreatment viral suppression; 2 patients (6%) relapsed and 6 (16%) achieved virologic breakthrough.[1]

      Signs and symptoms
      Initial symptoms of hepatitis C are often extrahepatic, most commonly involving the joints, muscle, and skin. Examples include the following:

      Arthralgias
      Paresthesias
      Myalgias
      Pruritus
      Sicca syndrome
      Sensory neuropathy
      Symptoms characteristic of complications from advanced or decompensated liver disease are related to synthetic dysfunction and portal hypertension, such as the following:

      Mental status changes (hepatic encephalopathy)
      Ankle edema and abdominal distention (ascites)
      Hematemesis or melena (variceal bleeding)
      Physical findings usually are not abnormal until portal hypertension or decompensated liver disease develops. Signs in patients with decompensated liver disease include the following:

      Hand signs: Palmar erythema, Dupuytren contracture, asterixis, leukonychia, clubbing
      Head signs: Icteric sclera, temporal muscle wasting, enlarged parotid gland, cyanosis
      Fetor hepaticus
      Gynecomastia, small testes
      Abdominal signs: Paraumbilical hernia, ascites, caput medusae, hepatosplenomegaly, abdominal bruit
      Ankle edema
      Scant body hair
      Skin signs: Spider nevi, petechiae, excoriations due to pruritus

      Other common extrahepatic manifestations include the following:

      Cryoglobulinemia: Membranoproliferative glomerulonephritis
      Idiopathic thrombocytopenic purpura
      Lichen planus[2]
      Keratoconjunctivitis sicca
      Raynaud syndrome
      Sjögren syndrome
      Porphyria cutanea tarda
      Necrotizing cutaneous vasculitis
      Non-Hodgkin lymphoma
      See Clinical Presentation for more detail.

      Diagnosis
      General baseline studies in patients with suspected hepatitis C include the following:

      Complete blood cell count with differential
      Liver function tests, including alanine aminotransferase level
      Thyroid function studies
      Screening tests for coinfection with HIV or hepatitis B virus (HBV)
      Screening for alcohol abuse, drug abuse, or depression
      Tests for detecting hepatitis C virus (HCV) infection include the following:

      Hepatitis C antibody testing: Enzyme immunoassays (EIAs), rapid diagnostic tests (RDTs), and point-of-care tests (POCTs)
      Recombinant immunoblot assay
      Qualitative and quantitative assays for HCV RNA (based on polymerase chain reaction [PCR] or transmission-mediated amplification [TMA])
      HCV genotyping
      Serologic testing (essential mixed cryoglobulinemia is a common finding)
      Liver biopsy is not mandatory before treatment but may be helpful. Some restrict it to the following situations:

      Management
      Treatment of acute hepatitis C includes the following:

      6 months of standard interferon (IFN) therapy is commonly successful
      Initiation of therapy is typically 2-4 months after onset of illness
      The 2 goals of treatment of chronic hepatitis C are as follows :

      To achieve sustained eradication of HCV (ie, sustained virologic response)
      To prevent progression to cirrhosis, hepatocellular carcinoma (HCC), and decompensated liver disease necessitating liver transplantation

      Treatment of chronic hepatitis C includes the following:

      Monotherapy (initial studies; not current standard of care)
      Combination therapy: IFN with ribavirin, IFN with the addition of a polyethylene glycol molecule (pegylated IFN; PEG-IFN), PEG-IFN with ribavirin
      Protease inhibitors (eg, boceprevir and telaprevir) as third component of combination therapy
      Recommendations for nonresponse or relapse[3] include the following:

      No SVR after a full course of PEG-IFN plus ribavirin: Do not re-treat, even with a different PEG-IFN
      No response to antiviral therapy, advanced fibrosis: Screen for hepatocellular carcinoma (HCC) and varices, and evaluate for liver transplantation if appropriate
      Mild fibrosis: Monitor without treatment

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