Chronic hepatitis is a condition characterized by inflammation of the liver parenchyma lasting for more than six months. It has variable clinical features ranging from no symptoms to fulminant liver failure irrespective of the cause of chronic hepatitis. Several viruses (hepatitis B, C, D, and E ) are known to cause chronic active hepatitis with progression to cirrhosis [1] [2] as well as hepatocellular carcinoma. Chronic hepatitis develops over several years [1]. Other causes of chronic hepatitis include autoimmune hepatitis, drugs like isoniazid, nitrofurantoin and methyldopa (long-standing use), alcohol, non-alcoholic steatohepatitis, deficiency of alpha -1-antitrypsin, Wilson's disease, and hemochromatosis.

Non-specific symptoms of anorexia, easy fatigability, malaise with low-grade fever and upper quadrant abdominal discomfort may be seen in cases of chronic hepatitis although, many patients are asymptomatic and diagnosed incidentally due to elevated liver enzymes. In advanced stages of chronic hepatitis, features of cirrhosis like hepatosplenomegaly, palmar erythema, parotid enlargement, spider nevi, gynecomastia and even ascites, portal hypertension and hepatic encephalopathy may be present. Cholestasis can produce symptoms of jaundice, acholic stools, pruritus, and steatorrhoea. In women with autoimmune chronic hepatitis, features of other organ involvement such as arthralgias, menstrual irregularities, ulcerative colitis, thyroiditis, pulmonary fibrosis, nephritis and hemolytic anemia are seen. Extra-hepatic manifestation like lichen planus, vasculitis, porphyria cutanea tarda, glomerulonephritis, cryoglobulinemia and even lymphomas are noted in chronic hepatitis secondary to hepatitis C while ataxia with other neurological manifestation has been reported in chronic hepatitis E [3] [4].

• Pain

  OUTCOMES: Positive outcome by medication and operation demonstrates that his phosphorus and serum calcium levels were maintained within normal range and pain in the right thigh region was improved from visual analogue pain score (VAS) 7 before surgery [ncbi.nlm.nih.gov]

  Tell your health care provider right away if you have stomach area pain that may be a symptom of this type of blood clot New or worsened cataracts (a clouding of the lens in the eye). [us.promacta.com]

  Dengue can provoke alterations in hepatic functions and typical symptoms of acute hepatitis, such as pain in the right hypochondrium, hepatomegaly, jaundice and elevated transaminase levels. [scielo.br]

• Fatigue

  Except for reduced motivation other dimensions of fatigue were significantly higher among those with CHB compared to healthy controls (p CONCLUSIONS: Poor HRQOL and fatigue are widespread among patients with CHB. [ncbi.nlm.nih.gov]

  Usually minimal if present at all and include nonspecific symptoms of weakness, fatigue, intermittent nausea and abdominal discomfort. Serum Enzyme Elevations. [livertox.nih.gov]

  Symptoms can include: fatigue muscle aches loss of appetite Most symptoms of chronic hepatitis C don’t appear until cirrhosis develops and the liver begins to fail. [healthline.com]

  People with symptoms most commonly complain of fatigue. Fatigue worsens throughout the day and may even be debilitating. [drugs.com]

• Chronic Fatigue Syndrome

  Alleged link between hepatitis B vaccine and chronic fatigue syndrome. Can Dis Wkly Rep 1991;17:215--6. Herroelen L, de Keyser J, Ebinger G. Central-nervous-system demyelination after immunisation with recombinant hepatitis B vaccine. [cdc.gov]

• Abdominal Pain

  (H&E stain) Specialty Infectious disease, gastroenterology, hepatology Symptoms Yellowish skin, poor appetite, abdominal pain Classification D ICD-10: K75.9 ICD-9-CM: 573.3 MeSH: D006505 DiseasesDB: 20061 External resources MedlinePlus: 001154 WHO fact [en.wikipedia.org]

  But over time, they can experience the following: tiredness weight loss nausea abdominal pain severe itching jaundice (yellow discoloration of the skin and eyes) Eventually, people can have complications such as fluid in the abdomen and difficulty thinking [hepc.liverfoundation.org]

  Acute infection may occur with limited or no symptoms, or may include symptoms such as jaundice (yellowing of the skin and eyes), dark urine, extreme fatigue, nausea, vomiting and abdominal pain. [web.archive.org]

  Blood clots in the liver's main artery may cause abdominal pain. The following tests will be done: Blood tests to check liver function ( AST and ALT ). These readings can be very high with ischemia. Doppler ultrasound of the blood vessels of liver. [nlm.nih.gov]

• Joint Effusion

  A 21-year-old African (Ghanaian) man with chronic hepatitis B infection was referred to our Endocrine unit as having acromegaly with changing facial features, enlarging hands and feet, and large knee joint effusions which affected activities of daily [ncbi.nlm.nih.gov]

• Palmar Erythema

  In advanced stages of chronic hepatitis, features of cirrhosis like hepatosplenomegaly, palmar erythema, parotid enlargement, spider nevi, gynecomastia and even ascites, portal hypertension and hepatic encephalopathy may be present. [symptoma.com]

  erythema Patients with advanced cirrhosis may develop ascites or esophageal varices Serum enzyme levels usually fluctuate but may be elevated 2x to 10x Many patients with mild chronic hepatitis C have persistently normal serum aminotransferase levels [pathologyoutlines.com]

  Palmar erythema. Jaundice. Clubbing. Dupuytren's contracture (alcoholic cirrhosis). Xanthomas: palmar creases or above the eyes in primary biliary cirrhosis. Initial hepatomegaly may be followed by a small liver in well-established cirrhosis. [patient.info]

  Often, particularly with HCV, the first findings are Signs of chronic liver disease (eg, splenomegaly, spider nevi, palmar erythema) Complications of cirrhosis (eg, portal hypertension, ascites, encephalopathy) A few patients with chronic hepatitis develop [merckmanuals.com]

• Hirsutism

  Hirsutism. Investigation of chronic hepatitis Urinalysis : bilirubin and urobilinogen. Blood tests: FBC (associated anaemia, thrombocytopenia, raised MCV with alcohol abuse), clotting studies (clotting impairment with hepatic dysfunction). [patient.info]

• Dysarthria

  INTRODUCTION: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a brainstem disorder characterized by perivascular pathologic reaction with lymphocyte infiltration and leading to diplopia, facial palsy, dysarthria [ncbi.nlm.nih.gov]

The workup in all cases should begin with a detailed history and physical examination. As the etiology of chronic hepatitis can be variable like congenital alpha-1-antitrypsin deficiency, viral, autoimmune or long-standing usage of drugs and alcohol, the workup should specifically note previous history of hepatitis, high risk behavior (drug /alcohol abuse, multiple sexual partners), tattoos /piercings, history of incarceration, blood/ blood product transfusion, surgery, autoimmune diseases etc). Needle tracks, features of icterus, cirrhosis, and cholestasis should be looked for during physical examination.

Routine laboratory tests like complete blood count, urinalysis, stool analysis, liver enzymes, serum proteins and, coagulation profile are obtained. If hepatitis is confirmed on laboratory tests then specific tests to detect etiology of the chronic hepatitis are performed. These include viral serology, autoantibodies, alpha-1-antitrypsin levels, immunoglobulins, ceruloplasmin levels (in children to rule out Wilson's disease). Serum iron, ferritin, and total iron-binding capacity levels can help detect hemochromatosis as the cause of chronic hepatitis.

If an asymptomatic patient is detected with elevated liver enzymes and if they were born between 1945 and 1965, they should be evaluated for hepatitis C. Cryoglobulin and rheumatoid factor levels are assessed in patients with chronic hepatitis secondary to hepatitis C.

Liver biopsy is the gold standard for the diagnosis of chronic hepatitis and provides information about the extent of cellular necrosis, parenchymal fibrosis and inflammation [5] [6]. Histopathology can also detect steatohepatitis and iron deposition and helps to plan further disease management and prognosis [7]. Fibroscan, an ultrasound-based procedure can detect liver fibrosis in advanced cases while blood tests like FIBROSpect II, HepaScore, and HCV FIBROSURE are used to detect mild and severe stages of liver fibrosis.

1. Previsani N, Lavanchy D. World Health Organization. Hepatitis D. (WHO/CDS/CSR/NCS/2001.1). 2001. Accessed January 24,2017.
2. Adhami T, Levinthal G. Hepatitis D. The Cleveland Clinic Disease Management Project. May 29, 2002.
3. Kamar N, Bendall RP, Peron JM, et al. Hepatitis E virus and neurologic disorders. Emerg Infect Dis. 2011;17:173–179.
4. Kamar N, Weclawiak H, Guilbeau-Frugier C, et al. Hepatitis E virus and the kidney in solid-organ transplant patients. Transplantation. 2012;93:617–623.
5. European Association for Study of Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol. 2014;60:392–420.
6. Dienstag JL. The role of liver biopsy in chronic hepatitis C. Hepatology. 2002;36:S152–S160.
7. Bedossa P, Moucari R, Chelbi E, et al. Evidence for a role of nonalcoholic steatohepatitis in hepatitis C: a prospective study. Hepatology. 2007;46:380–387.